Terapia con láser para el tratamiento de cicatrices hipertróficas y queloides
Resumen
Antecedentes
Las cicatrices hipertróficas y queloides son afecciones cutáneas frecuentes que aparecen como resultado de la cicatrización anormal de las heridas. Pueden causar picor, dolor y tener un efecto físico y psicológico negativo en la vida de los pacientes. Existen distintos métodos utilizados para mejorar estas cicatrices, como los corticosteroides intralesionales, la cirugía y, más recientemente, la terapia con láser. Dado que la terapia con láser es cara y podría tener efectos adversos, es fundamental evaluar los posibles efectos beneficiosos y perjudiciales de esta terapia para el tratamiento de las cicatrices hipertróficas y queloides.
Objetivos
Evaluar los efectos de la terapia con láser para el tratamiento de cicatrices hipertróficas y queloides.
Métodos de búsqueda
En marzo de 2021 se realizaron búsquedas en el Registro especializado del Grupo Cochrane de Heridas (Cochrane Wounds), en CENTRAL, MEDLINE, Embase, CINAHL EBSCO Plus y LILACS. Para identificar estudios adicionales, también se buscaron estudios en curso y no publicados en registros de ensayos clínicos, y se examinaron las listas de referencias de los estudios pertinentes incluidos, así como en revisiones, metanálisis e informes de tecnología sanitaria. No hubo restricciones en cuanto al idioma, la fecha de publicación ni el lugar de los estudios.
Criterios de selección
Se incluyeron ensayos controlados aleatorizados (ECA) para el tratamiento de las cicatrices hipertróficas o queloides (o ambas), que compararon la terapia con láser con placebo, ninguna intervención u otra intervención.
Obtención y análisis de los datos
Dos autores de la revisión seleccionaron de forma independiente los estudios, extrajeron los datos, evaluaron el riesgo de sesgo de los estudios incluidos y realizaron las evaluaciones con el método GRADE de la certeza de la evidencia. Un tercer autor de la revisión arbitró en caso de desacuerdos.
Resultados principales
Se incluyeron 15 ECA, con 604 participantes (niños y adultos), con tamaños muestrales que variaron de diez a 120 participantes (media de 40,27). Cuando los estudios asignaron al azar a diferentes partes de la misma cicatriz, cada segmento de cicatriz constituyó la unidad de análisis (906 segmentos de cicatriz). La duración del seguimiento de los participantes varió de 12 semanas a 12 meses. Todos los ensayos incluidos tenían un alto riesgo de sesgo en al menos un dominio: todos los estudios se consideraron de alto riesgo de sesgo debido a la falta de cegamiento de los participantes y del personal. La variabilidad de los tipos de intervención, los controles, los periodos de seguimiento y las limitaciones con los datos proporcionados supusieron la agrupación de los datos para una comparación (y solo dos desenlaces dentro de esta). Varios desenlaces secundarios de la revisión (resultado cosmético, tolerancia, preferencia por diferentes formas de tratamiento, adherencia y cambio en la calidad de vida) no se proporcionaron en ninguno de los estudios incluidos.
Láser versus ningún tratamiento:
Se encontró evidencia de certeza baja que indica que podría haber una mayor mejoría de las cicatrices hipertróficas y queloides (es decir, cicatrices menos graves) en las cicatrices tratadas con láser de colorante pulsado (LCI) de 585 nm en comparación con ningún tratamiento (razón de riesgos [RR] 1,96; intervalo de confianza [IC] del 95%: 1,11 a 3,45; dos estudios, 60 segmentos de cicatriz).
No está claro si el láser fraccionado no ablativo (LFNA) influye en la gravedad de las cicatrices hipertróficas en comparación con ningún tratamiento (evidencia de certeza muy baja).
No está claro si el láser fraccionado de dióxido de carbono (CO2) influye en la gravedad de las cicatrices hipertróficas y queloides en comparación con ningún tratamiento (evidencia de certeza muy baja).
Ocho estudios informaron sobre los efectos adversos relacionados con el tratamiento, pero no proporcionaron suficientes datos para realizar análisis adicionales.
Láser versus otros tratamientos:
Se desconoce si que el tratamiento con LCI de 585 nm repercute en la gravedad de las cicatrices hipertróficas y queloides en comparación con el corticosteroide intralesional acetónido de triamcinolona (ACT), el fluorouracilo (5‐FU) intralesional o el uso combinado de ACT más 5‐FU (evidencia de certeza muy baja). Tampoco se sabe con certeza si el láser de erbio influye en la gravedad de las cicatrices hipertróficas en comparación con el ACT (evidencia de certeza muy baja).
Otras comparaciones incluyeron el LCI de 585 nm versus las láminas de gel de silicona, el láser fraccionado de CO2 versus el ACT y el láser fraccionado de CO2 versus el verapamilo. Sin embargo, los autores no aportaron suficientes datos sobre la gravedad de las cicatrices para comparar las intervenciones.
Dado que solo se dispone de evidencia de certeza muy baja sobre los efectos adversos relacionados con el tratamiento, como el dolor, la carbonización (quemadura de la piel que ennegrece la superficie), la telangiectasia (una afección en la que los pequeños vasos sanguíneos causan líneas rojas como hilos en la piel), la atrofia de la piel (adelgazamiento de la piel), las decoloraciones purpúricas, la hipopigmentación (el color de la piel se aclara) y la erosión (pérdida de parte de la capa superior de la piel, dejando una superficie desnuda) secundaria a la formación de ampollas, no es posible establecer conclusiones sobre la comparación de estos tratamientos.
Láser más otro tratamiento versus otro tratamiento:
No está claro si el LCI de 585 nm más ACT más 5‐FU da lugar a un mayor porcentaje de mejoría de buena a excelente en la gravedad de las cicatrices hipertróficas y queloides en comparación con ACT más 5‐FU, ya que la certeza de la evidencia se ha considerado muy baja.
Debido a la evidencia de certeza muy baja, tampoco se sabe si el láser de CO2 más ACT influye en la gravedad de las cicatrices queloides en comparación con la criocirugía más ACT.
La evidencia también es muy incierta con respecto al efecto del láser de granate de aluminio itrio inducido por neodimio (Nd:YAG por sus siglas en inglés) más el corticosteroide intralesional Diprospan más 5‐FU sobre la gravedad de la cicatriz en comparación con Diprospan más 5‐FU y sobre el efecto del láser de helio‐neón (He‐Ne) más decametil tetrasiloxano, polidimetilsiloxano y crema de ciclopentasiloxano sobre la gravedad de la cicatriz en comparación con decametil tetrasiloxano, polidimetilsiloxano y crema de ciclopentasiloxano.
Solo se dispone de evidencia de certeza muy baja sobre los efectos adversos relacionados con el tratamiento, como el dolor, la atrofia, el eritema, la telangiectasia, la hipopigmentación, el rebrote, la hiperpigmentación (el color de la piel se vuelve más oscuro) y la despigmentación (la pérdida de color de la piel). Por lo tanto, no es posible establecer conclusiones sobre la comparación de estos tratamientos.
Conclusiones de los autores
No hay evidencia suficiente para apoyar o refutar la efectividad de la terapia con láser para el tratamiento de las cicatrices hipertróficas y queloides. La información disponible tampoco es suficiente para llevar a cabo un análisis más exacto sobre los efectos adversos del tratamiento relacionados con la terapia con láser. Debido a la heterogeneidad de los estudios, a los resultados contradictorios, a los problemas de diseño de los estudios y al pequeño tamaño muestral, se deben llevar a cabo más ensayos de alta calidad, con escalas validadas y conjuntos básicos de desenlaces. Estos ensayos deben tener en cuenta la opinión y los valores de los usuarios, la necesidad de un seguimiento a largo plazo y la necesidad de informar sobre la tasa de recurrencia de las cicatrices para determinar si el láser podría lograr resultados superiores en comparación con otros tratamientos de las cicatrices hipertróficas y queloides.
PICO
Resumen en términos sencillos
Terapia con láser para cicatrices hipertróficas y queloides
¿Qué se estudió en la revisión?
Las cicatrices hipertróficas y queloides son cicatrices en relieve y con bultos que se forman cuando una herida no cicatriza correctamente. Estas cicatrices pueden estar descoloridas o enrojecidas y también pueden causar dolor y picor. Existen varios tratamientos disponibles, incluyendo geles de silicona y corticoides.
La terapia con láser podría ser un tratamiento alternativo para este tipo de cicatrices. Durante la terapia con láser, se dispara en determinadas zonas de la piel un potente haz de luz que puede romper el tejido dañado. Existen diferentes tipos de terapia con láser en función del tipo de piel del paciente y de la naturaleza de la cicatriz. La terapia con láser es cara y tiene efectos secundarios potencialmente dañinos, por lo que es importante establecer si es segura y eficaz.
¿Cuál es el objetivo de esta revisión?
El objetivo de esta revisión fue investigar si la terapia con láser es un tratamiento efectivo para las personas con cicatrices hipertróficas y queloides. Para responder a esta pregunta, los investigadores de Cochrane recopilaron y analizaron todos los estudios pertinentes y encontraron 15 ensayos controlados aleatorizados.
¿Cuáles son los resultados principales de la revisión?
Se incluyeron 15 estudios que datan de 1999 a 2019, con 604 participantes (niños y adultos de ambos sexos). Los tamaños de los estudios eran pequeños (de diez a 120 participantes) y la duración del seguimiento de los participantes fue de 12 semanas a 12 meses. Los estudios analizaron el cambio de la gravedad de las cicatrices evaluado por los profesionales sanitarios o los participantes.
En los estudios se compararon diferentes tipos de dispositivos láser con ningún tratamiento y con otros métodos de tratamiento. La terapia con láser combinada con otro tratamiento también se comparó con este tratamiento solo.
No existe seguridad acerca de si la terapia con láser sola o combinada con otros tratamientos mejora la gravedad de las cicatrices hipertróficas o queloides en comparación con ningún tratamiento u otros tratamientos, ya que la certeza de toda la evidencia disponible es baja o muy baja. Esto se debe al escaso número de estudios, las comparaciones diversas, los resultados contradictorios, el reducido número de participantes y la falta de datos disponibles.
Se han notificado algunos efectos secundarios del tratamiento con láser, como daños en la piel o en los vasos sanguíneos subyacentes, enrojecimiento y entumecimiento. Sin embargo, la certeza de la evidencia es demasiado baja como para conocer con certeza la frecuencia de estos efectos secundarios.
Mensajes clave
En conjunto, los resultados de estos estudios no permiten afirmar si el uso de algún tipo de terapia con láser es más o menos eficaz que otros tratamientos disponibles para las cicatrices hipertróficas y queloides. Dado que los estudios solo proporcionaron evidencia de certeza muy baja en relación con los posibles efectos secundarios, no se tiene mucha confianza en los resultados de los estudios disponibles actualmente y no se sabe si algún tipo de terapia con láser produce más efectos perjudiciales que beneficiosos en comparación con ningún tratamiento u otros tratamientos.
¿Qué grado de actualización tiene esta revisión?
Se buscaron estudios publicados hasta el 23 de marzo de 2021.
Authors' conclusions
Summary of findings
| Laser therapycompared with no treatment for treating hypertrophic and keloid scars | ||||||
| Patient or population: patients with hypertrophic and keloid scars | ||||||
| Outcomes | Anticipated absolute effects (95% CI) | Relative effect | № of scar segment | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with no treatment | Risk with Laser therapy | |||||
| Scar severity ‐ 585‐nm Pulsed‐Dye Laser (PDL) versus no treatment ‐ patient self‐assessment of scar improvement of 50% or higher ‐ hypertrophic and keloid scars ‐ follow‐up: 32 weeks | Study population | RR 1.96 | 60 | ⊕⊕⊝⊝1,2 |
There may be more hypertrophic and keloid scar improvement (that is scars are less severe) in 585‐nm PDL‐treated scars compared with no treatment after 32 weeks. | |
| 400 per 1000 | 784 per 1000 | |||||
| Incidence and severity of treatment‐related adverse effects ‐ 585‐nm PDL versus no treatment ‐ mild to moderate discomfort or pain related to treatment ‐ hypertrophic and keloid scars ‐follow‐up: 32 weeks | Two split‐scar trials (n = 60) reported this outcome. In these studies, participants reported mild to moderate discomfort or pain in 10 out of 30 (10/30) (33%) PDL treated areas versus 0 out of 30 (0/30) (0%) no treatment areas (RR 8.62; 1.10 to 67.39). | ⊕⊝⊝⊝2,3 | It is uncertain whether there is any difference in the incidence and severity of treatment‐related adverse effects in 585‐nm PDL‐treated hypertrophic and keloid scars compared with no treatment after 32 weeks. | |||
| Incidence and severity of treatment‐related adverse effects ‐ 585‐nm PDL versus no treatment ‐ purpura ‐ hypertrophic and keloid scars ‐ follow‐up: 32 weeks | Two split‐scar trials (n = 60) reported this outcome. In these studies, purpura was observed in 40 out of 40 (40/40) (100%) PDL treated areas versus 0 out of 20 (0/20) (0%) no treatment areas (RR 21.32; 3.14 to 144.86). | ⊕⊝⊝⊝2,3 | ||||
| Scar severity ‐ Non‐Ablative Fractional Laser (NAFL) versus no treatment ‐ health professional global assessment measured on a visual analogue scale (VAS) ranging from 0 to 100 mm (0 = as normal skin and 100 = worst possible scar) ‐ hypertrophic scars ‐ follow‐up: 3 months | Study population | RR 2.00 (0.85 to 4.69) | 36 (1 study) | ⊕⊝⊝⊝3,4 | It is uncertain whether there is any difference in the scar severity in NAFL‐treated hypertrophic scars compared with no treatment after 3 months. | |
| 278 per 1000 | 556 per 1000
| |||||
| Scar severity ‐ NAFL versus no treatment ‐ patient global assessment measured on a VAS ranging from 0 to 100 mm (0 = as normal skin and 100 = worst possible scar) ‐ hypertrophic scars ‐ follow‐up: 3 months | One split‐scar trial (n = 36) reported this outcome. In this study, the authors reported an improvement in scar severity in NAFL treated hypertrophic scars compared with no treatment on the patient global assessment at 1 month (reported P = 0.006) and 3 months (reported P = 0.02). | ⊕⊝⊝⊝5,6 | ||||
| Scar severity ‐ NAFL versus no treatment ‐ Patient and Observer Scar Assessment Scale (POSAS) (higher scores = worse scar appearance) ‐ hypertrophic scars ‐ follow‐up: up to 3 months | One split‐scar trial (n = 36) reported this outcome. In this study, the authors reported an improvement in scar severity in NAFL treated hypertrophic scars compared with no treatment on the participant part of the scale at 1 month and 3 months. The size of the difference was not reported and no data for the observer part of the scale was presented. | ⊕⊝⊝⊝5,6 | ||||
| Incidence and severity of treatment‐related adverse effects ‐ NAFL versus no treatment ‐ scar worsening ‐ hypertrophic scars ‐ follow‐up: 3 months | One split‐scar trial (n = 20) reported this outcome. In this study, 3 out of 10 (3/10) (30%) NAFL treated areas versus 0 out of 10 (0/10) (0%) no treatment areas were considered by the patients to have worsened (RR 7.00; 0.41 to 120.16). | ⊕⊝⊝⊝3,7 | It is uncertain whether there is any difference in the incidence and severity of treatment‐related adverse effects in NAFL‐treated hypertrophic scars compared with no treatment after 3 months. | |||
| Incidence and severity of treatment‐related adverse effects ‐ NAFL versus no treatment ‐ hyperpigmentation ‐ hypertrophic scars ‐ follow‐up: 3 months | One split‐scar trial (n = 36) reported this outcome. In this study, hyperpigmentation was observed in 1 out of 18 (1/18) (6%) NAFL treated areas versus 0 out of 18 (0/18) (0%) no treatment areas (RR 3.00; 0.13 to 69.09). | ⊕⊝⊝⊝3,5 | ||||
| Scar severity ‐ Fractional Carbon Dioxide (CO2) Laser versus no treatment ‐ Vancouver Burn Scar (VBS) scale (higher scores = worse scar appearance) ‐ hypertrophic scars ‐ follow‐up: up to 3 months | Study population | NA | 104 (2 studies) | ⊕⊝⊝⊝6,8 | It is uncertain whether there is any difference in the scar severity in Fractional CO2‐treated hypertrophic and keloid scars compared with no treatment after up to 3 months, and in Fractional CO2‐treated hypertrophic scars compared with no treatment after at least 1 month. | |
| Baseline mean in the no treatment group was 7.6 | MD 1.30 lower | |||||
| Scar severity ‐ Fractional CO2 Laser versus no treatment ‐ VBS (higher scores = worse scar appearance) ‐ keloid scars ‐ follow‐up: 3 months | Study population | NA | 24 (1 study) | ⊕⊝⊝⊝6,9 | ||
| Baseline mean in the no treatment group was 7.6 | MD 1.90 lower | |||||
| Scar severity ‐ Fractional CO2 Laser versus no treatment ‐ POSAS scale (higher scores = worse scar appearance) ‐ hypertrophic scars ‐ follow‐up: at least 1 month | Study population | NA | 80 (1 study) | ⊕⊝⊝⊝6,10 | ||
| Baseline mean in the no treatment group was 29.9 | MD 4.13 higher (1.24 lower to 9.50 higher) | |||||
| *The risk in the intervention group (and its 95% confidence interval) is based on the mean risk in the comparison group and the relative effect of the intervention (and its 95% CI). ƚThe assumed risk in the comparison group is based on the event rate observed in the control arms of included trials. Where no events occurred, the risk was not calculated.
VAS: visual analogue scale ‐ ranging from 0 to 100 mm (0 = normal skin and 100 = worst possible scar); Patient self‐assessment ‐ based on a 4‐point scale (1 = 0 to 25% improvement, 2 = 25 to 50% improvement, 3 = 50 to 75% improvement, and 4 = 75% or greater improvement); POSAS: Patient and Observer Scar Assessment Scale ‐ the lowest score (6) reflects normal skin, and the highest score (60) reflects the worst imaginable scar; VBS: Vancouver Burn Scar Assessment Scale ‐ severity of scar was determined by numeric value from a minimum of 0 to 13 as the most severe form. CI: Confidence Interval; CO2: carbon dioxide;LDTA: (Low‐Density Treatment Arm of NAFL), HDTA: (High‐Density Treatment Arm of NAFL); MD: Mean Difference; NAFL: Non‐Ablative Fractional Laser ;PDL: Pulsed‐Dye Laser; RR: Risk Ratio; VBS: Vancouver Burn Scar Assessment Scale. | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1 Downgraded 1 level for serious imprecision due to small number of events. 2 Downgraded 1 level for serious risk of bias (lack of blinding of participants and assessors (patient‐reported outcome), and unclear sequence generation and allocation concealment). 3 Downgraded 2 levels for very serious imprecision due to small number of events and large confidence interval. 4 Downgraded 1 level for serious risk of bias (lack of blinding of participants). 5 Downgraded 1 level for serious risk of bias (lack of blinding of participants and assessors (patient‐reported outcome)). 6 Downgraded 2 levels for very serious imprecision due to small sample size and large confidence interval. 7 Downgraded 1 level for serious risk of bias (lack of blinding of participants and assessors (patient‐reported outcome), incomplete outcome data, and unclear allocation concealment). 8 Downgraded 1 level for serious risk of bias (selective reporting in one study, and lack of blinding of participants and incomplete outcome data in 2 studies). 9 Downgraded 1 level for serious risk of bias (lack of blinding of participants, incomplete outcome data and selective reporting). 10 Downgraded 1 level for serious risk of bias (lack of blinding of participants and assessors (patient‐reported outcome) and incomplete outcome data). | ||||||
| Laser therapy compared with other treatments for treating hypertrophic and keloid scars | ||||||
| Patient or population: participants with hypertrophic and keloid scars | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of scar segments | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with other treatments | Risk with Laser therapy | |||||
| Scar severity ‐ 585‐nm Pulsed‐Dye Laser (PDL) versus Triamcinolone acetonide (TAC) ‐ Vancouver Burn Scar (VBS) (Higher score = worse scar appearance) ‐ hypertrophic scars ‐ follow‐up: up to 12 months | Study population | NA | 80 | ⊕⊝⊝⊝1,2 | It is uncertain whether there is any difference in the scar severity in PDL‐treated hypertrophic and keloid scars compared with TAC after up to 12 months. | |
| Baseline mean in the other treatment group was 6.7 | MD 2.5 lower | |||||
| Scar severity ‐ 585‐nm PDL versus TAC ‐ patient self‐assessment of scar improvement of 50% or higher, or patients considering the scar better or much better ‐ hypertrophic and keloid scars ‐ follow‐up: up to 12 months | One split‐scar trial (n = 20) and one parallel trial (n = 80) reported this outcome. In the split scar trial, 8 out of 10 (8/10) (80%) PDL treated areas versus 10 out of 10 (10/10) (100%) TAC treated areas were considered to have improved 50% or more by participants (RR 0.81; 0.57 to 1.14), and in the parallel trial, 28 out of 40 participants (28/40) (70%) treated with PDL and 12 out of 40 participants (12/40) (30%) treated with TAC considered their scars better or much better (RR 2.33; 1.39 to 3.91). | ⊕⊝⊝⊝3,4 | ||||
| Incidence and severity of treatment‐related adverse effects ‐ 585‐nm PDL versus TAC: sequelae ‐ hypertrophic and keloid scars ‐ follow‐up: 32 weeks | Study population | RR 0.09 | 20 | ⊕⊝⊝⊝3,5 | It is uncertain whether there is any difference in the incidence and severity of treatment‐related adverse effects in PDL‐treated hypertrophic and keloid scars compared with TAC after 32 weeks.
| |
| 500 per 1000 | 45 per 1000 | |||||
| Incidence and severity of treatment‐related adverse effects ‐ 585‐nm PDL versus TAC ‐ mild to moderate pain related to treatment ‐ hypertrophic and keloid scars ‐ follow‐up: 32 weeks | One split‐scar trial (n = 20) reported this outcome. In this study, participants reported to have felt mild to moderate pain during the intervention in 10 out of 10 (10/10) (100%) TAC treated areas versus in 9 out of 10 (9/10) (90%) PDL treated areas (RR 0.90; 0.69 to 1.18). | ⊕⊝⊝⊝3,5 | ||||
| Scar severity ‐ 585‐nm PDL versus 5‐FU ‐ patient self‐assessment of scar improvement of 50% or higher ‐ hypertrophic and keloid scars ‐ follow‐up: 32 weeks | One split‐scar trial (n = 20) reported this outcome. In this study, 8 out of 10 (8/10) (80%) PDL treated areas versus 10 out of 10 (10/10) (100%) 5‐FU treated areas were reported by the participants to have improved 50% or more (RR 0.81; 0.57 to 1.14). | ⊕⊝⊝⊝3,5 | It is uncertain whether there is any difference in the scar severity in PDL‐treated hypertrophic and keloid scars compared with 5‐FU after 32 weeks. | |||
| Incidence and severity of treatment‐related adverse effects ‐ 585‐nm PDL versus 5‐FU ‐ mild to moderate pain related to treatment ‐ hypertrophic and keloid scars ‐ follow‐up: 32 weeks | One split‐scar trial (n = 20) reported this outcome. In this study, participants reported to have felt mild to moderate pain during the intervention in 9 out of 10 (9/10) (90%) PDL treated areas versus in 10 out of 10 (10/10) (100%) 5‐FU treated areas (RR 0.90; 0.69 to 1.18). | ⊕⊝⊝⊝3,5 | It is uncertain whether there is any difference in the incidence and severity of treatment‐related adverse effects in PDL‐treated hypertrophic and keloid scars compared with 5‐FU after 32 weeks. | |||
| Incidence and severity of treatment‐related adverse effects ‐ 585‐nm PDL versus 5‐FU ‐ purpura ‐ hypertrophic and keloid scars ‐ follow‐up: 32 weeks | One split‐scar trial (n = 20) reported this outcome. In this study, purpura was observed in 10 out of 10 (10/10) (100%) PDL treated areas versus in 2 out of 10 (2/10) (20%) 5‐FU treated areas (RR 4.20; 1.40 to 12.58). | ⊕⊝⊝⊝3,5 | ||||
| Scar severity ‐ 585‐nm PDL versus TAC plus 5‐FU ‐ patient self‐assessment of scar improvement of 50% or higher ‐ hypertrophic and keloid scars ‐ follow‐up: 32 weeks | Study population | RR 0.89 | 20 | ⊕⊝⊝⊝3,5 | It is uncertain whether there is any difference in the scar severity in PDL‐treated hypertrophic and keloid scars compared with TAC plus 5‐FU after 32 weeks. | |
| 900 per 1000 | 801 per 1000 | |||||
| Incidence and severity of treatment‐related adverse effects ‐ 585‐nm PDL versus TAC plus 5‐FU ‐ mild to moderate pain related to treatment ‐ hypertrophic and keloid scars ‐ follow‐up: 32 weeks | One split‐scar trial (n = 20) reported this outcome. In this study, participants reported to have felt mild to moderate pain during the intervention in 9 out of 10 (9/10) (90%) PDL treated areas versus in 10 out of 10 (10/10) (100%) TAC plus 5‐FU treated areas (RR 0.90; 0.69 to 1.18). | ⊕⊝⊝⊝3,5 | It is uncertain whether there is any difference in the incidence and severity of treatment‐related adverse effects in PDL‐treated hypertrophic and keloid scars compared with TAC plus 5‐FU after 32 weeks. | |||
| Incidence and severity of treatment‐related adverse effects ‐ 585‐nm PDL versus TAC plus 5‐FU ‐ purpura ‐ hypertrophic and keloid scars ‐ follow‐up: 32 weeks | One split‐scar trial (n = 20) reported this outcome. In this study, purpura was observed in 10 out of 10 (10/10) (100%) PDL treated areas versus in 3 out of 10 (3/10) (30%) TAC plus 5‐FU treated areas (RR 3.00; 1.25 to 7.19). | ⊕⊝⊝⊝3,5 | ||||
| Incidence and severity of treatment‐related adverse effects ‐ 585‐nm PDL versus silicone gel sheeting ‐ pain during laser treatments ‐ hypertrophic scars ‐ follow‐up: 24 weeks | One split‐scar trial (n = 40) reported this outcome. In this study, participants reported to have felt pain during laser treatment in 1 out of 20 (1/20) (5%) PDL treated areas versus in 0 out of 20 (0/20) (0%) silicone gel sheeting treated areas (RR 3.00; 0.13 to 69.52). | ⊕⊝⊝⊝3,6 | It is uncertain whether there is any difference in the incidence and severity of treatment‐related adverse effects in PDL‐treated hypertrophic scars compared with silicone gel sheeting after 24 weeks. | |||
| Incidence and severity of treatment‐related adverse effects ‐ 585‐nm PDL versus silicone gel sheeting ‐ skin irritation ‐ hypertrophic scars ‐ follow‐up: 24 weeks | One split‐scar trial (n = 40) reported this outcome. In this study, participants reported to have felt skin irritation related to laser treatment in 0 out of 20 (0/20) (0%) PDL treated areas versus in 1 out of 20 (1/20) (5%) silicone gel sheeting treated areas (RR 0.33; 0.01 to 7.72). | ⊕⊝⊝⊝3,6 | ||||
| Scar severity ‐ erbium laser versus TAC ‐ VBS (Higher scores = worse scar appearance) ‐ hypertrophic scars ‐ follow‐up: up to 12 months | Baseline mean in the other treatment group was 6.7 | MD 2.10 lower | NA | 80 | ⊕⊝⊝⊝1,2 | It is uncertain whether there is any difference in the scar severity in erbium‐treated hypertrophic scars compared with TAC after up to 12 months. |
| Scar severity ‐ erbium laser versus TAC ‐ patient self‐assessment ‐ patients considering the scar much better ‐ hypertrophic scars ‐ follow‐up: up to 12 months | Study population | RR 2.17 | 80 | ⊕⊝⊝⊝3,7 | ||
| 300 per 1000 | 651 per 1000 | |||||
| Incidence and severity of treatment‐related adverse effects ‐ fractional carbon dioxide (CO2) laser versus TAC ‐ pain at injection site ‐ keloid scars ‐ follow‐up: 24 weeks | Study population | RR 0.25 (0.06 to 1.03) | 40 | ⊕⊝⊝⊝3,8 | It is uncertain whether there is any difference in the incidence and severity of treatment‐related adverse effects in fractional CO2‐treated keloid scars compared with TAC after 24 weeks. | |
| 400 per 1000 | 100 per 1000 | |||||
| Incidence and severity of treatment‐related adverse effects ‐ fractional CO2 laser versus TAC ‐ telangectasia ‐ keloid scars ‐ follow‐up: 24 weeks | Study population | RR 0.20 (0.01 to 3.92) | 40 | ⊕⊝⊝⊝3,8 | ||
| 100 per 1000 | 20 per 1000 | |||||
| Incidence and severity of treatment‐related adverse effects ‐ fractional CO2 laser versus TAC ‐ skin atrophy ‐ keloid scars ‐ follow‐up: 24 weeks | Study population | RR 0.33 (0.01 to 7.72) | 40 | ⊕⊝⊝⊝3,8 | ||
| 50 per 1000 | 17 per 1000 | |||||
| Incidence and severity of treatment‐related adverse effects ‐ fractional CO2 laser versus TAC ‐ charring ‐ keloid scars ‐ follow‐up: 24 weeks | One parallel trial (n = 40) reported this outcome. In this study, charring was observed in 3 out of 20 (3/20) (15%) participants treated with fractional CO2 laser and 0 out of 20 (0/20) (0%) participants treated with TAC (RR 7.00; 0.38 to 127.32). | ⊕⊝⊝⊝3,8 | ||||
| Incidence and severity of treatment‐related adverse effects ‐ fractional CO2 laser versus verapamil ‐ pain at injection site ‐ keloid scars ‐ follow‐up: 24 weeks | One parallel trial (n = 40) reported this outcome. In this study, pain at injection site was reported by 2 out of 20 (2/20) (10%) participants treated with fractional CO2 laser group and 0 out of 20 (0/20) (0%) participants treated with verapamil (RR 5.00; 0.26 to 98.00). | ⊕⊝⊝⊝3,8 | It is uncertain whether there is any difference in the incidence and severity of treatment‐related adverse effects in fractional CO2‐treated keloid scars compared with verapamil after 24 weeks. | |||
| Incidence and severity of treatment‐related adverse effects ‐ fractional CO2 laser versus verapamil ‐ charring ‐ keloid scars ‐ follow‐up: 24 weeks | One parallel trial (n = 40) reported this outcome. In this study, charring was observed in 3 out of 20 (3/20) (15%) participants treated with fractional CO2 laser group and 0 out of 20 (0/20) (0%) participants treated with verapamil group (RR 7.0; 0.38 to 127.32) | ⊕⊝⊝⊝3,8 | ||||
| *The risk in the intervention group (and its 95% confidence interval) is based on the mean risk in the comparison group and the relative effect of the intervention (and its 95% CI). ƚThe assumed risk in the comparison group is based on the event rate observed in the control arms of included trials. Where no events occurred, the risk was not calculated.
