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Dexamethasone-cyclophosphamide pulse therapy for autoimmune-vesiculobullous disorders at Victoria hospital, Bangalore

  • Author(s): Sacchidanand, S
  • Hiremath, NC
  • Natraj, HV
  • Revathi, TN
  • Rani, Shobha, RH
  • Pradeep, Geeta
  • Tenneti, Vijay
  • et al.
Main Content

Dexamethasone-cyclophosphamide pulse therapy for autoimmune-vesiculobullous disorders at Victoria hospital, Bangalore
S Sacchidanand1, NC Hiremath1, HV Natraj1, TN Revathi1, Shobha Rani RH2, Geeta Pradeep2, and Vijay Tenneti2.
Dermatology Online Journal 9 (5): 2

From the Department of Skin and Sexually Transmitted Diseases,Victoria Hospital, Bangalore Medical College1, and the Department of Pharmacy Practice, Al-Ameen College of Pharmacy2, Bangalore India. sacchi60@rediffmail.com iadvlsec@rediffmail.com

Abstract

Pemphigus is the commonest autoimmune vesiculobullous disorder on the Indian subcontinent. The mainstay treatment of the disease is systemic steroids and other immunosuppressive therapies. We evaluated the pattern of treatment as originally presented by Pasricha et al. in 1988 and by Surindar Kanwar in 1990. Starting in April 2001, we enrolled 50 patients with autoimmune vesiculobullous disorders for dexamethasone-cyclophosphamide pulse therapy [DCP] in our hospital. Of these, six (12 %) patients are currently in the fourth phase of treatment, ten (20 %) are in the third phase, fifteen (30 %) in the second phase, and twelve (24 %) patients are in the first phase. Treatment was discontinued by six patients, and one fatality secondary to hyperglycemia and mucormycosis. Our findings are consistent with previous reports that DCP therapy is very effective in the treatment of vesiculobullous disorders.



Introduction

Pemphigus vulgaris is a chronic autoimmune blistering disease of skin and mucous membrane. Prior to the advent of corticosteroids, the majority of patients with pemphigus vulgaris died, usually from overwhelming sepsis [1]. Patient survival has improved dramatically since systemic corticosteroids were introduced. To minimize the iatrogenic effects of systemic corticosteroids, alternative therapies have been introduced such as immunosuppressive drugs (azathioprine, cyclophosphamide, methotrexate, mycophenolate mofetil), gold, tetracyclines, dapsone, and intravenous immunoglobulins [2, 3].

Pulse therapy, the big shot [4], refers to the discontinuous intravenous infusion of very high doses of corticosteroids over a short time. Doses of each pulse are not standardized but are usually 500-1000 mg methylprednisolone or 100-200 mg dexamethasone. The aim of pulse therapy is to achieve a faster response and stronger efficacy and to decrease the need for long-term use of systemic corticosteroids. There is an apparent contradiction that pulsed administration of high-dose steroids is used to achieve a steroid-sparing effect. The expected steroid-sparing effect of pulse therapy has yet to be convincingly demonstrated [5].

Pulse therapy using a combination of corticosteroids and immunosuppressive drugs is reported to reduce the morbidity and mortality from pemphigus vulgaris. This treatment regimen, described by Pasricha et al. [6] and by Kanwar [7], forms the basis for our study. We attempt to evaluate the efficacy and safety of dexamethasone-cyclophosphamide pulse therapy (DCP) with respect to remission of symptoms in patients diagnosed with pemphigus vulgaris in our tertiary care hospital in Bangalore, over the time period of 3 years.


Methods

This study enrolled 50 patients diagnosed with autoimmune-vesiculobullous disorders admitted to the hospital between April 2001 and August 2003. Details of history, physical findings, laboratory data, treatment, and followup were recorded. The diagnosis of pemphigus was based on clinical criteria and Tzanck smear. All the patients were admitted to the hospital for the initiation of pulse therapy.

