A Study of Dexamethasone - Cyclophosphamide Pulse Therapy in Pemphigus Patients

INTRODUCTION : The term “Pulse Therapy” has been used for a system of administering drugs in which a very high dose of the drug is given over a very short period for getting a quick result, and then the drug is withdrawn completely till it is needed or used again. Pulse therapy (the big shot) defined as administration of large (supra pharmacological) dose of drugs in an intermittent manner, to enhance the therapeutic effects and to reduce the iatrogenic side effects of drugs. It is a relatively recent concept; this method has been observed to produce superior therapeutic results which cannot be produced by the conventional methods of giving daily dosages while the side effects of the drugs are reduced very significantly. The list of dermatological indications for pulse therapy is increasing day by day and now it includes pemphigus and other autoimmune bullous diseases, collagen vascular diseases like systemic lupus erythematosus, progressive systemic sclerosis, Dermatomyositis, allergic vasculitis, Pyoderma gangrenosum, Prurigo nodularis, generalized lichen planus, resistant alopecia universalis, sarcoidosis, psoriasis, Darrier’s disease, fast spreading vitiligo, airborne contact dermatitis. The auto immune vesiculo bullous diseases are a heterogenous group of diseases. They are classified on the basis of their clinical, histopathological and immuno pathological features. They can be broadly classified histopathologically into epidermal and sub-epidermal blistering dermatoses.Though these disorders are rare in general population, for a given patient the impact of the diseases on the quality of the life can be devastating. The severity is often variable and the course is unpredictable and may even be fatal. Pemphigus is the commonest autoimmune vesiculobullous disorder of the Indian subcontinent5. The main treatment for pemphigus lies in using corticosteroids and other similar drugs which do help the patient to recover from the disease but whenever an attempt is made to withdraw the drugs the disease tends to became active again. Long term use of these drugs lead to some serious side effects. The Dexamethasone cyclophosphamide pulse therapy pioneered by Dr.Pasricha et al. consists of giving dexamethasone and cyclophosphamide in a very large doses on three consecutive days and repeated at fixed 28 days interval. In this method these drugs are claimed to knock out the disease process so that the patient recovers completely while the side effects are very much reduced and almost insignificant6. It is claimed that there is almost no risk of a relapse or recurrence provided the treatment has been taken strictly as per the recommendations7. With the ever increasing use of DCP pulse therapy in dermatology there is an increasing necessity for studies to evaluate its efficacy and side effect profile, and this study is an attempt in that direction. AIM OF THE STUDY : This study of Dexamethasone Cyclophosphamide Pulse therapy in Pemphigus patients was undertaken 1. To find out the clinical efficacy of DCP therapy in Pemphigus patients. 2. To find out the various side effects of the regimen. MATERIALS AND METHODS : The material for this study was from the patients attending the skin OPD, Government Rajaji Hospital, Madurai Medical College, Madurai with pemphigus, during the period of June 2005 – June 2007. Inclusion Criteria: 1. Above 18 years of age 2. The patients with pemphigus vulgaris, pemphigus foliaceus, pemphigus erythematosus registered during the period from June 2005 –June 2007 and whose diagnosis was confirmed by Histopathological examination and Direct immunofluorescence. Exclusion Criteria : 1. Age below 18 years. 2. Uncontrolled diabetes mellitus/ Hypertension. However diabetic and hypertensive patients were included, if their disease was under control with appropriate therapy. The routine antidiabetic and antihypertensive drugs were continued in the same dose along with DCP. However six units of insulin was added to counter the effect of 5% dextrose in diabetic patients. 3. Severe systemic diseases where high dose steroids are contra-indicated. 4. Pregnant and lactating mothers. 5. Patients on long term systemic steroids therapy. 6. Pemphigus patients in whom the diagnosis could not be confirmed by DIF. 7. Patients who had not completed their family. After applying the criteria mentioned above, 26 cases of pemphigus enrolled for pulse therapy and followed up from June 2005 – June 2007. After their informed consent they were hospitalized and thorough general, systemic and dermatological examinations were done. Relevant Baseline investigations like complete haemogram, routine blood biochemistry, urine examination, electro-cardiography, chest X-ray, semen analysis, baseline Fitzpatrick skin typing were done. Dexamethasone Cyclophospamide pulse therapy was administered to each patient, strictly adhering to the prescribed guidelines. Due importance was given to patient education regarding the disease process and the treatment regimen. During every pulse, complete blood count, urine analysis especially for red blood cells, electrocardiogram, blood sugar, blood urea, serum electrolytes, liver function tests, stool examination for occult blood, ophthalmic examination for cataract, blood pressure recording and weight charting were done. RESULTS : In this study, 26 cases of Pemphigus patients from the outpatient Department of Dermatology, Government Rajaji Hospital, Madurai were treated with Dexamethasone Cyclophosphamide pulse therapy and observed during the period of June 2005 – June 2007; The following observations were made. Of the 26 pemphigus patients 18 (70%) patients had pemphigus vulgaris, 7 (26%) patients had pemphigus foliaceus, and 1 (4%) patient had pemphigus erythematosus. Thus pemphigus vulgaris is by far the most predominant type of pemphigus requiring DCP therapy. CONCLUSION : 1. Pemphigus vulgaris is by far the commonest epidermal autoimmune vesiculobullous disorder that requires Dexamethasone cyclophosphamide pulse therapy. 2. An overwhelming majority of patients requiring DCP for Pemphigus are in the reproductive age group. 3. DCP significantly improves patient compliance by reducing the duration of hospital stay. 4. The average number of pulses required to achieve clinical remission is significantly higher than the figures mentioned in the available literature. 5. Septicaemia is the commonest cause of death in patients receiving DCP. 6. Metabolic side effects attributable to long term steroid therapy are significantly lower in patients treated with DCP. 7. An universally acceptable clinical grading of Pemphigus is needed to objectively assess the baseline severity and subsequent improvement. It would also allow for a fair comparison of the results reported by different centres. 8. Potentially irreversible gonadal suppression appears to be the most important side effect against which the benefits of DCP have to be weighed. 9. Ways and means to reduce the gonadal toxicity of DCP need to be explored, as DCP therapy is likely to stay as the treatment of choice in autoimmune vesiculobullous diseases