Vancouver Burn Scar (VBS) Assessment Scale ‐ severity of scar was determined by numeric value from a minimum of 0 to 13 as the most severe form. Patient self‐assessment ‐ based on a 4‐point scale (1 = 0 to 25% improvement, 2 = 25 to 50% improvement, 3 = 50 to 75% improvement, and 4 = 75% or greater improvement). CI: Confidence Interval; CO2: carbon dioxide; MD: Mean Difference; PDL: Pulsed‐Dye Laser;RR: Risk Ratio; TAC: Triamcinolone acetonide;5‐FU: 5‐fluorouracil;VBS: Vancouver Burn Scar Assessment Scale;. | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1 Downgraded 2 levels for very serious imprecision due to small sample size and large confidence interval. 2 Downgraded 1 level due to serious risk of bias (lack of blinding of participants, selective reporting, and unclear sequence generation and allocation concealment). 3 Downgraded 2 levels for very serious imprecision due to small number of events and large confidence interval. 4 Downgraded 1 level due to serious risk of bias (lack of blinding of participants and assessors (patient‐reported outcome) and unclear sequence generation and allocation concealment in 2 studies, and selective reporting in 1 study). 5 Downgraded 1 level due to serious risk of bias (lack of blinding of participants and assessors (patient‐reported outcome) and unclear sequence generation and allocation concealment). 6 Downgraded 1 level due to serious risk of bias (lack of blinding of participants and assessors (patient‐reported outcome) and unclear allocation concealment). 7 Downgraded 1 level due to serious risk of bias (lack of blinding of participants and assessors (patient‐reported outcome) and selective reporting, and unclear sequence generation and allocation concealment). 8 Downgraded 1 level due to serious risk of bias (lack of blinding of participants and assessors (patient‐reported outcome), and unclear allocation concealment and selective reporting). | ||||||
| Laser therapy plus other treatment compared with other treatment for treating hypertrophic and keloid scars | ||||||
| Patient or population: participants with hypertrophic and keloid scars | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of scar segments | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with other treatment | Risk with Laser therapy plus other treatment | |||||
| Scar severity ‐ 585‐nm pulsed‐dye laser (PDL) plus triamcinolone acetonide (TAC) plus 5‐Fluorouracil (5‐FU) versus TAC plus 5‐FU ‐ blinded observer assessment of good to excellent scar improvement ‐ hypertrophic and keloid scars ‐ follow‐up: 12 weeks | Study population | RR 1.75 (0.95 to 3.22) | 40 | ⊕⊝⊝⊝1,2 | It is uncertain whether there is any difference in the scar severity in PDL plus TAC plus 5‐FU‐treated hypertrophic and keloid scars compared with TAC plus 5‐FU after 12 weeks. | |
| 400 per 1000 | 700 per 1000 | |||||
| Scar severity ‐ 585‐nm PDL plus TAC plus 5 FU versus TAC plus 5‐FU ‐ patient self‐assessment of good to excellent scar improvement ‐ hypertrophic and keloid scars ‐ follow‐up: 12 weeks | Study population | RR 1.36 (0.85 to 2.18) | 40 | ⊕⊝⊝⊝1,3 | ||
| 550 per 1000 | 748 per 1000 | |||||
| Scar severity ‐ carbon dioxide (CO2) laser plus TAC versus cryosurgery plus TAC. Mean percentage reduction ‐ blinded observer assessment ‐ keloid scars ‐ follow‐up: 12 months | Study population | NA | 60 (1 study) | ⊕⊝⊝⊝4,5 | It is uncertain whether there is any difference in the scar severity in CO2 plus TAC‐treated keloid scars compared with cryosurgery plus TAC after 12 months. | |
| Baseline mean in the other treatment group was 74.44 | MD 16.11 lower | |||||
| Scar severity ‐ CO2 laser plus TAC versus cryosurgery plus TAC Mean percentage reduction ‐ patient self‐assessment score (higher scores = worse scar appearance) ‐ keloid scars ‐ follow‐up: 12 months | Study population | NA | 60 (1 study) | ⊕⊝⊝⊝4,6 | ||
| Baseline mean in the other treatment group was 74.26 | MD 7.59 lower | |||||
| Incidence of treatment‐related adverse effects: CO2 laser plus TAC versus cryosurgery plus TAC ‐ atrophy ‐ keloid scars ‐ follow‐up: 12 months | Study population | RR 1.13 (0.70 to 1.82) | 60 (1 study) | ⊕⊝⊝⊝4,6 | It is uncertain whether there is any difference in the incidence and severity of treatment‐related adverse effects in CO2 plus TAC‐treated keloid scars compared with cryosurgery plus TAC after 12 months.
| |
| 500 per 1000 | 565 per 1000 | |||||
| Incidence of treatment‐related adverse effects ‐ CO2 laser plus TAC versus cryosurgery plus TAC ‐ erythema ‐ keloid scars ‐ follow‐up: 12 months | Study population | RR 1.50 (0.47 to 4.78) | 60 (1 study) | ⊕⊝⊝⊝4,6 | ||
| 133 per 1000 | 200 per 1000 | |||||
| Incidence of treatment‐related adverse effects ‐ CO2 laser plus TAC versus cryosurgery plus TAC ‐ telangiectasia ‐ keloid scars ‐ follow‐up: 12 months | Study population | RR 0.33 (0.07 to 1.52) | 60 (1 study) | ⊕⊝⊝⊝4,6 | ||
| 200 per 1000 | 66 per 1000 | |||||
| Incidence of treatment‐related adverse effects ‐ CO2 laser plus TAC versus cryosurgery plus TAC ‐ hypopigmentation ‐ keloid scars ‐ follow‐up: 12 months | Study population | RR 0.60 (0.16 to 2.29) | 60 (1 study) | ⊕⊝⊝⊝4,6 | ||
| 167 per 1000 | 100 per 1000 | |||||
| Scar severity ‐ Neodymium‐doped yttrium aluminium garnet (Nd:YAG) laser plus Diprospan plus 5‐FU versus Diprospan plus 5‐FU ‐ blinded observer assessment of good to excellent scar improvement ‐ keloid scars ‐ follow‐up: 3 months | Study population | RR 1.45 (0.88 to 2.41) | 46 (1study) | ⊕⊝⊝⊝1,7 | It is uncertain whether there is any difference in the scar severity in Nd:YAG plus Diprospan plus 5‐FU‐treated keloid scars compared with Diprospan plus 5‐FU after 3 months. | |
| 478 per 1000 | 693 per 1000 | |||||
| Scar severity: Nd:YAG laser plus Diprospan plus 5‐FU versus Diprospan plus 5‐FU ‐ patient self‐assessment of scar improvement of 50% or higher ‐ keloid scars ‐ follow‐up: 3 months | Study population | RR 1.38 (0.91 to 2.10) | 46 (1study) | ⊕⊝⊝⊝1,8 | ||
| 565 per 1000 | 780 per 1000 | |||||
| Incidence and severity of treatment‐related adverse effects: Nd:YAG laser plus Diprospan plus 5‐FU versus Diprospan plus 5‐FU ‐ keloid scars ‐ follow‐up: 3 months | One parallel trial (n = 46) reported this outcome. In this study, almost all injections were reported by participants as being painful, and the sites treated by Nd:YAG laser became purpuric (which lasted for 7 to 10 days). | ⊕⊝⊝⊝1,8 | It is uncertain whether there is any difference in the incidence and severity of treatment‐related adverse effects in Nd:YAG plus Diprospan plus 5‐FU‐treated keloid scars compared with Diprospan plus 5‐FU after 3 months. | |||
| Scar severity ‐ Helium‐Neon (He‐Ne) laser plus decamethyltetrasiloxane, polydimethylsiloxane and cyclopentasiloxane cream versus decamethyltetrasiloxane, polydimethylsiloxane and cyclopentasiloxane cream ‐ Vancouver Scar scale (VSS) (higher scores = worse scar appearance) ‐ hypertrophic scars ‐ follow‐up: 12 weeks | One split‐scar trial (n = 30) reported this outcome. In this study, a significant decrease in the median values of VSS of the intervention area compared with the control area (P = 0.003) | ⊕⊝⊝⊝4,9 | It is uncertain whether there is any difference in the scar severity in He‐Ne plus decamethyltetrasiloxane, polydimethylsiloxane and cyclopentasiloxane cream‐treated hypertrophic scars compared with decamethyltetrasiloxane, polydimethylsiloxane and cyclopentasiloxane cream after 12 weeks. | |||
| Incidence of treatment‐related adverse effects ‐ 595‐nm PDL plus verapamil versus verapamil ‐ regrowth ‐ keloid scars ‐ follow‐up: 24 weeks | Study population | RR 1.50 (0.27 to 8.22) | 50 (1study) | ⊕⊝⊝⊝1,10 | It is uncertain whether there is any difference in the incidence and severity of treatment‐related adverse effects in PDL plus verapamil‐treated keloid scars compared with verapamil after 24 weeks.
| |
| 80 per 1000 | 120 per 1000 | |||||
| Incidence of treatment‐related adverse effects ‐ 595‐nm PDL plus verapamil versus verapamil ‐ pain related to treatment ‐ keloid scars ‐ follow‐up: 24 weeks | One parallel trial (n = 50) reported this outcome. In this study, pain at injection site was reported by 1 out of 25 (1/25) (4%) participants treated with 595‐nm PDL plus verapamil and by 0 out of 25 (0/15) (0%) participants treated with verapamil (RR 3.00; 0.13 to 70.30) | ⊕⊝⊝⊝1,10 | ||||
| Incidence of treatment‐related adverse effects ‐ 595‐nm PDL plus verapamil versus verapamil ‐ hyperpigmentation ‐ keloid scars ‐ follow‐up: 24 weeks | One parallel trial (n = 50) reported this outcome. In this study, hyperpigmentation was observed in 2 out of 25 (2/25) (8%) participants treated with 595‐nm PDL plus verapamil and by 0 out of 25 (0/15) (0%) participants treated with verapamil (RR 5.00; 0.25 to 99.16) | ⊕⊝⊝⊝1,10 | ||||
| Incidence of treatment‐related adverse effects ‐ 595‐nm PDL plus verapamil versus verapamil ‐ depigmentation ‐ keloid scars ‐ follow‐up: 24 weeks | Study population | RR 1.00 (0.07 to 15.12) | 50 (1study) | ⊕⊝⊝⊝1,10 | ||
| 40 per 1000 | 40 per 1000 | |||||
| Incidence of treatment‐related adverse effects ‐ 595‐nm PDL plus verapamil versus verapamil ‐ purpura ‐ keloid scars ‐ follow‐up: 24 weeks | One parallel trial (n = 50) reported this outcome. In this study, hyperpigmentation was observed in 7 out of 25 (7/25) (28%) participants treated with 595‐nm PDL plus verapamil and by 0 out of 25 (0/15) (0%) participants treated with verapamil (RR 15.00; 0.90 to 249.30) | ⊕⊝⊝⊝1,10 | ||||
| Incidence of treatment‐related adverse effects ‐ 595‐nm PDL plus verapamil versus verapamil ‐ total ‐ keloid scars ‐ follow‐up: 24 weeks | Study population | RR 4.67 (1.53 to 14.26) | 50 (1study) | ⊕⊝⊝⊝1,10 | ||
| 120 per 1000 | 560 per 1000 | |||||
| *The risk in the intervention group (and its 95% confidence interval) is based on the mean risk in the comparison group and the relative effect of the intervention (and its 95% CI). ƚThe assumed risk in the comparison group is based on the event rate observed in the control arms of included trials. Where no events occurred, the risk was not calculated. ‐ Diprospan contains betamethasone disodium phosphate plus betamethasone dipropionate.
Patient self‐assessment ‐ based on a 4‐point scale (1 = 0 to 25% improvement, 2 = 25 to 50% improvement, 3 = 50 to 75% improvement, and 4 = 75% or greater improvement); VBS: Vancouver Burn Scar Assessment Scale ‐ severity of scar was determined by numeric value from a minimum of 0 to 13 as the most severe form. CI: Confidence Interval; ; CO:2 carbon dioxide;5‐FU: 5‐fluorouracil; He‐Ne: Helium‐Neon; NdYAG: neodymium‐doped yttrium aluminium garnet; PDL: Pulsed‐Dye Laser; RR: Risk Ratio; TAC: Triamcinolone acetonide. | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1 Downgraded 2 levels for very serious imprecision due to small number of events and large confidence interval. 2 Downgraded 1 level due to serious risk of bias (lack of blinding of participants, incomplete outcome data and selective reporting, and unclear sequence generation and allocation concealment). 3 Downgraded 1 level due to serious risk of bias (lack of blinding of participants and assessors (patient‐reported outcome), incomplete outcome data and selective reporting, and unclear sequence generation and allocation concealment) 4 Downgraded 2 levels for very serious imprecision due to small sample size and large confidence interval. 5 Downgraded 1 level due to serious risk of bias (lack of blinding of participants and incomplete outcome data, and unclear selective reporting). 6 Downgraded 1 level due to serious risk of bias (lack of blinding of participants and assessors (patient‐reported outcome) and incomplete outcome data, and unclear selective reporting). 7 Downgraded 1 level due to serious risk of bias (lack of blinding of participants and incomplete outcome data, and unclear sequence generation and allocation concealment). 8 Downgraded 1 level due to serious risk of bias (lack of blinding of participants and assessors (patient‐reported outcome) and incomplete outcome data, and unclear sequence generation and allocation concealment). 9 Downgraded 1 level due to serious risk of bias (lack of blinding of participants and selective reporting, and unclear sequence generation, allocation concealment and incomplete outcome data). 10 Downgraded 1 level due to serious risk of bias (lack of blinding of participants and assessors (patient‐reported outcome), and unclear sequence generation, allocation concealment and incomplete outcome data). | ||||||
Background
Description of the condition
Hypertrophic and keloid scars (usually referred to as keloids) represent common skin conditions (Bouzari 2007) which result from abnormal wound healing (Seifert 2009). They can affect any part of the skin's surface that has suffered traumatic or infectious injury (Köse 2008), however, those areas of the skin where there is increased stretching tension (e.g. trunk, upper arm/shoulder (deltoid region), and knees) are more susceptible to the appearance of keloid and hypertrophic scars. They present as raised scars with a smooth surface, firm when palpitated, and their colour can vary from pink‐purple to pale (hypopigmented) or dark (hyperpigmented). They can be associated with symptoms such as itching (pruritus) and pain (Asilian 2006). In some cases, due to the physical and psychological impacts caused by these scars, patients with keloid and hypertrophic scars may report impairment in their quality of life (Bock 2006).
The anatomical location of the initial skin lesion, a history of trauma or infection associated with the initial injury, a burn injury, sutures under tension, adolescence, pregnancy, and family history are considered to be risk factors for the appearance of hypertrophic scars and keloids (Alster 2003; Seifert 2009). During the normal healing process, several cells and chemical substances work together to promote tissue repair. In this process the production and subsequent degradation of collagen usually act in equilibrium, resulting in a scar healing normally. This balance is altered in keloids and hypertrophic scars, where there is higher production of collagen and lower levels of collagen degradation (Cho 2010). The collagen accumulates in the lesion, resulting in excessive scar tissue. Despite their similarities, keloids and hypertrophic scars have some clinical, pathological, and evolutive differences (Seifert 2009).
Both genetic predisposition and skin injury play major roles in the development of keloid and hypertrophic scars (Alster 2003). While keloids may occur at any age, they usually occur in individuals between 10 and 30 years of age (Berman 1996). They affect between 4.5% and 16% of black and Hispanic populations, with an incidence of up to 16% in black Africans (Alster 2003). They occur less frequently in populations with lighter skin. The incidence of hypertrophic scars is probably higher than that of keloid scars (Köse 2008), ranging from 5% to 37% in white people (Li‐Tsang 2005), but precise data are lacking. The prevalence of hypertrophic scars ranges from 15% to 63% in white people (Li‐Tsang 2005). Both keloid and hypertrophic scars tend to recur after treatment (Cassuto 2010).
Clinically, keloids appear as raised scars, exceeding the boundaries of the original injury (Mutalik 2005). They can arise within a few months of the initial injury and often show gradual and undefined growth. They can be of different sizes and patterns and are frequently associated with itching and burning. Keloid scars do not regress spontaneously and usually affect the chest, shoulders, back, posterior neck and ear lobes, but rarely the palms and soles (Seifert 2009). In contrast, hypertrophic scars do not exceed the limits of the original skin injury, and are rarely wider than 1 cm. They usually occur around four weeks after the original injury, grow strongly for a few months, and then tend to regress spontaneously within one year (Seifert 2009).
Due to the recurrent aspect of the lesions, their slowly progressive nature, and the lack of a gold standard therapy, the treatment of hypertrophic scars and keloids represents a significant challenge (Cassuto 2010). Frequently, the treatment of both types of scars is performed by associating two or more techniques (Bouzari 2007, Gupta 2011), looking for a synergistic and or complementary action, or both at different levels of the healing process, with variable results reported in the literature. The main therapies used in the treatment of hypertrophic and keloid scars include medicinal treatments, compressive treatment, surgical treatments, treatment with radiation, and treatment with light sources.
Among the medicinal treatments, corticosteroids are considered as first‐line drugs in the treatment of hypertrophic and keloid scars, and are most often used in intralesional applications (Gupta 2011). Other medicinal treatments are the use of intralesional bleomycin (Alster 2003) and intralesional 5‐ Fluorouracil (Mutalik 2005). Silicone is used in its varied forms, including gel, cream, spray or flexible gel sheeting (Alster 2003). Regarding surgical treatments, cryosurgery can be useful as it causes tissue ischaemia (which is a reduction in blood flow) and necrosis of scar tissue (Alster 2003; Berman 1996). Surgeries to remove scar volume, by removal of its core, or of the entire scar can also be performed (Gupta 2011). Other treatments include light sources such as Intense Pulsed Light (IPL), which aims to promote vascular ischaemia, interfering with collagen production (Erol 2008), and laser therapy. Different laser devices are used, aiming to improve the appearance of hypertrophic and keloid scars by direct destruction of the tissue (fractional or conventional ablative lasers), with consequent reduction in scar volume; coagulation of scar tissue (non‐ablative lasers, fractioned or not), with consequent remodeling of the local collagen and scar improvement; or even by destruction of the scar microvascularisation, leading to ischaemia and consequent reduction in scar volume (Alster 2003; Berman 1996).
Description of the intervention
Different laser systems have been used in the treatment of hypertrophic and keloid scars over the last 30 years (Bouzari 2007; Gupta 2011). The mechanism of lasers follows the principle of 'selective photothermolysis' (Anderson 1983). According to this principle, a light with a specific wavelength emitted by a laser device acts on a specific target, which responds to this wavelength. This target is called "chromophore".
Different skin structures respond to different wavelengths, so it is necessary to find a laser device that emits a laser beam with a wavelength equal or similar to that of the structure that needs to be reached. This laser beam will 'search' for the structure within the skin that has the same or similar wavelength (the "chromophore"), and then destroy it selectively ("selective photothermolysis").
The patient's skin type (skin type I: pale white skin, blue or green eyes, blond or red hair; type II: fair skin, blue eyes; type III: darker white skin; type IV: light brown skin; type V: brown skin; type VI: dark brown or black skin), the energy released by the device in a certain area (also called fluence), the spot size of the laser light and the speed with which this beam reaches the target, are all factors that influence the results obtained with laser therapy.
A laser can be classified as ablative or non‐ablative according to its effect on tissue. Ablative lasers remove part or all of the tissues on which they are applied. They act on the water present in these tissues, causing them to vaporise. Examples of ablative laser devices include carbon dioxide (CO2), argon, and 2940 nm erbium‐doped yttrium aluminium garnet (Er:YAG) laser. Non‐ablative lasers act on different structures, such as the melanin pigment or intracellular haemoglobin, leading to necrosis (death) of these structures, without, however, removing them. An example of a non‐ablative laser device is the pulsed‐dye laser (PDL) (Manuskiatti 2007).
How the intervention might work
The exact mechanism of action by which laser therapy could improve hypertrophic and keloid scars severity is still unknown. Laser devices such as CO2 (Gupta 2011; Kantor 1985), argon, and 2940 nm Er:YAG (Mutalik 2005) can cause scar removal through the interaction of the laser energy with the water present in the treated skin, leading to reduction in the lesion volume. Non‐ablative lasers (e.g. 585 nm PDL,1064 nm Q‐switched neodymium‐doped yttrium aluminium garnet (Nd:YAG) laser with low fluence, 532 nm frequency‐doubled Nd:YAG, and 1064 nm Nd:YAG) can cause destruction (coagulation/necrosis) of the capillaries, through the absorption of laser light energy by blood inside the veins (i.e. intravascular haemoglobin; Asilian 2006). The destruction of blood vessels decreases blood flow (hypoperfusion) to the treated area, with a consequent decrease in local tissue oxygenation (hypoxia). Changes occur in the tissues as a result of the hypoxia, with the production of new collagen, heating of collagen fibres, dissociation of disulphide bonds (which keep collagen fibres together), and collagen fibre realignment (Cho 2010; Mutalik 2005). In this way, laser therapy reorganises collagen deposition in the hypertrophic and keloid scars and improves their clinical aspect and symptoms (Karsai 2007). The number of laser treatment sessions and the intervals between each session may vary according to the scar and laser device used. Every patient is individually examined and treated by his/her doctor, according to the characteristics of the scar in question.
Why it is important to do this review
Hypertrophic and keloid scars result from abnormal wound healing and have cosmetic implications. They occur in women and men of all ethnicities, often between the ages of 10 and 30 years, and can have a negative impact on a person's physical functioning and quality of life (Bock 2006). There are many different treatments for hypertrophic and keloid scars, but there is no gold standard therapy. Laser therapy is an option currently used in the treatment and prevention of keloids and hypertrophic scars, which underlines the need for a systematic review of the most reliable studies.
Objectives
To assess the effects of laser therapy for treating hypertrophic and keloid scars.
Methods
Criteria for considering studies for this review
Types of studies
We considered all randomised controlled trials (RCTs) comparing laser therapy with no intervention or another intervention for treating hypertrophic or keloid scars (or both). We did not include cluster‐randomised and cross‐over studies.
Types of participants
People with hypertrophic or keloid scars (or both), who had been diagnosed by a health professional, with no restrictions regarding age, sex, or ethnicity.
