Autoimmune syndrome induced by adjuvants (ASIA) in the Middle East: morphea following silicone implantation.

Morphea and other scleroderma-like skin conditions are occasionally linked with exposure to chemical compounds such as silicone. We treated a 56-year-old woman with generalized severe skin induration accompanied with systemic symptoms and peripheral eosinophilia, which appeared 2.5 years after breast silicone implantation and abdominal liposuction. Blood test results and histopathological examination of her skin suggested the diagnosis of morphea overlapping with eosinophilic fasciitis. Her skin disease was presumed to be an autoimmune reaction to silicone implantation. While the removal of the implants did not improve her illness, treatment with 1 mg/kg prednisone and PUVA bath was initiated, with some improvement. This patient illustrates an example of ASIA (Autoimmune Syndrome Induced by Adjuvants), as her disease appeared following exposure to an adjuvant stimulus, with 'typical', although not well-defined, autoimmune manifestations.

Photochemotherapy for localized morphoea: effect on clinical and molecular markers.

BACKGROUND: Effective treatment options for morphoea remain limited. As a result, there has been increasing interest in the role of phototherapy in the management of this condition. Aims. We report the findings of a study in which 13 patients with localized morphoea were treated with oral (n = 11) and topical (n = 2) psoralen ultraviolet (PUVA) phototherapy. METHODS: The clinical effect on disease activity was assessed using a skin score adapted from the modified Rodnan score. The effect on serological and immunohistochemical markers was also measured. RESULTS: In total, 11/13 patients showed an improvement in their skin score after phototherapy, with the mean reduction in score being 62.9% (P = 0.003, Wilcoxon signed rank test). After treatment with PUVA, there was a fall in circulating levels of vascular cell adhesion molecule in 10/13 patients (P = 0.059) and a significant increase in tumour necrosis factor-alpha in 9 of 13 patients (P = 0.036). In the five patients in whom CD3 and CD4 was measured, all showed a reduction in CD3 (P = 0.025), with a fall in CD4 (P = 0.046) seen in four of the five patients. CONCLUSIONS: PUVA is associated with clinical improvement in patients with morphoea, as shown by significant improvement in the skin score. However, in one patient who had been simultaneously started on ciclosporin, this improvement could not be attributed to the phototherapy alone. Although the sample size was small, we also found that certain lymphocyte markers, adhesion molecules and cytokines are affected by this treatment, helping to further clarify the mechanism of action of PUVA treatment.

[Localized scleroderma (morphea)]. / Sclérodermies localisées ou morphées.

DEFINITION AND FREQUENCY: Localized scleroderma, also known as morphea, is a sclerotic condition limited to the skin. The specific clinical entity depends on the extent, linear disposition and depth of the lesions. Morphea is ten times more prevalent than systemic sclerosis, and its prognosis is generally good: superficial forms resolve within 3 years. NO SYSTEMIC INVOLVEMENT: In the absence of symptoms, examinations to detect systemic involvement are purposeless. Plaque morphea is the most frequent clinical presentation. Serious manifestations include extensive morphea that may involve the entire skin or linear forms, especially in children, where they may be severe, especially on the face. There are no immunological markers clearly associated with morphea and no causative agents have been implicated in its pathogenesis, although sclerodermiform dermatitis is reported to be associated with some drugs and toxic agents. TREATMENT: There is no consensual treatment for morphea. Treatment should be decided according to severity and extent of lesions. Limited lesions may be treated with local steroids such as class IV corticosteroids. Systemic treatment (methotrexate) should be discussed in extensive and linear forms when there is a risk of functional or esthetic complications.

Localized scleroderma.

PURPOSE OF REVIEW: Localized scleroderma, also known as morphoea, has a variety of clinical manifestations that can include systemic involvement. Early recognition, diagnosis and treatment may improve the long-term outcome. RECENT FINDINGS: A large multicentre study coordinated by the Pediatric Rheumatology European Society has yielded important information on the epidemiology and clinical manifestations of juvenile localized scleroderma, especially as it pertains to systemic manifestations. Previous results using methotrexate and corticosteroids have been confirmed. Studies on phototherapy have also demonstrated efficacy. A new immunomodulator, imiquimod, has shown promise in an initial case series. SUMMARY: Studies over the past year highlight the wide range of extracutaneous manifestations and different forms of localized scleroderma and suggest that treatment may be beneficial.

Ultraviolet A1-induced downregulation of human beta-defensins and interleukin-6 and interleukin-8 correlates with clinical improvement in localized scleroderma.

