Avascular bone necrosis. A complication of long-term corticosteroid therapy.

A patient with pemphigus vulgaris, treated with long term corticosteroids, developed avascular necrosis of the head of the femur and humerus, bilaterally. This patient emphasizes the fact that the use of corticosteroids in dermatologic disorders may be a predisposing cause in avascular necrosis, and that this is another side effect of long-term corticosteroid therapy. This patient is particularly remarkable in that both hips and both shoulders were involved.     

A Comparative Effectiveness Research of Azathioprine and Cyclophosphamide on the Clinical and Serological Response in Pemphigus Vulgaris

Context:A prospective study was carried out to examine the efficacy of cyclophosphamide and azathioprine in pemphigus vulgaris.Aims:To compare the clinical and serological effect of azathioprine and cyclophosphamide in pemphigus patients.Results:Azathioprine had a slower onset of action with a statistically significant improvement seen by 6 months (P = 0.016). Cyclophosphamide had a faster onset of action (3 months) though there was no statistical difference in the efficacy between the two at the end of 6 months. The (RonT) was 33.3–44.4% for azathioprine and 28.8–42.9% for cyclophosphamide at 6 months. Though ELISA had a high sensitivity and specificity for diagnosis, as a tool for assessing therapeutic response a significant decrease was seen only till 3 months. This was restricted to Dsg1 for the azathioprine group and both Dsg3 and Dsg1 levels for the cyclophosphamide group. There were two deaths, both in the cyclophosphamide group.Conclusions:Azathiorpine and cyclophosphamide are equally effective for mucosal and cutaneous disease in pemphigus after 6 months of therapy. Dsg ELISA is useful for diagnosis of pemphigus but is not a useful tool for monitoring response to therapy.     

Localized Pemphigus Vegetans without Mucosal Involvement

Pemphigus vegetans is a rare variant of pemphigus vulgaris. A 62-year-old woman presented with erythematous moist vegetative plaque on the left breast and left groin. There was no mucosal involvement. Histopathological and direct immunofluorescence findings were suggestive of pemphigus vegetans. She showed excellent response to oral steroids. Literature is scarcely available on the limited involvement with pemphigus vegetans without mucosal involvement.     

Assessing the autoantibody levels in relation to disease severity and therapy response in pemphigus patients

Background:

In pemphigus, autoantibodies are directed against adhesion molecules, which make the junctions between keratinocytes, and thus determining their level can reflect the disease activity.

Aim:

The purpose of this study is to determine the clinical significance of the autoantibody levels in pemphigus management.

Materials and Methods:

The clinical features of 47 pemphigus vulgaris patients were assessed and patients′ sera were investigated by indirect immunofluorescence using monkey esophagus as a substrate for autoantibody levels.

Results:

We found a significant correlation between antibody titers and mucosal severity scores. Initial antibody titers of the patients with at least one mucosal lesion at the end of the first month of the therapy were found significantly higher than the patients who had no mucosal lesion. With the therapy, lesions resolved earlier than the antibody titers.

Conclusion:

In patients with pemphigus, especially in cases who were not treated before, sera antibody levels are a valuable tool in evaluating disease severity and choosing initial treatment. In patients who had been taking any systemic treatment, it is difficult to make a relationship between antibody levels and disease severity, because therapy improves disease earlier than the antibody titers. However, estimating antibody levels can be helpful for clinicians in disease management, in reducing or ceasing treatment dosage and anticipating recurrence.     

Serum Angiotensin Converting Enzyme in Pemphigus Vulgaris

Background:

Pemphigus vulgaris is an autoimmune blistering skin disease with unknown etiology. Drugs such as angiotensin-converting enzyme (ACE) inhibitors may contribute in the pathogenesis of pemphigus.

Objective:

We plan this essay to evaluate the serum ACE level in pemphigus vulgaris patients in comparison with healthy controls to recognize its possible role in disease pathogenesis or activity.