Types of interventions
We considered trials in which laser therapy was used to treat hypertrophic or keloid scars (or both), with any kind of laser device, using any fluency, course duration, number of sessions, and follow‐up time, compared either with no intervention or any other type of therapy.
Types of outcome measures
Primary outcomes
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Severity of keloid or hypertrophic scars (or both) measured by health professional and/or participant using a specific scale (as defined by the authors).
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Incidence and severity of treatment‐related adverse effects.
Secondary outcomes
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Scar size, colour, height, length, width, pliability, skin surface texture, pruritus and pain (non‐treatment related).
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Cosmesis/aesthetic scar appearance (defined by patient opinion and/or health professional observations).
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Patient tolerance (measured by reported side effects and adverse reactions).
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Preference for different modes of treatment measured by patient choice after receiving at least two different types of treatment.
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Adherence (measured by health professional and/or patient report).
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Patient's quality of life measured by a validated scale (36‐Item Short Form Health Survey (SF‐36), EuroQol (EQ‐5D58); (Ching 2003).
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Recurrence of the condition.
Search methods for identification of studies
We aimed to identify all relevant RCTs regardless of language or publication status (published, unpublished, in press, or in progress).
Electronic searches
We searched the following electronic databases to identify reports of relevant clinical trials:
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Cochrane Wounds Specialised Register (searched 23 March 2021);
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Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library via the Cochrane Register of Studies (searched 23 March 2021);
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MEDLINE Ovid including In‐Process & Other Non‐Indexed Citations (1946 to 23 March 2021);
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Embase Ovid(1974 to 23 March 2021);
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CINAHL Plus EBSCO (Cumulative Index to Nursing and Allied Health Literature (1937 to 23 March 2021);
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LILACS (Latin American and Caribbean Health Science Information database) via VHL (Virtual Health Library; 1982 to 23 March 2021).
The search strategies for the Cochrane Wounds Specialised Register, CENTRAL, MEDLINE Ovid, Embase Ovid and CINAHL Plus EBSCO can be found in Appendix 1. In MEDLINE Ovid, we combined the subject‐specific strategy with the sensitivity‐ and precision‐maximising version of the Cochrane Highly Sensitive Search Strategy for identifying randomised trials (2008 revision) (Lefebvre 2021). We combined the Embase Ovid search with the Ovid Embase filter developed by Cochrane UK (Lefebvre 2021). We combined the CINAHL Plus EBSCO search with the trial filter developed by Glanville 2019. There were no restrictions with respect to language, date of publication, or study setting.
We also searched the following clinical trials registries:
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US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (www.clinicaltrials.gov; searched 23 March 2021);
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World Health Organization International Clinical Trials Registry Platform (www.who.int/clinical-trials-registry-platform; searched 23 March 2021).
Searching other resources
We aimed to identify other potentially eligible trials or ancillary publications by searching the reference lists of retrieved included trials, as well as relevant systematic reviews, meta‐analyses, and health technology assessment reports. We contacted specialists in the field, authors of the included studies, and laser device manufacturers for any possible unpublished data. We did not perform a separate search for adverse effects of interventions used, we only considered treatment‐related adverse effects described in included studies.
Data collection and analysis
Data collection and analysis were carried out according to methods stated in the published protocol (Leszczynski 2015), based on the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2021).
Selection of studies
After merging the search results and removing duplicate records, we examined titles and abstracts to select the relevant reports. At least two review authors (RL, ACPNP or CAPS) independently screened the studies identified by the literature search. We retrieved and examined the full text of selected studies for compliance with eligibility criteria and in the case of any disagreements (at this or at any other stage as listed below), a third review author (EMKS) was consulted. Reasons for exclusion of studies after full text retrieval are recorded in the 'Characteristics of excluded studies' table. We included a Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) flow chart to document the screening process, Figure 1 (Moher 2009).
Study flow diagram.
Data extraction and management
At least two review authors (RL, ACPNP or CAPS) extracted data independently and collected data on a data extraction form. We resolved discrepancies in the results by discussion. We collected the following information.
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Study features:
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publication details (e.g. year, country, authors);
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study design;
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population data (e.g. age, ethnicity, baseline aspects of keloid and hypertrophic scars, such as severity, duration, symptoms, history of prior trauma or infection at the scar sites, and history concerning treatments and responses);
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details of interventions (e.g. number of laser treatment sessions, regimen, fluence, scheme, adjunctive therapies, increasing or decreasing fluence, who delivered the intervention, the location of the intervention);
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size of the scars;
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cause of the scars;
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treatment duration;
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number of participants randomised into each treatment group;
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number of participants in each group who were cured or failed treatment;
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numbers of participants lost to follow‐up;
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duration of follow‐up;
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source of funding for the trial;
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care setting.
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Outcomes and results:
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types of outcome measures;
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timing of outcomes;
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results;
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treatment‐related adverse effects.
Follow‐up data were extracted on the basis that long‐term follow‐up occurs 12 months or more from the beginning of the treatment; intermediate‐term follow‐up occurs between three months and 12 months from the beginning of the treatment; and short‐term follow‐up occurs less than three months from the beginning of the treatment. These criteria were established by the authors of this review, since there is no consensus about the follow‐up in the literature.
Where studies had multiple publications, the main study report was used as the reference, with additional details being supplemented from secondary papers.
Assessment of risk of bias in included studies
At least two review authors (RL, ACPNP or CAPS) independently assessed each included study using the Cochrane tool for assessing risk of bias (Higgins 2021). This tool addresses six specific domains, namely sequence generation, allocation concealment, blinding, incomplete outcome data, selective outcome reporting, and other issues (see Appendix 2 for details of the criteria on which the judgements were based). We completed a risk of bias table for each eligible study. We discussed any disagreements among all review authors to achieve a consensus. We presented assessment of risk of bias using a risk of bias summary figure (see Figure 2), which presents all the judgements in a cross‐tabulation of study by entry. This display of internal validity indicates the weight the reader can give the results of each study.
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Measures of treatment effect
The measures of treatment effect were calculated whenever data were available. We calculated risk ratios (RRs) and 95% confidence intervals (CIs) for dichotomous variables. We also calculated the mean difference (MD) and 95% CIs for continuous outcomes.
Unit of analysis issues
When multiple scars of the body received the same intervention, with a separate outcome judgement made for each body part, and the number of body parts was used as the denominator in the analysis, we planned to analyse the data similarly to the situation in cluster‐randomised trials (Higgins 2021). We anticipated a possible unit‐of analysis issue if individual participants with multiple scars were randomised, the allocated treatment was used on multiple scars per participant (or perhaps only for some participants), and then data were presented and analysed by scar not person. This is a type of clustered data, such that the participant is the 'cluster', and presents a unit of analysis error which inflates precision. If there had been studies that contained some or all clustered data, we would have reported this alongside information on whether data had been (incorrectly) treated as independent. We would have recorded this as part of the risk of bias assessment. We would not have undertaken further calculation to adjust for clustering. However, no studies of this type were included.
Dealing with missing data
Where there were missing or unavailable data, we contacted the study authors to request additional information. Because the study authors failed to respond, we reported dropout rates in the 'Characteristics of included studies' tables of the review, and used intention‐to‐treat analysis. All participants were analysed according to their randomisation allocation. Although we planned to perform sensitivity analysis, excluding participants with missing data, to assess the strength of the results (Higgins 2021), due to the lack of information in the included RCTs, this was not possible.
Assessment of heterogeneity
We considered clinical and methodological heterogeneity and quantified heterogeneity among the pooled estimates using the I2 measure calculated by Review Manager software (RevMan 2020). This illustrates the percentage of the variability in the effect estimates resulting from heterogeneity rather than sampling error. Whilst the I2 measure was used to quantify heterogeneity, a holistic assessment of heterogeneity more broadly taking into account study, intervention, population and outcome features was used to guide synthesis decisions.
Assessment of reporting biases
We planned to assess reporting biases or small study effects by drawing a funnel plot (trial effect versus trial size), assuming a sufficient number of studies (more than 10 for each outcome) were included in the review. As we did not have this number of studies, a funnel plot was not created.
Data synthesis
We considered clinical and methodological heterogeneity. We planned to pool data when studies appeared appropriately similar in terms of type of scar, intervention type, duration of follow‐up, and outcome type. Within comparisons, we pooled paired data separately (e.g. from split‐scar designs) from data from parallel‐group trials where both study types were available. (Lesaffre 2009). Where data synthesis was inappropriate, we provide a narrative overview.
We presented data using forest plots where possible. For dichotomous outcomes we presented the summary estimate as an RR with 95% CI. Where continuous outcomes were measured in the same way across studies, we present pooled mean differences (MD) with 95% CI. We planned to pool standardised mean difference (SMD) estimates where studies measured the same outcome using different methods; however, no outcomes were measured using different methods. We included studies where multiple treatment groups relevant to the review were compared with only one control group, and present the data separately for these comparisons.
Subgroup analysis and investigation of heterogeneity
We intended to perform subgroup analyses to consider the following:
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types of laser devices;
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different fluences and schemes;
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duration of treatment.
If we had found substantial heterogeneity and sufficient data, we planned to investigate the possible causes by exploring the impact of the condition of the individuals and the interventions (e.g. participant characteristics such as skin type, and addition of adjuvant therapies) using subgroup analyses. However, these analyses were not possible because of insufficient data.
Sensitivity analysis
If there had been an adequate number of studies, we would have performed sensitivity analyses based on separation of studies according to risk of bias. This would have been performed by excluding the studies most susceptible to bias on the basis of our risk of bias assessment, namely those with inadequate randomisation sequence generation, allocation concealment, high levels of post‐randomisation losses or exclusions, and unclear or unblinded outcome assessment.
Summary of findings and assessment of the certainty of the evidence
We present the main results of the review in summary of findings tables. These tables present key information concerning the certainty of the evidence, the magnitude of the effects of the interventions examined, and the sum of the available data for the main outcomes (Schünemann 2021a). The summary of findings tables also include an overall grading of the evidence related to each of the main outcomes using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach. The GRADE approach defines the certainty of a body of evidence as the extent to which one can be confident that an estimate of effect or association is close to the true quantity of specific interest. We evaluated the certainty of evidence considering within‐trial risk of bias (methodological quality), directness of evidence, heterogeneity, precision of effect estimates and risk of publication bias (Schünemann 2021b). We present the following outcomes in the summary of findings tables:
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severity of keloid or hypertrophic scars;
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incidence and severity of treatment‐related adverse effects.
Results
Description of studies
Results of the search
We searched the databases previously described (up to 23 March 2021) and this search retrieved 5746 citations. After assessing the abstracts for inclusion criteria, 44 citations were assessed in full. Of these, 17 studies were excluded with justification, 11 studies are ongoing, one study is awaiting classification and 15 randomised controlled trials (RCTs) were included in this systematic review, Figure 1.
Included studies
We included 15 RCTs in the review (Alsharnoubi 2018; Asilian 2006; Azzam 2016; Behera 2016; Blome‐Eberwein 2016; Chen 2017; Daoud 2019; Khattab 2019; Lin 2011; Manuskiatti 2001; Manuskiatti 2002; Omranifard 2007; Srivastava 2019; Verhaeghe 2013; Wittenberg 1999), with a total of 604 participants. The included studies evaluated different types of lasers with various types of control interventions, including no intervention and different injectable drugs (see Characteristics of included studies).
Care setting
Six studies were conducted in the USA (Blome‐Eberwein 2016; Daoud 2019; Lin 2011; Manuskiatti 2001; Manuskiatti 2002; Wittenberg 1999), two in Iran (Asilian 2006; Omranifard 2007), one in Belgium (Verhaeghe 2013), three in Egypt (Alsharnoubi 2018; Azzam 2016; Khattab 2019), two in India (Behera 2016; Srivastava 2019), and one in China (Chen 2017).
Four studies were conducted in private clinics (Asilian 2006; Manuskiatti 2001; Manuskiatti 2002; Omranifard 2007), six in hospitals (Alsharnoubi 2018; Behera 2016; Chen 2017; Lin 2011; Srivastava 2019; Verhaeghe 2013), two in outpatient clinics of University departments or University Hospitals (Azzam 2016; Khattab 2019), one in an outpatient burn centre (Blome‐Eberwein 2016), and two studies did not specify care settings (Daoud 2019; Wittenberg 1999).
Design
All of the 15 included studies were single‐centre RCTs, published between 1999 and 2019. The length of participant follow‐up of the studies ranged from 12 weeks to 12 months.
Five studies (Alsharnoubi 2018; Behera 2016; Blome‐Eberwein 2016; Khattab 2019; Verhaeghe 2013) compared two trial arms. Six studies (Asilian 2006; Chen 2017; Daoud 2019; Omranifard 2007; Wittenberg 1999; Srivastava 2019) assessed three trial arms each. Three studies (Azzam 2016; Lin 2011; Manuskiatti 2001) evaluated four trial arms each, and one study (Manuskiatti 2002) assessed five trial arms.
Among the included studies, six were parallel group (Asilian 2006; Behera 2016; Chen 2017; Khattab 2019; Omranifard 2007; Srivastava 2019), and nine were split‐scar design (Alsharnoubi 2018; Azzam 2016; Blome‐Eberwein 2016; Daoud 2019; Lin 2011; Manuskiatti 2001; Manuskiatti 2002; Verhaeghe 2013; Wittenberg 1999).
Sample sizes
The number of participants included in each RCT ranged from 10 (Lin 2011; Manuskiatti 2001; Manuskiatti 2002) to 120 (Omranifard 2007), with a total of 604 participants included across the review and a mean of 40.27 participants per trial. A total of 906 scar segments (unit of analysis) were assessed.
Participants
Participants included children and adults (age range from 2 to 81 years) of both sexes, skin types I‐VI, presenting hypertrophic and/or keloid scars. Almost all studies specified inclusion and exclusion criteria, except three (Blome‐Eberwein 2016; Daoud 2019 Manuskiatti 2002), which reported only inclusion criteria. Some of the exclusion criteria were pregnancy, lactation, scars with previous treatment, and participants with a history of isotretinoin use within the six months prior to laser treatment. Three trials only included participants with hypertrophic scars (Lin 2011; Verhaeghe 2013; Wittenberg 1999).
Interventions
In this review, we included trials comparing laser therapy for treating hypertrophic and/or keloid scars with other therapies (including no treatment). Different kinds of laser devices were evaluated, as well as different laser treatment regimens. The number of laser sessions varied from one (Behera 2016) to 24 (Alsharnoubi 2018), with a mean of 6.13 sessions, and the frequency of administration varied from twice a week (Alsharnoubi 2018) to one session every eight weeks (Wittenberg 1999). Different kinds of laser treatments were compared with no treatment (Table 1), with other treatments (Table 2) or were combined with other kinds of laser treatments and compared with other treatments (Table 3). Only two authors reported who had performed the laser sessions (in Blome‐Eberwein 2016 and Verhaeghe 2013 where laser sessions were performed by health professionals).
| Comparison | Outcome | Trials (participants) | Definition of outcome in trial/measurement details | Data reported |
| 585‐nm PDL versus no treatment | Scar severity | 2 RCTs (Manuskiatti 2001; 10 participants; 40 segments and Manuskiatti 2002, 10 participants; 20 segments) | Manuskiatti 2001 and Manuskiatti 2002: categories of 25% increments of improvement in scar severity after 32 weeks (graded by the patient) | Number of participants with an improvement of 50% or higher in the scar severity
Manuskiatti 2001: Laser: 23/30
Manuskiatti 2002: Laser: 8/10 |
| 585‐nm PDL versus no treatment | Incidence and severity of treatment‐related adverse effects | 3 RCTs (Manuskiatti 2001; 10 participants; 40 segments, Manuskiatti 2002, 10 participants; 20 segments, and Wittenberg 1999; 20 participants; 40 segments) | Manuskiatti 2001: immediate treatment reactions, including purpuric discolorations and erosion secondary to blistering, and adverse sequelae during 32 weeks.
Manuskiatti 2002: immediate treatment reactions included mild to moderate pain during treatment, burning sensation, spots of purpura, erosion secondary to blistering. Treatment‐related adverse sequelae including hypopigmentation, telangiectasia, and skin atrophy during 32 weeks.
Wittenberg 1999: no definition was provided. Duration: 40 weeks. | Manuskiatti 2001 and 2002: in all participants treated with the PDL the area became purpuric and a small number of participants with skin phototype VI reported erosions.
Wittenberg 1999: one (1/20) participant dropped out due to pain during laser treatment. |
| 585‐nm PDL versus no treatment | Scar size, colour, height, length, width, pliability, skin surface texture, pruritus and pain | 3 RCTs (Manuskiatti 2001; 10 participants; 30 segments and Manuskiatti 2002: 10 participants; 20 segments; Wittenberg 1999; 20 participants; 40 segments) | Manuskiatti 2001 and 2002: scar height evaluated using a dial calliper, erythema using a hand‐held colorimeter after 32 weeks.
Wittenberg 1999: blood flow (erythema), elasticity and volume, burning, pruritus, and pain not related to treatment after 40 weeks. | Manuskiatti 2001, 2002: scar height improvement in laser treated areas when compared with control (P < 0.05, and P = 0.005, respectively) (data presented only in graphs)
Wittenberg 1999: No statistically significant differences between groups were detected for erythema (P = 0.26), elasticity (P = 0.76), volume (P = 0.13), burning (P = 0.75), pruritus (P = 0.99), and pain not related to treatment (P = 0.41) (results presented only in graphs). |
| NAFL versus no treatment | Scar severity | 2 RCTS (Verhaeghe 2013; 22 participants, 44 segments; Lin 2011; 20 participants; 20 scars) | Verhaeghe 2013: POSAS: containing vascularisation, pigmentation, thickness, relief, pliability, and surface area (observer part) and pain not related to treatment, itching, colour, stiffness, thickness, and relief (patient part) (range 6 to 60) after 3 months.
Lin 2011: categories of 25% increments of improvement in scar severity (graded by the participants and 2 blinded observers) after 3 months. | Verhaeghe 2013 (36 segments analysed): Number of participants who got better according to HPGA and PGA. Control: 1/18 POSAS: Patient part (P = .047) Observer part: not significant (details not provided)
Lin 2011: HDTA laser: not significant LDTA: P = 0.001 (data presented only in graphs) |
| NAFL versus no treatment | Incidence and severity of treatment‐related adverse effects | 2 RCTS (Verhaeghe 2013; 22 participants, 44 segments; Lin 2011; 20 participants; 20 scars) | Verhaeghe 2013: treatment‐related adverse effects included erythema, edema, burning sensation, crusts, purpura, vesicles, hyperpigmentation. Duration: 3 months
Lin 2011: side effects, including worsening (erythema, pigmentation, or texture), discolouration, exfoliation, swelling, scabbing, and pain related to treatment, rated on a quartile scale (0 = none, 1 = mild, 2 = moderate, and 3 = severe) during the 3 month‐period. | Verhaege 2013: Percentage of participants reporting treatment‐related adverse effects 4 days after treatment (out of 18 analysed): Erythema: 70% Edema: 20% Burning sensation: 18% Crusts: 15% Purpura: 7% purpura Vesicles: 3% After 3 months: Hyperpigmentation: 1 participant *In a small group of participants, the treated part improved less than the untreated part. Median pain (related to treatment) score (IQR) on a VAS (0 = no pain and 100 = worst possible pain) was: Session 3: 53.0 (22.5–71.0) Session 4: 48.0 (23.5–78.5)
Lin 2011: Number of participants reporting scar worsening HDTA: 3/10
Higher risk of erythema, exfoliation, and pain related to treatment with HDTA compared with LDTA (P = 0.05, P = 0.02, P = 0.01, respectively) (data on side effects were presented only in graphs). |
| NAFL versus no treatment | Scar size, colour, height, length, width, pliability, skin surface texture, pruritus and pain | 2 RCTS (Verhaeghe 2013; 22 participants, 44 segments; Lin 2011; 20 participants; 20 scars) | Verhaeghe 2013: redness, pigmentation, and skin texture after 3 months
Lin 2011: erythema, pigmentation, texture after 3 months | Verhaeghe 2013: No significant difference in redness, pigmentation, and skin texture (details not provided)
Lin 2011: Mean + SD Erythema: Control: 0.89 + 0.95 LDTA: 1.06 + 1.26 Pigmentation: HDTA: 1.06 + 0.95 Control: 0.94 + 0.82 LDTA: 0.79 + 0.76 Control: 0.71 + 0.76 Texture: HDTA: 2 + 0.76 Control: 1.78 + 0.89 LDTA: 2.19 + 0.95 |
| Fractional CO2 Laser versus no treatment | Scar severity | 3 RCTS (Azzam 2016: 30 participants; 60 segments, Blome‐Eberwein 2016: 36 participants; 80 scars, Daoud 2019: 23 participants; 46 segments) | Azzam 2016: patient satisfaction, as follows: excellent = more than 75 %, good = 50 to 75%, moderate = 25 to 50 % and poor = less than 25 % improvement after 3 months
Azzam 2016 and Blome‐Eberwein 2016 used the VSS, including pliability, height, colour, and vascularity
Blome‐Eberwein 2016 and Daoud 2019: POSAS including: vascularisation, pigmentation, thickness, relief, pliability, and surface area (observer), itching, colour, and pain not related to treatment stiffness, thickness, and relief (patient) (range 6 to 60) after up to 6 months | Azzam 2016: Number of participants that reported each satisfaction Keloid scar participants Excellent: 6/12 Good: 3/12 Moderate: 3/12 Hypertrophic scar patients Good: 1/7 Moderate: 2/7 Poor: 2/7
Azzam 2016: Keloid scar patients Laser: 5.7 + 2.2 Control: 7.6 + 1.0 Hypertrophic scar patients Laser: 4.6 + 2.5 Control: 7.6 + 2.9
Blome‐Erbewein 2016 VSS (Mean + SD) Hypertrophic scar patients Laser: 6.5 + 2.39 Control: 6.41 + 2.31
Blome‐Eberwein 2016 POSAS Pre‐treatment Post‐treatment Laser: 28.51 ± 12.85 Control: 24.38 ± 11.41
Daoud 2019 Significant improvements in all categories except for colour (P < 0.001) (results presented in graphs) |
| Fractional CO2 Laser versus no treatment | Incidence and severity of treatment‐related adverse effects | 1 RCT (Daoud 2019 23 participants; 46 scar segments) | No definition provided | The authors mention that no treatment‐related adverse effects were reported |
| Fractional CO2 Laser versus no treatment | Scar size, colour, height, length, width, pliability, skin surface texture, pruritus and pain | 2 RCTS (Azzam 2016: 30 participants; 60 segments;,Blome‐Eberwein 2016: 36 participants; 80 scars) | Azzam 2016: pruritus and pain not related to treatment after 3 months
Blome‐Eberwein 2016 Scar pliability and height evaluated with suction cup and ultrasound, colour; erythema and pigmentation assessed with Dermaspectrometer), sensation, pruritus, and pain not related to treatment evaluated with POSAS after up to 6 months | Azzam: number of participants complaining of pruritus and pain Pruritus: 16 Pain: 5 (details not provided)
Blome‐Eberwein 2016: pliability, height, recoil Mean and SD – before and after treatment Scar height Pre‐intervention Laser: 3.15 ± 0.37 Control: 2.658 ± 0.344 Post‐treatment: Laser: 2.34 ± 0.313 Control: 2.46 ± 0.342 |
HDTA: high‐density treatment arm; HPGA: Health Professional Global Assessment; IQR: interquartile range; LDTA: low‐density treatment arm; PGA: patient global assessment; POSAS: Patient and Observer Scar Assessment Scale; (In POSAS, highest values indicate worse scar or sensation); SD: standard deviation; VAS: visual analogue scale; VSS: Vancouver Scar Scale.
