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

BACKGROUND: If administered properly, dexamethasone cyclophosphamide pulse (DCP) therapy has the potential to effect lifelong recovery from pemphigus. AIMS: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: The modifications employed in this study could ensure the cure of all pemphigus patients by using DCP therapy administered at a private clinic.

Pigmentary disorders in India.

This article addresses pigmentary disorders relevant to India. Many of these disorders are easily spotted because of the Indians' darker complexion. The authors examine hypopigmentary and hyperpigmentary disorders, defining the main characteristics of each and their relevance to the people of India, including social as well as physical ramifications. The authors propose the treatments available to Indians exhibiting these skin disorders.

Efficacy of H, antihistamine, corticosteroids and cyclophosphamide in the treatment of chronic dermographic urticaria.

H, antihistamines relieve urticaria by blocking the action of histamine on the target tissue, while demonstration of autoantibodies in the sera of a proportion of the patients having chronic idiopathic urticaria, use of immunosuppressive drugs for the treatment of these patients has acquired the greater rationality. We evaluated the role of corticosteroids and cyclophosphamide in the treatment of chronic dermographic urticaria. Twenty-five patients, 13 males and 12 females, between 18-53 years in age, having chronic dermographic urticaria were taken up for this study. The patients were divided into three groups. Group I patients (n=9) were treated with cetirizine hydrochloride 10 mg per day orally, group II patients (n=7) were treated with betamethasone 2 mg along with cyclophosphamide 50 mg along with cetirizine 10 mg per day for a total period of 4 weeks. The patients were evaluated every week to record the therapeutic response and side effects, and then followed up without treatment for a period of 6 months to look for recurrence of the urticaria, if any. Six patients in group I and all the patients in group II and group III had complete remission while the remaining patients in group I had partial relief. The side effects included drowsiness in 4 patients. All the patients in group II had weight gain, 4 patients had acne and 2 patients developed cushingoid features. Majority of the patients relapsed within 3 days after stopping the treatment. Supplementation of the treatment with oral corticosteroids or cyclophosphamide was more effective in controlling the symptoms as compared to cetirizine alone. But a four weeks supplementation was not adequate for preventing the relapses when the drugs were withdrawn.

Long term topical application of lactic acid/lactate lotion as a preventive treatment for acne vulgaris.

In an open clinical study, efficacy of 5% aqueous solution of lactate for preventing acne was evaluated in 22 patients. Lactate lotion was used topically all over the face twice a day and continued like a cosmetic for 1 year. Systematic antibiotics were given for periods of 4 weeks whenever the disease was severe. The effect of the treatment was evaluated by counting the number of comedones, inflammatory lesions and cysts separately once a month and recording them graphically. The greatest reduction in the lesion counts was achieved in 8-24 weeks for the inflammatory lesions and 8-30 weeks for the comedones. At the end of 1 year 90-100% reduction of the inflammatory lesions was achieved in 40.9% patients and non-inflammatory lesions in 22.7% patients. The remaining patients showed 50-90% reduction, while 2 patients showed less than 50% reduction in the non-inflammatory lesions. Thus, most of the patients showed significant reduction in the lesion counts. Aggravations were associated with the hot and the rainy season and required concomitant treatment with oral antibiotics.

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

BACKGROUND: 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. OBJECTIVES: To study the effect of DCP therapy for pemphigus on PA function. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Azathioprine as a corticosteroid sparing agent for the treatment of dermatitis caused by the weed Parthenium.

Air-borne contact dermatitis caused by Parthenium hysterophorus is a serious problem in India. Patients with this condition have to use corticosteroids regularly in order to maintain clinical remissions, but prolonged usage causes serious side-effects. The weed cannot be eradicated. We have used 3 therapeutic regimens with azathioprine, which led to an effective control with minimal side-effects even when used for long periods. A total of 22 patients (group I) were given 50 mg azathioprine twice a day; 11 patients (group II) received 50 mg azathioprine per day and 300 mg azathioprine every 28 days, and 10 patients (group III) were given 50 mg azathioprine twice a day along with 300 mg azathioprine every 28 days. The duration of treatment varied from 6 months to 3 years. Twenty patients in group I and 9 patients each in groups II and III had complete remission. Nine, 7 and 6 patients in the respective groups needed additional oral betamethasone 1-2 mg per day for brief periods only during the peak season in order to maintain complete remission. One patient in each group had only partial relief. The need for oral betamethasone during the second and the third year was further reduced. One patient each in group I and group II could not continue azathioprine due to the side-effects of the drug.

Failure of pentoxifylline to affect air- borne contact dermatitis caused by parthenium.

Twelve patients, 9 males and 3 females between 22 to 65 years in age having air-borne contact dermatitis (ABCD) for 6 months to 12 years were included in this study. The diagnosis in each patient was confirmed by patch tests. Six of these patients (group I) were treated with pentoxifylline 400 mg three times a day orally in addition to topical clobetasol propionate and oral betamethasone 1.0 to 2.0 mg per day for 5 to 10 weeks. The other 6 patients (group II) were given the same treatment for the same duration but without pentoxifylline. The response to the treatment in both the groups was almost the same. The patients treated with pentoxifylline did not have any added benefit. There were no significant side effects of the therapy in either of the groups.

Chemo-inflammation-an effective treatment for freckles.