BACKGROUND: In previous studies, distinct immunological abnormalities have been reported in localized scleroderma (LS). Several pro-inflammatory cytokines have been demonstrated at increased levels in sera of patients with LS in parallel with disease activity. Human beta-defensins (hBDs) are peptides with antimicrobial activity, but have been also shown to be implicated in tissue injury, scarring and wound healing. hBD expression in LS, a condition resembling pathological scarring due to excessive stimulation of matrix synthesis and fibroblast activation, has so far not been investigated. Ultraviolet (UV) A1 phototherapy, the most recent advance in the treatment of LS, targets T-cell dermal inflammatory infiltrates via induction of various cytokines and soluble factors besides well-known effects on collagen metabolism. OBJECTIVES: We sought to investigate the effects of UVA1 on the expression and modulation of hBDs and several pro-inflammatory cytokines in LS. METHODS: UVA1 phototherapy was performed five times weekly for 8 weeks resulting in a total of 40 treatment sessions (single dose 20 J cm2, cumulative dose 800 J cm2). hBD-1, hBD-2 and hBD-3 mRNA as well as tumour necrosis factor-alpha, transforming growth factor-beta, interleukin (IL) -2, IL-4, IL-6 and IL-8 mRNA expression were determined by quantitative real-time reverse transcription-polymerase chain reaction in lesional and unaffected skin of patients with LS. RESULTS: Skin status markedly improved in all 14 patients, resulting in a significant reduction of the clinical score from baseline to the end of treatment. hBD-1, hBD-2 and hBD-3 mRNA levels were higher in lesional skin compared with unaffected skin and skin from healthy volunteers. Following UVA1 phototherapy, hBD-1 mRNA decreased in lesional, but not in unaffected skin. hBD-3 mRNA levels significantly decreased after UVA1 in lesional skin, whereas an increase of hBD-3 was observed in unaffected skin. IL-6 and IL-8 mRNA levels were significantly elevated in lesional skin and significantly decreased after UVA1 irradiation, whereas mRNA for both cytokines remained unchanged in irradiated unaffected skin. The decrease of hBD-1, hBD-3, IL-6 and IL-8 mRNA paralleled the extent of disease and response to UVA1 phototherapy. CONCLUSIONS: hBDs and IL-6 and IL-8, cytokines with pivotal importance in sclerotic skin diseases, are downregulated by UVA1 in the lesional skin of patients with LS. Their pathogenetic relevance with respect to clinical improvement needs further investigation.

[Extracorporeal photopheresis--treatment option in scleromyxedema?]. / Extrakorporale Photopherese--Therapieoption beim Skleromyxödem?

Scleromyxedema is an uncommon disease of unclear etiology. Therapy is difficult. Two patients with scleromyxedema were treated with extracorporeal photopheresis (ECP). The first patient has been treated unsuccessfully for 3 months with PUVA-bath-therapy and for one year with cyclophosphamide and prednisolone. Thus supplementary treatment with ECP was initiated, as the cyclophosphamide and prednisolone were gradually reduced. After 29 cycles of ECP, the skin lesions had almost disappeared and the associated myopathy also resolved. In the second patient initial monotherapy with ECP was started after PUVA-bath-therapy for 3 months did not show any effect. After temporary improvement with ECP every four weeks, the skin lesions relapsed, so oral cyclophosphamide was added. These two cases confirm the effect of ECP in scleromyxedema, but probably combination therapy is at least initially more successful.

Medium-dose UVA1 phototherapy in localized scleroderma and its effect in CD34-positive dendritic cells.

BACKGROUND: UVA1 radiation seems to be effective in morphea. CD34+ dendritic cells are significantly decreased in lesional skin of morphea patients. OBJECTIVE: We evaluated the therapeutic effectiveness of medium-dose UVA1 phototherapy in localized scleroderma and its effect in the number of dermal CD34+ dendritic cells in skin biopsy specimens of these patients. METHOD: Patients were irradiated with UVA1 (30 J/cm(2)) 30 times. Dermal CD34+ dendritic cells were counted before and after therapy. RESULTS: There was clinical improvement after UVA1 irradiation. Dermal CD34+ dendritic cells significantly increased after UVA1 irradiation. CONCLUSION: Medium-dose UVA1 therapy is effective in the treatment of localized morphea. Effectiveness is associated with an increase in the number of CD34+ dendritic cells in the dermis.

Localized and systemic scleroderma.

Scleroderma is a broad term encompassing both localized and systemic sclerosis. Localized scleroderma is a cutaneous limited fibrosis that manifests as plaque morphea, generalized morphea, linear scleroderma, and deep morphea. Systemic scleroderma (sclerosis) can manifest as either limited or diffuse disease. Limited systemic sclerosis is typically preceded by Raynaud's phenomenon, involves cutaneous sclerosis distal to the elbows, with gastrointestinal and pulmonary fibrosis, and anticentromere antibody positivity. Diffuse systemic scleroderma is characterized by simultaneous Raynaud's phenomenon, cutaneous skin involvement proximal to the elbow with gastrointestinal, pulmonary, renal and cardiac fibrosis, and positive serology for antitopoisomerase and anti-RNAP III antibodies. This article discusses the classification, epidemiology, pathogenesis, clinical manifestations, treatment, and prognosis of the scleroderma.

[The immune status of scleroderma patients undergoing electroacupuncture]. / Immunnyi status bol'nykh sklerodermiei pri élektroakupunkture.

Examinations of the immune status of 53 patients with local scleroderma (LS) have revealed changes in the cell-mediated (a deficit of T-lymphocyte population in the presence of an unchanged B-lymphocyte count) and humoral immunity (hyperproduction of the circulating immune complexes, of immunoglobulins A and M, the presence of antibodies to fixed lymphocytes). The patients have been treated by electroacupuncture according to an original method, effecting the points that stimulate suppressed immunity. 1-3 courses of treatment have yielded good results in 83% of the patients, mostly with the early stages of the disease. The treatment has been associated with a positive time course of a number of disturbed parameters of immune homeostasis; a correlation between the clinical and immunological efficacy of therapy has been noted.