| Comparison | Trials (participants) | Outcome | Definition of outcome in trial/measurement details | Data reported |
| 585‐nm PDL versus TAC | 2 RCTs (Omranifard 2007: 80 participants; 80 scars and Manuskiatti 2002: 10 participants; 20 segments) | Scar severity | Omranifard 2007: Patient Satisfaction assessed by VBS, including pigmentation, vascularity, pliability and height (photographs were taken). Self‐assessment: number of participants who considered their scars better or much better after up to 12 months Manuskiatti 2002: categories of 25% increments of improvement in scar severity after 32 weeks (graded by the participant) | Omranifard 2007: VBS (Mean + SD) Post‐treatment PDL: 4.2 + 1.6 TAC: 6.7 + 1.6 Self‐assessment PDL: 70% TAC: 30% Manuskiatti 2002: Number of participants with a 50% improvement or higher PDL: 8/10 TAC: 10/10 |
| 585‐nm PDL versus TAC | 2 RCTs (Omranifard 2007: 80 participants; 80 scars and Manuskiatti 2002: 10 participants; 20 segments) | Incidence and severity of treatment‐related adverse effects | Omranifard 2007: complications, such as textural or discolouration (hypo‐ or hyperpigmentation) during up to 12 months Manuskiatti 2002: Immediate treat reactions included mild to moderate pain during treatment, burning sensation, spots of purpura, erosion secondary to blistering. Treatment‐related adverse sequelae including hypopigmentation, telangiectasia, and skin atrophy during 32 weeks. | Omranifard 2007: no complication was observed Manuskiatti 2002: Sequelae: PDL: 0/10 Control: 10/10 (further details not provided) |
| 585‐nm PDL versus TAC | 2 RCTs (Omranifard 2007: 80 participants; 80 scars and Manuskiatti 2002: 10 participants; 20 segments) | Scar size, colour, height, length, width, pliability, skin surface texture, pruritus and pain | Omranifard 2007: vascularity, using a transparent tool for blanching the scar. Scar height scores: calliper by measuring the maximum vertical elevation of the scar above the normal skin after up to 12 months Manuskiatti 2002: scar height evaluated using a dial calliper, erythema using a hand‐held colorimeter after 32 weeks. | Omranifard 2007: Vascularity (Mean) Pre‐treatment PDL: 2.3 TAC: 2.3 Post‐treatment PDL: 1.1 TAC: 1.95 Height (Mean) Pre‐treatment PDL: 2.16 TAC: 2.18 Post‐treatment PDL: 1.32 TAC: 1.93 Manuskiatti 2002: No significant difference between groups in height (results presented only in graphs) |
| 585‐nm PDL versus 5‐FU | 1 RCT (Manuskiatti 2002: 10 participants; 20 segments) | Scar severity | Manuskiatti 2002: categories of 25% increments of improvement in scar severity after 32 weeks (graded by the participant). | Manuskiatti 2002: Number of participants with a 50% improvement or higher PDL: 8/10 |
| 585‐nm PDL versus 5‐FU | 1 RCT (Manuskiatti 2002: 10 participants; 20 segments) | Incidence and severity of treatment‐related adverse effects | Manuskiatti 2002: immediate treatment reactions included mild to moderate pain during treatment and spots of purpura during 32 weeks. | Manuskiatti 2002: Purpura: 5‐FU: 2/10
No permanent sequelae were reported in the areas submitted to laser therapy or 5‐FU. |
| 585‐nm PDL versus 5‐FU | 1 RCT (Manuskiatti 2002: 10 participants; 20 segments) | Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain | Manuskiatti2002: scar height evaluated using a dial calliper, erythema using a hand‐held colorimeter after 32 weeks. | No significant difference between groups in height (results presented only in graphs) |
| 585‐nm PDL versus TAC plus 5‐FU | 1 RCT (Manuskiatti 2002: 10 participants; 20 segments) | Scar severity | Manuskiatti 2002: categories of 25% increments of improvement in scar severity after 32 weeks (graded by the participant). | Manuskiatti 2002: Number of participants with a 50% improvement or higher PDL: 8/10 TAC plus 5‐FU: 9/10 |
| 585‐nm PDL versus TAC plus 5‐FU | 1 RCT (Manuskiatti 2002: 10 participants; 20 segments) | Incidence and severity of treatment‐related adverse effects | Manuskiatti 2002: immediate treatment reactions included mild to moderate pain during treatment and spots of purpura during 32 weeks. | Manuskiatti 2002: Purpura: 5‐FU: 3/10
No permanent sequelae were reported in the areas submitted to laser therapy or 5‐FU. |
| 585‐nm PDL versus TAC plus 5‐FU | 1 RCT (Manuskiatti 2002: 10 participants; 20 segments) | Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain | Manuskiatti2002: scar height evaluated using a dial calliper, erythema using a hand‐held colorimeter after 32 weeks. | Mild to moderate pain not related to treatment PDL: 9/10 TAC plus 5‐FU: 10/10 No significant difference between groups in height (results presented only in graphs). |
| 585‐nm PDL versus Silicone Gel Sheeting | 1 RCT (Wittenberg 1999; 20 participants; 40 segments) | Incidence and severity of treatment‐related adverse effects | Wittenberg 1999: No definition is provided | Wittenberg 1999: one participant dropped out due to pain during laser treatment. One participant did not use SGS because of skin irritation. |
| Erbium laser versus TAC | 1 RCT (Omranifard 2007: 80 participants; 80 scars) | Scar severity | Omranifard 2007: Patient Satisfaction assessed by VBS, including pigmentation, vascularity, pliability and height. (photographs were taken) Self‐assessment: improvement of the scars severity after up to 12 months. | Omranifard 2007: VBS (Mean + SD) Post‐treatment Erbium: 4.6 + 1.9 TAC: 6.7 + 1.6 Self‐assessment (number of participants who considered their scars better or much better) Erbium: 65% TAC: 30% |
| Erbium laser versus TAC | 1 RCT (Omranifard 2007: 80 participants; 80 scars) | Incidence and severity of treatment‐related adverse effects | Omranifard 2007: complications, such as textural or discoloration (hypo‐ or hyperpigmentation) during up to 12 months. | Omranifard 2007: no complication was observed |
| Erbium laser versus TAC | 1 RCT (Omranifard 2007: 80 participants; 80 scars) | Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain | Omranifard 2007: vascularity, using a transparent tool for blanching the scar. Scar height scores: calliper by measuring the maximum vertical elevation of the scar above the normal skin after up to 12 months. | Omranifard 2007: Vascularity (Mean) pre‐treatment Erbium: 2.4 TAC: 2.3 Post‐treatment Erbium: 1.15 TAC: 1.95 Height (Mean) Pre‐treatment Erbium: 2.18 TAC: 2.18 Post‐treatment Erbium: 1.39 TAC: 1.93 |
| Fractional CO2 Laser versus TAC | 1 RCT (Srivastava 2019; 40 participants; 40 scars) | Scar severity | Srivastava 2019: VSS | Srivastava 2019 Results of full scale were not reported |
| Fractional CO2 Laser versus TAC | 1 RCT (Srivastava 2019; 40 participants; 40 scars) | Incidence and severity of treatment‐related adverse effects | Srivastava 2019: pain at injection site, telangiectasia, skin atrophy and charring were evaluated and reported (when they occurred) during 24 weeks. | Srivastava 2019: Number of participants reporting treatment‐related adverse effects Pain at injection site FCO2: 2/20 TAC: 8/20 Telangiectasia FCO2: 0/20 TAC: 2/20 Skin atrophy FCO2: 0/20 TAC: 1/20 Charring FCO2: 3/20 TAC: 0/20 |
| Fractional CO2 Laser versus TAC | 1 RCT (Srivastava 2019; 40 participants; 40 scars) | Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain | Srivastava 2019: height measured with callipers; vascularity by visual inspection; pliability by palpation; pigmentation after blanching (using a piece of clear plastic sheet till scar flattening occurred) and comparing it with the surrounding skin, pruritus, and pain not related to treatment after 24 weeks. | Srivastava 2019: Height (Mean + SD) Pre‐treatment FCO2: 1.95 + 0.76 TAC: 1.75 + 0.64 Post‐treatment TAC: 0 + 0 Vascularity Pre‐treatment FCO2: 2.05 + 0.69 TAC: 1.65 + 0.49 Post‐treatment TAC: 0 + 0 Pliability Pre‐treatment FCO2: 1.85 + 0.67 TAC: 1.9 + 0.64 Post‐treatment TAC: 0 + 0 Pigmentation Pre‐treatment FCO2: 1.60 + 0.50 TAC: 1.7 + 0.47 Post‐treatment TAC: 0.8 + 0.41 |
| Fractional CO2 Laser versus Verapamil | 1 RCT (Srivastava 2019; 40 participants 40 scars) | Scar severity | Srivastava 2019: VSS | Srivastava 2019: Results of full scale were not reported |
| Fractional CO2 Laser versus Verapamil | 1 RCT (Srivastava 2019; 40 participants 40 scars) | Incidence and severity of treatment‐related adverse effects | Srivastava 2019: pain at injection site, telangiectasia, skin atrophy and charring were evaluated and reported (when they occurred) during 24 weeks. | Srivastava 2019: Number of participants reporting treatment‐related adverse effects Pain at injection site FCO2: 2/20 Verapamil: 0/20 Telangiectasia FCO2: 0/20 Verapamil: 0/20 Skin atrophy FCO2: 0/20 Verapamil: 0/20 Charring FCO2: 3/20 Verapamil: 0/20 |
| Fractional CO2 Laser versus Verapamil | 1 RCT (Srivastava 2019; 40 participants 40 scars) | Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain | Srivastava 2019: height measured with callipers; vascularity by visual inspection; pliability by palpation; pigmentation after blanching (using a piece of clear plastic sheet till scar flattening occurred) and comparing it with the surrounding skin, pruritus, and pain not related to treatment after 24 weeks. | Srivastava 2019: Height (Mean + SD) Pre‐treatment FCO2: 1.95 + 0.76 Verapamil: 2.05 + 0.6 Post‐treatment Verapamil: 0.05 + 0.22 Vascularity Pre‐treatment FCO2: 2.05 + 0.69 Verapamil: 1.95 + 0.69 Post‐treatment Verapamil: 0.1 + 0.31 Pliability Pre‐treatment FCO2: 1.85 + 0.67 Verapamil: 2.1 + 0.64 Post‐treatment FCO2: 0.9 + 0.31 Verapamil: 0 + 0 Pigmentation Pre‐treatment FCO2: 1.60 + 0.50 Verapamil: 1.65 + 0.49 Post‐treatment Verapamil: 0.55 + 0.51 |
5‐FU: Fluorouracil; PDL: Pulsed‐Dye Laser; TAC: Triamcinolone acetonide;VSS: Vancouver Scar scale.
| Comparison | N. of Trials | Outcome | Definition of outcome in trial/measurement details | Data reported |
| 585‐nm PDL plus TAC plus 5 FU versus TAC plus 5‐FU | 1 RCT (Asilian 2006; 43 participants; 43 scars) | Scar severity | Asilian 2006: patient and Observer: no improvement; poor = up to 25% improvement; fair = 26% to 50% improvement; good = 51% to 75% improvement; (for the observer assessment photographs were taken) after 12 weeks | Asilian 2006: Number of participants and observers reporting good to excellent improvement OA 585‐nm PDL plus TAC plus 5 FU: 14/20 TAC plus 5‐FU: 8/20 PSA 585‐nm PDL plus TAC plus 5 FU: 15/20 TAC plus 5‐FU: 11/20 |
| 585‐nm PDL plus TAC plus 5 FU versus TAC plus 5‐FU | 1 RCT (Asilian 2006; 43 participants; 43 scars) | Incidence and severity of treatment‐related adverse effects | Asilian 2006: treatment‐related adverse effects including the presence of purpuric areas by observer interviews during 12 weeks | Asilian 2006: In the TAC plus 5‐FU plus PDL group the lesions became purpuric which lasted from 7 to 10 days |
| 585‐nm PDL plus TAC plus 5 FU versus TAC plus 5‐FU | 1 RCT (Asilian 2006; 43 participants; 43 scars) | Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain | Asilian 2006: scar length and width using a dial calliper, height using a calliper, erythema, pliability, and pruritus: graded by the observer on a 5‐point scale: 0 = no; 1 = mild; 2 = moderate; 3 = severe; and 4 = very severe. | Asilian 2006: Erythema Pre‐treatment PDL plus TAC plus 5‐FU: 3.2 TAC plus 5‐FU: 3.3 Post‐treatment TAC plus 5‐FU plus PDL: 1.2 TAC plus 5‐FU: 1.9 Reduction in height (average lesion) TAC plus 5‐FU: 77% PDL plus TAC plus 5‐FU: 79% |
| CO2 Laser plus TAC versus Cryosurgery plus TAC | 1 RCT (Behera 2016: 60 participants; 101 scars) | Scar severity | Behera 2016: patient and observer on a 5‐point scale as, poor = up to 25% improvement; fair = 26% to 50% improvement; good = 51% to 75% improvement; and excellent = 76% to 100% improvement (for the observer assessment photographs were taken) VSS after up to 12 months | Behera 2016: Number (%) of participants with an improvement of 50% or higher in the scar: PSA: CO2 Laser plus TAC: 27 (75%); Cryosurgery plus TAC: 21 (77.78%) OA: CO2 Laser plus TAC: 22 (61.12%); Cryosurgery plus TAC: 23 (85.18%) VSS: CO2 Laser plus TAC: 19 (52.78%); Cryosurgery plus TAC: 17 (62.96%) |
| CO2 Laser plus TAC versus Cryosurgery plus TAC | 1 RCT (Behera 2016: 60 participants; 101 scars) | Recurrence | Behera 2016: no definition was provided (after up to 12 months) | Behera 2016: CO2 Laser plus TAC: 6 (16.66%) Cryosurgery plus TAC: 0 (0%) |
| CO2 Laser plus TAC versus Cryosurgery plus TAC | 1 RCT (Behera 2016: 60 participants; 101 scars) | Incidence and severity of treatment‐related adverse effects | Behera 2016: no definition was provided (during up to 12 months) | Behera 2016: Number (%) of participants with atrophy CO2 Laser plus TAC: 17 (47.23%); Cryosurgery plus TAC: 15 (55.56%) |
| CO2 Laser plus TAC versus Cryosurgery plus TAC | 1 RCT (Behera 2016: 60 participants; 101 scars) | Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain | Behera 2016: height: using a dial calliper, volume, pruritus, and pain not related to treatment after up to 12 months | Behera 2016: CO2 Laser plus TAC: 49.31 + 50.42; Cryosurgery plus TAC: 65.46 + 35.63 Volume (Mean percentage reduction + SD): CO2 Laser plus TAC: 54.81 + 47.96; Cryosurgery plus TAC: 72.69 + 37.75 |
| Nd:YAG laser plus Intralesional corticosteroid plus 5‐FU versus Intralesional corticosteroid plus 5‐FU | 1 RCT (Chen 2017: 46 participants; 46 scars) | Scar severity | Chen 2017: patient and observer on a 5‐point scale as, poor = up to 25% improvement; fair = 26% to 50% improvement; good = 51% to 75% improvement; and excellent = 76% to 100% improvement (for the observer assessment photographs were taken) after 3 months. | Chen 2017: OA: Number (%) of participants with an improvement of 51% or higher in the scar: Nd:YAG laser plus Intralesional corticosteroid plus 5‐FU: 16 (69.57%); Intralesional corticosteroid plus 5‐FU: 11 (47.83%) PSA: Nd:YAG laser plus Intralesional corticosteroid plus 5‐FU: 18 (78.26%); Intralesional corticosteroid plus 5‐FU: 13 (56.52%%) |
| Nd:YAG laser plus Intralesional corticosteroid plus 5‐FU versus Intralesional corticosteroid plus 5‐FU | 1 RCT (Chen 46 participants; 46 scars) | Incidence and severity of treatment‐related adverse effects | Chen 2017: no definition was provided (during 3 months) | Chen 2017: Almost all injections were painful. Nd:YAG plus Intralesional corticosteroid plus 5‑FU: the site treated by Nd:YAG became purpuric, which lasted for 7 to 10 days. No adverse textural or pigmentary alterations, and no ulcers or erosions were observed in either groups. No further information was provided regarding adverse events in the trial. |
| Nd:YAG laser plus Intralesional corticosteroid plus 5‐FU versus Intralesional corticosteroid plus 5‐FU | 1 RCT (Chen 46 participants; 46 scars) | Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain | Chen 2017: erythema, pliability, and pruritus were graded by the observer on a 5‐point scale: 0 = no erythema; 1 = mild erythema; 2 = moderate erythema; 3 = severe erythema; and 4 = very severe erythema after 3 months. | Chen 2017: Erythema (P < 0.05), pliability (P < 0.05), and pruritus (P < 0.05) were significantly lower in the laser group (data provided only in graphs). |
| He‐Ne laser plus Decamethyltetrasiloxane, Polydimethylsiloxane and Cyclopentasiloxane cream versus Decamethyltetrasiloxane, Polydimethylsiloxane and Cyclopentasiloxane cream | 1 RCT (Alsharnoubi 2018: 15 participants; 30 segments) | Scar severity | Alsharnoubi 2018: VSS, including skin thickness, pigmentation, and vascularity after 3 months. | Alsharnoubi 2018: VSS: median values Pre‐treatment: 9 (value of the whole scar) Post treatment He‐Ne laser plus Decamethyltetrasiloxane, Polydimethylsiloxane and Cyclopentasiloxane cream: 4; Decamethyltetrasiloxane, Polydimethylsiloxane and Cyclopentasiloxane cream: 6; Height score: Pre‐treatment: 2 (value of the whole scar) Post treatment He‐Ne laser plus Decamethyltetrasiloxane, Polydimethylsiloxane and Cyclopentasiloxane cream: 1; Decamethyltetrasiloxane, Polydimethylsiloxane and Cyclopentasiloxane cream: 2 |
| He‐Ne laser plus Decamethyltetrasiloxane, Polydimethylsiloxane and Cyclopentasiloxane cream versus Decamethyltetrasiloxane, Polydimethylsiloxane and Cyclopentasiloxane cream | 1 RCT (Alsharnoubi 2018: 15 participants; 30 scar segments) | Incidence and severity of treatment‐related adverse effects | Definition was not provided | No treatment‐related adverse effects were reported. |
| He‐Ne laser plus Decamethyltetrasiloxane, Polydimethylsiloxane and Cyclopentasiloxane cream versus Decamethyltetrasiloxane, Polydimethylsiloxane and Cyclopentasiloxane cream | 1 RCT (Alsharnoubi 2018: 15 participants; 30 scar segments) | Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain | Alsharnoubi 2018: scar thickness using an ultrasound imaging system, perfusion (erythema) using a Laser Doppler perfusion imager. | Alsharnoubi 2018: Skin thickness (mean ± SD) Pre‐treatment: 0.52 ± 0.17 mm (whole scar) Post treatment He‐Ne laser plus Decamethyltetrasiloxane, Polydimethylsiloxane and Cyclopentasiloxane cream: 0.34 ± 0.09 mm; Decamethyltetrasiloxane, Polydimethylsiloxane and Cyclopentasiloxane cream: 0.43 ± 0.13 mm Perfusion Pre‐treatment: 1.27 ± 0.54 V (whole scar) Post treatment He‐Ne laser plus Decamethyltetrasiloxane, Polydimethylsiloxane and Cyclopentasiloxane cream: 0.8 ± 0.23 V; Decamethyltetrasiloxane, Polydimethylsiloxane and Cyclopentasiloxane cream: 0.77 ± 0.24 V Pigmentation Pre‐treatment: 2 (whole scar) Post Treatment He‐Ne laser plus Decamethyltetrasiloxane, Polydimethylsiloxane and Cyclopentasiloxane cream: 0; Decamethyltetrasiloxane, Polydimethylsiloxane and Cyclopentasiloxane cream: 2; Vascularity Pre‐treatment: 2 (whole scar) Post Treatment He‐Ne laser plus Decamethyltetrasiloxane, Polydimethylsiloxane and Cyclopentasiloxane cream: 1 Decamethyltetrasiloxane, Polydimethylsiloxane and Cyclopentasiloxane cream: 1 (data presented in graphs) |
| PDL plus intralesional verapamil versus intralesional verapamil | 1 RCT (Khattab 2019; 40 participants; 50 keloid scars) | Scar severity | Khattab 2019: VSS, keloid height measured with callipers; pliability by palpation; vascularity by visual inspection, and pigmentation scored after blanching and comparing it with the surrounding skin after 24 weeks. | Khattab 2019: Height (Mean + SD) PDL plus verapamil: 0.21 ± 0.56; Verapamil: 3.10±1.85 Pliabilty: PDL plus verapamil: 0.20±0.41; Verapamil: 2.07±0.26 Vascularity PDL plus verapamil: 0.03 ± 0.70; Verapamil: 0.87±0.74 Pigmentation PDL plus verapamil: 0.13 ± 0.35; Verapamil: 0.27±0.70 |
| PDL plus intralesional verapamil versus intralesional verapamil | 1 RCT (Khattab 2019; 40 participants; 50 keloid scars) | Incidence and severity of treatment‐related adverse effects | Khattab 2019: treatment‐related adverse effects were regrowth, pain, hyperpigmentation, depigmentation, and purpura during 24 weeks. | Khattab 2019: Treatment‐related adverse events: |
| PDL plus intralesional verapamil versus intralesional verapamil | 1 RCT (Khattab 2019; 40 participants; 50 keloid scars) | Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain | Khattab 2019: height, vascularity, pliability, and pigmentation were assessed at 24 weeks. | Khattab 2019: Verapamil: 0.87 + 0.74 Pliability PDL plus verapamil: 0.2 + 0.41; Verapamil: 2.07 + 0.26 Pigmentation PDL plus verapamil: 0.13 + 0.35; Verapamil: 0.27 + 0.7 |
5‐FU: Fluorouracil; NdYAG: neodymium‐doped yttrium aluminium garnet; PDL: Pulsed‐Dye Laser; SD: standard deviation; TAC: Triamcinolone acetonide;VSS: Vancouver Scar scale.
Outcomes
The primary outcome of severity of keloid or hypertrophic scars (or both), assessed using a range of specific scales across studies, for both participant and health professional‐reported data, and incidence and severity of treatment‐related adverse effects were reported in 12 of the studies evaluated (Alsharnoubi 2018; Asilian 2006; Behera 2016; Chen 2017; Daoud 2019; Khattab 2019; Lin 2011; Manuskiatti 2001; Manuskiatti 2002; Omranifard 2007; Srivastava 2019; Verhaeghe 2013). Azzam 2016 ,and Blome‐Eberwein 2016 did not report treatment‐related adverse effects. Wittenberg 1999 only reported treatment‐related adverse effects.
Secondary outcomes were reported as follows.
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Alsharnoubi 2018: skin thickness, pigmentation, and vascularity
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Asilian 2006: colour, height, length, width, pliability, and pruritus
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Azzam 2016: pruritus and pain
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Behera 2016: height, volume, pruritus and pain
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Blome‐Eberwein 2016: colour, height, pliability, sensation, pruritus and pain
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Chen 2017: erythema, pliability, and pruritus
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Daoud 2019: colour, matte versus shiny, contour, distortion, and texture
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Khattab 2019: overall appearance, dyschromia (discolourisation), the degree of hypertrophy, and texture
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Lin 2011: size, colour, and texture
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Manuskiatti 2001: colour, height, pliability, texture, pruritus and pain
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Manuskiatti 2002: colour, height, and pliability
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Omranifard 2007: colour, height, and patient tolerance
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Srivastava 2019: height, pigmentation, vascularity, and pliability
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Verhaeghe 2013: pain, itching, colour, stiffness, thickness, relief, vascularity, pigmentation, pliability, and surface area
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Wittenberg 1999: size, pliability, colour, pruritus and pain.
Callipers, colorimeters, ultrasound, cutometer, spectrometer, molds, and forms were used to evaluate these parameters.
Excluded studies
Of the 44 full‐text articles evaluated, 17 were excluded and the reasons for their exclusion are described in Characteristics of excluded studies.
One study is awaiting classification (Maari 2017) and 11 are ongoing studies see Characteristics of ongoing studies.
Risk of bias in included studies
We evaluated and presented the risk of bias of each RCT as part of the Characteristics of included studies tables. Figure 2 presents the judgments of the review authors on the methodological appraisal as percentages across all included studies. Figure 3 presents the judgements of the review authors on the methodological appraisal of each risk of bias item of the included studies. All studies were assessed as being at high risk of bias for at least one domain.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Allocation
Seven studies described their sequence generation methods (Azzam 2016; Behera 2016; Blome‐Eberwein 2016; Lin 2011; Srivastava 2019; Verhaeghe 2013; Wittenberg 1999) and were rated as low risk of bias. Four RCTs (Azzam 2016; Behera 2016; Blome‐Eberwein 2016; Verhaeghe 2013) also provided an adequate description of allocation concealment and were rated as low risk of bias: meaning they were considered as low risk for bias arising from the randomisation process.
Blinding
Since we were comparing a procedure (laser therapy) with other therapies and blinding is difficult from a practical perspective, participants and interventionists were not blinded in any of the RCTs evaluated and they were considered as high risk for performance bias. Twelve trials (Alsharnoubi 2018; Asilian 2006; Azzam 2016; Behera 2016; Blome‐Eberwein 2016; Chen 2017; Daoud 2019; Lin 2011; Omranifard 2007; Srivastava 2019; Verhaeghe 2013; Wittenberg 1999) had blinded observers, so were rated as low risk for detection bias for non‐participant reported outcomes. The remaining three RCTs Khattab 2019; Manuskiatti 2001; Manuskiatti 2002) did not mention the blinding of the evaluators and were rated as unclear risk of bias.
Incomplete outcome data
In four trials (Manuskiatti 2001; Manuskiatti 2002; Omranifard 2007; Srivastava 2019), all participants completed the study, and these trials were considered as low risk of bias. Two RCTs (Verhaeghe 2013; Wittenberg 1999) reported dropouts, but explained the reasons, and were also rated as low risk of bias. Two trials (Alsharnoubi 2018; Khattab 2019) did not provide enough information to judge if there were losses, and these trials were rated as unclear risk of bias. Two trials (Blome‐Eberwein 2016; Lin 2011) had substantial losses and although the reasons for the losses were explained, the authors performed as‐treated analyses. Thus, these trials were rated as high risk of bias. Five trials (Asilian 2006; Azzam 2016; Behera 2016; Chen 2017; Daoud 2019) had losses and did not provide enough information about the reasons for dropouts, so were considered at high risk of bias.
Selective reporting
Four trials (Alsharnoubi 2018; Asilian 2006; Azzam 2016; Omranifard 2007) did not describe the data for all parameters analysed, and their protocols were not available, so they were considered as high risk of bias. Eight RCTs (Blome‐Eberwein 2016; Chen 2017; Khattab 2019; Lin 2011; Manuskiatti 2001; Manuskiatti 2002; Verhaeghe 2013; Wittenberg 1999) reported all parameters specified in the methods section or in their protocols, so were rated as low risk of bias. Three trials (Behera 2016; Daoud 2019; Srivastava 2019) were considered as unclear risk of bias as the authors described the findings for all parameters analysed, however, they did not explain what kind of tool they used to analyse these parameters and no trial protocol was available.
Other potential sources of bias
All split‐scar trials performed paired analyses as required so we did not consider them to be at risk of bias in terms of analytical approach. There were no other potential sources of bias noted in any of the included studies, and all of them were rated as low risk of bias.
Effects of interventions
See: Summary of findings 1 Laser therapy compared with no treatment for treating hypertrophic and keloid scars; Summary of findings 2 Laser therapy compared with other treatments for treating hypertrophic and keloid scars; Summary of findings 3 Laser therapy plus other treatment compared with other treatment for treating hypertrophic and keloid scars
The variability of intervention types, controls, follow‐up periods and limited data reported meant we could only pool data for one comparison (and only two outcomes within this). We report below the results of the effects of interventions, with subgroup analyses, considering the latest time points available in the included studies. The secondary outcomes ‐ cosmesis, tolerance, preference for different modes of treatment, adherence, and change in quality of life ‐ were not reported in any of the included studies.
1. Laser versus no treatment
585‐nm pulsed‐dye laser (PDL) versus no treatment (3 studies)
Scar severity measured by health professional and/or participant using a specific scale
We pooled data from Manuskiatti 2001 and Manuskiatti 2002. There may be more hypertrophic and keloid scar improvement (that is scars are less severe) in 585‐nm PDL‐treated scars compared with no treatment after 32 weeks: risk ratio (RR) 1.96 (95% confidence interval (CI): 1.11 to 3.45, two studies, 60 scar segments (based on unblinded patient self‐assessment of improvement of 50% or higher between the laser treated areas and the control areas) (Analysis 1.1). This is low‐certainty evidence, downgraded once for serious imprecision and once for serious risk of bias.
Incidence and severity of treatment‐related adverse effects
Three studies reported incidence of adverse effects related to treatment (Wittenberg 1999, Manuskiatti 2001, Manuskiatti 2002) (Table 1). It is uncertain whether the 585‐nm PDL impacts on the incidence of treatment‐related adverse effects. This is very low certainty evidence, downgraded twice for very serious imprecision and once for serious risk of bias (summary of findings Table 1) (Analysis 1.2).
Scar size, colour, height, length, width, pliability, skin surface texture, pruritus and pain
Three studies which were at high risk of bias evaluated these outcomes (Wittenberg 1999, Manuskiatti 2001 and Manuskiatti 2002).
In Wittenberg 1999, the study authors reported there were no significant differences in blood flow (erythema), elasticity and volume between intervention and control groups at the end of the follow up period. Results were presented graphically and not analysed here further. There was also no reported difference between groups in patients who rated scar burning, pruritus, and pain not related to treatment.
