Mycophenolate mofetil and cyclosporin treatment for recalcitrant pyoderma gangrenosum

Abstract

A 68-year-old woman with an uneventful medical history developed painful ulcers on both shins over a period of 6 months. She had large, inflamed, shallow, pretibial ulcers on both legs with a violaceous, partly bullous, and necrotic, undermined border. Diagnosis of pyoderma gangrenosum (PD) was confirmed by a biopsy specimen, which showed massive inflammatory-cell infiltration, thrombosis of dermal vessels, and leucocytoclastic vasculitis. Except for mild hyperthyroidism, no disease usually associated with PD was found. Treatment was begun with oral steroids (120 then 80 mg methylprednisolone per day) and clofazimine (200 mg/day). After 2 weeks, due to disease progression, cyclosporin was added (250 mg/day) but had to be discontinued as severe hypertension developed. Steroids were raised to 120 mg/day and cyclophosphamide therapy was started (500 mg intravenously on day 1, 50 mg by mouth on days 2–7). The lesions responded well at first, but recurrence developed after discontinuation of cyclophosphamide due to severe neutropenia. Over the next few months, the ulcers grew continuously despite treatment with high-dose intravenous immunoglobulins, dapsone, several cycles of high-dose intravenous steroids, and thalidomide 200 mg daily, each treatment having been given over several weeks. The ulcers now involved muscles and tendons of both shins. Reintroduction of cyclosporin (250 mg by mouth, this time tolerated with only mild hypertension) also had no effect. The patient was fed intravenously. The ulcers had to be debrided three times under general anaesthesia, requiring the excision of both Achilles tendons and parts of extensor muscles and tendons due to progressive necrosis. After 10 months of unsuccessful treatment, we decided to start mycophenolate mofetil (MM) 2 g/day by mouth in addition to cyclosporin and intravenous steroids. Autologous thrombocytic factors (platelet derived wound healing factors [PDWHF] Curative Technologies GmbH, Moers, Germany) were applied topically. After 14 days, the ulcers had stable borders. Healing continued until, 7 weeks after the introduction of MM, a split-thickness, meshed skin graft could be done. Healing was complete after another 4 weeks and has been now for a further 8 weeks without corticosteroids and with a reduced dose of 100 mg cyclosporin and 1 g/day MM, the latter tolerated without any side-effects. MM is effective in the prevention of renal transplant rejection. As a potent, non-competitive inhibitor of inosinmonophosphate-dehydrogenase, it influences the function of lymphocytes via the inhibition of purine synthesis. Its sideeffects are mostly restricted to mild gastrointestinal symptoms. Some evidence exists that it may also be effective in rheumatoid arthritis, psoriasis, and bullous pemphigoid. In our case, the first stable response after 10 months occurred after introduction of MM in addition to cyclosporin. Because cyclosporin monotherapy had been unsuccessful in this patient, we believe that the combination of MM and cyclosporin was the effective treatment, although application of PDWHF may have helped.