Dexamethasone-cyclophosphamide Pulse Therapy Research Articles

Dexamethasone-Cyclophosphamide Pulse Therapy in Pemphigus

Autoimmune pemphigus is a group of severe blistering diseases. Although corticosteroids have dramatically altered the prognosis of pemphigus, morbidity and mortality resulting from the adverse effects of systemic corticosteroids remain high. Dexamethasone-cyclophosphamide pulse (DCP) therapy was introduced to diminish the adverse effects of prolonged conventional daily dose regimens. To report our experience with the use of the DCP regimen in patients with autoimmune pemphigus. In the period 1998-2002, 72 patients with various forms of autoimmune pemphigus treated with DCP therapy were included, of whom 36 patients were previously treated with conventional corticosteroid therapy, and 36 were newly diagnosed patients. Of the 72 patients, 43 completed treatment, while 13 patients did not respond adequately to the treatment and continued with the conventional daily regimen, nine patients were lost to follow-up, and seven patients died. Two of these deaths were probably a consequence of DCP therapy. DCP regimen is a beneficial treatment for patients with pemphigus, sparing the adverse effects of conventional regimens.

Dexamethasone-cyclophosphamide pulse therapy in progressive systemic sclerosis

Dexamethasone-cyclophosphamide pulse therapy in progressive systemic sclerosis

Outcome of dexamethasone-cyclophosphamide pulse therapy in pemphigus: A case series

Pemphigus disorders are a group of serious and potentially life-threatening diseases affecting skin and/or mucus membranes. Dexamethasone-cyclophosphamide pulse (DCP) therapy has shown promising results in the management of these diseases. The objective of the study was to assess the outcome of DCP therapy in pemphigus. Pemphigus patients who had been treated with DCP therapy from 2001 to 2008 were prospectively and retrospectively analyzed. A total of 65 pemphigus patients were enrolled. Male to female ratio was 1 : 1.82. Mean age of patients was 44.65 +/- 11.85 years with a range of 14 to 73 years. Thirty two patients completed phase I, of which 28 (9 in phase II, 7 in phase III and 12 in phase III) were maintaining remission and four patients relapsed. Relapse was observed only in patients who discontinued or took irregular treatment. Six patients were declared cured of disease. Five patients died during phase I. Dexamethasone-cyclophosphamide pulse therapy is not absolutely free from adverse effects. Most of the immediate side effects were expected, tolerable and did not pose any problem in continuing treatment. There was a slight increased incidence of weight gain, hypertension, diabetes mellitus, cataract and Cushingoid habitus, since most of our patients also received additional daily oral steroids. Also, there was a high incidence of secondary pyogenic infections of skin lesions and oral candidiasis during phase I. Staphylococcus aureus was the commonest bacteria isolated from the pus of skin lesions. Most of the alterations in laboratory parameters were transitory or correctable, and did not pose a problem in continuing therapy. DCP therapy was found to be effective in inducing and maintaining remission in pemphigus, provided the patients receive regular and complete treatment.

Systemic sclerosis and dexamethasone cyclophosphamide pulse therapy

Systemic sclerosis and dexamethasone cyclophosphamide pulse therapy

Current regimen of pulse therapy for pemphigus: Minor modifications, improved results