Freckles are fairly common and considered to be incurable. We have developed a new technique called "Chemo-inflammation" with which we have treated 5 patients (4 girls and one boy) having extensive freckles with excellent results. All the freckles disappeared completely from the treated areas and there has been no recurrence so far. The technique consists of applying a liquid based on an alkyl sulphate, on the affected skin and repeating the application every hour for a day till the entire skin develops adequate inflammation. The liquid is then washed off with tap water and the skin is treated with topical (or systemic) corticosteroids till the inflammation subsides and the treated skin peels off and attains its normal texture. This generally happens within a week or so. Post-inflammatory hyperpigmemation has to be prevented by adequate anti-inflammatory treatment. Otherwise there are no precautions.

MHC class II alleles and haplotypes in patients with pemphigus vulgaris from India.

Pemphigus vulgaris (PV) is a blistering disease of the skin and mucous membranes characterized by an autoantibody response against a keratinocyte adhesion molecule, desmoglein 3, causing acantholysis and blister formation. We compared high resolution MHC class II alleles and haplotype frequencies (HLA-DRB, DQA1 and DQB1) in 37 patients with PV to 89 haplotypes of normal relatives from New Delhi and Ahmedabad. We found that PV patients had significantly increased frequencies of DRB1*1404 (P < 0.0001), DQA1*0101 (P = 0.001), and DQB1*0503 (P < 0.0001). These associations were due to the increased frequencies of the haplotype HLA-DRB1*1404, DRB3*0202, DQA1*0101, DQB1*0503 in patients compared to control haplotypes (p < 0.0001). Also, patients from Ahmedabad had a significant increase in HLA-DQB1*0302 (p = 0.03). An identical amino acid sequence (Leu-Leu-Glu-Arg-Arg-Arg-Ala-Glu), in positions 67-74 of the beta domain of DRB alleles is restricted to some DR14 alleles. Therefore, there are three possible explanations for class II allele involvement in autoantibody in PV patients with class II haplotypes marked by HLA-DR14. First, the class II alleles could be markers for an unidentified susceptibility gene in linkage disequilibrium with them. Second, the primary association could be with DQB1*0503 and the association with HLA-DR14 alleles would be the result of linkage disequilibrium. Third, the HLA-DRB1 locus susceptibility could involve a specific amino acid sequence in the third hypervariable region shared by several HLA-DR14 alleles.

Toxic epidermal necrolysis.

BACKGROUND: Most studies on drug-induced toxic epidermal necrolysis (TEN) report a high mortality rate. This has been attributed partly to the use of corticosteroids for its treatment. However, we consider corticosteroids to be the sheet anchor for saving the patients having TEN. MATERIALS AND METHODS: Our approach to the treatment of this disease consists of administering a relatively high dose of corticosteroids to control the reaction at the earliest possible time and then withdrawing corticosteroids at the fastest possible rate. RESULTS: As illustrated by the five case reports, the reaction is controlled within 24 to 48 hours and the corticosteroids are withdrawn within the next 7 to 10 days. During this period, the skin also shows almost complete healing. With the confidence gained with this approach, we undertake the provocation test as a rule in every patient to find the actual drug responsible for the reaction.. CONCLUSIONS: Corticosteroids used in an appropriate dosage schedule constitute an important component of the treatment for TEN to ensure early recovery.

Azathioprine as a corticosteroid-sparing agent in air-borne contact dermatitis.

Two patients having air-borne contact dermatitis (ABCD) caused by Parthenium hysterophorus.for 10 and 15 years respectively and without having had complete remissions in spite of oral betamethasone in a dose of 2-3 mg per day, experienced complete relief while taking 50-100 mg azathioprine for 5 and 12 weeks without having to take systemic corticosteroids. There were no side effects of azathioprine. With further experience and standardization of the treatment schedule, it may be possible to use azathioprine as a corticosteroid-sparing agent to reduce the side effects of corticosteroids in patients having ABCD.

Alopecia totalis treated with oral mini-pulse (OMP) therapy with betamethasone.

An 8-year-old girl having alopecia areata which progressed to alopecia totalis in 1½ years showed an incomplete regrowth of the hair when treated with our standard regime of 1 mg betamethasone per day orally in spite of the treatment having been continued for 8 months. She had also increased her body weight by 4 kg during this period. On instituting the OMP regime consisting of 5 mg betamethasone as a single oral dose with breakfast on two consecutive days per week, she showed complete regrowth of the hair over the entire scalp during the next 3 months, and there were no side effects. We recommend OMP as another choice for patients having alopecia areata especially in recalcitrant cases where the treatment has to be given for prolonged periods.

Topical fluocinolone acetonide acetate ointment in autosomal dominant congenital hypotrichosis.

Hypotrichosis present at birth occurring as an isolated defect in three members of an Afghan family and transmitted as an autosomal dominant trait, responded to topical applications of fluocinolone acetonide acetate ointment. The patients were a 9-year-old boy, his 7-year-old sister and their 30-year-old mother who since birth, had sparse, light-coloured and thin hairs on their scalp which would not grow longer than 1 cm in length. Microscopic examination revealed the hairs to be thin and fragile, but of a uniform thickness. Some of the hairs showed secondary trichorrhexis. Following topical applications of 0.1% fluocinolone ointment, the hairs became coarser and increased in length from an ayerage of 0.7 cm before treatment to 6.2 and 7.1 cm in the two children after 10 months. The mother who started the treatment later also showed improvement.