In Manuskiatti 2001 and Manuskiatti 2002, the authors reported scar height reduction in laser treated areas when compared with control (P < 0.05, and P = 0.005, respectively). The results were presented graphically, with no data for further analysis.
Nonablative fractional laser (NAFL) versus no treatment (2 studies)
Scar severity measured by health professional and/or participant using a specific scale
From Verhaeghe 2013 it is unclear whether NAFL impacts on hypertrophic scar severity compared with no treatment when measured using a blinded health professional global assessment at three months, as this is very low‐certainty evidence, downgraded twice due to very serious imprecision and once for serious risk of bias) (Analysis 2.1).
In Verhaeghe 2013, the authors described an improvement in the patient global assessment (PGA) at one month (reported P = 0.006) and three months (reported P = 0.02) after the final NAFL treatment with no further data available. The certainty of evidence was assessed as very low, downgraded twice due to very serious imprecision and once for serious risk of bias.
In Verhaeghe 2013 the authors reported an improvement in NAFL treated hypertrophic scars compared with no treatment on the participant part of the Patient and Observer Scar Assessment Scale (POSAS) at one month and three months, however the size of the difference was not reported. No data for the observer part of the scale was presented. This is very low‐certainty evidence, downgraded twice due to very serious imprecision and once for serious risk of bias.
For patient self‐assessments in Lin 2011 we were unable to fully analyse the data, because the results were presented only in graphs and did not allow extraction.
Incidence and severity of treatment‐related adverse effects
It is uncertain whether NAFL treatment leads to a higher incidence of treatment‐related adverse effects. This is very low‐certainty evidence, downgraded twice for very serious imprecision and once for serious risk of bias (summary of findings Table 1) (Analysis 2.2).
Scar size, colour, height, length, width, pliability, skin surface texture, pruritus and pain
In a small study which was at high risk of bias (Lin 2011), two different parameters of NAFL, including a high‐density treatment arm (HDTA) and a low‐density treatment arm (LDTA), were compared with a control intervention for the treatment of hypertrophic scars. In this study, small differences that were imprecise were noted between HDTA treated groups compared with the control group for a range of outcomes: erythema mean difference ((MD) 0.44; 95% CI ‐0.54 to 1.42), pigmentation (MD 0.12; 95% CI ‐0.66 to 0.90]) and texture (MD 0.22; 95% CI ‐0.50 to 0.94). Similarly, small and imprecise differences were also found for LDTA treated groups when compared with the control group: erythema (MD 0.12; 95% CI: ‐0.96 to 1.20), pigmentation (MD 0.08; 95% CI: ‐0.59 to 0.75) and texture (MD 0.56; 95% CI: ‐0.27 to 1.39) (Analysis 2.3). Erythema, pigmentation and texture were assessed based on a four‐point scale (where 0 was no improvement or worsened, and 3 was a marked improvement).
Verhaeghe 2013 reported no improvement in redness and pigmentation of skin scars (skin reflectance measurements) treated with NAFL, when compared with control, one and three months after the final treatment.
Fractional CO2 laser versus no treatment (3 studies)
Azzam 2016 compared ablative fractional CO2 laser for treating hypertrophic and keloid scars with no treatment. Blome‐Eberwein 2016 and Daoud 2019 compared ablative fractional CO2 laser for treating hypertrophic scars with no treatment.
Scar severity measured by health professional and/or participant using a specific scale
It is uncertain whether fractional CO2 impacts on hypertrophic scar severity compared with no treatment as evaluated with the Vancouver Burn Scar (VBS) scale by blinded observers (Azzam 2016; Blome‐Eberwein 2016) or impacts on keloid scar severity (Azzam 2016) after up to six months. The evidence is of very low certainty, as we downgraded twice for very serious imprecision, and once for serious risk of bias (Analysis 3.1).
The evidence is very uncertain about the effect of fractional CO2 compared with no treatment on scar severity based on the POSAS values (Analysis 3.2). The evidence is of very low certainty, as we downgraded twice for very serious imprecision and once for serious risk of bias (summary of findings Table 1).
Incidence and severity of treatment‐related adverse effects
These data were not assessed in Azzam 2016 and Blome‐Eberwein 2016. In Daoud 2019; there were no treatment‐related adverse effects reported.
Scar size, colour, height, length, width, pliability, skin surface texture, pruritus and pain
In a study which was at high risk of bias (Blome‐Eberwein 2016), pliability, height (in the suction cup), and "recoil" of hypertrophic scars were reported as not improving significantly in the laser group or in the control group. No, or only small, differences that were imprecise were noted between fractional CO2 laser‐treated groups compared with control group for a range of outcomes: scar height assessed by ultrasound (MD ‐0.12 millimetres (mm); 95% CI ‐0.27 to 0.03); erythema and pigmentation assessed by dermatospectrometry (MD 0.73; 95% CI ‐1.27 to 2.73, and MD ‐1.14; ‐7.16 to 4.88, respectively), and scar‐related pruritus and pain not related to treatment assessed as part of the POSAS (MD 0.41; 95% CI ‐0.66 to 1.48, and MD 0.41; 95% CI ‐0.63 to 1.45, respectively) (Analysis 3.3).
Azzam 2016 reported that scar pain not related to treatment decreased in six (54.5%) of the 11 participants (three had keloid and three had hypertrophic scars), and the pruritus disappeared in 11 (68.8%) (seven had keloid and four had hypertrophic scars) of the 16 cases after treatment. Results for this trial were not presented by treatment arm and no further data were available for analysis.
2. Laser versus other treatments
585‐nm PDL versus triamcinolone acetonide (TAC) (2 studies)
Scar severity measured by health professional and/or participant using a specific scale
It is uncertain whether PDL impacts on hypertrophic scar severity compared with TAC when measured using blinded observer assessment (Omranifard 2007) (Analysis 4.1) or on hypertrophic and keloid scar severity compared with TAC when measured using patient self‐assessment (PSA) (Manuskiatti 2002, Omranifard 2007) (Analysis 4.2), as the certainty of evidence was assessed as very low, downgraded twice due to very serious imprecision and once due to serious risk of bias.
Incidence and severity of treatment‐related adverse effects
In Omranifard 2007, no complications were reported. In Manuskiatti 2002, it is unclear whether 585‐nm PDL leads to more treatment‐related adverse effects, including sequelae (Analysis 4.3) or treatment‐related pain (Analysis 4.3) than TAC, as the evidence was rated as very low certainty, downgraded twice due to very serious imprecision and once due to serious risk of bias (summary of findings Table 2).
Scar size, colour, height, length, width, pliability, skin surface texture, pruritus and pain
In Manuskiatti 2002, the results were presented in graphs, with no data for further analysis. In Omranifard 2007 no measures of variability were provided and no further analysis was possible (Table 2)
585‐nm PDL versus 5‐Fluorouracil (5‐FU) (1 study)
Scar severity measured by health professional and/or participant using a specific scale
It is uncertain whether PDL impacts on hypertrophic and keloid scar severity measured using patient self‐assessment compared with 5‐FU (Manuskiatti 2002) (Analysis 5.1). The certainty of the evidence is very low, downgraded twice due to very serious imprecision and once due to serious risk of bias.
Incidence and severity of treatment‐related adverse effects
It is uncertain whether 585‐nm PDL treatment impacts on the incidence of treatment‐related adverse effects compared with 5‐FU. The certainty of the evidence is very low, downgraded twice due to very serious imprecision and once due to serious risk of bias (summary of findings Table 2) (Analysis 5.2).
Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain
The results were presented only graphically and further data extraction and analyses were not possible.
585‐nm PDL versus TAC plus 5‐FU (1 study)
Scar severity measured by health professional and/or participant using a specific scale
It is uncertain whether PDL impacts on hypertrophic and keloid scar severity compared with TAC plus 5‐FU for the participant assessments. The certainty of the evidence is very low downgraded twice due very serious imprecision and once due to serious risk of bias (Analysis 6.1) (Manuskiatti 2002).
Incidence and severity of treatment‐related adverse effects
It is uncertain whether 585‐nm PDL treatment impacts on the incidence of treatment‐related adverse effects compared with TAC plus 5‐FU. The certainty of the evidence is very low, downgraded twice due to very serious imprecision and once due to serious risk of bias (summary of findings Table 2) (Analysis 6.2).
Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain
Authors reported the changes in height, erythema and pliability between intervention areas only in graphical formats that did not allow data extraction and further analyses.
585‐nm PDL versus silicone gel sheeting (1 study)
Scar severity measured by health professional and/or participant using a specific scale
This outcome was not reported.
Incidence and severity of treatment‐related adverse effects
It is uncertain whether 585‐nm PDL treatment impacts on the incidence of treatment‐related adverse effects compared with silicone gel sheeting. The certainty of the evidence is very low, downgraded twice due to very serious imprecision and once due to serious risk of bias (summary of findings Table 2) (Analysis 7.1).
Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain
In a small study which was at high risk of bias (Wittenberg 1999), the study authors reported that 585‐nm PDL treatment did not improve blood flow, volume and pruritus in hypertrophic scars when compared with silicone gel sheeting. There was also no reported difference between groups in patients who rated scar elasticity, burning, and pain not related to treatment. Results were presented graphically and not analysed further here.
Erbium laser versus TAC (1 study)
Scar severity measured by health professional and/or participant using a specific scale
It is uncertain whether erbium laser impacts on hypertrophic scar severity compared with TAC treatment assessed with VBS score (Analysis 8.1) and obtained through patient self‐assessment measured by the number of patients considering the scar better or much better (Analysis 8.2) (Omranifard 2007). The certainty of this evidence was very low, downgraded twice due to very serious imprecision and once due to serious risk of bias.
Incidence and severity of treatment‐related adverse effects
The authors reported no complications such as permanent pigmentation change, ulceration or infection in either treatment group.
Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain
These outcomes were not reported.
Fractional CO2 Laser versus TAC (1 study)
Scar severity measured by health professional and/or participant using a specific scale
The authors did not report the means of the full Vancouver Scar Scale (VSS), reporting only separate results of keloid scar height, vascularity, pigmentation, and pliability (Srivastava 2019).
Incidence and severity of treatment‐related adverse effects
It is uncertain whether fractional CO2 laser treatment impacts on treatment‐related adverse effects, including the incidence of pain at injection site, telangiectasia (a condition in which tiny blood vessels cause thread‐like red lines on the skin), skin atrophy, and charring (skin burning so that its surface becomes blackened) compared with TAC (Analysis 9.1). The certainty of evidence was rated as very low. We downgraded the evidence twice for very serious imprecision and once for serious risk of bias (summary of findings Table 2).
Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain
A small study which was at high risk of bias assessed these outcomes (Srivastava 2019). In this study, height was measured with callipers, vascularity was assessed by visual inspection, pliability was assessed by palpation, and pigmentation was scored after blanching and comparing it with the surrounding skin.
After 12 weeks of treatment, the results of this study suggested no or only a small difference between treatments in the assessment of height (MD 0.90; 95% CI 0.60 to 1.20), vascularity (MD 0.70; 95% CI 0.37 to 1.03), and pliability (MD 0.40; 95% CI 0.13 to 0.67) (Analysis 9.2). Regarding pigmentation, no further analysis was possible based on reported data.
After 24 weeks of treatment, it was not possible to analyse whether there were differences between fractional laser and TAC for scar height, vascularity and pliability based on reported data. Data on keloid scar pigmentation suggested no, or only a small difference, between treatments (MD 0.00; 95% CI ‐0.25 to 0.25; one study, 40 participants, 40 scars) (Analysis 9.3).
Fractional CO2 laser versus intralesional verapamil (1 study)
Scar severity measured by health professional and/or participant using a specific scale
Although the authors used VSS, they did not report the means of the full scale, reporting only the separate results of keloid scar height, vascularity pigmentation, and pliability (Srivastava 2019).
Incidence and severity of treatment‐related adverse effects
It is uncertain whether fractional CO2 laser treatment impacts on the incidence of treatment‐related adverse effects, including pain at injection site and charring (skin burning so that its surface becomes blackened) compared with intralesional verapamil (Analysis 10.1). No treatment‐related adverse effects occurred in the verapamil group. No events of teleangiectasia or skin atrophy (skin thinning) occurred in either groups. The certainty of evidence is very low, downgraded twice due to very serious imprecision and once due to serious risk of bias (summary of findings Table 2).
Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain
Only one small study which was at high risk of bias assessed these outcomes (Srivastava 2019). In this study, height was measured with callipers, pliability was assessed by palpation, vascularity was assessed by visual inspection, and pigmentation was scored after blanching and comparing it with the surrounding skin.
After 12 weeks of treatment, the results of this study suggested no or only a small difference between treatments in the assessment of height (MD 0.30; 95% CI ‐0.00 to 0.60), pigmentation (MD ‐0.40; 95% CI ‐0.68 to ‐0.12), vascularity (MD 0.10; 95% CI ‐0.17 to 0.37), and pliability (MD 0.10; 95% CI ‐0.19 to 0.39) (Analysis 10.2).
After 24 weeks of treatment, these results also suggested no, or only a small difference between treatments in the assessment of keloid scar height (MD 0.20; 95% CI ‐0.02 to 0.42), scar pigmentation (MD 0.25; 95% CI ‐0.04 to 0.54), and scar vascularity (MD 0.35; 95% CI 0.09 to 0.61) (Analysis 10.3). No quantitative analysis was possible regarding pliability as SD in the verapamil group was 0.
3. Laser plus other treatment versus other treatment
585‐nm PDL plus TAC plus 5 FU versus TAC plus 5‐FU (1 study)
Scar severity measured by health professional and/or participant using a specific scale
The evidence is uncertain about the effect of 585‐nm PDL plus TAC plus 5 FU compared with TAC plus 5‐FU on hypertrophic and keloid scar severity assessed by a blinded observer assessment, and by patient self‐assessment at 12 weeks (Analysis 11.1) (Asilian 2006). The certainty of evidence was rated as very low, downgraded twice for imprecision and once for serious risk of bias.
Incidence and severity of treatment‐related adverse effects
At the end of the study, no treatment‐related adverse effects were observed in either group.
Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain
A small study which was at high risk of bias, (Asilian 2006), assessed these outcomes. At the end of the study, the study authors reported that the erythema score in the TAC plus 5‐FU plus PDL group was lower than in the TAC plus 5‐FU group (reported P< 0.05) (Table 3). In this study, erythema was graded by the observer on a 5‐point scale, where 0 was no erythema and 4 was very severe erythema. Results were presented graphically and not analysed further here.
CO2 laser plus TAC versus cryosurgery plus TAC (1 study)
Scar severity measured by health professional and/or participant using a specific scale
It is unclear whether CO2 Laser plus TAC impacts on keloid scar severity compared with cryosurgery plus TAC when measured using blinded observer assessment, patient self‐assessment and VBS Assessment Scale, respectively (Analysis 12.1). The certainty of this evidence was rated as very low downgraded twice due to very serious imprecision and once due to serious risk of bias.
Incidence and severity of treatment‐related adverse effects
It is also uncertain whether there is a difference between groups in the incidence of treatment‐related adverse effects (Analysis 12.2). The certainty of this evidence was rated as very low, downgraded twice due to very serious imprecision and once due to serious risk of bias.
Change in scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain
A small study which was at high risk of bias, (Behera 2016), assessed this outcomes. After 12 months, the results of this study suggested no or only a small difference in scar height (MD ‐ 16.15 mm, 95% CI: ‐38.24 to 5.94, one study, 60 scar segments) or volume (MD ‐17.88, 95% CI: ‐39.72 to 3.96, one study, 60 segments scars) (Analysis 12.3). The authors reported a difference between groups in pain not related to treatment (P = 0.0010) favouring CO2 laser, but no difference in pruritus score (P = 0.2262). We could not extract or analyse relevant data further.
Recurrence of the condition
In Behera 2016, at 12 months, there was a recurrence of 6 keloid scars (16.66%), all of which belonged to the CO2 laser group (RR: 13.00; 95% CI: 0.76 to 220.96; one study, 60 scar segments) (Analysis 12.4)
Neodymium‐doped yttrium aluminium garnet (Nd:YAG) laser plus intralesional corticosteroid (diprospan, including betamethasone disodium phosphate plus betamethasone dipropionate) plus 5‐FU versus intralesional corticosteroid (diprospan, including betamethasone disodium phosphate plus betamethasone dipropionate) plus 5‐FU (1 study)
Scar severity measured by health professional and/or participant using a specific scale
It is uncertain whether Nd:YAG laser plus intralesional corticosteroid diprospan plus 5‐FU impacts on keloid scar severity compared with Intralesional corticosteroid diprospan plus 5‐FU when measured using the number of patients and blinded observers reporting good to excellent improvement (Analysis 13.1) (Chen 2017). This evidence is of very low certainty downgraded twice due to very serious imprecision and once due to serious risk of bias.
Incidence and severity of treatment‐related adverse effects
It is also uncertain whether there is a difference between groups in the incidence of treatment‐related adverse effects. Almost all injections were reported by participants as being painful, and the sites treated by Nd:YAG laser became purpuric (which lasted for 7‐10 days). No treatment‐related adverse textural or pigmentary alterations, and no ulcers or erosions were observed in either groups. The certainty of evidence is very low, downgraded twice due to very serious imprecision and once due to serious risk of bias
Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain
A small study which was at high risk of bias, (Chen 2017), assessed these outcomes. During this study, the observer compared images of the lesions, and rated the erythema, pliability and pruritus of the lesions on a 5‑point scale where 0 was no and 4 was very severe. In the third month, erythema (P < 0.05), pliability (P< 0.05), and pruritus (P < 0.05) were reported by the authors to be significantly lower in the Nd:YAG plus intralesional corticosteroid plus 5‐FU laser group than in the intralesional corticosteroid plus 5‐FU group. These data were provided only in graphs and we could not extract further data to analyse.
He‐Ne laser plus decamethyltetrasiloxane, polydimethylsiloxane and cyclopentasiloxane cream versus decamethyltetrasiloxane, polydimethylsiloxane and cyclopentasiloxane cream (1 study)
Scar severity measured by health professional and/or participant using a specific scale
In Alsharnoubi 2018, the authors reported a significant decrease in the median values of VSS of the intervention area compared with the control areas (P = 0.003). Study authors reported these results only in graphical formats that did not allow data extraction and further analyses. This evidence was rated as very low certainty, downgraded twice due to very serious imprecision and once due to serious risk of bias.
Incidence and severity of treatment‐related adverse effects
It is also uncertain whether there is a difference between groups in the incidence of treatment‐related adverse effects. No treatment‐related adverse effects were reported in either groups.
Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain
A small study which was at high risk of bias, (Alsharnoubi 2018) assessed these outcomes. The skin thickness after the treatment measured by ultrasonography was slightly smaller in the laser treated hypertrophic scar segments (MD ‐0.09 mm; 95% CI ‐0.17 to ‐0.01; one study; 15 participants; 30 segments) (Analysis 14.1)
595 nm PDL plus intralesional verapamil versus intralesional verapamil (1 study)
Scar severity measured by health professional and/or participant using a specific scale
In Khattab 2019, although the authors used the VSS, they did not report the means of the full scale, reporting only the separate results of keloid scar height, vascularity pigmentation, and pliability.
Incidence and severity of treatment‐related adverse effects
It is uncertain whether there is a difference in the incidence of treatment‐related adverse effects (Analysis 15.1). The certainty of evidence was rated as very low, downgraded twice due to very serious imprecision and once due to serious risk of bias (summary of findings Table 3).
Change in scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain
A small study which was at high risk of bias assessed these outcomes (Khattab 2019). After 12 weeks of treatment, measures of keloid scar height (MD ‐2.61; 95% CI ‐3.68 to ‐1.54; one study; 40 participants; 50 scars) and pliability (MD ‐2.06; 95% CI ‐2.46 to ‐1.66; one study; 40 participants; 50 scars) were lower in 595 nm PDL plus verapamil group. However, the results of this study suggested no or only a small difference between groups for vascularity (MD 0.06; 95% CI ‐0.34 to 0.46) and pigmentation (MD ‐0.27; 95% CI ‐0.62 to 0.08) (Analysis 15.2).
After 24 weeks of treatment, laser was superior to verapamil in the assessment of height (MD ‐2.89; 95% CI ‐3.65 to ‐2.13; one study; 40 participants; 50 scars), vascularity (MD ‐0.84; 95% CI ‐1.24 to ‐0.44; one study; 40 participants; 50 scars), and pliability (MD ‐1.87 95%CI ‐2.06 to ‐1.68; one study; 40 participants; 50 scars). No statistically significant difference was found between groups for pigmentation (Analysis 15.3).
Discussion
Summary of main results
In this review, we found eight studies (Wittenberg 1999, Manuskiatti 2001, Manuskiatti 2002, Lin 2011, Verhaeghe 2013, Azzam 2016, Blome‐Eberwein 2016, Daoud 2019) that compared laser treatments with no treatment. There is low‐certainty evidence from two randomised controlled trials (RCTs) (Manuskiatti 2001, Manuskiatti 2002) indicating that 585‐nm pulsed‐dye laser (PDL) may reduce keloid and hypertrophic scar severity compared with no treatment, based on unblinded patient self‐assessments of improvement of 50% or more over a 32‐week period of follow‐up. Of note, although these studies suggest that PDL may reduce scar severity compared with no treatment, we have not found any adequate studies showing the minimally clinically important differences in any of the severity rating scales, which makes it difficult for the professionals to transpose these results to clinical practice. The evidence for all other outcomes is uncertain. Adverse effects associated with treatment delivery and secondary outcomes, including erythema, elasticity, volume, and height were assessed by small studies at high risk of bias that either reported imprecise estimates or presented results only graphically, without further data to analyse.
Other types of laser therapy, such as non‐ablative fractional laser (NAFL) (Lin 2011, Verhaeghe 2013) and fractional CO2 (Azzam 2016, Blome‐Eberwein 2016, Daoud 2019), were compared with no treatment. However, results regarding the effectiveness of NAFL on the severity of scars are not consistent when assessed by participants compared with assessment by health professionals. Similarly, the results regarding the fractional CO2 laser are conflicting. While one study on keloid scars showed a possible benefit of using fractional CO2 as compared with no treatment, the pooled results from two RCTs on hypertrophic scars did not show the same results. Because the studies provide inconsistent results, have a small number of patients, exhibit important methodological limitations, and have poorly reported their data, no conclusion can be drawn from these results.
We also found four studies that compared laser treatments with other treatments (Wittenberg 1999, Manuskiatti 2002, Omranifard 2007, Srivastava 2019) and five studies that compared laser combined with other treatments versus other treatments (Asilian 2006, Behera 2016, Chen 2017, Alsharnoubi 2018, Khattab 2019). However, the evidence from these studies is also limited, mainly by the risk of bias and imprecision of effect estimates. As the overall certainty of the available evidence for all these comparisons and all outcomes is very low, it is also unclear whether laser alone or combined with other treatments, in general, results in a difference in the severity of scars when compared with other treatments.
Overall completeness and applicability of evidence
The small number of participants, varying schemes of laser therapy, different types of lasers, and comparisons of different treatment options, made it difficult to compare the results obtained. Currently, several types of lasers are available, such as 585 nm PDL, NAFL, Fractional CO2 Laser, erbium, neodymium‐doped yttrium aluminium garnet (Nd:YAG), and helium‐neon (He‐Ne) laser. The best available evidence is of low‐certainty from two RCTs (Manuskiatti 2001, Manuskiatti 2002) on 585‐nm PDL. The results of these studies suggest 585‐nm PDL may reduce keloid and hypertrophic scars severity compared with no treatment. Of note, PDL 585 nm was one of the first developed types of lasers, and availability of the devices in clinical practice may have influenced the amount of research performed with the types of lasers (Vrijman 2011).
As a result of the lack of robust, homogeneous evidence, most of the data were presented as narrative analyses to permit the individual evaluation of the results obtained with each type of laser. Some outcomes which we originally intended to evaluate, such as cosmesis, patient's preferred treatment, adherence, and quality of life, were not addressed in the included studies and the majority of the trials had short follow‐up periods. To help guide clinical practice, we also planned to perform subgroup analyses on different types of laser devices, fluences, schemes, and duration of treatment. However, current available evidence is insufficient to draw any conclusions or support the routine use of any type of laser to treat hypertrophic and keloid scars in clinical practice.
Quality of the evidence
Fifteen RCTs with a total of 604 participants were included. Nevertheless, several limitations in the included studies should be underscored. Although blinding of participants and personnel may be very difficult from a practical perspective, except for one study (Verhaeghe 2013), all trials included in this review had other important methodological limitations and a high or unclear risk of bias for at least two domains. Of note, only one trial (Behera 2016) reported the scar recurrence rates during the follow‐up period, which is clinically important outcome, and a prevalent condition. This limitation brings into question the long‐term effects of these interventions.
Of note, several of our results were based on split‐scar trials. Although all split‐scar trials used paired analyses and we have not combined the results of split‐scar trials with those from parallel studies, we should interpret these results carefully. We should not rule out the possibility of "spill‐over" of the treatment from one scar segment to the other.
Due to small sample sizes, small numbers of studies, unblinded assessments, and attrition bias, the certainty of the evidence comparing laser treatment with no treatment, laser treatment with other treatments, and laser plus other treatment with other treatment, is low to very low. Furthermore, in some cases, data were also insufficiently reported or reported in ways that did not allow extraction and further analysis. Therefore, none of the available trials were of high‐methodological quality and the true efficacy of laser therapy may not be fully clarified until high‐quality trials are published.
Potential biases in the review process
The most important databases, clinical trials, contacts with specialists and other research sources were included in our study searches in order to identify and collect all relevant RCTs, regardless of language or publication status. Moreover, strict collection and evaluation of data was performed by the review authors in order to avoid errors in the conduct of this systematic review. Some data were only available in incomplete formats in graphs and did not allow for extraction. Although we tried to contact the authors, we did not receive a response. We were also unable to assess publication bias due to the insufficient number of included RCTs in each comparison. Nevertheless, we believe this scientifically‐rigorous systematic review exposes literature gaps and provides critical data upon which to base further trials and protocols.
Agreements and disagreements with other studies or reviews
We did not find a systematic review that evaluated laser therapy for treating both hypertrophic and keloid scars, but we found a systematic review assessing the effects of laser and intense pulsed light (IPL) for the treatment of hypertrophic scars (Vrijman 2011). Differently from this review, Vrijman 2011 evaluated not only RCTs, but also non‐randomised trials, in which only hypertrophic scars were treated with laser or IPL. Our search strategy was also broader than in Vrijman 2011, and included MEDLINE, Embase and CENTRAL, as well as other databases, such as EBSCO CINAHL, LILACS, Clinicaltrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform and European Union (EU) Clinical Trials Register Platform (ICTRP). We excluded trials comparing laser in both arms without control areas and non‐randomised clinical trials, in order to minimise bias. Due to the different parameters used to select the studies and evaluate the data between this systematic review and that published by Vrijman 2011, the findings could not be compared.