If administered properly, dexamethasone cyclophosphamide pulse (DCP) therapy has the potential to effect lifelong recovery from pemphigus. The objective of this paper is to highlight various parameters of DCP therapy and also, to report the effects of a few modifications in the regimen. An analysis of 123 patients treated with the DCP/DP regimen over a period of five years (1998 to 2002) is presented here. Seventeen patients who did not start/continue the treatment and three patients who died during the treatment have been excluded from the analysis. Twenty patients who had not yet started families were given only dexamethasone pulses (DPs) while 103 patients received DCPs. Low dose (50 mg/day) cyclophosphamide was used as in the standard regimen. The three modifications introduced into the regimen were: (1) an additional daily dose of oral betamethasone sufficient to control the disease activity during phase I, which was progressively tapered off completely as the patient recovered, (2) use of systemic antibiotics if the patient had skin lesions, and oral anti-candida drugs if the patient had oral ulcers until complete healing, and (3) insistence on thorough cleaning of the skin and scalp with a normal soap and shampoo, and proper maintenance of oral hygiene in spite of skin/mucosal lesions. The regimen consisted of DCP/DP repeated in exactly 28-day cycles, along with 50 mg cyclophosphamide per day, insistence on completing the treatment and avoiding irregular pulses in all patients. The number of DCPs/DPs during phase I varied in different patients depending upon the dose of betamethasone used and the rate of recovery, but phase II (nine DCPs/DPs in exactly 28-day cycles along with 50 mg cyclophosphamide per day) and phase III (only 50 mg cyclophosphamide per day) was fixed at nine months each. This was followed by posttreatment follow-up (phase IV). At present, all the patients are in complete remission. The confirmed period of posttreatment, disease-free follow-up period has already been more than five years in 62 patients, 3-5 years in 41 patients, 2-3 years in three patients and less than two years in six patients. Eight DCP patients and three DP patients developed a relapse (the relapse rates thus being 7.7 and 15% respectively) and received a second course of pulse therapy. They are also in remission at present. The duration of phase I was three months in 62 patients, 4-5 months in 28 patients, 6-9 months in 13, 10-12 months in nine patients and more than 12 months in 11 patients. The maximum daily dose of betamethasone used in these patients was nil in 17 patients, 1-2 mg in 85, 3-4 mg in 16, and> 4 mg in five patients. The modifications employed in this study could ensure the cure of all pemphigus patients by using DCP therapy administered at a private clinic.

Prolonged remission of pemphigus induced by dexamethasone-cyclophosphamide pulse therapy

Prolonged remission of pemphigus induced by dexamethasone-cyclophosphamide pulse therapy

Pemphigus in North India

Pemphigus is an autoimmune mucocutaneous blistering disease caused by antibodies against desmogleins Dsg-1 and Dsg-3. The epidemiology of the disease varies in different countries. In India, pemphigus is relatively common, with considerable interstate variation. The objective of this study was to review the demography, clinical features, and treatment aspects of pemphigus in North India. The case records of pemphigus patients registered from 1988 to 2004 were retrospectively analyzed. The age, sex, residential particulars, site of onset of disease, duration between involvement of skin and mucosa, subtype and course of the disease, and treatments offered were analyzed. Of the 328 patients, 302 (92%) were pemphigus vulgaris and the remaining 26 (8%) were pemphigus foliaceous patients. The mean age at onset was 39.27 years for males and 38.57 years for females. The majority of patients were from the states of Punjab and Haryana. The majority of patients were treated with dexamethasone-cyclophosphamide pulse (DCP) therapy, and the number of DCPs required for inducing remission correlated roughly with the severity of the disease. The mortality rate was 4% in the total sample. North Indian patients of pemphigus have a relatively younger age at onset. The majority of patients were from the states of Punjab and Haryana. The response to DCP therapy was good, and with DCP, the additional dose of oral steroids that was required to control the activity of the disease was less than 30 mg/d, which is much less than the dosage used in the standard conventional regimens.

Twelve‐year clinico‐therapeutic experience in pemphigus: A retrospective study of 54 cases

Pemphigus, a common immunobullous disease of skin and mucous membranes affecting both sexes of all ages, was almost fatal before the advent of corticosteroids. Better strategies to avoid their side-effects and recent introduction of adjuvant therapy has further improved its prognosis. As the treatment remains need-based and patient-specific, different regimens and strategies have evolved, each with its own merits and demerits. This retrospective hospital-based study was carried out to understand the clinico-therapeutic aspects of pemphigus in our clinic. Medical records of all new patients admitted to our hospital with the diagnosis of pemphigus from 1990 to 2002 were analyzed. The diagnosis was mainly clinical and confirmed by positive Tzanck's test and histopathology. All patients were assessed clinically on a severity score of 1+ to 4+. These patients had received treatment with dexamethasone-cyclophosphamide pulse (DCP) therapy, oral mini-pulse (OMP) with betamethasone, or intramuscular triamcinolone acetonide alone or with azathioprine, dapsone or cyclophosphamide. They were followed up for clinical remission and side-effects of therapy. There were a total of 54 new patients comprising 53.7% females and 46.3% males, and 12.9% of these were < 18 years of age. Pemphigus vulgaris was the commonest clinical type seen in 81.48% and mucosal involvement was seen in 63.63% of cases. The severity of mucosal lesions was not proportionate to that of cutaneous lesions. Associated diseases seen were seropositive rheumatoid arthritis, hypertension, diabetes mellitus and hyperthyroidism in one case each. Dexamethasone-cyclophosphamide pulse therapy was given to 75% of the pemphigus vulgaris patients while those having less severe disease were treated with other regimens. In general, clinical remission was seen after 2-16 (mean 6.5) DCP doses. Two patients have been in complete remission for the last 5 and 7 years of completion of DCP therapy, respectively. Addition of other adjuvants to corticosteroids was also helpful. However, azathioprine 50 mg/day was not as effective as cyclophosphamide 50 mg/day. Menstrual irregularities, amenorrhoea, azoospermia, rise in blood pressure and glycosuria were the major side-effects seen during DCP pulse therapy. Drop out rate was unacceptably high with all modes of treatment, although with DCP therapy it appears to be partly owing to early disease control. There was no mortality in this series. Pemphigus vulgaris is the commonest clinical type. Mucosal surfaces other than the oral cavity are uncommonly involved, it may herald the onset of disease and takes longer to heal. Dexamethasone-cyclophosphamide pulse therapy seems to have a definite advantage over treatment with steroids alone, especially in terms of better control of disease activity, near absence of steroid side-effects and significantly reduced hospital stay. However, ways and means to reduce gonadal toxicity of adjuvants need to be explored as DCP therapy is likely to stay as a treatment of choice.