Laboratory evaluation at the time of enrollment included a complete hemogram, ESR estimation, urine examination, kidney function tests, stool occult blood, chest x-ray, and an electrocardiogram. The investigations were repeated prior to each pulse treatment and also during followup.

The patients were monitored not only for improvement of their disease but also for hypertension, weight gain, secondary amenorrhoea, hair loss, urinary symptoms, acid peptic disease, cataract formation, and other adverse effects attributed to DCP therapy.

The treatment schedule was divided into four phases. In the first phase patients received dexamethasone (100 mg dissolved in 500 ml 5 % dextrose) by slow intravenous drip over 2 hours on 3 consecutive days, along with cyclophosphamide (500 mg) on day 1. These pulses (DCP) were repeated every 4 weeks. Between the pulses, the patients received only once-daily oral cyclophosphamide (50 mg). The first phase is continued until the patient attains remission, defined as the absence of fresh lesions and disappearance of existing lesions.

Once remission is achieved, the patients were entered into phase 2. In this phase the monthly pulse of cyclophosphamide and dexamethasone are continued along with daily oral cyclophosphamide for a minimum of 6 months. In phase 3, the monthly pulses were stopped but patients continued to receive 50 mg oral cyclophosphamide daily for an additional year. In phase 4, medications were withdrawn and the patients were followed up for any adverse effects and relapses.


Results

Out of the 50 patients of autoimmune vesiculobulous disorders 44 (88 %) patients had pemphigus vulgaris, 2 (4 %) patients had pemphigus foliaceous, 2 (4%) patients had bullous pemphigoid and 2 (4 %) had dermatitis herpetiformis. The age range of the patients was 18-62 years (tables 1 and 2).

Table 1
Disease Number of patients (%)

Pemphigus vulgaris 44 (88)
Pemphigus foliaceous 2 (4)
Bullous pemphigoid 2 (4)
Dermatitis herpetiformis 2 (4)


Table 2

Age group in years Number of patients (%)
15-25 6 (12)
26-35 13 (26)
36-45 17 (34)
46-55 12 (24)



Figure 1
Sex distribution of patients

All the patients had extensive involvement when admitted to the hospital. During the followup studies, 41 (82 %) patients achieved remission, 2 (4 %) patients relapsed, 2 (4 %) patients discontinued treatment, and patient died secondary to hyperglycemia and mucormycosis (table 3).

Table 3. Disease status following initiation of DCP therapy

Outcome Number of patients (%)
Remission 41 (82)
Relapse 2 (4)
Discontinued 6 (12)
Death 1 (2)


Of the 50 enrolled patients, 6 (12 %) patients are in phase 4, 10 (20 %) are in phase 3, 15 (30 %) are in phase 2, and 12 (24 %) are in phase 1 of treatment (Figure 2).


Figure 2
Phase distribution

Conclusions

The results of this study indicate a high degree of positive outcome among patients diagnosed with a variety of autoimmune vesiculobullous disorders. All 50 patients enrolled in the study had advanced disease. Clinical remission was achieved by 70 percent of our patients by the third pulse of first phase. Most of the patients who discontinued the treatment were from distant locations and could not take monthly pulses. Because pulse therapy is so effective, this treatment regimen should be adopted by other centers in the state so that this high dropout rate can be minimized.

Pemphigus patients with many years of steroid-induced complications were among those who responded well to this pulse therapy regimen. Although the overall response varies from patient to patient, there appears to be a correlation between the overall response and the stage of the disease at initiation of the therapy. In addition to resulting in a complete remission, this therapy is also associated with a significant decrease in disease-related mortality. Another important advantage reported with DCP therapy is a remarkable freedom from the side effects commonly associated with long-term steroid therapy and other immunosuppressive agents. These results are a preliminary report of an ongoing study and all the patients in phase 4 of treatment who have attained complete remission are required to be monitored at regular interval of 3 months for the coming 5 years.

References

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