Dexamethasone-cyclophosphamide Pulse Research Articles

Repigmentation in vitiligo universalis: Role of melanocyte density, disease duration, and melanocytic reservoir

Recent reports suggest that vitiligo lesions are not totally devoid of melanocytes. We report an interesting observation made in the vitiliginous skin of an Indian patient being treated for pemphigus vulgaris with dexamethasone cyclophosphamide pulse therapy. Our observations indicate that melanocytes are never completely absent in the depigmented epidermis and that these melanocytes can recover their functionality in vivo and in vitro under an appropriate stimulus.

Treatment of Pemphigus Vulgaris

Pemphigus vulgaris is a rare, chronic, autoimmune mucocutaneous blistering disease. The disease can progress to involve the skin and multiple mucosae. Pemphigus vulgaris can be associated with a high morbidity and significant mortality rate. Treatment of the condition can be challenging. Conventional therapy primarily consists of systemic corticosteroids and immunosuppressant agents. In some patients with pemphigus vulgaris, these agents fail to provide an effective clinical response or have significant adverse effects. We evaluated data on 792 patients with pemphigus vulgaris retrieved from PubMed, covering the period 1973-2004. Only patients reported in the English literature were included in this review. Recently, several new therapeutic agents and treatment modalities have been described for the treatment of patients with pemphigus vulgaris. Some therapeutic agents that were used in the past and abandoned have recently regained favor. This review focuses on the therapeutic uses of dapsone, methotrexate, mycophenolate mofetil, chlorambucil, dexamethasone-cyclophosphamide pulse therapy, immunoablative therapy with cyclophosphamide, plasmapheresis, and extracorporeal photochemotherapy. Newer agents, such as intravenous immunoglobulin (IVIg) therapy and rituximab (an anti-CD20 chimeric monoclonal antibody), are also discussed. Among the oral agents, dapsone may be considered a first-line agent. This is primarily because the risk of potentially fatal adverse effects with this drug is lower than that associated with other available chemotherapeutic agents. In patients who are refractory to oral agents, alternative treatments have been used to prevent further disease progression. Recently, the use of IVIg therapy, with a defined protocol, has been reported to be beneficial. This therapy is promising since it may allow for discontinuation of all other therapies and is safe. The adverse effects from IVIg therapy are minimal. Furthermore, compared with other therapies, it provides a better quality of life.

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

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.

Long-Term Efficacy of Dexamethasone-Cyclophosphamide Pulse Therapy in Pemphigus

Background: Corticosteroids are used as a daily oral therapy or in a pulse form with or without various adjuvant drugs for the treatment of pemphigus. Our long-term experience with the use of dexamethasone-cyclophosphamide pulse therapy as a first-line treatment modality for pemphigus is presented. Methods: A retrospective analysis of records of pemphigus patients treated by dexamethasone-cyclophosphamide therapy was carried out. The treatment regimen consisted of the monthly administration of intravenous dexamethasone (136 mg) for 3 consecutive days with addition of intravenous cyclophosphamide (500 mg) on the second day. Oral cyclophosphamide (50 mg) daily and oral corticosteroids (low tapering doses) were given in the intervals between the pulses, till partial remission was achieved. Pulse therapy was then continued for another 6 months followed by daily oral cyclophosphamide (50 mg) for 1 year, which produced a complete remission. Results: A total of 36 patients, 32 with pemphigus vulgaris and 4 with pemphigus foliaceus, were treated with this regimen. Two to 8 pulses were required to achieve a partial remission, while the total number of pulses given for complete remission ranged from 8 to 32. The duration of pulse therapy correlated with both the disease severity and the time to achieve remission. All patients are now in complete remission with a follow-up of 0.5–12 years. Four patterns of remission were observed, related to the severity of disease. The response to pulse therapy was faster in the milder form of disease. The severe form of disease required more pulses as well as higher doses of intervening oral corticosteroids. Conclusions: Dexamethasone-cyclophosphamide pulse therapy is an effective form of treatment in pemphigus and results in long-lasting remissions.

Pituitary-adrenal function following dexamethasone-cyclophosphamide pulse therapy for pemphigus.