Study flow diagram.
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Comparison 1: 585‐nm Pulsed‐Dye Laser (PDL) versus no treatment, Outcome 1: Severity of scar: Patient self‐assessment (32 weeks)
Comparison 1: 585‐nm Pulsed‐Dye Laser (PDL) versus no treatment, Outcome 2: Incidence and severity of treatment‐related adverse effects (32 weeks)
Comparison 2: Non‐ablative Fractional Laser (NAFL) versus no treatment, Outcome 1: Severity of scar: Health Professional Global Assessment (3 months)
Comparison 2: Non‐ablative Fractional Laser (NAFL) versus no treatment, Outcome 2: Incidence and severity of treatment‐related adverse effects (3 months)
Comparison 2: Non‐ablative Fractional Laser (NAFL) versus no treatment, Outcome 3: Scar size, colour, height, length, width, pliability, skin surface texture, pruritus and pain (3 months)
Comparison 3: Fractional carbon dioxide (CO2) versus no treatment, Outcome 1: Severity of scar: Vancouver Burn Scar (VBS) scale (up to 6 months)
Comparison 3: Fractional carbon dioxide (CO2) versus no treatment, Outcome 2: Severity of scar: Patient and Observer Scar Assessment Scale (POSAS) (at least one month)
Comparison 3: Fractional carbon dioxide (CO2) versus no treatment, Outcome 3: Scar size, colour, height, length, width, pliability, skin surface texture, pruritus and pain (12 to 18 weeks)
Comparison 4: 585‐nm Pulsed‐Dye Laser (PDL) versus Triamcinolone acetonide (TAC), Outcome 1: Severity of scars: Vancouver Burn Scar (VBS) scale (up to 12 months)
Comparison 4: 585‐nm Pulsed‐Dye Laser (PDL) versus Triamcinolone acetonide (TAC), Outcome 2: Severity of scars: Patient self‐assessment (up to 12 months)
Comparison 4: 585‐nm Pulsed‐Dye Laser (PDL) versus Triamcinolone acetonide (TAC), Outcome 3: Incidence and severity of treatment‐related adverse effects (up to 12 months)
Comparison 5: 585‐nm Pulsed‐Dye Laser (PDL) versus 5‐Fluorouracil (5‐FU), Outcome 1: Severity of scars: Patient self‐assessment (32 weeks)
Comparison 5: 585‐nm Pulsed‐Dye Laser (PDL) versus 5‐Fluorouracil (5‐FU), Outcome 2: Incidence and severity of treatment‐related adverse effects (32 weeks)
Comparison 6: 585‐nm Pulsed‐Dye Laser (PDL) versus Triamcinolone acetonide (TAC) plus 5‐Fluorouracil (5‐FU), Outcome 1: Severity of scars: Patient self‐assessment (32 weeks)
Comparison 6: 585‐nm Pulsed‐Dye Laser (PDL) versus Triamcinolone acetonide (TAC) plus 5‐Fluorouracil (5‐FU), Outcome 2: Incidence and severity of treatment‐related adverse effects (32 weeks)
Comparison 7: 585‐nm Pulsed‐Dye Laser (PDL) versus Silicone Gel Sheeting, Outcome 1: Incidence and severity of treatment‐related adverse effects (24 weeks)
Comparison 8: Erbium laser versus Triamcinolone acetonide (TAC), Outcome 1: Severity of scars: Vancouver Burn Scar (VBS) scale (up to 12 months)
Comparison 8: Erbium laser versus Triamcinolone acetonide (TAC), Outcome 2: Severity of scars: Patient self‐assessment (up to 12 months)
Comparison 9: Fractional carbon dioxide (CO2) laser versus intralesional Triamcinolone acetonide (TAC), Outcome 1: Incidence of treatment‐related adverse effects (24 weeks)
Comparison 9: Fractional carbon dioxide (CO2) laser versus intralesional Triamcinolone acetonide (TAC), Outcome 2: Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain (12 weeks)
Comparison 9: Fractional carbon dioxide (CO2) laser versus intralesional Triamcinolone acetonide (TAC), Outcome 3: Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain (24 weeks)
Comparison 10: Fractional carbon dioxide (CO2) laser versus Intralesional Verapamil, Outcome 1: Incidence of treatment‐related adverse effects (24 weeks)
Comparison 10: Fractional carbon dioxide (CO2) laser versus Intralesional Verapamil, Outcome 2: Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain (12 weeks)
Comparison 10: Fractional carbon dioxide (CO2) laser versus Intralesional Verapamil, Outcome 3: Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain (24 weeks)
Comparison 11: 585‐nm Pulsed‐Dye Laser (PDL) plus Triamcinolone acetonide (TAC) plus 5‐Fluorouracil (5‐FU) versus TAC plus 5‐FU, Outcome 1: Severity of scars (12 weeks)
Comparison 12: Carbon dioxide (CO2) Laser plus Triamcinolone acetonide (TAC) versus Cryosurgery plus TAC, Outcome 1: Severity of scars (12 months)
Comparison 12: Carbon dioxide (CO2) Laser plus Triamcinolone acetonide (TAC) versus Cryosurgery plus TAC, Outcome 2: Incidence and severity of treatment‐related adverse effects (12 months)
Comparison 12: Carbon dioxide (CO2) Laser plus Triamcinolone acetonide (TAC) versus Cryosurgery plus TAC, Outcome 3: Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain(12 months)
Comparison 12: Carbon dioxide (CO2) Laser plus Triamcinolone acetonide (TAC) versus Cryosurgery plus TAC, Outcome 4: Recurrence of the condition (12 months)
Comparison 13: Neodymium‐doped yttrium aluminum garnet (Nd:YAG) laser plus intralesional corticosteroid diprospan plus 5‐Fluorouracil (5‐FU) versus Intralesional corticosteroid diprospan plus 5‐FU, Outcome 1: Severity of scars (3 months)
Comparison 14: Helium–neon (He‐Ne) laser plus Decamethyltetrasiloxane, Polydimethylsiloxane and Cyclopentasiloxane cream versus Decamethyltetrasiloxane, Polydimethylsiloxane and Cyclopentasiloxane cream, Outcome 1: Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain (12 weeks)
Comparison 15: 595‐nm Pulsed‐Dye Laser (PDL) plus intralesional verapamil versus intralesional verapamil, Outcome 1: Incidence of treatment‐related adverse effects (24 weeks)
Comparison 15: 595‐nm Pulsed‐Dye Laser (PDL) plus intralesional verapamil versus intralesional verapamil, Outcome 2: Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain (change from baseline) (12 weeks)
Comparison 15: 595‐nm Pulsed‐Dye Laser (PDL) plus intralesional verapamil versus intralesional verapamil, Outcome 3: Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain (change from baseline) (24 weeks)
| Laser therapycompared with no treatment for treating hypertrophic and keloid scars | ||||||
| Patient or population: patients with hypertrophic and keloid scars | ||||||
| Outcomes | Anticipated absolute effects (95% CI) | Relative effect | № of scar segment | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with no treatment | Risk with Laser therapy | |||||
| Scar severity ‐ 585‐nm Pulsed‐Dye Laser (PDL) versus no treatment ‐ patient self‐assessment of scar improvement of 50% or higher ‐ hypertrophic and keloid scars ‐ follow‐up: 32 weeks | Study population | RR 1.96 | 60 | ⊕⊕⊝⊝1,2 |
There may be more hypertrophic and keloid scar improvement (that is scars are less severe) in 585‐nm PDL‐treated scars compared with no treatment after 32 weeks. | |
| 400 per 1000 | 784 per 1000 | |||||
| Incidence and severity of treatment‐related adverse effects ‐ 585‐nm PDL versus no treatment ‐ mild to moderate discomfort or pain related to treatment ‐ hypertrophic and keloid scars ‐follow‐up: 32 weeks | Two split‐scar trials (n = 60) reported this outcome. In these studies, participants reported mild to moderate discomfort or pain in 10 out of 30 (10/30) (33%) PDL treated areas versus 0 out of 30 (0/30) (0%) no treatment areas (RR 8.62; 1.10 to 67.39). | ⊕⊝⊝⊝2,3 | It is uncertain whether there is any difference in the incidence and severity of treatment‐related adverse effects in 585‐nm PDL‐treated hypertrophic and keloid scars compared with no treatment after 32 weeks. | |||
| Incidence and severity of treatment‐related adverse effects ‐ 585‐nm PDL versus no treatment ‐ purpura ‐ hypertrophic and keloid scars ‐ follow‐up: 32 weeks | Two split‐scar trials (n = 60) reported this outcome. In these studies, purpura was observed in 40 out of 40 (40/40) (100%) PDL treated areas versus 0 out of 20 (0/20) (0%) no treatment areas (RR 21.32; 3.14 to 144.86). | ⊕⊝⊝⊝2,3 | ||||
| Scar severity ‐ Non‐Ablative Fractional Laser (NAFL) versus no treatment ‐ health professional global assessment measured on a visual analogue scale (VAS) ranging from 0 to 100 mm (0 = as normal skin and 100 = worst possible scar) ‐ hypertrophic scars ‐ follow‐up: 3 months | Study population | RR 2.00 (0.85 to 4.69) | 36 (1 study) | ⊕⊝⊝⊝3,4 | It is uncertain whether there is any difference in the scar severity in NAFL‐treated hypertrophic scars compared with no treatment after 3 months. | |
| 278 per 1000 | 556 per 1000
| |||||
| Scar severity ‐ NAFL versus no treatment ‐ patient global assessment measured on a VAS ranging from 0 to 100 mm (0 = as normal skin and 100 = worst possible scar) ‐ hypertrophic scars ‐ follow‐up: 3 months | One split‐scar trial (n = 36) reported this outcome. In this study, the authors reported an improvement in scar severity in NAFL treated hypertrophic scars compared with no treatment on the patient global assessment at 1 month (reported P = 0.006) and 3 months (reported P = 0.02). | ⊕⊝⊝⊝5,6 | ||||
| Scar severity ‐ NAFL versus no treatment ‐ Patient and Observer Scar Assessment Scale (POSAS) (higher scores = worse scar appearance) ‐ hypertrophic scars ‐ follow‐up: up to 3 months | One split‐scar trial (n = 36) reported this outcome. In this study, the authors reported an improvement in scar severity in NAFL treated hypertrophic scars compared with no treatment on the participant part of the scale at 1 month and 3 months. The size of the difference was not reported and no data for the observer part of the scale was presented. | ⊕⊝⊝⊝5,6 | ||||
| Incidence and severity of treatment‐related adverse effects ‐ NAFL versus no treatment ‐ scar worsening ‐ hypertrophic scars ‐ follow‐up: 3 months | One split‐scar trial (n = 20) reported this outcome. In this study, 3 out of 10 (3/10) (30%) NAFL treated areas versus 0 out of 10 (0/10) (0%) no treatment areas were considered by the patients to have worsened (RR 7.00; 0.41 to 120.16). | ⊕⊝⊝⊝3,7 | It is uncertain whether there is any difference in the incidence and severity of treatment‐related adverse effects in NAFL‐treated hypertrophic scars compared with no treatment after 3 months. | |||
| Incidence and severity of treatment‐related adverse effects ‐ NAFL versus no treatment ‐ hyperpigmentation ‐ hypertrophic scars ‐ follow‐up: 3 months | One split‐scar trial (n = 36) reported this outcome. In this study, hyperpigmentation was observed in 1 out of 18 (1/18) (6%) NAFL treated areas versus 0 out of 18 (0/18) (0%) no treatment areas (RR 3.00; 0.13 to 69.09). | ⊕⊝⊝⊝3,5 | ||||
| Scar severity ‐ Fractional Carbon Dioxide (CO2) Laser versus no treatment ‐ Vancouver Burn Scar (VBS) scale (higher scores = worse scar appearance) ‐ hypertrophic scars ‐ follow‐up: up to 3 months | Study population | NA | 104 (2 studies) | ⊕⊝⊝⊝6,8 | It is uncertain whether there is any difference in the scar severity in Fractional CO2‐treated hypertrophic and keloid scars compared with no treatment after up to 3 months, and in Fractional CO2‐treated hypertrophic scars compared with no treatment after at least 1 month. | |
| Baseline mean in the no treatment group was 7.6 | MD 1.30 lower | |||||
| Scar severity ‐ Fractional CO2 Laser versus no treatment ‐ VBS (higher scores = worse scar appearance) ‐ keloid scars ‐ follow‐up: 3 months | Study population | NA | 24 (1 study) | ⊕⊝⊝⊝6,9 | ||
| Baseline mean in the no treatment group was 7.6 | MD 1.90 lower | |||||
| Scar severity ‐ Fractional CO2 Laser versus no treatment ‐ POSAS scale (higher scores = worse scar appearance) ‐ hypertrophic scars ‐ follow‐up: at least 1 month | Study population | NA | 80 (1 study) | ⊕⊝⊝⊝6,10 | ||
| Baseline mean in the no treatment group was 29.9 | MD 4.13 higher (1.24 lower to 9.50 higher) | |||||
| *The risk in the intervention group (and its 95% confidence interval) is based on the mean risk in the comparison group and the relative effect of the intervention (and its 95% CI). ƚThe assumed risk in the comparison group is based on the event rate observed in the control arms of included trials. Where no events occurred, the risk was not calculated.
VAS: visual analogue scale ‐ ranging from 0 to 100 mm (0 = normal skin and 100 = worst possible scar); Patient self‐assessment ‐ based on a 4‐point scale (1 = 0 to 25% improvement, 2 = 25 to 50% improvement, 3 = 50 to 75% improvement, and 4 = 75% or greater improvement); POSAS: Patient and Observer Scar Assessment Scale ‐ the lowest score (6) reflects normal skin, and the highest score (60) reflects the worst imaginable scar; VBS: Vancouver Burn Scar Assessment Scale ‐ severity of scar was determined by numeric value from a minimum of 0 to 13 as the most severe form. CI: Confidence Interval; CO2: carbon dioxide;LDTA: (Low‐Density Treatment Arm of NAFL), HDTA: (High‐Density Treatment Arm of NAFL); MD: Mean Difference; NAFL: Non‐Ablative Fractional Laser ;PDL: Pulsed‐Dye Laser; RR: Risk Ratio; VBS: Vancouver Burn Scar Assessment Scale. | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1 Downgraded 1 level for serious imprecision due to small number of events. 2 Downgraded 1 level for serious risk of bias (lack of blinding of participants and assessors (patient‐reported outcome), and unclear sequence generation and allocation concealment). 3 Downgraded 2 levels for very serious imprecision due to small number of events and large confidence interval. 4 Downgraded 1 level for serious risk of bias (lack of blinding of participants). 5 Downgraded 1 level for serious risk of bias (lack of blinding of participants and assessors (patient‐reported outcome)). 6 Downgraded 2 levels for very serious imprecision due to small sample size and large confidence interval. 7 Downgraded 1 level for serious risk of bias (lack of blinding of participants and assessors (patient‐reported outcome), incomplete outcome data, and unclear allocation concealment). 8 Downgraded 1 level for serious risk of bias (selective reporting in one study, and lack of blinding of participants and incomplete outcome data in 2 studies). 9 Downgraded 1 level for serious risk of bias (lack of blinding of participants, incomplete outcome data and selective reporting). 10 Downgraded 1 level for serious risk of bias (lack of blinding of participants and assessors (patient‐reported outcome) and incomplete outcome data). | ||||||
| Laser therapy compared with other treatments for treating hypertrophic and keloid scars | ||||||
| Patient or population: participants with hypertrophic and keloid scars | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of scar segments | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with other treatments | Risk with Laser therapy | |||||
| Scar severity ‐ 585‐nm Pulsed‐Dye Laser (PDL) versus Triamcinolone acetonide (TAC) ‐ Vancouver Burn Scar (VBS) (Higher score = worse scar appearance) ‐ hypertrophic scars ‐ follow‐up: up to 12 months | Study population | NA | 80 | ⊕⊝⊝⊝1,2 | It is uncertain whether there is any difference in the scar severity in PDL‐treated hypertrophic and keloid scars compared with TAC after up to 12 months. | |
| Baseline mean in the other treatment group was 6.7 | MD 2.5 lower | |||||
| Scar severity ‐ 585‐nm PDL versus TAC ‐ patient self‐assessment of scar improvement of 50% or higher, or patients considering the scar better or much better ‐ hypertrophic and keloid scars ‐ follow‐up: up to 12 months | One split‐scar trial (n = 20) and one parallel trial (n = 80) reported this outcome. In the split scar trial, 8 out of 10 (8/10) (80%) PDL treated areas versus 10 out of 10 (10/10) (100%) TAC treated areas were considered to have improved 50% or more by participants (RR 0.81; 0.57 to 1.14), and in the parallel trial, 28 out of 40 participants (28/40) (70%) treated with PDL and 12 out of 40 participants (12/40) (30%) treated with TAC considered their scars better or much better (RR 2.33; 1.39 to 3.91). | ⊕⊝⊝⊝3,4 | ||||
| Incidence and severity of treatment‐related adverse effects ‐ 585‐nm PDL versus TAC: sequelae ‐ hypertrophic and keloid scars ‐ follow‐up: 32 weeks | Study population | RR 0.09 | 20 | ⊕⊝⊝⊝3,5 | It is uncertain whether there is any difference in the incidence and severity of treatment‐related adverse effects in PDL‐treated hypertrophic and keloid scars compared with TAC after 32 weeks.
| |
| 500 per 1000 | 45 per 1000 | |||||
| Incidence and severity of treatment‐related adverse effects ‐ 585‐nm PDL versus TAC ‐ mild to moderate pain related to treatment ‐ hypertrophic and keloid scars ‐ follow‐up: 32 weeks | One split‐scar trial (n = 20) reported this outcome. In this study, participants reported to have felt mild to moderate pain during the intervention in 10 out of 10 (10/10) (100%) TAC treated areas versus in 9 out of 10 (9/10) (90%) PDL treated areas (RR 0.90; 0.69 to 1.18). | ⊕⊝⊝⊝3,5 | ||||
| Scar severity ‐ 585‐nm PDL versus 5‐FU ‐ patient self‐assessment of scar improvement of 50% or higher ‐ hypertrophic and keloid scars ‐ follow‐up: 32 weeks | One split‐scar trial (n = 20) reported this outcome. In this study, 8 out of 10 (8/10) (80%) PDL treated areas versus 10 out of 10 (10/10) (100%) 5‐FU treated areas were reported by the participants to have improved 50% or more (RR 0.81; 0.57 to 1.14). | ⊕⊝⊝⊝3,5 | It is uncertain whether there is any difference in the scar severity in PDL‐treated hypertrophic and keloid scars compared with 5‐FU after 32 weeks. | |||
| Incidence and severity of treatment‐related adverse effects ‐ 585‐nm PDL versus 5‐FU ‐ mild to moderate pain related to treatment ‐ hypertrophic and keloid scars ‐ follow‐up: 32 weeks | One split‐scar trial (n = 20) reported this outcome. In this study, participants reported to have felt mild to moderate pain during the intervention in 9 out of 10 (9/10) (90%) PDL treated areas versus in 10 out of 10 (10/10) (100%) 5‐FU treated areas (RR 0.90; 0.69 to 1.18). | ⊕⊝⊝⊝3,5 | It is uncertain whether there is any difference in the incidence and severity of treatment‐related adverse effects in PDL‐treated hypertrophic and keloid scars compared with 5‐FU after 32 weeks. | |||
| Incidence and severity of treatment‐related adverse effects ‐ 585‐nm PDL versus 5‐FU ‐ purpura ‐ hypertrophic and keloid scars ‐ follow‐up: 32 weeks | One split‐scar trial (n = 20) reported this outcome. In this study, purpura was observed in 10 out of 10 (10/10) (100%) PDL treated areas versus in 2 out of 10 (2/10) (20%) 5‐FU treated areas (RR 4.20; 1.40 to 12.58). | ⊕⊝⊝⊝3,5 | ||||
| Scar severity ‐ 585‐nm PDL versus TAC plus 5‐FU ‐ patient self‐assessment of scar improvement of 50% or higher ‐ hypertrophic and keloid scars ‐ follow‐up: 32 weeks | Study population | RR 0.89 | 20 | ⊕⊝⊝⊝3,5 | It is uncertain whether there is any difference in the scar severity in PDL‐treated hypertrophic and keloid scars compared with TAC plus 5‐FU after 32 weeks. | |
| 900 per 1000 | 801 per 1000 | |||||
| Incidence and severity of treatment‐related adverse effects ‐ 585‐nm PDL versus TAC plus 5‐FU ‐ mild to moderate pain related to treatment ‐ hypertrophic and keloid scars ‐ follow‐up: 32 weeks | One split‐scar trial (n = 20) reported this outcome. In this study, participants reported to have felt mild to moderate pain during the intervention in 9 out of 10 (9/10) (90%) PDL treated areas versus in 10 out of 10 (10/10) (100%) TAC plus 5‐FU treated areas (RR 0.90; 0.69 to 1.18). | ⊕⊝⊝⊝3,5 | It is uncertain whether there is any difference in the incidence and severity of treatment‐related adverse effects in PDL‐treated hypertrophic and keloid scars compared with TAC plus 5‐FU after 32 weeks. | |||
| Incidence and severity of treatment‐related adverse effects ‐ 585‐nm PDL versus TAC plus 5‐FU ‐ purpura ‐ hypertrophic and keloid scars ‐ follow‐up: 32 weeks | One split‐scar trial (n = 20) reported this outcome. In this study, purpura was observed in 10 out of 10 (10/10) (100%) PDL treated areas versus in 3 out of 10 (3/10) (30%) TAC plus 5‐FU treated areas (RR 3.00; 1.25 to 7.19). | ⊕⊝⊝⊝3,5 | ||||
| Incidence and severity of treatment‐related adverse effects ‐ 585‐nm PDL versus silicone gel sheeting ‐ pain during laser treatments ‐ hypertrophic scars ‐ follow‐up: 24 weeks | One split‐scar trial (n = 40) reported this outcome. In this study, participants reported to have felt pain during laser treatment in 1 out of 20 (1/20) (5%) PDL treated areas versus in 0 out of 20 (0/20) (0%) silicone gel sheeting treated areas (RR 3.00; 0.13 to 69.52). | ⊕⊝⊝⊝3,6 | It is uncertain whether there is any difference in the incidence and severity of treatment‐related adverse effects in PDL‐treated hypertrophic scars compared with silicone gel sheeting after 24 weeks. | |||
| Incidence and severity of treatment‐related adverse effects ‐ 585‐nm PDL versus silicone gel sheeting ‐ skin irritation ‐ hypertrophic scars ‐ follow‐up: 24 weeks | One split‐scar trial (n = 40) reported this outcome. In this study, participants reported to have felt skin irritation related to laser treatment in 0 out of 20 (0/20) (0%) PDL treated areas versus in 1 out of 20 (1/20) (5%) silicone gel sheeting treated areas (RR 0.33; 0.01 to 7.72). | ⊕⊝⊝⊝3,6 | ||||
| Scar severity ‐ erbium laser versus TAC ‐ VBS (Higher scores = worse scar appearance) ‐ hypertrophic scars ‐ follow‐up: up to 12 months | Baseline mean in the other treatment group was 6.7 | MD 2.10 lower | NA | 80 | ⊕⊝⊝⊝1,2 | It is uncertain whether there is any difference in the scar severity in erbium‐treated hypertrophic scars compared with TAC after up to 12 months. |
| Scar severity ‐ erbium laser versus TAC ‐ patient self‐assessment ‐ patients considering the scar much better ‐ hypertrophic scars ‐ follow‐up: up to 12 months | Study population | RR 2.17 | 80 | ⊕⊝⊝⊝3,7 | ||
| 300 per 1000 | 651 per 1000 | |||||
| Incidence and severity of treatment‐related adverse effects ‐ fractional carbon dioxide (CO2) laser versus TAC ‐ pain at injection site ‐ keloid scars ‐ follow‐up: 24 weeks | Study population | RR 0.25 (0.06 to 1.03) | 40 | ⊕⊝⊝⊝3,8 | It is uncertain whether there is any difference in the incidence and severity of treatment‐related adverse effects in fractional CO2‐treated keloid scars compared with TAC after 24 weeks. | |
| 400 per 1000 | 100 per 1000 | |||||
| Incidence and severity of treatment‐related adverse effects ‐ fractional CO2 laser versus TAC ‐ telangectasia ‐ keloid scars ‐ follow‐up: 24 weeks | Study population | RR 0.20 (0.01 to 3.92) | 40 | ⊕⊝⊝⊝3,8 | ||
| 100 per 1000 | 20 per 1000 | |||||
| Incidence and severity of treatment‐related adverse effects ‐ fractional CO2 laser versus TAC ‐ skin atrophy ‐ keloid scars ‐ follow‐up: 24 weeks | Study population | RR 0.33 (0.01 to 7.72) | 40 | ⊕⊝⊝⊝3,8 | ||
| 50 per 1000 | 17 per 1000 | |||||
| Incidence and severity of treatment‐related adverse effects ‐ fractional CO2 laser versus TAC ‐ charring ‐ keloid scars ‐ follow‐up: 24 weeks | One parallel trial (n = 40) reported this outcome. In this study, charring was observed in 3 out of 20 (3/20) (15%) participants treated with fractional CO2 laser and 0 out of 20 (0/20) (0%) participants treated with TAC (RR 7.00; 0.38 to 127.32). | ⊕⊝⊝⊝3,8 | ||||
| Incidence and severity of treatment‐related adverse effects ‐ fractional CO2 laser versus verapamil ‐ pain at injection site ‐ keloid scars ‐ follow‐up: 24 weeks | One parallel trial (n = 40) reported this outcome. In this study, pain at injection site was reported by 2 out of 20 (2/20) (10%) participants treated with fractional CO2 laser group and 0 out of 20 (0/20) (0%) participants treated with verapamil (RR 5.00; 0.26 to 98.00). | ⊕⊝⊝⊝3,8 | It is uncertain whether there is any difference in the incidence and severity of treatment‐related adverse effects in fractional CO2‐treated keloid scars compared with verapamil after 24 weeks. | |||
| Incidence and severity of treatment‐related adverse effects ‐ fractional CO2 laser versus verapamil ‐ charring ‐ keloid scars ‐ follow‐up: 24 weeks | One parallel trial (n = 40) reported this outcome. In this study, charring was observed in 3 out of 20 (3/20) (15%) participants treated with fractional CO2 laser group and 0 out of 20 (0/20) (0%) participants treated with verapamil group (RR 7.0; 0.38 to 127.32) | ⊕⊝⊝⊝3,8 | ||||
| *The risk in the intervention group (and its 95% confidence interval) is based on the mean risk in the comparison group and the relative effect of the intervention (and its 95% CI). ƚThe assumed risk in the comparison group is based on the event rate observed in the control arms of included trials. Where no events occurred, the risk was not calculated.
