Marcella Grundmann-Kollmann

Mycophenolate mofetil: A new therapeutic option in the treatment of blistering autoimmune diseases

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.

Combination phototherapy of psoriasis with narrow-band UVB irradiation and topical tazarotene gel ☆

BACKGROUND Narrow-band UVB (311 nm) phototherapy offering an emission spectrum closely conforming to the peak of the action spectrum for clearing psoriasis has significantly improved phototherapy for psoriasis. Because the majority of the commonly used topical therapies in treatment of psoriasis have limitations, a need for new topical agents remains. Tazarotene has been shown to be efficacious in plaque-type psoriasis. Combination of narrow-band UVB with topical agents has been shown to enhance efficacy of both treatment modalities. OBJECTIVE We attempted to evaluate the efficacy of narrow-band UVB phototherapy in combination with topical tazarotene. METHODS Ten patients with stable plaque psoriasis were treated with narrow-band UVB. In addition, topical tazarotene 0.05% was applied once daily to one side of the body. The follow-up period was 4 weeks. Efficacy was assessed separately for both body halves by means of a modified Psoriasis Area and Severity Index (PASI). RESULTS Both treatment modalities notably reduced the PASI scores with values being significantly lower in skin areas treated with narrow-band UVB phototherapy in combination with topical tazarotene. CONCLUSION The addition of tazarotene to narrow-band UVB phototherapy promotes more effective, faster clearing of psoriasis compared with UVB (311 nm) monotherapy.

Phototherapy for atopic eczema with narrow-band UVB ☆ ☆☆

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.

Narrowband UV-B phototherapy in the treatment of cutaneous graft versus host disease.

Graft versus host disease (GVHD) is an important problem following allogenic bone marrow transplantation (BMT). The beneficial effects of photochemotherapy with psoralens plus UVA irradiation (PUVA) have been described repeatedly; however, PUVA is limited by a wide range of unwanted effects. A novel improved form of UV-B phototherapy, narrowband UV-B, has been proven to be very effective in T-cell mediated dermatoses. Therefore, we investigated the effect of narrowband UV-B phototherapy (5 times per week) in 10 patients with cutaneous GVHD (grade 2-3) resistant to standard immunosuppressive drugs. It was tolerated well by all patients, and no side effects were observed. Skin lesions showed complete clearance in 7 out of 10 patients within 3 to 5 weeks. 3 patients showed significant improvement of GVHD. We suggest that narrowband UV-B phototherapy is a nonaggressive treatment that may benefit patients with cutaneous GVHD who already take high doses of immunosuppressive drugs.

Chronic sclerodermic graft-versus-host disease refractory to immunosuppressive treatment responds to UVA1 phototherapy☆☆☆

Graft-versus-host disease is a frequent complication of allogenic bone marrow transplantation. Approximately 10% of patients suffering from chronic graft-versus-host disease develop sclerodermic graft-versus-host disease of the skin, which often does not respond to conventional immunosuppressive therapy. An alternative to immunosuppressive treatment is photochemotherapy. We describe a patient with chronic sclerodermic graft-versus-host disease who did not respond to a combination therapy of cyclosporine and prednisone and later mycophenolate mofetil plus prednisone. A combination therapy of mycophenolate mofetil (2 g/day) and low-dose UVA(1) therapy (single dose, 20 J/cm(2), 4 times per week over 6 weeks) resulted in striking clinical improvement of sclerodermic graft-versus-host disease.

Treatment of severe recalcitrant dermatoses of the palms and soles with PUVA-bath versus PUVA-cream therapy

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.

Narrowband UVB and cream psoralen-UVA combination therapy for plaque-type psoriasis