Methods:

This study was planned and performed in the dermatology clinics of Shahid Beheshti University of MedicalSciences’ Hospitals between July 2010 and June 2011. Patients with new onset of pemphigus vulgaris were enrolled in our study. Control subjects were frequency-matched to cases by sex and age. Serum ACE was determined by the spectrophotometric method.

Results:

Thirty-four patients with pemphigus vulgaris and 35 healthy individuals were recruited in the study. No statistical significant difference was detected in the mean level of serum ACE of the two groups (t-test, P = 0.11). The mean ACE level was significantly lower in male patients compared with male controls (P = 0.04). Moreover, a significant higher serum ACE level of patients with cutaneous involvement was observed compared to patients with mucosal involvement (P = 0.02).

Conclusions:

Despite lack of any significant difference of serum ACE level between pemphigus and control group, the serum ACE level was considerably lower in male pemphigus vulgaris patients compared with male controls. Therefore, ACE might have some association with pemphigus vulgaris especially in male patients; however, further studies are required to confirm this association.     

Childhood pemphigus

BACKGROUND: Five children with pemphigus are reported: three with pemphigus vulgaris, one with pemphigus vegetans, and one with pemphigus foliaceus. Only one case of juvenile pemphigus vegetans has been published in the literature. MATERIALS AND METHODS: All three patients with pemphigus vulgaris were treated with oral corticosteroid; in two cases, azathioprine was added for steroid-sparing effect. The patient with pemphigus vegetans had a clinical presentation resembling pemphigus vulgaris, but the lesions in the perianal area healed as hypertrophic granulation tissue. He was treated with oral corticosteroid, azathioprine, and intralesional corticosteroid. The patient with pemphigus foliaceus presented with exfoliative dermatitis, and was treated with oral corticosteroid; methotrexate was added later for steroid-sparing purposes RESULTS: The patients were followed up for 1-4 years; the prognosis of childhood pemphigus is good. CONCLUSIONS: Long-term follow-up is needed to detect flaring of the disease and the side-effects of immunosuppressive drugs.     

Inguinal pseudotumor: relapse of a pemphigus after 15 years' remission

INTRODUCTION: Pemphigus vegetans (PV) is a rare type of pemphigus vulgaris. We report a patient with pemphigus vulgaris relapsing as an isolated vegetative tumour. CASE REPORT: A 59-year-old man was seen in February 2001 for a tumour on the right groin. He had received systemic corticosteroids and cyclophosphamide for pemphigus vulgaris from 1974 to 1985, and he had been in complete remission since 1985. At the time of evaluation, a 10 x 5 x 5 cm, smooth vegetative tumour was seen on the right groin. Biopsies showed spongiosis, acanthosis and some acantholysis. Direct immunofluorescence showed strong deposition of immunoglobulin G within the intercellular substance of the epidermis. Indirect immunofluorescence revealed anti-intercellular antibodies at a titer of 1/800. Immunoblot analysis showed reactivity with the 130 kD pemphigus vulgaris antigen. PVg was diagnosed. Local corticosteroid treatment was initiated. The patient was disease-free at follow-up three years later. DISCUSSION: Localised forms of pemphigus are very rare. Twenty four other cases have been reported among them just one case of localised PV. Our case report is very unusual because of the variability of the expression of the disease, the high antibody level, the absence of trigger factors, and the efficacy of the local corticosteroid treatment.     

A Clinicopathological Study of Pemphigus in Eastern India with Special Reference to Direct Immunofluorescence

