Treatment strategy with multidrug therapy and tonsillectomy pulse therapy for childhood-onset severe IgA nephropathy.

BACKGROUND: IgA nephropathy is a typical chronic glomerulonephritis that tends to occur in childhood. METHOD: We reviewed the report on pathogenesis, treatment strategy with multidrug therapy and tonsillectomy pulse therapy for childhood-onset severe IgA nephropathy to clarify the pathophysiology and treatment of IgA nephropathy in childhood. RESULTS: In recent years, it has been found that the pathogenesis at onset is associated with aberrant glycosylation at the IgA1 hinge. Given this genetic background, the aberrantly glycosylated IgA1immune complex produced by antigen-stimulated T cells and B cells is deposited in the glomeruli. Inflammation is induced via activation of the complement, macrophages and mesangial cells, and glomerular damage progresses thereafter. Treatment is selected according to the severity of IgA nephropathy. In order to prevent the development of renal damage, it is important to control the associated immune responses. For severe IgA nephropathy, in particular, multidrug therapy with prednisolone, immunosuppressants, and angiotensin enzyme synthesis inhibitors and tonsillectomy methylprednisolone pulse therapy are now performed- and, as a result, the number of renal deaths has decreased and the long-term prognosis has improved. CONCLUSION: The prognosis of IgA nephropathy is improving. In the future, it will be important to develop a treatment method that takes into consideration the fact that children are in their growth and development stage and, therefore, seeks to minimizes side effects.

Effect of intravenous pulse dexamethasone versus daily oral prednisolone on bone mineral density in dermatology patients: Is it a site-specific response?

BACKGROUND: The use of glucocorticoids in various forms of administration is complicated by their systemic side effects. Although intravenous pulse therapy is considered to have lesser systemic side effects, there are few studies in literature comparing the effects of intravenous pulse glucocorticoids versus oral daily glucocorticoids on bone mineral density. AIM: To compare the effects of intravenous pulse glucocorticoids and oral daily glucocorticoids on bone mineral density with the aim of finding any site-specific osteopenic side effect. METHODS: The study was conducted by the department of dermatology of Postgraduate Institute of Medical Education and Research, Chandigarh, India. The study comprised of two groups of patients. Group A consisted of 28 patients with pemphigus vulgaris who received intravenous pulses of dexamethasone at 4 weekly intervals. Group B consisted of 21 patients with airborne contact dermatitis who received oral daily prednisolone therapy. All the patients had a dual X-ray absorptiometry scan at baseline, and at 3 and 6 months of follow-up. The results were analyzed as changes in bone mineral density. RESULTS: There was loss of bone mineral density at lumbar spine and the head of radius in both the groups. At the lumbar spine, Group B showed more reduction in bone mineral density at 3 months whereas in Group A it was more at the head of radius. In patients on oral steroids, the lumbar spine was significantly more affected than the head of radius at both 3 and 6 months of follow-up. However, in patients on intravenous pulse steroids, both the sites were equally affected at 3 and 6 months. LIMITATIONS: In our study, we used different glucocorticoids in the two groups: prednisolone in the oral daily group and dexamethasone in the intravenous pulse steroids group. A similar reduction in bone mineral density in both the groups may have been due to a longer half-life or more bone-directed side effects of dexamethasone as compared to prednisolone. CONCLUSION: Dermatologists need to be aware of the detrimental effects of high-dose intravenous pulsed glucocorticoids on bone mineral density and assessment of this parameter should be done before the initiation of therapy and also at regular intervals thereafter. During follow up, either the lumbar spine or the head of radius can be used to assess the osteopenic effect of intravenous pulse steroids, whereas the lumbar spine is a better site for this evaluation in patients on oral steroids.

Pemphigus in North-Western Yemen: A therapeutic study of 75 cases.