Vancouver Burn Scar (VBS) Assessment Scale ‐ severity of scar was determined by numeric value from a minimum of 0 to 13 as the most severe form. Patient self‐assessment ‐ based on a 4‐point scale (1 = 0 to 25% improvement, 2 = 25 to 50% improvement, 3 = 50 to 75% improvement, and 4 = 75% or greater improvement). CI: Confidence Interval; CO2: carbon dioxide; MD: Mean Difference; PDL: Pulsed‐Dye Laser;RR: Risk Ratio; TAC: Triamcinolone acetonide;5‐FU: 5‐fluorouracil;VBS: Vancouver Burn Scar Assessment Scale;. | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1 Downgraded 2 levels for very serious imprecision due to small sample size and large confidence interval. 2 Downgraded 1 level due to serious risk of bias (lack of blinding of participants, selective reporting, and unclear sequence generation and allocation concealment). 3 Downgraded 2 levels for very serious imprecision due to small number of events and large confidence interval. 4 Downgraded 1 level due to serious risk of bias (lack of blinding of participants and assessors (patient‐reported outcome) and unclear sequence generation and allocation concealment in 2 studies, and selective reporting in 1 study). 5 Downgraded 1 level due to serious risk of bias (lack of blinding of participants and assessors (patient‐reported outcome) and unclear sequence generation and allocation concealment). 6 Downgraded 1 level due to serious risk of bias (lack of blinding of participants and assessors (patient‐reported outcome) and unclear allocation concealment). 7 Downgraded 1 level due to serious risk of bias (lack of blinding of participants and assessors (patient‐reported outcome) and selective reporting, and unclear sequence generation and allocation concealment). 8 Downgraded 1 level due to serious risk of bias (lack of blinding of participants and assessors (patient‐reported outcome), and unclear allocation concealment and selective reporting). | ||||||
| Laser therapy plus other treatment compared with other treatment for treating hypertrophic and keloid scars | ||||||
| Patient or population: participants with hypertrophic and keloid scars | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of scar segments | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with other treatment | Risk with Laser therapy plus other treatment | |||||
| Scar severity ‐ 585‐nm pulsed‐dye laser (PDL) plus triamcinolone acetonide (TAC) plus 5‐Fluorouracil (5‐FU) versus TAC plus 5‐FU ‐ blinded observer assessment of good to excellent scar improvement ‐ hypertrophic and keloid scars ‐ follow‐up: 12 weeks | Study population | RR 1.75 (0.95 to 3.22) | 40 | ⊕⊝⊝⊝1,2 | It is uncertain whether there is any difference in the scar severity in PDL plus TAC plus 5‐FU‐treated hypertrophic and keloid scars compared with TAC plus 5‐FU after 12 weeks. | |
| 400 per 1000 | 700 per 1000 | |||||
| Scar severity ‐ 585‐nm PDL plus TAC plus 5 FU versus TAC plus 5‐FU ‐ patient self‐assessment of good to excellent scar improvement ‐ hypertrophic and keloid scars ‐ follow‐up: 12 weeks | Study population | RR 1.36 (0.85 to 2.18) | 40 | ⊕⊝⊝⊝1,3 | ||
| 550 per 1000 | 748 per 1000 | |||||
| Scar severity ‐ carbon dioxide (CO2) laser plus TAC versus cryosurgery plus TAC. Mean percentage reduction ‐ blinded observer assessment ‐ keloid scars ‐ follow‐up: 12 months | Study population | NA | 60 (1 study) | ⊕⊝⊝⊝4,5 | It is uncertain whether there is any difference in the scar severity in CO2 plus TAC‐treated keloid scars compared with cryosurgery plus TAC after 12 months. | |
| Baseline mean in the other treatment group was 74.44 | MD 16.11 lower | |||||
| Scar severity ‐ CO2 laser plus TAC versus cryosurgery plus TAC Mean percentage reduction ‐ patient self‐assessment score (higher scores = worse scar appearance) ‐ keloid scars ‐ follow‐up: 12 months | Study population | NA | 60 (1 study) | ⊕⊝⊝⊝4,6 | ||
| Baseline mean in the other treatment group was 74.26 | MD 7.59 lower | |||||
| Incidence of treatment‐related adverse effects: CO2 laser plus TAC versus cryosurgery plus TAC ‐ atrophy ‐ keloid scars ‐ follow‐up: 12 months | Study population | RR 1.13 (0.70 to 1.82) | 60 (1 study) | ⊕⊝⊝⊝4,6 | It is uncertain whether there is any difference in the incidence and severity of treatment‐related adverse effects in CO2 plus TAC‐treated keloid scars compared with cryosurgery plus TAC after 12 months.
| |
| 500 per 1000 | 565 per 1000 | |||||
| Incidence of treatment‐related adverse effects ‐ CO2 laser plus TAC versus cryosurgery plus TAC ‐ erythema ‐ keloid scars ‐ follow‐up: 12 months | Study population | RR 1.50 (0.47 to 4.78) | 60 (1 study) | ⊕⊝⊝⊝4,6 | ||
| 133 per 1000 | 200 per 1000 | |||||
| Incidence of treatment‐related adverse effects ‐ CO2 laser plus TAC versus cryosurgery plus TAC ‐ telangiectasia ‐ keloid scars ‐ follow‐up: 12 months | Study population | RR 0.33 (0.07 to 1.52) | 60 (1 study) | ⊕⊝⊝⊝4,6 | ||
| 200 per 1000 | 66 per 1000 | |||||
| Incidence of treatment‐related adverse effects ‐ CO2 laser plus TAC versus cryosurgery plus TAC ‐ hypopigmentation ‐ keloid scars ‐ follow‐up: 12 months | Study population | RR 0.60 (0.16 to 2.29) | 60 (1 study) | ⊕⊝⊝⊝4,6 | ||
| 167 per 1000 | 100 per 1000 | |||||
| Scar severity ‐ Neodymium‐doped yttrium aluminium garnet (Nd:YAG) laser plus Diprospan plus 5‐FU versus Diprospan plus 5‐FU ‐ blinded observer assessment of good to excellent scar improvement ‐ keloid scars ‐ follow‐up: 3 months | Study population | RR 1.45 (0.88 to 2.41) | 46 (1study) | ⊕⊝⊝⊝1,7 | It is uncertain whether there is any difference in the scar severity in Nd:YAG plus Diprospan plus 5‐FU‐treated keloid scars compared with Diprospan plus 5‐FU after 3 months. | |
| 478 per 1000 | 693 per 1000 | |||||
| Scar severity: Nd:YAG laser plus Diprospan plus 5‐FU versus Diprospan plus 5‐FU ‐ patient self‐assessment of scar improvement of 50% or higher ‐ keloid scars ‐ follow‐up: 3 months | Study population | RR 1.38 (0.91 to 2.10) | 46 (1study) | ⊕⊝⊝⊝1,8 | ||
| 565 per 1000 | 780 per 1000 | |||||
| Incidence and severity of treatment‐related adverse effects: Nd:YAG laser plus Diprospan plus 5‐FU versus Diprospan plus 5‐FU ‐ keloid scars ‐ follow‐up: 3 months | One parallel trial (n = 46) reported this outcome. In this study, almost all injections were reported by participants as being painful, and the sites treated by Nd:YAG laser became purpuric (which lasted for 7 to 10 days). | ⊕⊝⊝⊝1,8 | It is uncertain whether there is any difference in the incidence and severity of treatment‐related adverse effects in Nd:YAG plus Diprospan plus 5‐FU‐treated keloid scars compared with Diprospan plus 5‐FU after 3 months. | |||
| Scar severity ‐ Helium‐Neon (He‐Ne) laser plus decamethyltetrasiloxane, polydimethylsiloxane and cyclopentasiloxane cream versus decamethyltetrasiloxane, polydimethylsiloxane and cyclopentasiloxane cream ‐ Vancouver Scar scale (VSS) (higher scores = worse scar appearance) ‐ hypertrophic scars ‐ follow‐up: 12 weeks | One split‐scar trial (n = 30) reported this outcome. In this study, a significant decrease in the median values of VSS of the intervention area compared with the control area (P = 0.003) | ⊕⊝⊝⊝4,9 | It is uncertain whether there is any difference in the scar severity in He‐Ne plus decamethyltetrasiloxane, polydimethylsiloxane and cyclopentasiloxane cream‐treated hypertrophic scars compared with decamethyltetrasiloxane, polydimethylsiloxane and cyclopentasiloxane cream after 12 weeks. | |||
| Incidence of treatment‐related adverse effects ‐ 595‐nm PDL plus verapamil versus verapamil ‐ regrowth ‐ keloid scars ‐ follow‐up: 24 weeks | Study population | RR 1.50 (0.27 to 8.22) | 50 (1study) | ⊕⊝⊝⊝1,10 | It is uncertain whether there is any difference in the incidence and severity of treatment‐related adverse effects in PDL plus verapamil‐treated keloid scars compared with verapamil after 24 weeks.
| |
| 80 per 1000 | 120 per 1000 | |||||
| Incidence of treatment‐related adverse effects ‐ 595‐nm PDL plus verapamil versus verapamil ‐ pain related to treatment ‐ keloid scars ‐ follow‐up: 24 weeks | One parallel trial (n = 50) reported this outcome. In this study, pain at injection site was reported by 1 out of 25 (1/25) (4%) participants treated with 595‐nm PDL plus verapamil and by 0 out of 25 (0/15) (0%) participants treated with verapamil (RR 3.00; 0.13 to 70.30) | ⊕⊝⊝⊝1,10 | ||||
| Incidence of treatment‐related adverse effects ‐ 595‐nm PDL plus verapamil versus verapamil ‐ hyperpigmentation ‐ keloid scars ‐ follow‐up: 24 weeks | One parallel trial (n = 50) reported this outcome. In this study, hyperpigmentation was observed in 2 out of 25 (2/25) (8%) participants treated with 595‐nm PDL plus verapamil and by 0 out of 25 (0/15) (0%) participants treated with verapamil (RR 5.00; 0.25 to 99.16) | ⊕⊝⊝⊝1,10 | ||||
| Incidence of treatment‐related adverse effects ‐ 595‐nm PDL plus verapamil versus verapamil ‐ depigmentation ‐ keloid scars ‐ follow‐up: 24 weeks | Study population | RR 1.00 (0.07 to 15.12) | 50 (1study) | ⊕⊝⊝⊝1,10 | ||
| 40 per 1000 | 40 per 1000 | |||||
| Incidence of treatment‐related adverse effects ‐ 595‐nm PDL plus verapamil versus verapamil ‐ purpura ‐ keloid scars ‐ follow‐up: 24 weeks | One parallel trial (n = 50) reported this outcome. In this study, hyperpigmentation was observed in 7 out of 25 (7/25) (28%) participants treated with 595‐nm PDL plus verapamil and by 0 out of 25 (0/15) (0%) participants treated with verapamil (RR 15.00; 0.90 to 249.30) | ⊕⊝⊝⊝1,10 | ||||
| Incidence of treatment‐related adverse effects ‐ 595‐nm PDL plus verapamil versus verapamil ‐ total ‐ keloid scars ‐ follow‐up: 24 weeks | Study population | RR 4.67 (1.53 to 14.26) | 50 (1study) | ⊕⊝⊝⊝1,10 | ||
| 120 per 1000 | 560 per 1000 | |||||
| *The risk in the intervention group (and its 95% confidence interval) is based on the mean risk in the comparison group and the relative effect of the intervention (and its 95% CI). ƚThe assumed risk in the comparison group is based on the event rate observed in the control arms of included trials. Where no events occurred, the risk was not calculated. ‐ Diprospan contains betamethasone disodium phosphate plus betamethasone dipropionate.
Patient self‐assessment ‐ based on a 4‐point scale (1 = 0 to 25% improvement, 2 = 25 to 50% improvement, 3 = 50 to 75% improvement, and 4 = 75% or greater improvement); VBS: Vancouver Burn Scar Assessment Scale ‐ severity of scar was determined by numeric value from a minimum of 0 to 13 as the most severe form. CI: Confidence Interval; ; CO:2 carbon dioxide;5‐FU: 5‐fluorouracil; He‐Ne: Helium‐Neon; NdYAG: neodymium‐doped yttrium aluminium garnet; PDL: Pulsed‐Dye Laser; RR: Risk Ratio; TAC: Triamcinolone acetonide. | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1 Downgraded 2 levels for very serious imprecision due to small number of events and large confidence interval. 2 Downgraded 1 level due to serious risk of bias (lack of blinding of participants, incomplete outcome data and selective reporting, and unclear sequence generation and allocation concealment). 3 Downgraded 1 level due to serious risk of bias (lack of blinding of participants and assessors (patient‐reported outcome), incomplete outcome data and selective reporting, and unclear sequence generation and allocation concealment) 4 Downgraded 2 levels for very serious imprecision due to small sample size and large confidence interval. 5 Downgraded 1 level due to serious risk of bias (lack of blinding of participants and incomplete outcome data, and unclear selective reporting). 6 Downgraded 1 level due to serious risk of bias (lack of blinding of participants and assessors (patient‐reported outcome) and incomplete outcome data, and unclear selective reporting). 7 Downgraded 1 level due to serious risk of bias (lack of blinding of participants and incomplete outcome data, and unclear sequence generation and allocation concealment). 8 Downgraded 1 level due to serious risk of bias (lack of blinding of participants and assessors (patient‐reported outcome) and incomplete outcome data, and unclear sequence generation and allocation concealment). 9 Downgraded 1 level due to serious risk of bias (lack of blinding of participants and selective reporting, and unclear sequence generation, allocation concealment and incomplete outcome data). 10 Downgraded 1 level due to serious risk of bias (lack of blinding of participants and assessors (patient‐reported outcome), and unclear sequence generation, allocation concealment and incomplete outcome data). | ||||||
| Comparison | Outcome | Trials (participants) | Definition of outcome in trial/measurement details | Data reported |
| 585‐nm PDL versus no treatment | Scar severity | 2 RCTs (Manuskiatti 2001; 10 participants; 40 segments and Manuskiatti 2002, 10 participants; 20 segments) | Manuskiatti 2001 and Manuskiatti 2002: categories of 25% increments of improvement in scar severity after 32 weeks (graded by the patient) | Number of participants with an improvement of 50% or higher in the scar severity
Manuskiatti 2001: Laser: 23/30
Manuskiatti 2002: Laser: 8/10 |
| 585‐nm PDL versus no treatment | Incidence and severity of treatment‐related adverse effects | 3 RCTs (Manuskiatti 2001; 10 participants; 40 segments, Manuskiatti 2002, 10 participants; 20 segments, and Wittenberg 1999; 20 participants; 40 segments) | Manuskiatti 2001: immediate treatment reactions, including purpuric discolorations and erosion secondary to blistering, and adverse sequelae during 32 weeks.
Manuskiatti 2002: immediate treatment reactions included mild to moderate pain during treatment, burning sensation, spots of purpura, erosion secondary to blistering. Treatment‐related adverse sequelae including hypopigmentation, telangiectasia, and skin atrophy during 32 weeks.
Wittenberg 1999: no definition was provided. Duration: 40 weeks. | Manuskiatti 2001 and 2002: in all participants treated with the PDL the area became purpuric and a small number of participants with skin phototype VI reported erosions.
Wittenberg 1999: one (1/20) participant dropped out due to pain during laser treatment. |
| 585‐nm PDL versus no treatment | Scar size, colour, height, length, width, pliability, skin surface texture, pruritus and pain | 3 RCTs (Manuskiatti 2001; 10 participants; 30 segments and Manuskiatti 2002: 10 participants; 20 segments; Wittenberg 1999; 20 participants; 40 segments) | Manuskiatti 2001 and 2002: scar height evaluated using a dial calliper, erythema using a hand‐held colorimeter after 32 weeks.
Wittenberg 1999: blood flow (erythema), elasticity and volume, burning, pruritus, and pain not related to treatment after 40 weeks. | Manuskiatti 2001, 2002: scar height improvement in laser treated areas when compared with control (P < 0.05, and P = 0.005, respectively) (data presented only in graphs)
Wittenberg 1999: No statistically significant differences between groups were detected for erythema (P = 0.26), elasticity (P = 0.76), volume (P = 0.13), burning (P = 0.75), pruritus (P = 0.99), and pain not related to treatment (P = 0.41) (results presented only in graphs). |
| NAFL versus no treatment | Scar severity | 2 RCTS (Verhaeghe 2013; 22 participants, 44 segments; Lin 2011; 20 participants; 20 scars) | Verhaeghe 2013: POSAS: containing vascularisation, pigmentation, thickness, relief, pliability, and surface area (observer part) and pain not related to treatment, itching, colour, stiffness, thickness, and relief (patient part) (range 6 to 60) after 3 months.
Lin 2011: categories of 25% increments of improvement in scar severity (graded by the participants and 2 blinded observers) after 3 months. | Verhaeghe 2013 (36 segments analysed): Number of participants who got better according to HPGA and PGA. Control: 1/18 POSAS: Patient part (P = .047) Observer part: not significant (details not provided)
Lin 2011: HDTA laser: not significant LDTA: P = 0.001 (data presented only in graphs) |
| NAFL versus no treatment | Incidence and severity of treatment‐related adverse effects | 2 RCTS (Verhaeghe 2013; 22 participants, 44 segments; Lin 2011; 20 participants; 20 scars) | Verhaeghe 2013: treatment‐related adverse effects included erythema, edema, burning sensation, crusts, purpura, vesicles, hyperpigmentation. Duration: 3 months
Lin 2011: side effects, including worsening (erythema, pigmentation, or texture), discolouration, exfoliation, swelling, scabbing, and pain related to treatment, rated on a quartile scale (0 = none, 1 = mild, 2 = moderate, and 3 = severe) during the 3 month‐period. | Verhaege 2013: Percentage of participants reporting treatment‐related adverse effects 4 days after treatment (out of 18 analysed): Erythema: 70% Edema: 20% Burning sensation: 18% Crusts: 15% Purpura: 7% purpura Vesicles: 3% After 3 months: Hyperpigmentation: 1 participant *In a small group of participants, the treated part improved less than the untreated part. Median pain (related to treatment) score (IQR) on a VAS (0 = no pain and 100 = worst possible pain) was: Session 3: 53.0 (22.5–71.0) Session 4: 48.0 (23.5–78.5)
Lin 2011: Number of participants reporting scar worsening HDTA: 3/10
Higher risk of erythema, exfoliation, and pain related to treatment with HDTA compared with LDTA (P = 0.05, P = 0.02, P = 0.01, respectively) (data on side effects were presented only in graphs). |
| NAFL versus no treatment | Scar size, colour, height, length, width, pliability, skin surface texture, pruritus and pain | 2 RCTS (Verhaeghe 2013; 22 participants, 44 segments; Lin 2011; 20 participants; 20 scars) | Verhaeghe 2013: redness, pigmentation, and skin texture after 3 months
Lin 2011: erythema, pigmentation, texture after 3 months | Verhaeghe 2013: No significant difference in redness, pigmentation, and skin texture (details not provided)
Lin 2011: Mean + SD Erythema: Control: 0.89 + 0.95 LDTA: 1.06 + 1.26 Pigmentation: HDTA: 1.06 + 0.95 Control: 0.94 + 0.82 LDTA: 0.79 + 0.76 Control: 0.71 + 0.76 Texture: HDTA: 2 + 0.76 Control: 1.78 + 0.89 LDTA: 2.19 + 0.95 |
| Fractional CO2 Laser versus no treatment | Scar severity | 3 RCTS (Azzam 2016: 30 participants; 60 segments, Blome‐Eberwein 2016: 36 participants; 80 scars, Daoud 2019: 23 participants; 46 segments) | Azzam 2016: patient satisfaction, as follows: excellent = more than 75 %, good = 50 to 75%, moderate = 25 to 50 % and poor = less than 25 % improvement after 3 months
Azzam 2016 and Blome‐Eberwein 2016 used the VSS, including pliability, height, colour, and vascularity
Blome‐Eberwein 2016 and Daoud 2019: POSAS including: vascularisation, pigmentation, thickness, relief, pliability, and surface area (observer), itching, colour, and pain not related to treatment stiffness, thickness, and relief (patient) (range 6 to 60) after up to 6 months | Azzam 2016: Number of participants that reported each satisfaction Keloid scar participants Excellent: 6/12 Good: 3/12 Moderate: 3/12 Hypertrophic scar patients Good: 1/7 Moderate: 2/7 Poor: 2/7
Azzam 2016: Keloid scar patients Laser: 5.7 + 2.2 Control: 7.6 + 1.0 Hypertrophic scar patients Laser: 4.6 + 2.5 Control: 7.6 + 2.9
Blome‐Erbewein 2016 VSS (Mean + SD) Hypertrophic scar patients Laser: 6.5 + 2.39 Control: 6.41 + 2.31
Blome‐Eberwein 2016 POSAS Pre‐treatment Post‐treatment Laser: 28.51 ± 12.85 Control: 24.38 ± 11.41
Daoud 2019 Significant improvements in all categories except for colour (P < 0.001) (results presented in graphs) |
| Fractional CO2 Laser versus no treatment | Incidence and severity of treatment‐related adverse effects | 1 RCT (Daoud 2019 23 participants; 46 scar segments) | No definition provided | The authors mention that no treatment‐related adverse effects were reported |
| Fractional CO2 Laser versus no treatment | Scar size, colour, height, length, width, pliability, skin surface texture, pruritus and pain | 2 RCTS (Azzam 2016: 30 participants; 60 segments;,Blome‐Eberwein 2016: 36 participants; 80 scars) | Azzam 2016: pruritus and pain not related to treatment after 3 months
Blome‐Eberwein 2016 Scar pliability and height evaluated with suction cup and ultrasound, colour; erythema and pigmentation assessed with Dermaspectrometer), sensation, pruritus, and pain not related to treatment evaluated with POSAS after up to 6 months | Azzam: number of participants complaining of pruritus and pain Pruritus: 16 Pain: 5 (details not provided)
Blome‐Eberwein 2016: pliability, height, recoil Mean and SD – before and after treatment Scar height Pre‐intervention Laser: 3.15 ± 0.37 Control: 2.658 ± 0.344 Post‐treatment: Laser: 2.34 ± 0.313 Control: 2.46 ± 0.342 |
| HDTA: high‐density treatment arm; HPGA: Health Professional Global Assessment; IQR: interquartile range; LDTA: low‐density treatment arm; PGA: patient global assessment; POSAS: Patient and Observer Scar Assessment Scale; (In POSAS, highest values indicate worse scar or sensation); SD: standard deviation; VAS: visual analogue scale; VSS: Vancouver Scar Scale. | ||||
| Comparison | Trials (participants) | Outcome | Definition of outcome in trial/measurement details | Data reported |
| 585‐nm PDL versus TAC | 2 RCTs (Omranifard 2007: 80 participants; 80 scars and Manuskiatti 2002: 10 participants; 20 segments) | Scar severity | Omranifard 2007: Patient Satisfaction assessed by VBS, including pigmentation, vascularity, pliability and height (photographs were taken). Self‐assessment: number of participants who considered their scars better or much better after up to 12 months Manuskiatti 2002: categories of 25% increments of improvement in scar severity after 32 weeks (graded by the participant) | Omranifard 2007: VBS (Mean + SD) Post‐treatment PDL: 4.2 + 1.6 TAC: 6.7 + 1.6 Self‐assessment PDL: 70% TAC: 30% Manuskiatti 2002: Number of participants with a 50% improvement or higher PDL: 8/10 TAC: 10/10 |
| 585‐nm PDL versus TAC | 2 RCTs (Omranifard 2007: 80 participants; 80 scars and Manuskiatti 2002: 10 participants; 20 segments) | Incidence and severity of treatment‐related adverse effects | Omranifard 2007: complications, such as textural or discolouration (hypo‐ or hyperpigmentation) during up to 12 months Manuskiatti 2002: Immediate treat reactions included mild to moderate pain during treatment, burning sensation, spots of purpura, erosion secondary to blistering. Treatment‐related adverse sequelae including hypopigmentation, telangiectasia, and skin atrophy during 32 weeks. | Omranifard 2007: no complication was observed Manuskiatti 2002: Sequelae: PDL: 0/10 Control: 10/10 (further details not provided) |
| 585‐nm PDL versus TAC | 2 RCTs (Omranifard 2007: 80 participants; 80 scars and Manuskiatti 2002: 10 participants; 20 segments) | Scar size, colour, height, length, width, pliability, skin surface texture, pruritus and pain | Omranifard 2007: vascularity, using a transparent tool for blanching the scar. Scar height scores: calliper by measuring the maximum vertical elevation of the scar above the normal skin after up to 12 months Manuskiatti 2002: scar height evaluated using a dial calliper, erythema using a hand‐held colorimeter after 32 weeks. | Omranifard 2007: Vascularity (Mean) Pre‐treatment PDL: 2.3 TAC: 2.3 Post‐treatment PDL: 1.1 TAC: 1.95 Height (Mean) Pre‐treatment PDL: 2.16 TAC: 2.18 Post‐treatment PDL: 1.32 TAC: 1.93 Manuskiatti 2002: No significant difference between groups in height (results presented only in graphs) |
| 585‐nm PDL versus 5‐FU | 1 RCT (Manuskiatti 2002: 10 participants; 20 segments) | Scar severity | Manuskiatti 2002: categories of 25% increments of improvement in scar severity after 32 weeks (graded by the participant). | Manuskiatti 2002: Number of participants with a 50% improvement or higher PDL: 8/10 |
| 585‐nm PDL versus 5‐FU | 1 RCT (Manuskiatti 2002: 10 participants; 20 segments) | Incidence and severity of treatment‐related adverse effects | Manuskiatti 2002: immediate treatment reactions included mild to moderate pain during treatment and spots of purpura during 32 weeks. | Manuskiatti 2002: Purpura: 5‐FU: 2/10
No permanent sequelae were reported in the areas submitted to laser therapy or 5‐FU. |
| 585‐nm PDL versus 5‐FU | 1 RCT (Manuskiatti 2002: 10 participants; 20 segments) | Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain | Manuskiatti2002: scar height evaluated using a dial calliper, erythema using a hand‐held colorimeter after 32 weeks. | No significant difference between groups in height (results presented only in graphs) |
| 585‐nm PDL versus TAC plus 5‐FU | 1 RCT (Manuskiatti 2002: 10 participants; 20 segments) | Scar severity | Manuskiatti 2002: categories of 25% increments of improvement in scar severity after 32 weeks (graded by the participant). | Manuskiatti 2002: Number of participants with a 50% improvement or higher PDL: 8/10 TAC plus 5‐FU: 9/10 |
| 585‐nm PDL versus TAC plus 5‐FU | 1 RCT (Manuskiatti 2002: 10 participants; 20 segments) | Incidence and severity of treatment‐related adverse effects | Manuskiatti 2002: immediate treatment reactions included mild to moderate pain during treatment and spots of purpura during 32 weeks. | Manuskiatti 2002: Purpura: 5‐FU: 3/10
No permanent sequelae were reported in the areas submitted to laser therapy or 5‐FU. |
| 585‐nm PDL versus TAC plus 5‐FU | 1 RCT (Manuskiatti 2002: 10 participants; 20 segments) | Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain | Manuskiatti2002: scar height evaluated using a dial calliper, erythema using a hand‐held colorimeter after 32 weeks. | Mild to moderate pain not related to treatment PDL: 9/10 TAC plus 5‐FU: 10/10 No significant difference between groups in height (results presented only in graphs). |
| 585‐nm PDL versus Silicone Gel Sheeting | 1 RCT (Wittenberg 1999; 20 participants; 40 segments) | Incidence and severity of treatment‐related adverse effects | Wittenberg 1999: No definition is provided | Wittenberg 1999: one participant dropped out due to pain during laser treatment. One participant did not use SGS because of skin irritation. |
