Treatment of pemphigus vulgaris and bullous pemphigoid with mycophenolate mofetil monotherapy.
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Biomedical subjects
Publications and source records attributed to M Kerscher.
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Disabling pansclerotic morphea of childhood is the most severe variant of localized scleroderma. It is characterized by rapid progression of deep cutaneous fibrosis expanding over large areas of body surface. The prognosis in terms of normal life activity is poor and the disease may even take a fatal course. Presented is a case with extremely severe and rapidly progressive lesions resulting in cutaneous ulcerations joint contractures, and multilaing deformities of the extremities. Histopathological analysis revealed extensive intravascular calcinosis of the small vessels, which may be an important factor in the pathogenesis of this poorly understood disease. UVA1-phototherapy was performed and induced a softening of sclerosis and a distinct decrease of skin thickness. Based on these observations UVA1-phototherapy may be promising in the treatment of extensive sclerotic disease of this kind, and possibly other diseases accompanied by excessive sclerosis.
BACKGROUND: Mycophenolate mofetil (MMF), an ester of mycophenolic acid (MPA), was approved by the Food and Drug Administration in 1995 and is currently primarily indicated for the prophylaxis of rejection in renal transplant patients. The drug seems also to be of value in the treatment of psoriasis and rheumatic arthritis. Recently there have been 6 reported cases of successful treatment of blistering autoimmune diseases with MMF in combination with high dose prednisone therapy. OBJECTIVE: On the basis of these reports we administered this new treatment regimen to several patients with blistering autoimmune diseases. Besides using a combination of MMF and high-dose prednisone we wanted to evaluate whether MMF monotherapy is also effective in the treatment of blistering autoimmune diseases. METHODS: We administered MMF to 5 patients who had severe pemphigus vulgaris or bullous pemphigoid. Two patients received MMF in combination with high-dose prednisone therapy and 3 patients received MMF monotherapy. To our knowledge, this is the first report of successful treatment of pemphigus vulgaris and bullous pemphigoid with MMF monotherapy. RESULTS: All patients were completely free of symptoms within 8 to 11 weeks of therapy. Patients who had received MMF monotherapy responded as well to treatment as those who received a combination of MMF and high-dose prednisone. CONCLUSION: Our experiences strongly suggest that MMF monotherapy may be effective for patients even with severe pemphigus vulgaris and bullous pemphigoid. In addition, MMF monotherapy, at least over the short term, offers the advantage of fewer side effects in comparison to immunosuppressive combination therapy and was well tolerated by our patients.
Management of atopic dermatitis has been less than satisfactory. Conventional therapy has not been particularly successful, and prolonged use of topical corticosteroids and systemic immunosuppressant drugs (eg, corticosteroids, cyclosporine, azathioprine) can result in severe cutaneous and systemic effects. We decided to evaluate the effect of UVB at 311 nm to treat 5 patients with moderate to severe atopic dermatitis. In each patient a mean cumulative dose of 9.2 J/cm2 was applied over a mean of 19 irradiations. Narrow-band UVB notably reduced atopic dermatitis after 3 weeks in all patients.
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PUVA-bath therapy has proven to avoid many side effects associated with oral 8-methoxypsoralen (8-MOP) treatment. In order to investigate the effectiveness of topical PUVA-bath therapy (PUVA-soak therapy) on chronic palmoplantar dermatoses, 30 patients with plaque-type psoriasis, pustular psoriasis, endogenous eczema, dyshidrotic eczema and hyperkeratotic dermatitis of the palms and soles were treated over 8 weeks with PUVA-soak using 8-MOP. No additional treatment except skin moisturising cream such as unguentum emulsificans aquosum was used during the study period. The single UVA-doses applied ranged from 0.3 to 3.0 J/cm2 (mean single dose of 1.8 J/cm2), with a mean cumulative dose of 48.6 J/cm2 per patient. Altogether 26 of 30 patients responded well within 8 weeks of treatment with 63% of all patients showing a complete remission and 23% showing considerable improvement, as shown by flattening of plaques, decreased scaling and erythema, as well as decreased vesicle and pustule formation. The condition responding best to our therapy was palmoplantar psoriasis followed by atopic eczema. Hyperkeratotic dermatitis displayed the poorest responding rates in this study. Unwanted side effects such as erythema, pain, blistering or patchy hyperpigmentation were not observed in any of the patients. We conclude that PUVA-soak therapy can be highly efficient in the treatment of palmoplantar dermatoses, especially in the management of palmoplantar psoriasis.
PUVA-bath therapy developed into a first line topical PUVA therapy, and gel and cream preparations have been described as alternative modes of topical 8-MOP application. Because bath-PUVA can be difficult to manage, topical PUVA therapy using 8-MOP gel or cream preparations may become an important alternative when treating localised skin diseases. However, controlled comparisons of efficacy with this alternative topical PUVA therapy are lacking. We therefore compared the efficacy of PUVA-cream therapy with PUVA-bath therapy in 12 patients with recalcitrant dermatoses of the palms and soles using a left/right trial design. These patients responded well to both treatment modalities, meaning that both could be used successfully to treat recalcitrant dermatoses of the palms and soles.