BACKGROUND: The incidence of pemphigus, though not documented, seems to be quite high in Yemen. There is no universal consensus on the treatment of this disease. AIMS: The aim was to evaluate the efficacy and side effects of different therapeutic regimens used in patients of pemphigus in North-Western Yemen. PATIENTS AND METHODS: Seventy-five Yemeni patients (39 males and 36 females) were included. Diagnosis was based on clinical features, histopathology and the Tzanck test. Results of treatment with these different therapeutic regimens were compared: (1) dexamethasone-cyclophosphamide pulse (DCP), (2) dexamethasone pulse with oral azathioprine, (3) oral prednisolone with azathioprine, (4) oral prednisolone with oral cyclophosphamide, and (5) prednisolone monotherapy. RESULTS: Pemphigus vulgaris (PV) was diagnosed in 46 patients, pemphigus foliaceus (PF) in 23, pemphigus vegetans (PVEG) in 5 and pemphigus herpetiformis (PH) in one. Among the 16 patients who received regular DCP therapy, 13 were in remission for 6 months to 11 years without medications (phase 4). Remission without pharmacotherapy could not be achieved with the other regimens and steroid-induced side-effects appeared to be more than with DCP. LIMITATIONS: Immunofluorescence was not available to confirm the diagnosis of pemphigus. Randomization was not done. CONCLUSION: The DCP regimen seemed to be superior to the other regimens used.

Weekly azathioprine pulse versus daily azathioprine in the treatment of Parthenium dermatitis: A non-inferiority randomized controlled study.

BACKGROUND: Azathioprine in daily doses has been shown to be effective and safe in the treatment of Parthenium dermatitis. Weekly pulses of azathioprine (WAP) are also effective, but there are no reports comparing the effectiveness and safety of these two regimens in this condition. AIMS: To study the efficacy and safety of WAP and daily azathioprine in Parthenium dermatitis. METHODS: Sixty patients with Parthenium dermatitis were randomly assigned to treatment with azathioprine 300 mg weekly pulse or azathioprine 100 mg daily for 6 months. Patients were evaluated every month to assess the response to treatment and side effects. RESULTS: The study included 32 patients in the weekly azathioprine group and 28 in the daily azathioprine group, of whom 25 and 22 patients respectively completed the study. Twenty-three (92%) patients on WAP and 21 (96%) on daily azathioprine had a good or excellent response. The mean pretreatment clinical severity score decreased from 26.4±14.5 to 4.7±5.1 in the WAP group, and from 36.1±18.1 to 5.7±6.0 in the daily azathioprine group, which was statistically significant and comparable (P=0.366). Patients on WAP had a higher incidence of adverse effects (P=0.02). LIMITATIONS: The study had a small sample size and the amount of clobetasol propionate used in each patient was not determined, though it may not have affected the study outcome due to its comparable use in both groups. CONCLUSIONS: Azathioprine 300 mg weekly pulse and 100 mg daily dose are equally effective and safe in the treatment of Parthenium dermatitis.

Factors affecting the duration of phase I of dexamethasone - cyclophosphamide pulse therapy.

BACKGROUND: The introduction of dexamethasone-cyclophosphamide pulse (DCP) therapy for the pemphigus group of disorders by Pasricha has revolutionized the therapy for pemphigus. There are very few studies regarding factors affecting duration of phase I of the DCP. AIMS: Our purpose was to study the relationship between various factors and duration of the phase I. METHODS: A retrospective study of 98 patients of pemphigus on Dexamethasone Pulse therapy was conducted. Patients were classified according to duration of Phase 1 as those with phase I less than 6 months and those more than 6 months and analyzed for variable factors affecting duration of phase I. RESULTS: Disease severity in pemphigus significantly prolonged the duration of phase I of DCP. Longer duration was also observed in patients on concurrent oral steroid therapy (both statistically significant). CONCLUSION: The findings from our study help us to address patient expectations and apprehensions regarding duration of therapy. A detailed understanding of the various patient and disease related factors responsible for affecting Phase I duration will help in better management of the patient, and the disease.

Assessment of the therapeutic benefit of dexamethasone cyclophosphamide pulse versus only oral cyclophosphamide in phase II of the dexamethasone cyclophosphamide pulse therapy: a preliminary prospective randomized controlled study.