Systemic corticosteroid therapy is known to lead to pituitary-adrenal (PA) suppression. Although patients treated for pemphigus with dexamethasone-cyclophosphamide pulse (DCP) therapy have shown no evidence of PA suppression, no study has been conducted to study this possible side-effect of DCP therapy. To study the effect of DCP therapy for pemphigus on PA function. A cross-sectional study was carried out in 33 patients who completed phase II of DCP therapy in a single centre, a large teaching hospital in New Delhi, India. Serum cortisol levels following adrenocorticotrophic hormone stimulation were analysed in 31 patients. Seventeen (55%) patients showed suppressed PA function. Suppressed function occurred more frequently in patients who had received pulses of dexamethasone in addition to DCP therapy in the first phase of treatment (P = 0.055). Suppressed PA function occurs in about half of patients who receive DCP therapy for pemphigus. These patients probably do not require routine replacement therapy with corticosteroids but may need supplementation during periods of stress.

Curative treatment for pemphigus

The recent article by Bystryn and Steinman¹is an excellent review of pemphigus treatments but did not discuss the impact of the dexamethasonecyclophosphamide pulse (DCP) therapy regimen as we use it. We would like to describe the long-term follow-up of 79 patients we described 8 years ago²to substantiate our claim that the DCP therapy regimen can indeed cure pemphigus.^2-4 Briefly, the DCP regimen consists of administering dexamethasone (100 mg) intravenously on 3 consecutive days along with cyclophosphamide (500 mg) on 1 of these days and repeating DCP treatment at exactly 28-day intervals^2-7In between the DCP doses, the patient receives only cyclophosphamide (50 mg/d orally). During the early part of the therapy most patients develop clinical lesions in between the DCP treatments, but the disease becomes progressively milder until the patient is in complete clinical remission (phase 1). After this, the patient is given 6 more

Curative Treatment for Pemphigus

The recent article by Bystryn and Steinman 1 is an excellent review of pemphigus treatments but did not discuss the impact of the dexamethasonecyclophosphamide pulse (DCP) therapy regimen as we use it. We would like to describe the long-term follow-up of 79 patients we described 8 years ago 2 to substantiate our claim that the DCP therapy regimen can indeed cure pemphigus. 2-4 Briefly, the DCP regimen consists of administering dexamethasone (100 mg) intravenously on 3 consecutive days along with cyclophosphamide (500 mg) on 1 of these days and repeating DCP treatment at exactly 28-day intervals 2-7 In between the DCP doses, the patient receives only cyclophosphamide (50 mg/d orally). During the early part of the therapy most patients develop clinical lesions in between the DCP treatments, but the disease becomes progressively milder until the patient is in complete clinical remission (phase 1). After this, the patient is given 6 more

Das vernarbende Pemphigoid ? ein therapeutisches Problem

Cicatricial pemphigoid is an autoimmune subepidermal blistering disease of the skin and mucous membranes. We report on eight patients in whom the clinical diagnosis was confirmed by direct immunofluorescence. The patients' age averaged 69 years; seven were female and one male. Initial symptoms were erosions of the oral mucous membranes in four patients, skin blisters in three patients, and in one patient an ocular involvement was the first manifestation of the disease. Indirect immunofluorescence on NaCl-split human skin revealed circulating IgG antibodies binding to the roof of the artificial blister in three patients. Immunoblotting of epidermal and dermal extracts disclosed binding of IgG antibodies of one of these patients to an epidermal 230-kD protein, whereas IgA-antibodies showed no specific binding. In four of five patients with a strong ocular involvement IgA deposits were found by direct immunofluorescence. These studies were done on biopsies of perilesional skin or oral mucous membranes, and they were positive in one patient even before the first ocular lesions appeared. Therefore, finding of IgA deposits by direct immunofluorescence may be taken as a prognostic criterion allowing selection of the proper treatment. We treated six patients with a dexamethasone-cyclophosphamide pulse therapy, while two patients received dapsone orally. The involvement of skin and oral mucous membrane responded well to both regimens, whereas the ocular lesions were progressive, except in one patient. On the basis of our eight cases, we discuss both options and limitations in the treatment of cicatricial pemphigoid and review new aspects of the pathogenesis of this disease.

Dexamethasone‐Cyclophosphamide Pulse Therapy in Pemphigus

Fifty patients with pemphigus (45 pemphigus vulgaris, 5 pemphigus foliaceus) were treated with dexamethasone-cyclophosphamide pulse therapy. The pulse consisted of 136 mg dexamethasone dissolved in 5% dextrose given in a drip over a period of 1-2 hours on 3 consecutive days. In addition, 500 mg cyclophosphamide was added in the drip on the first day. Such pulses were given at monthly intervals. In between the pulses patients were given 50 mg cyclophosphamide orally each day. The results were encouraging, the chief advantage being freedom from side effects of corticosteroid therapy. The lesions healed in 3-4 days and the patients were able to resume their work within one week. Further scope of such therapy in pemphigus is discussed.