BACKGROUND Psoralen-UVA (PUVA) and narrowband UVB (311-nm) therapy are considered to be first-line phototherapies for patients with moderate to severe psoriasis. To reduce side effects as a result of systemic resorption of psoralens, topical PUVA therapies have been developed and proven to be effective in the treatment of psoriasis. OBJECTIVE We sought to evaluate the combination therapy of narrowband UVB plus cream PUVA on selected psoriatic plaques compared with narrowband UVB or cream PUVA alone. METHODS A total of 30 patients (Psoriasis Area and Severity Index score of 8-15) were included in the randomized study. The combination therapy consisting of narrowband UVB whole-body irradiation followed by cream PUVA therapy for selected psoriatic plaques was evaluated in 10 patients with chronic plaque-stage psoriasis. For comparison, the therapeutic efficacy, number of treatments, and cumulative UV doses until remission (Psoriasis Area and Severity Index score < 4) of cream PUVA therapy or narrowband UVB alone was determined in 10 patients, respectively. RESULTS Both monotherapies induced clearance of psoriatic lesions in all patients within 5 to 7 weeks. Mean number of treatments for cream PUVA was 24 +/- 5; for narrowband UVB was 21 +/- 3. The mean cumulative UVA dose was 45.0 +/- 16.3 J/cm(2) and the mean cumulative UVB dose was 17.1 +/- 4.1 J/cm(2). Combination therapy resulted in complete clearance of lesions in all patients after 3 to 4 weeks. Mean number of treatment was 14 +/- 2, mean cumulative UVA dose was 18.7 +/- 4.7 J/cm(2), and mean cumulative UVB dose was 8.2 +/- 3.3 J/cm(2). The number of treatments (P <.001, analysis of variance), UVA dose (P <.001, t test), and UVB dose (P <.001, t test) were significantly reduced compared with both monotherapies. CONCLUSIONS Our results indicate that a combination therapy of narrowband UVB plus cream PUVA appears to have a significantly higher efficacy compared with either monotherapy. The cumulative UV doses were significantly lower in the combination therapy. We conclude that cream PUVA can be used in addition to narrowband UVB for areas that tend to clear less quickly than the rest of the body.

Time course of 8-methoxypsoralen concentrations in skin and plasma after topical (bath and cream) and oral administration of 8-methoxypsoralen

The combination of 8‐methoxypsoralen with ultraviolet A exposure (PUVA therapy) is a standard treatment for a variety of dermatoses. The following three variants have been described: oral, bath, or cream PUVA. To achieve optimal therapeutic effects, ultraviolet A irradiation should be performed at the time of maximum photosensitivity, that is, at the time of maximum 8‐methoxypsoralen tissue concentrations.

Mycophenolate mofetil monotherapy for pemphigus vulgaris

Sir, Treatment of autoimmune blistering diseases remains difficult due to the potential side-effects of conventional immunosuppressive drugs and new therapeutic options with an improved benefit/risk ratio are desirable. In dermatology, successful treatment of pemphigus vulgaris and pemphigoid has been reported with mycophenolate mofetil in combination with highdose prednisone. We report a 78-year-old male Caucasian patient with severe pemphigus vulgaris and diabetes mellitus who was treated with mycophenolate mofetil monotherapy. A 78-year-old man had suffered from pemphigus vulgaris since 1995. Autoantibodies against 130 kDa pemphigus antigen were confirmed by Western immunoblotting of serum. The patient had received high-dose prednisone monotherapy (1 mg/kg body weight) and a combination of azathioprine (1 ́5 mg/kg body weight) and prednisone (0 ́5 mg/kg body weight). While having high-dose prednisone therapy he developed severe diabetes, requiring reduction of the prednisone dose. During combination therapy of azathioprine and a reduced dose of prednisone he developed thrombocytopenia. Owing to diabetic nephrosclerosis with hypertension, cyclosporin A was contraindicated. We therefore decided to start mycophenolate mofetil (MMF) monotherapy, at a dose of 1 g twice daily. No new blisters and erosions occurred after 2 weeks and the patient cleared completely after 6 weeks. Mycophenolate mofetil was tolerated without any side-effects for the complete follow-up period. The patient is still free of symptoms. As MMF inhibits the de novo pathway of purine synthesis that is used by lymphocytes it seems to be more specific for B and T lymphocytes than azathioprine. Therefore, it might have a higher immunosuppressive activity than azathioprine with fewer unwanted effects. The most common reported side-effect of mycophenolate mofetil is gastrointestinal disturbance followed by reversible, dose-related haematological effects. Very few cases of lymphoproliferative disorders have been reported. The drug does not produce clinically significant nephrotoxicity or liver damage, therefore it may be of value for patients who cannot take cyclosporin A or methotrexate because of diabetic nephrosclerosis with hypertension or thrombocytopenia. We describe a case of mycophenolate mofetil monotherapy in pemphigus vulgaris. This therapy was tolerated very well by our patient. Compared with the reports of BoÈhm et al. and Enk et al. we found mycophenolate mofetil monotherapy for our patient as effective as the reported combination therapy with mycophenolate mofetil and glucocorticosteroids. This observation warrants randomized clinical trials comparing the efficacy of MMF monotherapy with a combination therapy of MMF and glucocorticosteroids, and conventional immunosuppressive treatment for patients with pemphigus vulgaris.

Cream PUVA therapy for scleredema adultorum.

q 2000 British Association of Dermatologists, British Journal of Dermatology, 142, 1047±1070 withdrawn. Rebound phenomena during or following CyA withdrawal are probably under reported and may be seen more frequently with intermittent than continuous CyA therapy. As the use of short-course CyA is becoming very popular in the treatment of psoriasis, dermatologists should be aware that even small dose reductions may precipitate the development of GPP.