Intravenous dexamethasone‐cyclophosphamide pulse therapy in comparison with oral methylprednisolone‐azathioprine therapy in patients with pemphigus: Results of a multicenter prospectively randomized study

Pemphigus is a potentially life-threatening autoimmune blistering skin disease usually treated with high-dose corticosteroids in combination with immunosuppressive drugs. In a multicenter, prospectively randomized study we compared efficacy and side effects of a dexamethasone-cyclophosphamide (D/C) pulse therapy with a methylprednisolone-azathioprine (M/A) therapy in 22 patients with newly diagnosed pemphigus vulgaris and pemphigus foliaceus. The 11 patients of the M/A group were treated with daily doses of methylprednisolone (initially 2 mg/kg body weight) and azathioprine (2-2,5 mg/kg body weight) which were subsequently tapered. D/C pulse therapy in 11 patients consisted of intravenous administration of 100 mg dexamethasone/d on 3 consecutive days along with cyclophosphamide (500 mg) on day one. Pulses were initially repeated every 2-4 weeks and then at increasing intervals. In between the pulses, oral cyclophosphamide (50 mg) was given daily for 6 months. Within 24 months after treatment initiation, 5/11 patients of the D/C group had a remission (complete remissions after discontinuation of therapy in 3 patients) and 6/11 patients had a progression. In the M/A group, there were remissions in 9/11 patients (complete remissions after discontinuation of therapy in 3 patients) and progression in 1/11 patients. There were more relapses in M/A therapy after remission than in D/C therapy. Side effects were more common in the M/A group. These differences were not significant (p > 0,05). Because of the high number of progressions in patients treated with D/C therapy, we can not confirm the encouraging results of earlier reports about pulse D/C therapy. Nevertheless D/C therapy seemed to be better tolerated and, in case of primary efficacy, was associated with fewer recurrences than M/A therapy.

Dexamethasone-cyclophosphamide pulse therapy in systemic lupus erythematosus

Therapy systemic lupus erythematosus (SLE) has been generally discouraging. Methyl-prednisolone pulse therapy has been used for various connective tissue disorders. We used intravenous dexamethasone cyclophosphamide pulse therapy to treat SLE. Fourteen patients (10 females and 4 males) between the age of 15-48 years with definite or classical clinical criteria laid by American Rheumatism Association criteria were treated by Dexamethasone-Cyclophosphamide pulse (DCP) therapy at our center. It was possible to induce a complete clinical remission with DCP therapy in most of the patients thereby offering them life free from disease and drugs. The side effects commonly observed with conventional daily dose regimen of corticosteroids were not present or were mild. Almost all patients had good response after 3-4 pulses to allow them a normal life style. Fever, malar rash and oral ulceration responded early but photosensitivity, discoid rash, alopecia and joint pains took some more time.

Successful treatment of scleromyxedema with dexamethasone cyclophosphamide pulse therapy

Successful treatment of scleromyxedema with dexamethasone cyclophosphamide pulse therapy

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.