Background:Pemphigus is a group of chronic autoimmune vesico-bullous disorders in which the epidermis and the basement membrane zone are the focus of attack resulting in cutaneous and mucosal blister formation. Direct immunofluorescence (DIF) test is a very sensitive test for the diagnosisAim:To study the clinico histopathological patterns of pemphigus in eastern India. The study also aims to correlate DIF with clinical and histologic findings as well as severity of skin involvement [scoring systems].Results:In our study Pemphigus vulgaris (PV) was the predominant type with 32 cases followed by 8 cases of pemphigus foliaceus (PF) and a single case of IgA pemphigus. Mean age at presentation was late middle age. Majority of the patients, 26 (63.41%) initially had cutaneous involvement followed by mucosal involvement. In this study group 36 (87.80%) patients showed acantholytic cells on histopathological examination. Most patients of PV showed suprabasal blister 20 (62.50%) followed by intraspinous 5 (15.62%) and subcorneal 5 (15.62%) blister. In majority 28 (87.50%) of the PV patients IgG and C3 antibodies were deposited throughout the epidermis. The strength of antibody positivity was strong in most of the patients (71.87%). In cases of PF mostly IgG 6 (75%) antibodies were deposited in the upper epidermis. DIF intensity had poor correlation with disease activity/severity except in PF.Conclusion:Almost 85.36% cases of pemphigus were diagnosed clinicopathologically. But 6 cases couldn’t be diagnosed accurately on clinicopathological basis and in them DIF was confirmatory. Two cases of pure mucosal PV and 1 case of IgA pemphigus was confirmed by DIF. Two cases of bullous pemphigoid clinico-histologically mimicking PV were also excluded by DIF. So it appears from our study that DIF is confirmatory for diagnosis of pemphigus in all cases.     

Immunosuppressive therapy for pemphigus vulgaris complicated by malakoplakia of the bladder

Pemphigus vulgaris is an uncommon auto-immune disease which responds well to treatment with corticosteroids and azathioprine. Malakoplakia is a rare granulomatous disease associated with coliform infections and an altered cellular immune response. We report a 68-year-old female patient with pemphigus vulgaris who, after 2 years on maintenance prednisone and azathioprine immunotherapy, developed malakoplakia of the bladder associated with chronic E. coli urinary-tract infection. The malakoplakia responded well to treatment with cotrimoxazole, bethanechol chloride and ascorbic acid, combined with tapering of the corticosteroid dosage. Our patient presents an uncommon but interesting complication of long-term immunosuppressive therapy for pemphigus vulgaris.     

Cerebriform Cutaneous Lesions in Pemphigus Vegetans

Pemphigus vegetans is an autoimmune bullous disorder characterized by vegetating lesions commonly over the flexures. A 42-year-old female patient came with pemphigus vegetans presenting with interesting cerebriform morphology of the cutaneous lesions over the flexures. Cerebriform tongue, a morphology with typical pattern of sulci and gyri over dorsum of the tongue is a well-known sign seen in pemphigus vegetans. Interestingly, we noticed the typical sulci and gyri pattern in the skin lesions of pemphigus vegetans over the flexures of the body. This clinical sign can be used as a clue in the diagnosis of pemphigus vegetans. Morphology and physical characteristics are important for the diagnosis of the disease. Clinical signs always give a clue to the probable or possible diagnosis in most of the dermatological conditions.     

Assessment of bone mineral density by dual x-ray absorptiometry in dermatological patients treated by corticosteroids

Background:

Corticosteroids are mainstay of dermatological therapy and they are also a well known cause of osteoporosis. The objective of the present study was to find out the influence of the systemic intake of corticosteroids, either by the oral route or by IV pulse administration, on bone mineral density in dermatological patients using dual X-ray absorptiometry (DXA).

Materials and Methods:

This study was carried on 100 patients and 55 controls. The first group of patients included 55 patients undergoing long-term oral corticosteroid therapy daily and the second group included 45 patients who received IV dexamethasone pulse therapy. DXA was measured once for both the controls and patients in group 1. DXA was measured twice for patients in group 2, before starting pulse therapy (baseline DXA) and six months after regular treatment with pulse therapy (follow-up DXA).

Results:

The results show that significant reduction in BMD occurs in both groups, however, oral corticosteroids produce significantly more reduction in BMD in the lumbar spine. BMD was not found to be affected by the cumulative doses of corticosteroids, the duration of daily oral corticosteroid intake, or the number of IV dexamethasone pulses.

Conclusion:

Corticosteroid treatment causes significant BMD loss in patients treated by either route. Prophylactic treatment against osteoporosis is mandatory in patients receiving either form of corticosteroids.     