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Although the association between administration of the antitumor agent bleomycin and the development of cutaneous fibrosis is established, there are only a small number of cases of bleomycin-induced scleroderma described in the literature. We report the development of generalised scleroderma with wide spread hyperpigmentation in a 52-year-old male patient, who received a total dose of 360 mg bleomycin in combination with cisplatin and etoposid for therapy of a malignant testicular seminoma. The clinical cutaneous alterations as well as the histological findings were indistinguishable from those encountered in progressive systemic sclerosis (PSS). In contrast to PSS however, Raynaud's phenomenon, cutaneous calcinosis, teleangiectasia, arthritis and involvement of additional organs were all absent. PSS-typical auto-antibodies were negative. Even 18 months after discontinuation of the drug and treatment with UVA1 phototherapy (3-4 times per week with 20 J/cm2) as well as physiotherapy, the skin changes had still not resolved. Based on our case and a detailed review of the literature, we discuss characteristics of bleomycin-induced scleroderma including pathogenesis, treatment modalities and course.
BACKGROUND: Bath-PUVA is used to treat a variety of dermatoses. However, the kinetics of 8-methoxypsoralen during treatment are not completely clarified. OBJECTIVE: The purpose of this study was to investigate the intensity of the phototoxic response and the persistence of phototoxicity after bath-PUVA. METHODS: Twelve volunteers were exposed to UVA doses ranging from 0.5 to 40 J/cm2 from 10 to 240 minutes after bath-PUVA treatment. The resulting phototoxic response of the skin was determined. RESULTS: Irradiation 10 minutes after the psoralen bath led to the lowest assessed minimal phototoxic dose (MPD) of 1.42 J/cm2 (mean, SD +/- 0.29). Thereafter, the MPD increased significantly and sharply every hour. At 4 hours after the psoralen bath, UVA doses up to 40 J/cm2 failed to induce any phototoxic erythema (MPD). CONCLUSION: For optimal effects, UVA irradiation has to be administered immediately after the psoralen bath; no restrictive behavior is necessary after bath-PUVA treatment.
BACKGROUND: For treatment of localized scleroderma numerous treatments, including ones with potentially hazardous side effects, are currently used with only limited success. OBJECTIVE: We attempted to determine the efficacy of low-dose UVA1 irradiation in patients with severe localized scleroderma. METHODS: Patients were irradiated with 20 J/cm2 UVA1 for 12 weeks (total number of treatments: 30; cumulative UVA1 dose: 600 J/cm2). RESULTS: Low-dose UVA1 irradiation induced significant clinical improvement (clearance of > 80% of lesions) in 18 of 20 patients. Clearance was documented by clinical score as well as by 20 MHz ultrasound and histopathologic analysis. CONCLUSION: Low-dose UVA1 phototherapy can be highly effective for sclerotic plaques, even in patients with advanced localized scleroderma and with lesions rapidly evolving despite conventional therapy.
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Twelve patients with extensive lichen planus, resistant to different regimes of prior external and internal therapy, were treated with PUVA-bath photochemotherapy (psoralen bath followed by UVA irradiation) using bath water containing 0.5 mg/L of 8-methoxypsoralen (8-MOP). In 11 of the 12 patients, the skin lesions showed a significant improvement or even complete remission within six weeks of treatment. In one patient, only limited clinical improvement could be achieved. A mean of 19.1 (SD +/- 3.6) PUVA-bath treatments were carried out. The mean cumulative UVA-dose given until clearance of the lichen planus was 16.7 (SD +/- 4.8) J/cm2. No side effects were seen except an increased phototoxic reaction in two patients manifested as slight erythema. The results of this trial show, that PUVA-bath photochemotherapy with 8-MOP is an effective therapeutic alternative to all other known therapies in the treatment of extensive, exanthematic and also hypertrophic-hyperkeratotic lichen planus. In comparison to oral PUVA therapy and PUVA-bath therapy using 4,s',8-trimethoxypsoralen, balneophotochemotherapy with 8-MOP shows an excellent efficiency-side effect correlation. The clearance of the refractive skin lesions by balneophotochemotherapy with 8-MOP demonstrates the superiority of this therapy over all other common therapeutic modalities used for lichen planus.
A 66-year-old woman with longstanding lichen sclerosus et atrophicus improved strikingly with PUVA bath photochemotherapy over a period of 6 weeks. The cumulative UVA dose was 31.7 J/cm2; the single UVA dose ranged from 0.3 to 2.3 J/cm2. After 16 treatment sessions, the sclerotic lesions had softened greatly, while after 24 treatments, the skin lesions were almost completely cleared and pruritus was diminished. Histopathological analysis of biopsy specimens from previously affected sites as well as 20 MHz ultrasound examinations showed almost no residual sclerosis. Although long-term results are not yet available, PUVA bath photochemotherapy seems to be a promising and effective new treatment modality without systemic side effects for patients with disseminated lichen sclerosus et atrophicus.