Dexamethasone cyclophosphamide pulse therapy in pemphigus: experience in Kashmir valley

Introduction

The standard treatment of pemphigus comprises of systemic steroids and other immunosuppressive agents. Pulse treatment with cyclophosphamide and dexamethasone has been tried in many centers all around the globe. The results that have been obtained from different centers have been variable.[1],[2],[3] We have been treating our patients of pemphigus with the standard Dexamethasone Cyclophosphamide Pulse (DCP) therapy over the last three years. The experiences we have gained in this regard are being shared in this paper.

Materials and Methods

Thirty patients of pemphigus admitted to the hospital between October 1998 and August 2001 were enrolled for the study. The diagnosis of pemphigus was made on the basis of clinical criteria, Tzanck smear and direct immunofluore-scence examination [DIF]. Laboratory evaluation at the time of enrollment included a complete hemogram, ESR estimation, urine examination, kidney function tests, stool for occult blood, X-ray of the chest and an electrocardiograph. The investigations were repeated prior to each pulse treatment and during follow up also. The patients were monitored for improvement in their disease and also for hypertension, weight gain, secondary amenorrhoea, hair loss, urinary symptoms, acid peptic disease, cataract formation and other adverse effects of DCP therapy.

The treatment schedule was divided into four phases as in the original study. In the first phase the patients received monthly doses of 100mg of dexamethasone dissolved in 500m1 of dextrose by slow intravenous drip over 2 hours on three consecutive days along with 500mg of cyclophosphamide in the same infusion on Day 1. In between these monthly pulses the patients received 50mg of oral cyclophosphamide daily. Systemic steroids were usually not given in he intervening period unless the patient had troublesome recurrence of lesions. The recurrences, if present were however mild and did not require more than 30-40mg of prednisolone daily in addition to the oral cyclophosphamide dose. After achieving remission the patients passed on the next phase (phase 2). In this phase the monthly pulse of cyclophosphamide and dexamethasone were continued along with the daily oral Cyclophomide dose for a minimum of six months or until a negative DIF result. After this (phase 3) the monthly pulses were stopped but the patient continued to receive 50mg of oral cyclophosmide daily for another six months. In phase 4 this treatment was also withdrawn and the patients were lust followed up for any adverse effects and relapses.

Results

All the thirty patients who were enrolled for the study were suffering from pemphigus vulgaris. The age of the patients ranged from a minimum of 65 years to a maximum of 17 years with a mean of 32+ 3.0 years. The sex distribution was 13 males and 17 females [Figure - 1].

The duration of disease prior to starting the pulse therapy varied from a maximum of 8 days to a maximum of 6 years {mean =4.5 months} [Table - 1]. Only seven patients had been on oral steroids prior to the pulse therapy while the rest of 23 patients received DCP pulse as their first therapy.

Of our 30 patients, one patient had died while on the pulse treatment. The patient, aged 65 years was also suffering from typel diabetes mellitus and died of complications secondary to this disease. The maximum duration of continuous remission in these patients was 20 months after the end of primary treatment. Two patients are still receiving a maintenance dose of cyclophosphamide [phase 31. In 8 patients the remission is recent only (phase 2) while 7 patients are still in phase 1 [Figure - 2].

The commonest side effect observed was an increased susceptibility to infection, both bacterial and candidal, in three patients. The infections, however responded to conventional antibacterial and anticandidal treatments. The other side effects encountered were weight gain (in 2 patients), reactivation of pulmonary tuberculosis (in 1 patient), secondary amenorrhoea (in three patients) and precipitation of diabetes in one patient [Table - 2]

Discussion

Pemphigus is the commonest autoimmune bullous dermatosis found in Indian subcontinent[1]. The mainstay of treatment of the disease is systemic steroids and other immunosuppressive therapies. It has been claimed that a definitive and potent immunosuppressive therapy started at the initial stages of the disease can lead to a compete remission in such patients.[4] Dexamethasone cyclophosphamide pulse therapy has been tried in Pemphigus in India and abroad with variable results. Complete remission in this -disease has been reported with DCP therapy b) Posricha et al in their original paper′ and in their subsequent papers as well.[5] Other investigator; like Surinder and Kanwar have reported almost similar results in 1990.[2] In addition to causing a complete remission the therapy also reportedly leads to a significant decrease in the mortality rate associated with the disease.[1],[2] Another important advantage that has been reported with DCF therapy is a remarkable freedom from the side effect so commonly seen with long-term steroic therapy and other immunosuppressive agents.[1],[2],[3]

In our patient we have followed the pattern of treatment as has been given in the original studies by Pasricha et al in 1988 and by Surinder and Kanwar in 1990.The overall result that we have achieved have been quite encouraging and even better as compared to those reported in the above- mentioned studies. All of our patients have shown a remarkable response to DCP therapy irrespective of their disease severity and extent. Two of our patients had very severe and extensive disease with involvement of> 60--70% of their body surface area and both of them are now in complete remission and off all treatment. We are yet to see a patient not responding satisfactorily to the pulse treatment and the side effects observed with the treatment have been really negligible.