Definition
Localized morphea is a skin disorder of unknown cause. It is a chronic condition that presents as hardened areas of skin. At first the inflamed areas of the skin become faintly purple, then lose their colour, especially in the central area, and appear as thickened, waxy, ivory coloured areas, surrounded by a lilac‐coloured edge (Rowell 1992). Morphea can present in several different forms. One classification describes five forms: plaque, generalized, bullous, linear and deep. Plaque morphea is usually a round or oval lesion larger than one centimetre in diameter. Generalized morphea is the confluence of plaque morphea to involve more than two areas of the body. Bullous morphea presents with blisters over the area of hardening; linear morphea presents in a linear streak of hardening. It can be deeper and involve the underlying muscle or bone. When it happens on the face it can look like a scar from a sword and thus carries the name "en coup de sabre"; when it leads to loss of tissues on the face it carries the name "Parry‐Romberg syndrome." Deep morphea involves the structures under the skin, but does not occur in a linear pattern (Peterson 1995).

Epidemiology
In a study of the epidemiology of patients in Olmsted County, Minnesota, from 1960‐1993, the number of annual age and sex‐adjusted new cases was 0.3 per million population. Over the course of the study the rate increased by an average of 3.6% per year (Peterson 1997). The number of overall cases in the West Midlands, UK for the year ending May 31 1986, was 2 per million for adult men and 4.7 per million for adult women (Silman 1988). Studies have reported a female predominance with a 3:1 to 3:2 female to male ratio (Falanga 1986; Peterson 1997; Uziel 1994). It can affect all ages. The mean onset of disease in a group of 30 children studied was 7.9 years of age (Uziel 1994), the mean age at diagnosis in the Olmsted group was 33 years of age (Peterson 1997).

Causes
The cause of morphea is not well understood. Injury to the skin (Yamanaka 1999) and damage to the nerves (Littman 1989) have been proposed as the precipitating factors in individual cases. Though there have been several reports that cite an infectious agent called Borrelia burgdorferi as a possible causative agent for morphea (Fujiwara 1997; Ozkan 2000), there have been conflicting reports in the United States and elsewhere. Another skin condition with a similar appearance to morphea called acrodermatitis chronica atrophicans has been shown to be caused by a similar infectious agent called Borrelia afzelii, although this form of Borrelia is not widespread in the US, where Borrelia burgdorferipredominates (Wienecke 1994).

People with morphea have an increased incidence of autoimmune disorders such as hypothyroidism and diabetes, as do their relatives. This may suggest an immunologic basis for the disease (Harrington 1989).

Impact
The condition is generally self‐limiting, with a normal course of about two to six years, though recurrences are possible and disease can remain active for over 20 years. Darkening or lightening of the skin, and wasting of the skin and muscle can lead to considerable cosmetic, functional and psychological problems. Patients can present with joint aches, carpal tunnel syndrome, limb wasting, and growth failure of an extremity. Reduced joint movement or fixing of the joint due to stiffening of the skin and muscles around the joint has been reported in 19 to 56% of linear lesions involving the trunk and limbs, occasionally requiring surgery or even amputation (Falanga 1986; Peterson 1995).

Treatment
There are reports of numerous treatments for morphea, which can be divided into systemic agents i.e. taken by mouth or by injection, agents applied directly to the skin and phototherapy.

Systemic agents include D‐penicillamine (Falanga 1990), oral corticosteroids (Joly 1994) oral calcitriol (Hulshof 1994; Humbert 1990; Humbert 1995), sulphasalazine (Taveira 1999) and combinations of methotrexate and corticosteroids (Uziel 2000).

Systemic agents occasionally have serious side effects. D‐penicillamine can cause bone marrow suppression, allergic reactions, nephrotic syndrome and autoimmune disorders. Corticosteroids can contribute to elevated blood sugar, high blood pressure, heart failure, growth impairment, osteoporosis, and cataracts among other side effects. Oral calcitriol can cause elevated levels of calcium in the blood (hypercalcaemia). Sulphasalazine can cause reduced white blood cell levels (agranulocytosis) (Wolverton 2001).

Agents applied directly to the skin include the topical Vitamin D analogs, calcitriol (Koeger 1999) and calcipotriene (Cunningham 1998). Their possible side effects include hypercalcaemia, irritation, sensitivity to light and contact dermatitis. Topical corticosteroids have also been suggested (Rowell 1992), and their side effects include the ones listed for systemic corticosteroids as well as skin atrophy, stretch marks, dermatitis, facial hair, perioral dermatitis, acne, and increased susceptibility to infections (Wolverton 2001). Other agents such as interferon gammas can be injected directly into areas of morphea (Hunzelmann 1997).

Phototherapy is the use of light to treat the skin. There are several different types of light therapy using different wavelengths such as ultraviolet type A (UVA) or type B (UVB). In addition, certain medications called psoralens make patients more sensitive to the effects of light and can be used in combination with phototherapy. Phototherapeutic treatments that have been used for morphea include psoralen and UVA (PUVA) (Grundmann‐Kollma2000), calcipotriol and low‐dose UVA1 (Kreuter 2001), low‐dose UVA1 (Kerscher 1998), medium‐dose UVA1 (Camacho 2001), high‐dose UVA1 (Stege 1998), topical photodynamic therapy with 5‐aminolevulinic acid (Karrer 2000), and 585 nm pulsed dye laser (Eisen 2002). Short term use of phototherapy can result in itching, loss of nails, blistering of skin, increased hair, stomach upset, breathing problems, and recurrences of herpes simplex. Long‐term adverse effects include photoaging of the skin and an increased risk of skin cancers (Wolverton 2001).

If there is involvement of the joints, physical therapy including heat treatment and massage is indicated to maintain adequate joint motion (Falanga 1986). Associated joint problems may require surgical intervention.

One of the difficulties in studying interventions for morphea is the lack of a standardized method to measure improvement. Recent studies have suggested the use of ultrasound to quantify improvement based on degree of thickness of the skin (Hoffmann 1991; Mohrenschlager 1999).

Rational for doing a review
While morphea tends to be a self‐limiting disease it can have severe complications as outlined above. As evidenced by the long list of treatments tried, there is still widespread debate regarding which agents should be used for the treatment of this disease and at what stage systemic agents should be tried. One of the major issues is to establish which of the potentially toxic interventions are effective, so as to avoid doing harm to people with morphea. This review will examine the evidence available regarding the efficacy of interventions for morphea, to help evaluate the risks and possible benefits of treatment.