| Erbium laser versus TAC | 1 RCT (Omranifard 2007: 80 participants; 80 scars) | Scar severity | Omranifard 2007: Patient Satisfaction assessed by VBS, including pigmentation, vascularity, pliability and height. (photographs were taken) Self‐assessment: improvement of the scars severity after up to 12 months. | Omranifard 2007: VBS (Mean + SD) Post‐treatment Erbium: 4.6 + 1.9 TAC: 6.7 + 1.6 Self‐assessment (number of participants who considered their scars better or much better) Erbium: 65% TAC: 30% |
| Erbium laser versus TAC | 1 RCT (Omranifard 2007: 80 participants; 80 scars) | Incidence and severity of treatment‐related adverse effects | Omranifard 2007: complications, such as textural or discoloration (hypo‐ or hyperpigmentation) during up to 12 months. | Omranifard 2007: no complication was observed |
| Erbium laser versus TAC | 1 RCT (Omranifard 2007: 80 participants; 80 scars) | Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain | Omranifard 2007: vascularity, using a transparent tool for blanching the scar. Scar height scores: calliper by measuring the maximum vertical elevation of the scar above the normal skin after up to 12 months. | Omranifard 2007: Vascularity (Mean) pre‐treatment Erbium: 2.4 TAC: 2.3 Post‐treatment Erbium: 1.15 TAC: 1.95 Height (Mean) Pre‐treatment Erbium: 2.18 TAC: 2.18 Post‐treatment Erbium: 1.39 TAC: 1.93 |
| Fractional CO2 Laser versus TAC | 1 RCT (Srivastava 2019; 40 participants; 40 scars) | Scar severity | Srivastava 2019: VSS | Srivastava 2019 Results of full scale were not reported |
| Fractional CO2 Laser versus TAC | 1 RCT (Srivastava 2019; 40 participants; 40 scars) | Incidence and severity of treatment‐related adverse effects | Srivastava 2019: pain at injection site, telangiectasia, skin atrophy and charring were evaluated and reported (when they occurred) during 24 weeks. | Srivastava 2019: Number of participants reporting treatment‐related adverse effects Pain at injection site FCO2: 2/20 TAC: 8/20 Telangiectasia FCO2: 0/20 TAC: 2/20 Skin atrophy FCO2: 0/20 TAC: 1/20 Charring FCO2: 3/20 TAC: 0/20 |
| Fractional CO2 Laser versus TAC | 1 RCT (Srivastava 2019; 40 participants; 40 scars) | Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain | Srivastava 2019: height measured with callipers; vascularity by visual inspection; pliability by palpation; pigmentation after blanching (using a piece of clear plastic sheet till scar flattening occurred) and comparing it with the surrounding skin, pruritus, and pain not related to treatment after 24 weeks. | Srivastava 2019: Height (Mean + SD) Pre‐treatment FCO2: 1.95 + 0.76 TAC: 1.75 + 0.64 Post‐treatment TAC: 0 + 0 Vascularity Pre‐treatment FCO2: 2.05 + 0.69 TAC: 1.65 + 0.49 Post‐treatment TAC: 0 + 0 Pliability Pre‐treatment FCO2: 1.85 + 0.67 TAC: 1.9 + 0.64 Post‐treatment TAC: 0 + 0 Pigmentation Pre‐treatment FCO2: 1.60 + 0.50 TAC: 1.7 + 0.47 Post‐treatment TAC: 0.8 + 0.41 |
| Fractional CO2 Laser versus Verapamil | 1 RCT (Srivastava 2019; 40 participants 40 scars) | Scar severity | Srivastava 2019: VSS | Srivastava 2019: Results of full scale were not reported |
| Fractional CO2 Laser versus Verapamil | 1 RCT (Srivastava 2019; 40 participants 40 scars) | Incidence and severity of treatment‐related adverse effects | Srivastava 2019: pain at injection site, telangiectasia, skin atrophy and charring were evaluated and reported (when they occurred) during 24 weeks. | Srivastava 2019: Number of participants reporting treatment‐related adverse effects Pain at injection site FCO2: 2/20 Verapamil: 0/20 Telangiectasia FCO2: 0/20 Verapamil: 0/20 Skin atrophy FCO2: 0/20 Verapamil: 0/20 Charring FCO2: 3/20 Verapamil: 0/20 |
| Fractional CO2 Laser versus Verapamil | 1 RCT (Srivastava 2019; 40 participants 40 scars) | Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain | Srivastava 2019: height measured with callipers; vascularity by visual inspection; pliability by palpation; pigmentation after blanching (using a piece of clear plastic sheet till scar flattening occurred) and comparing it with the surrounding skin, pruritus, and pain not related to treatment after 24 weeks. | Srivastava 2019: Height (Mean + SD) Pre‐treatment FCO2: 1.95 + 0.76 Verapamil: 2.05 + 0.6 Post‐treatment Verapamil: 0.05 + 0.22 Vascularity Pre‐treatment FCO2: 2.05 + 0.69 Verapamil: 1.95 + 0.69 Post‐treatment Verapamil: 0.1 + 0.31 Pliability Pre‐treatment FCO2: 1.85 + 0.67 Verapamil: 2.1 + 0.64 Post‐treatment FCO2: 0.9 + 0.31 Verapamil: 0 + 0 Pigmentation Pre‐treatment FCO2: 1.60 + 0.50 Verapamil: 1.65 + 0.49 Post‐treatment Verapamil: 0.55 + 0.51 |
| 5‐FU: Fluorouracil; PDL: Pulsed‐Dye Laser; TAC: Triamcinolone acetonide;VSS: Vancouver Scar scale. | ||||
| Comparison | N. of Trials | Outcome | Definition of outcome in trial/measurement details | Data reported |
| 585‐nm PDL plus TAC plus 5 FU versus TAC plus 5‐FU | 1 RCT (Asilian 2006; 43 participants; 43 scars) | Scar severity | Asilian 2006: patient and Observer: no improvement; poor = up to 25% improvement; fair = 26% to 50% improvement; good = 51% to 75% improvement; (for the observer assessment photographs were taken) after 12 weeks | Asilian 2006: Number of participants and observers reporting good to excellent improvement OA 585‐nm PDL plus TAC plus 5 FU: 14/20 TAC plus 5‐FU: 8/20 PSA 585‐nm PDL plus TAC plus 5 FU: 15/20 TAC plus 5‐FU: 11/20 |
| 585‐nm PDL plus TAC plus 5 FU versus TAC plus 5‐FU | 1 RCT (Asilian 2006; 43 participants; 43 scars) | Incidence and severity of treatment‐related adverse effects | Asilian 2006: treatment‐related adverse effects including the presence of purpuric areas by observer interviews during 12 weeks | Asilian 2006: In the TAC plus 5‐FU plus PDL group the lesions became purpuric which lasted from 7 to 10 days |
| 585‐nm PDL plus TAC plus 5 FU versus TAC plus 5‐FU | 1 RCT (Asilian 2006; 43 participants; 43 scars) | Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain | Asilian 2006: scar length and width using a dial calliper, height using a calliper, erythema, pliability, and pruritus: graded by the observer on a 5‐point scale: 0 = no; 1 = mild; 2 = moderate; 3 = severe; and 4 = very severe. | Asilian 2006: Erythema Pre‐treatment PDL plus TAC plus 5‐FU: 3.2 TAC plus 5‐FU: 3.3 Post‐treatment TAC plus 5‐FU plus PDL: 1.2 TAC plus 5‐FU: 1.9 Reduction in height (average lesion) TAC plus 5‐FU: 77% PDL plus TAC plus 5‐FU: 79% |
| CO2 Laser plus TAC versus Cryosurgery plus TAC | 1 RCT (Behera 2016: 60 participants; 101 scars) | Scar severity | Behera 2016: patient and observer on a 5‐point scale as, poor = up to 25% improvement; fair = 26% to 50% improvement; good = 51% to 75% improvement; and excellent = 76% to 100% improvement (for the observer assessment photographs were taken) VSS after up to 12 months | Behera 2016: Number (%) of participants with an improvement of 50% or higher in the scar: PSA: CO2 Laser plus TAC: 27 (75%); Cryosurgery plus TAC: 21 (77.78%) OA: CO2 Laser plus TAC: 22 (61.12%); Cryosurgery plus TAC: 23 (85.18%) VSS: CO2 Laser plus TAC: 19 (52.78%); Cryosurgery plus TAC: 17 (62.96%) |
| CO2 Laser plus TAC versus Cryosurgery plus TAC | 1 RCT (Behera 2016: 60 participants; 101 scars) | Recurrence | Behera 2016: no definition was provided (after up to 12 months) | Behera 2016: CO2 Laser plus TAC: 6 (16.66%) Cryosurgery plus TAC: 0 (0%) |
| CO2 Laser plus TAC versus Cryosurgery plus TAC | 1 RCT (Behera 2016: 60 participants; 101 scars) | Incidence and severity of treatment‐related adverse effects | Behera 2016: no definition was provided (during up to 12 months) | Behera 2016: Number (%) of participants with atrophy CO2 Laser plus TAC: 17 (47.23%); Cryosurgery plus TAC: 15 (55.56%) |
| CO2 Laser plus TAC versus Cryosurgery plus TAC | 1 RCT (Behera 2016: 60 participants; 101 scars) | Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain | Behera 2016: height: using a dial calliper, volume, pruritus, and pain not related to treatment after up to 12 months | Behera 2016: CO2 Laser plus TAC: 49.31 + 50.42; Cryosurgery plus TAC: 65.46 + 35.63 Volume (Mean percentage reduction + SD): CO2 Laser plus TAC: 54.81 + 47.96; Cryosurgery plus TAC: 72.69 + 37.75 |
| Nd:YAG laser plus Intralesional corticosteroid plus 5‐FU versus Intralesional corticosteroid plus 5‐FU | 1 RCT (Chen 2017: 46 participants; 46 scars) | Scar severity | Chen 2017: patient and observer on a 5‐point scale as, poor = up to 25% improvement; fair = 26% to 50% improvement; good = 51% to 75% improvement; and excellent = 76% to 100% improvement (for the observer assessment photographs were taken) after 3 months. | Chen 2017: OA: Number (%) of participants with an improvement of 51% or higher in the scar: Nd:YAG laser plus Intralesional corticosteroid plus 5‐FU: 16 (69.57%); Intralesional corticosteroid plus 5‐FU: 11 (47.83%) PSA: Nd:YAG laser plus Intralesional corticosteroid plus 5‐FU: 18 (78.26%); Intralesional corticosteroid plus 5‐FU: 13 (56.52%%) |
| Nd:YAG laser plus Intralesional corticosteroid plus 5‐FU versus Intralesional corticosteroid plus 5‐FU | 1 RCT (Chen 46 participants; 46 scars) | Incidence and severity of treatment‐related adverse effects | Chen 2017: no definition was provided (during 3 months) | Chen 2017: Almost all injections were painful. Nd:YAG plus Intralesional corticosteroid plus 5‑FU: the site treated by Nd:YAG became purpuric, which lasted for 7 to 10 days. No adverse textural or pigmentary alterations, and no ulcers or erosions were observed in either groups. No further information was provided regarding adverse events in the trial. |
| Nd:YAG laser plus Intralesional corticosteroid plus 5‐FU versus Intralesional corticosteroid plus 5‐FU | 1 RCT (Chen 46 participants; 46 scars) | Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain | Chen 2017: erythema, pliability, and pruritus were graded by the observer on a 5‐point scale: 0 = no erythema; 1 = mild erythema; 2 = moderate erythema; 3 = severe erythema; and 4 = very severe erythema after 3 months. | Chen 2017: Erythema (P < 0.05), pliability (P < 0.05), and pruritus (P < 0.05) were significantly lower in the laser group (data provided only in graphs). |
| He‐Ne laser plus Decamethyltetrasiloxane, Polydimethylsiloxane and Cyclopentasiloxane cream versus Decamethyltetrasiloxane, Polydimethylsiloxane and Cyclopentasiloxane cream | 1 RCT (Alsharnoubi 2018: 15 participants; 30 segments) | Scar severity | Alsharnoubi 2018: VSS, including skin thickness, pigmentation, and vascularity after 3 months. | Alsharnoubi 2018: VSS: median values Pre‐treatment: 9 (value of the whole scar) Post treatment He‐Ne laser plus Decamethyltetrasiloxane, Polydimethylsiloxane and Cyclopentasiloxane cream: 4; Decamethyltetrasiloxane, Polydimethylsiloxane and Cyclopentasiloxane cream: 6; Height score: Pre‐treatment: 2 (value of the whole scar) Post treatment He‐Ne laser plus Decamethyltetrasiloxane, Polydimethylsiloxane and Cyclopentasiloxane cream: 1; Decamethyltetrasiloxane, Polydimethylsiloxane and Cyclopentasiloxane cream: 2 |
| He‐Ne laser plus Decamethyltetrasiloxane, Polydimethylsiloxane and Cyclopentasiloxane cream versus Decamethyltetrasiloxane, Polydimethylsiloxane and Cyclopentasiloxane cream | 1 RCT (Alsharnoubi 2018: 15 participants; 30 scar segments) | Incidence and severity of treatment‐related adverse effects | Definition was not provided | No treatment‐related adverse effects were reported. |
| He‐Ne laser plus Decamethyltetrasiloxane, Polydimethylsiloxane and Cyclopentasiloxane cream versus Decamethyltetrasiloxane, Polydimethylsiloxane and Cyclopentasiloxane cream | 1 RCT (Alsharnoubi 2018: 15 participants; 30 scar segments) | Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain | Alsharnoubi 2018: scar thickness using an ultrasound imaging system, perfusion (erythema) using a Laser Doppler perfusion imager. | Alsharnoubi 2018: Skin thickness (mean ± SD) Pre‐treatment: 0.52 ± 0.17 mm (whole scar) Post treatment He‐Ne laser plus Decamethyltetrasiloxane, Polydimethylsiloxane and Cyclopentasiloxane cream: 0.34 ± 0.09 mm; Decamethyltetrasiloxane, Polydimethylsiloxane and Cyclopentasiloxane cream: 0.43 ± 0.13 mm Perfusion Pre‐treatment: 1.27 ± 0.54 V (whole scar) Post treatment He‐Ne laser plus Decamethyltetrasiloxane, Polydimethylsiloxane and Cyclopentasiloxane cream: 0.8 ± 0.23 V; Decamethyltetrasiloxane, Polydimethylsiloxane and Cyclopentasiloxane cream: 0.77 ± 0.24 V Pigmentation Pre‐treatment: 2 (whole scar) Post Treatment He‐Ne laser plus Decamethyltetrasiloxane, Polydimethylsiloxane and Cyclopentasiloxane cream: 0; Decamethyltetrasiloxane, Polydimethylsiloxane and Cyclopentasiloxane cream: 2; Vascularity Pre‐treatment: 2 (whole scar) Post Treatment He‐Ne laser plus Decamethyltetrasiloxane, Polydimethylsiloxane and Cyclopentasiloxane cream: 1 Decamethyltetrasiloxane, Polydimethylsiloxane and Cyclopentasiloxane cream: 1 (data presented in graphs) |
| PDL plus intralesional verapamil versus intralesional verapamil | 1 RCT (Khattab 2019; 40 participants; 50 keloid scars) | Scar severity | Khattab 2019: VSS, keloid height measured with callipers; pliability by palpation; vascularity by visual inspection, and pigmentation scored after blanching and comparing it with the surrounding skin after 24 weeks. | Khattab 2019: Height (Mean + SD) PDL plus verapamil: 0.21 ± 0.56; Verapamil: 3.10±1.85 Pliabilty: PDL plus verapamil: 0.20±0.41; Verapamil: 2.07±0.26 Vascularity PDL plus verapamil: 0.03 ± 0.70; Verapamil: 0.87±0.74 Pigmentation PDL plus verapamil: 0.13 ± 0.35; Verapamil: 0.27±0.70 |
| PDL plus intralesional verapamil versus intralesional verapamil | 1 RCT (Khattab 2019; 40 participants; 50 keloid scars) | Incidence and severity of treatment‐related adverse effects | Khattab 2019: treatment‐related adverse effects were regrowth, pain, hyperpigmentation, depigmentation, and purpura during 24 weeks. | Khattab 2019: Treatment‐related adverse events: |
| PDL plus intralesional verapamil versus intralesional verapamil | 1 RCT (Khattab 2019; 40 participants; 50 keloid scars) | Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain | Khattab 2019: height, vascularity, pliability, and pigmentation were assessed at 24 weeks. | Khattab 2019: Verapamil: 0.87 + 0.74 Pliability PDL plus verapamil: 0.2 + 0.41; Verapamil: 2.07 + 0.26 Pigmentation PDL plus verapamil: 0.13 + 0.35; Verapamil: 0.27 + 0.7 |
| 5‐FU: Fluorouracil; NdYAG: neodymium‐doped yttrium aluminium garnet; PDL: Pulsed‐Dye Laser; SD: standard deviation; TAC: Triamcinolone acetonide;VSS: Vancouver Scar scale. | ||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1.1 Severity of scar: Patient self‐assessment (32 weeks) Show forest plot | 2 | 60 | Risk Ratio (M‐H, Random, 95% CI) | 1.96 [1.11, 3.45] |
| 1.2 Incidence and severity of treatment‐related adverse effects (32 weeks) Show forest plot | 3 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 1.2.1 Mild to moderate discomfort or pain related to treatment | 2 | 60 | Risk Ratio (M‐H, Random, 95% CI) | 8.62 [1.10, 67.39] |
| 1.2.2 Purpura | 2 | 60 | Risk Ratio (M‐H, Random, 95% CI) | 21.32 [3.14, 144.86] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 2.1 Severity of scar: Health Professional Global Assessment (3 months) Show forest plot | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 2.2 Incidence and severity of treatment‐related adverse effects (3 months) Show forest plot | 2 | Risk Ratio (M‐H, Random, 95% CI) | Totals not selected | |
| 2.2.1 High‐Density Treatment Arm (HDTA) versus control, scar worsening (3 months) | 1 | Risk Ratio (M‐H, Random, 95% CI) | Totals not selected | |
| 2.2.2 Non‐ablative fractional Laser (NAFL) versus no treatment, mild hyperpigmentation (3 months) | 1 | Risk Ratio (M‐H, Random, 95% CI) | Totals not selected | |
| 2.3 Scar size, colour, height, length, width, pliability, skin surface texture, pruritus and pain (3 months) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 2.3.1 High‐Density Treatment Arm (HDTA) versus control, erythema (3 months) | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 2.3.2 High‐Density Treatment Arm (HDTA) versus control, pigment (3 months) | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 2.3.3 High‐Density Treatment Arm (HDTA) versus control, texture (3 months) | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 2.3.4 Low‐Density Treatment Arm (LDTA) versus control, erythema (3 months) | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 2.3.5 Low‐Density Treatment Arm (LDTA) versus control, pigment (3 months) | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 2.3.6 Low‐Density Treatment Arm (LDTA) versus control, texture (3 months) | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 3.1 Severity of scar: Vancouver Burn Scar (VBS) scale (up to 6 months) Show forest plot | 2 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 3.1.1 Hypertrophic scar | 2 | 104 | Mean Difference (IV, Random, 95% CI) | ‐1.30 [‐4.32, 1.71] |
| 3.1.2 Keloid scar | 1 | 36 | Mean Difference (IV, Random, 95% CI) | ‐1.90 [‐3.02, ‐0.78] |
| 3.2 Severity of scar: Patient and Observer Scar Assessment Scale (POSAS) (at least one month) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 3.3 Scar size, colour, height, length, width, pliability, skin surface texture, pruritus and pain (12 to 18 weeks) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 3.3.1 Height | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 3.3.2 Erythema | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 3.3.3 Pigmentation | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 3.3.4 Pain not related to treatment | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 3.3.5 Pruritus | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 4.1 Severity of scars: Vancouver Burn Scar (VBS) scale (up to 12 months) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 4.2 Severity of scars: Patient self‐assessment (up to 12 months) Show forest plot | 2 | Risk Ratio (M‐H, Random, 95% CI) | Totals not selected | |
| 4.2.1 Split‐scar trial | 1 | Risk Ratio (M‐H, Random, 95% CI) | Totals not selected | |
| 4.2.2 Parallel trial | 1 | Risk Ratio (M‐H, Random, 95% CI) | Totals not selected | |
| 4.3 Incidence and severity of treatment‐related adverse effects (up to 12 months) Show forest plot | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 4.3.1 Sequelae (32 weeks) | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 4.3.2 Mild to moderate pain during the intervention (32 weeks) | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 5.1 Severity of scars: Patient self‐assessment (32 weeks) Show forest plot | 1 | Risk Ratio (M‐H, Random, 95% CI) | Totals not selected | |
| 5.2 Incidence and severity of treatment‐related adverse effects (32 weeks) Show forest plot | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 5.2.1 Mild to moderate discomfort or pain related to treatment | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 5.2.2 Purpura | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 6.1 Severity of scars: Patient self‐assessment (32 weeks) Show forest plot | 1 | Risk Ratio (M‐H, Random, 95% CI) | Totals not selected | |
| 6.2 Incidence and severity of treatment‐related adverse effects (32 weeks) Show forest plot | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 6.2.1 Mild to moderate discomfort or pain related to treatment | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 6.2.2 Purpura | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 7.1 Incidence and severity of treatment‐related adverse effects (24 weeks) Show forest plot | 1 | Risk Ratio (M‐H, Random, 95% CI) | Totals not selected | |
| 7.1.1 Pain during treatment | 1 | Risk Ratio (M‐H, Random, 95% CI) | Totals not selected | |
| 7.1.2 Skin irritation | 1 | Risk Ratio (M‐H, Random, 95% CI) | Totals not selected | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 8.1 Severity of scars: Vancouver Burn Scar (VBS) scale (up to 12 months) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 8.2 Severity of scars: Patient self‐assessment (up to 12 months) Show forest plot | 1 | Risk Ratio (M‐H, Random, 95% CI) | Totals not selected | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 9.1 Incidence of treatment‐related adverse effects (24 weeks) Show forest plot | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 9.1.1 Pain at injection site | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 9.1.2 Telangiectasia | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 9.1.3 Skin atrophy | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 9.1.4 Charring | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 9.2 Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain (12 weeks) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 9.2.1 Height (12 weeks) | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 9.2.2 Vascularity (12 weeks) | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 9.2.3 Pliability (12 weeks) | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 9.3 Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain (24 weeks) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 9.3.1 Pigmentation (24 weeks) | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 10.1 Incidence of treatment‐related adverse effects (24 weeks) Show forest plot | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 10.1.1 Charring (24 weeks) | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 10.1.2 Pain at injection site (24 weeks) | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 10.2 Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain (12 weeks) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 10.2.1 Height | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 10.2.2 Pigmentation | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 10.2.3 Vascularity | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 10.2.4 Pliability | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 10.3 Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain (24 weeks) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 10.3.1 Height | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 10.3.2 Pigmentation | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 10.3.3 Vascularity | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 11.1 Severity of scars (12 weeks) Show forest plot | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 11.1.1 Scar improvement good to excellent: observer assessment (12 weeks) | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 11.1.2 Scar improvement good to excellent: Patient self‐assessment (12 weeks) | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 12.1 Severity of scars (12 months) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 12.1.1 Mean percentage reduction in Observer Assessment score (12 months) | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 12.1.2 Mean percentage reduction in Patient Self‐Assessment score (12 months) | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 12.1.3 Mean percentage reduction in Vancouver Burn Scale (VBS) score (12 months) | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 12.2 Incidence and severity of treatment‐related adverse effects (12 months) Show forest plot | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 12.2.1 Atrophy (12 months) | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 12.2.2 Erythema (12 months) | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 12.2.3 Telangiectasia (12 months) | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 12.2.4 Hypopigmentation (12 months) | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 12.3 Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain(12 months) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 12.3.1 Mean percentage reduction of scar height (12 months) | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 12.3.2 Mean percentage reduction of scar volume (12 months) | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 12.4 Recurrence of the condition (12 months) Show forest plot | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 13.1 Severity of scars (3 months) Show forest plot | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 13.1.1 Scar improvement good to excellent: Observer assessment (3 months) | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 13.1.2 Scar improvement good to excellent: Patient self‐assessment (3 months) | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 14.1 Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain (12 weeks) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 14.1.1 Skin thickness (12 weeks) | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 15.1 Incidence of treatment‐related adverse effects (24 weeks) Show forest plot | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 15.1.1 Regrowth (24 weeks) | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 15.1.2 Treatment‐related pain (24 weeks) | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 15.1.3 Hyperpigmentation (24 weeks) | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 15.1.4 Depigmentation (24 weeks) | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 15.1.5 Purpura (24 weeks) | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 15.1.6 Total (24 weeks) | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 15.2 Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain (change from baseline) (12 weeks) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 15.2.1 Height (12 weeks) | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 15.2.2 Vascularity (12 weeks) | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 15.2.3 Pliability (12 weeks) | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 15.2.4 Pigmentation (12 weeks) | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 15.3 Scar size, colour, height, length, width and pliability, skin surface texture, pruritus and pain (change from baseline) (24 weeks) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 15.3.1 Height (24 weeks) | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 15.3.2 Vascularity (24 weeks) | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 15.3.3 Pliability (24 weeks) | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 15.3.4 Pigmentation (24 weeks) | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