BACKGROUND: Dexamethasone cyclophosphamide pulse (DCP) therapy is an established mode of treatment for pemphigus in India. AIMS: To assess the therapeutic benefit of additional DCPs (phase II, consolidation phase) versus immediate oral cyclophosphamide, usually used in phase III (maintenance phase), after initial DCP therapy (phase I) and to assess which laboratory test (DIF or ELISA) will reflect the clinical relapse best. METHODS: Nineteen newly recruited patients of pemphigus vulgaris (PV) received monthly DCPs in phase I and were then randomized into two groups. Group A (10 patients) received monthly DCPs for nine months and Group B (nine patients) received only oral cyclophosphamide for nine months. Direct immunofluorescence (DIF) and enzyme-linked immunosorbent assay (ELISA) were tested before starting DCP regimen, and at 0,3,6,9 months after randomization. RESULTS: Clinical relapse by the end of follow-up period occurred in only one patient in each group. In these cases, DIF became (again) positive before the relapse. No statistically significant difference between the two groups was found at three, six and nine months by ELISA indices and DIF grading. CONCLUSION: Although the DCP regimen is the standard therapy for pemphigus in India, we found no difference in the clinical outcome between patients receiving nine DCPs in phase II and patients shifted directly from phase I to III. Periodic testing using DIF and Dsg ELISA were found to be useful to monitor disease activity and predict a relapse. Further large scale studies are required to assess if patients can be shifted directly from phase I to III and maintained only on oral cyclophosphamide.

Randomized open comparative trial of dexamethasone-cyclophosphamide pulse and daily oral cyclophosphamide versus cyclophosphamide pulse and daily oral prednisolone in pemphigus vulgaris.

BACKGROUND: In various case series, pulse therapy has shown good results in pemphigus vulgaris (PV), with long-term remissions. AIMS: To compare the efficacy and side-effects of dexamethasone-cyclophosphamide pulse and daily oral cyclophosphamide (DCP+C) versus cyclophosphamide pulse and daily oral prednisolone (CP+P) in PV. METHODS: Twenty-eight active PV patients were randomized to receive either DCP with daily oral cyclophosphamide (Group A, n = 15) or CP with tapering doses of daily oral prednisolone (Group B, n = 13) for 12 months and followed-up for at least 3 months after stopping therapy. They were compared for time taken to achieve mucocutaneous disease control, achieve remission, relapse during treatment period, relapse after stopping therapy and side-effects. RESULTS: Of 28 cases, 25 (Group A - 15, Group B - 10) completed the study period and were analyzed. The time for initiation of cutaneous response and time to achieve complete disease remission were significantly lesser in group B. However, other efficacy parameters were comparable. In Group A, significant adverse events were dysgusea, hiccups, palpitation, nail discoloration, bone pain and urinary tract infection while in Group B, they included nausea, moon facies, flushing, secondary amenorrhea, steroid withdrawal symptoms and dyspnea due to weight gain. CONCLUSIONS: Early remission was achieved in group B but the relapse rates during the treatment phase or after stopping therapy were comparable. Both therapies had comparable side-effect profiles, although Group B showed greater steroid-induced adverse events.

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

BACKGROUND: 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. AIMS: The objective of the study was to assess the outcome of DCP therapy in pemphigus. METHODS: Pemphigus patients who had been treated with DCP therapy from 2001 to 2008 were prospectively and retrospectively analyzed. RESULTS: 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. CONCLUSIONS: DCP therapy was found to be effective in inducing and maintaining remission in pemphigus, provided the patients receive regular and complete treatment.

[Treatment of skin ulcers in collagen vascular diseases].

The causes of skin ulcers in collagen vascular diseases are complicated, and involve peripheral vascular complications, vasculitis, and thrombosis. It is necessary to determine the treatment, such as oral medication, infusion, ointment and surgery after careful consideration of its causes. This review shows skin manifestations of various collagen vascular diseases and the causes of skin ulcers in these diseases.