HYPERTROPHIC LUPUS VULGARIS: AN UNUSUAL PRESENTATION

Lupus vulgaris is the most common form of cutaneous tuberculosis occurring in previously sensitized individuals with a high degree of tuberculin sensitivity. Various forms including plaque, ulcerative, hypertrophic, vegetative, papular, and nodular forms have been described. A 30-year-old male patient presented with a very large hypertrophic lupus vulgaris lesion over left side of chest since 22 years. Histopathological examination showed granulomatous infiltration without caseation necrosis. The Mantoux reaction was strongly positive. Hypertrophic lupus vulgaris of such a giant size and that too at an unusual site is extremely rare and hence is being reported.     

Psoriatic Erythroderma and Hypothalamus-Pituitary Axis Suppression Due to Misuse of Systemic Steroid: Two Challenging Cases

Adding corticosteroid in homeopathic pills, self medication of steroid in the backdrop permanent cure in cases of psoriasis is not very uncommon in clinical practice in Indian subcontinent. First case a 52 year man, a known case of psoriasis vulgaris with psoriatic arthropathy of 15 years duration received multiple modalities of therapies without any satisfactory response. He was on self medication of tab prednisolone 10 mg daily with Cushingoid features. Second case a 22 year old boy, a known case of psoriasis from last 06 years was on Homeopathic treatment with Cushinoid features. Tapering of systemic steroid in first case and discontinuation of homeopathic drug in second case resulted in erythroderma and features of adrenal insufficiiency. Investigation revealed low morning cortisol and low cortisol following ACTH stimulation suggestive of HPA axis suppression. Planned withdrawal of steroid under the cover of short acting systemic steroid for short duration along with combination of immunosuppressants and supportive care gave an excellent result in both the cases.     

Hailey-Hailey Disease Responding to Thalidomide

Familial benign chronic pemphigus or Hailey-Hailey disease (HHD) is a rare autosomal dominant disorder characterized by the development of recurrent blisters and erosions in the intertriginous areas. Various topical and systemic treatment options include corticosteroids, topical 5-fluorouracil, topical vitamin D analogs, topical zinc oxide, dapsone, psoralen plus ultraviolet A, systemic retinoids, cyclosporine, methotrexate, and photodynamic therapy. In recalcitrant cases, further options including, invasive methods such as grenz ray therapy, carbon dioxide laser abrasion, and erbium: YAG laser ablation, dermabrasion, electron beam therapy, botulinum toxin, and full-thickness excision of affected skin with repair by split-thickness grafting have been reported as useful in treatment of HHD. We describe a case of HHD who was treated with several treatment modalities including antibiotics, corticosteroids, and dapsone earlier and when presented to us had a severe recalcitrant disease. Thalidomide, as a modality of treatment has been successfully used in few cases earlier. Our patient responded well to thalidomide.     

Pulse Therapy in Pemphigus: Ready Reckoner

Pulse therapy for the treatment of pemphigus has been in vogue for several years and is administered by many dermatologists across the world. However, even though there is enough evidence about its efficacy and methodology, there continue to be doubts and questions regarding the rationale of use of high dose intravenous steroids and steroid-sparing immunosuppressants. This article has aimed to provide clarity to young dermatology residents on the administration of pulse therapy, and the various controversies and modifications that have been mentioned in literature over the past couple of years.     

