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Cochrane Database of Systematic Reviews Protocol - Intervention

Genetic testing for prevention of severe drug‐induced skin rash

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Flowchart of interventions (genetic testing) and outcomes (skin rash) in a patient population prescribed drug X
Figures and Tables -
Figure 1

Flowchart of interventions (genetic testing) and outcomes (skin rash) in a patient population prescribed drug X

Table 1. Glossary of terms

Term

Explanation

Allele

One of two or more alternative forms of a gene at corresponding sites (loci) on homologous chromosomes

Hardy‐Weinberg equilibrium

This states that allele and genotype frequencies in a population will remain constant from generation to generation in the absence of other evolutionary influences

HLA

Human leukocyte antigen: a group of protein molecules located on bone marrow and other cells that can provoke an immune response

Hypersensitivity

A state of altered reactivity in which the body reacts with an exaggerated immune response to a foreign substance, such as a drug

Polymorphic

A variation in the DNA that is too common to be due merely to new mutation. A polymorphism must have a frequency of at least 1% in a population

Maculopapular rash

A rash with both macules (flat and coloured like a freckle) and papules (a small raised spot)

Figures and Tables -
Table 1. Glossary of terms
Table 2. Associations between drug‐induced skin injury and genetic variants in the HLA genes

Drugs associated with skin injury

Class of drug

HLA allele

Population

Reference

Stevens‐Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)

Allopurinol

Antiuric acid

B*5801

Han Chinese

Hung 2005

Thai

Tassaneeyakul 2009a

Japanese

Kaniwa 2008

Malay

Ding 2010

Carbamazepine

Antiepileptic

B*1502

Han Chinese

Cheung 2013; Chung 2004; Chong 2013; Hung 2006; Man 2007

Thai

Kulkantrakorn 2012; Locharernkul 2008; Tassaneeyakul 2010; Tangamornsuksan 2013

Malay

Ding 2010

Indian

Mehta 2009

A*3101

White

Amstutz 2013; McCormack 2011;

A*3101

Japanese

Ozeki 2011

Phenytoin

Antiepileptic

B*1502

Han Chinese

Hung 2010; Man 2007

Thai

Locharernkul 2008;

Oxicam

Non‐steroidal anti‐inflammatory drug (NSAID)

A2, B12

White

Roujeau 1987

Sulphamethoxazole

Antibiotic

A29, B12, DR7

White

Roujeau 1986

Hypersensitivity syndrome (DIHS or DRESS)

Abacavir

Antiretroviral

B*5701

White

Hetherington 2002; Hughes 2004; Mallal 2002; Mallal 2008; Martin 2004

African Americans

Hughes 2004a; Saag 2008

Aminopenicillins

Antibiotic

A2, Drw52

White

Romano 1998

Nevirapine

Antiretroviral

DRB1*01

White ‐ Australian

Martin 2005

DRB1*01

White ‐ French

Vitezica 2008

Cw8, B14

White ‐ Italian

Littera 2006

Cw8

Japanese

Gatanaga 2007

B*3505

Thai

Chantarangsu 2009

Cw4

Thai

Likanonsakul 2009

C*0404

Black African

Carr 2013

Cw*04

Chinese

Gao 2012

Aspirin

NSAIDS

DRB1*1302, DQB1*0609

Kim 2005; Palikhe 2008

NSAIDS

DR11

Quiralte 1999

Iodine contrast media

DR

White ‐ Spanish

Torres 2008

Paraphenylenediamine

Hair dye

DP

White ‐ German

Sieben 2002

Gold sodium thiomalate

Treatment of rheumatoid arthritis

DR5

White ‐ Spanish

Rodriguez‐Pérez 1994

Lamotrigine

Antiepileptic

B*5801, A*6801

White

Kazeem 2009

Trichloroethylene

Industrial solvent, dry cleaning

B*1301

Japanese

Li 2007; Watanabe 2010

Fixed drug eruptions

Co‐trimoxazole

Antibiotic

A30, B13, Cw6

White ‐ Turkish

Ozkaya‐Bayazit 2001

Feprazone

Analgesic

B22

Pellicano 1997

Figures and Tables -
Table 2. Associations between drug‐induced skin injury and genetic variants in the HLA genes