免疫抑制剂联合糖皮质激素治疗寻常型天疱疮疗效观察

目的:探讨环磷酰胺联合糖皮质激素治疗寻常型天疱疮的近、远期疗效。方法:收集近4年42例在我科住院经临床、病理确诊为寻常型天疱疮患者的详细资料,比较评估糖皮质激素联合硫唑嘌呤(AZP组)和糖皮质激素联合环磷酰胺(CTX组)治疗后的近、远期疗效。结果:近期疗效,AZP组痊愈率80.0%(16/20),未愈20.0%(4/20);CTX组痊愈率86.4%(19/22),未愈14.6%(3/22),两组相近,差异无统计学意义(P>0.05)。远期疗效,AZP组痊愈40.0%(8/20),控制35.0%(7/20),未控制25.0%(5/20);CTX组痊愈率81.8%(18/22),控制9.0%(2/22),未控制9.0%(2/22),两组差异有统计学意义(P<0.05)。结论:环磷酰胺静脉冲击(五日疗法)联合糖皮质激素疗法是治疗寻常型天疱疮的较好方法。     

A Cross-sectional Study of Direct Immunofluorescence in the Diagnosis of Immunobullous Dermatoses

Background:

Autoimmune blistering diseases are a group of bullous disorders characterized by pathogenic antibodies directed at the target antigens, which are components of the desmosomes or adhesion complex at the dermoepidermal junction. Direct immunofluorescence (DIF) is invaluable in the diagnosis of these lesions.

Aim:

The aim of this study was to evaluate the sensitivity of DIF in immunobullous dermatoses and to study the pattern of DIF. The study also aims to correlate DIF with clinical and histologic findings and to analyze discrepancies.

Materials and Methods:

Total 100 biopsies received over a period of 2 years in the Department of Pathology were analyzed. DIF, histopathology and clinical data were reviewed.

Results:

Out of 100, 89 cases showed DIF patterns concordant with clinical/histologic diagnosis. The sensitivity of DIF was 94.44% (51/58) in the pemphigus and 84% (21/25) in the bullous pemphigoid (BP) group, 100% each in dermatitis herpetiformis (2/2) and linear IgA disease (1/1). A total of 11 histologically proven cases of immunobullous lesions were DIF negative-four (three of pemphigus vulgaris and one of BP) due to having no epidermis, three (cases of BP) owing to sampling/technical errors and the remaining four (cases of pemphigus vulgaris) due to being on treatment.

Conclusion:

Immunofluorescence helps confirm the diagnosis of bullous lesions in which there is clinical and the histopathologic overlap. Sampling errors contributed to false negative (FN) results.     

Extensive keloidal healing of pemphigus vulgaris

Bullae of pemphigus vulgaris heal without scarring. We here report a patient of pemphigus vulgaris whose lesions healed with a one-month history of extensive flaccid bullae and uninfected erosions on the trunk and extremities along with superficial erosions in the oral mucosa. The clinical suspicion of pemphigus vulgaris was confirmed by histopathological and immunohistological examination. Pulse therapy with monthly parenteral dexamethasone and cyclophosphamide pulse was instituted. The cutaneous lesions on healing formed extensive keloidal scars despite high dose of monthly corticosteroid therapy.     

Intramuscular gold therapy for young patients with pemphigus vulgaris: a prospective, open, clinical study utilizing a dermatologist/rheumatologist team approach

Pemphigus vulgaris is a severe dermatosis, often requiring systemic corticosteroid therapy. The attempt to find disease-modifying and corticosteroid-reducing drugs is ongoing. In this open study, a combined dermatologist-rheumatologist Learn approach is utilized in attempting to control pemphigus vulgaris with intramuscular gold therapy. Intra-muscular gold seems to have been a particularly useful agent.     

Pemphigus Foliaceus Masquerading as IgA Pemphigus and Responding to Dapsone

A 14-year-old male presented with seven years history of recurrent episodes of fluid filled, itchy and eroded lesions over the body not responding to oral corticosteroids and azathioprine. Dermatological examination revealed crusted plaques and erosions in a seborrheic distribution. Histopathology of skin lesions and direct immunofluorescence were characteristic of pemphigus foliaceus. He was treated with dexamethasone pulse therapy with inadequate response. However, relapsing skin lesions revealed a circinate arrangement with a predilection to trunk and flexures. In view of clinical features suggestive of IgA pemphigus, he was started on dapsone, to which he responded dramatically in four weeks. However, repeat biopsy continued to reveal features of pemphigus foliaceus and ELISA for anti-desmoglein 1 antibodies was positive.