Bullous pemphigoid in India: Review of cases registered in an autoimmune bullous disease clinic.

Background Information on bullous pemphigoid in an Indian context is scarce. Aim To report clinico-demographic profile, associated comorbidities and prescription pattern of bullous pemphigoid patients in India. Methods This was a retrospective study, where past records of all bullous pemphigoid patients diagnosed and treated between November 2013 and October 2019 were accessed and analysed. Patients having a compatible clinical presentation with either histopathological and/or direct immunofluorescence evidence of bullous pemphigoid were included. Results There were 96 bullous pemphigoid patients, with a male: female ratio of 1.6:1. The mean age at diagnosis was 62.5 ± 2.2 years, with mean duration of illness 27.5 ± 4.5 months before presentation. Comorbidities were present in 80 (83%) patients, with type 2 diabetes mellitus (38.5%), hypertension (36.4%) and neurological illness (16.7%) being the commonest ones. Clinically, blisters were the predominant presentation in 81 (84.4%) patients. The majority (87.5%) of patients showed a predominant eosinophilic infiltrate on histopathology. Direct immunofluorescence revealed immunoglobulin G deposits with complement C3 in 77 (80.2%) cases. The majority of patients (77.1%) were treated with oral prednisolone, either alone (11.5%) or in combination (65.6%) with other topical and systemic agents. Topical steroids were used in 29.1%, azathioprine in 28%, dapsone in 16.7% and omalizumab in 6.2% of patients. Limitations The study is retrospective. Immunofluorescence on salt split skin, direct immunofluorescence serration pattern analysis, and immunoblotting were not performed. Hence, there is a possibility that a few included cases were suffering from other subepidermal autoimmune bullous diseases like epidermolysis bullosa acquisita or anti-p200 pemphigoid. Conclusion Bullous pemphigoid patients in this study had a younger age of onset and showed male preponderance. Comorbidities like type 2 diabetes, hypertension and neurological disorders were frequent. Cutaneous blisters were the most frequent clinical presentation. Systemic corticosteroids comprised the mainstay of therapy.

Diagnostic Utility of Biplex/Multiplex Polymerase Chain Reaction in Infectious Granulomatous Dermatitis in North Indian Population.

BACKGROUND: A definite diagnosis of infectious granulomatous dermatitis (IGD) is difficult for both practicing dermatologists and dermatopathologists due to overlapping clinical and histomorphological features. We aimed to explore the role of multiplex polymerase chain reaction (PCR) for identifying a definite etiological agent for diagnosis and appropriate treatment in IGD in formalin-fixed paraffin-embedded tissue. MATERIALS AND METHODS: Sixty-two cases of IGD were included, excluding leprosy. The histochemical stains including Ziehl-Neelsen, periodic acid-Schiff, and Giemsa were performed in all cases. A multiplex PCR was designed for detection of tuberculosis (TB) (IS6110 and mpt64), fungal infections (ITS1, ITS2; ZM1, and ZM3), and leishmaniasis (kDNA). The results of histomorphology, histochemical stains, and multiplex PCR were compared. RESULTS: Among 62 cases, the sensitivity rate of PCR detection for organisms was 16.7%, 0%, 100%, 72%, 75%, and 66.7% in patients with TB, suggestive of TB, leishmaniasis, fungal infections, and granulomatous dermatitis not otherwise specified and granulomatous dermatitis suggestive of fungus, respectively. The TB PCR using IS6110 primers was negative in all cases; however, PCR using mpt64 primers was positive in 33.33% cases of scrofuloderma. The histochemical stains including Ziehl-Neelsen for acid-fast bacilli, periodic acid-Schiff for fungus, and Giemsa for Leishman-Donovan bodies showed positivity in 11.3%, 43.5%, and 3.2%, respectively. CONCLUSION: A multiplex PCR (Mycobacterium tuberculosis, Leishmania, and panfungal) is highly recommended in all cases of IGD where an etiological agent is difficult to establish by skin biopsy and histochemical stains along with a clinicopathological correlation. This will augment in appropriate treatment and will reduce empirical treatment and morbidity in such patients.

Identification of clinical and immunological factors associated with clinical relapse of pemphigus vulgaris in remission.

BACKGROUND: Pemphigus vulgaris is a potentially fatal autoimmune epidermal blistering disease with a chronic and relapsing course. It is difficult to predict clinical relapse. Identification of clinical and immunological factors that are associated with early clinical relapse in a prospective study design may help in planning treatment for better maintenance of clinical remission. AIM: The aim of our study was to identify clinical and immunological factors associated with clinical relapse within 9 months of study inclusion in patients with pemphigus vulgaris in clinical remission. METHODS: Forty consecutive consenting patients who had been diagnosed to have pemphigus vulgaris and were in clinical remission on minimal therapy or off therapy were included. The patients were followed up every 3 months until 9 months. Clinical factors considered relevant were recorded at the beginning of the study. Immunological factors such as CD19+ B-cell count and CD19+CD27+ memory B cells/plasma cell count in peripheral blood were assessed at baseline [anti-desmoglein (Dsg) 1 and 3 titers were first assessed at 3 months, not at baseline] and repeated every 3 months, until 9 months or clinical relapse whichever was earlier. Direct immunofluorescence (DIF) of skin biopsy specimen was performed at study initiation and again at the time of clinical relapse or study completion, whichever occurred earlier. All patients completed the study. RESULTS: Of 40 patients, 11 (27.5%) experienced relapse as per definition, while 29 (72.5%) remained in complete remission. Clinical relapse during study duration was significantly more common in those who had onset of disease in oral mucosa [odds ratio (OR), 10.71; 95% confidence interval (CI) 1.21-94.86, P = 0.02], pruritus (OR 8.4; 95% CI 1.76-40.02, P = 0.01), and extensive cutaneous involvement during previous disease activity (OR 7.36; 95% CI 1.34-40.55, P = 0.03) and also pruritus during remission (P = 0.004). Immunological factors found to be significantly associated with early clinical relapse were raised CD19+ B-cell count at baseline (OR 7.84; 95% CI 1.39 - 53.41, P = 0.01), immunoglobulin G (OR 4.85; 95% CI 1.09-23.44, P = 0.04), and C3 (OR 20.33; 95% CI 3.02-199.5, P < 0.001) positivity in the intercellular space of the epidermis on DIF at study onset and rising anti-Dsg 3 antibody titers (OR 19.96; 95% CI 1.85- 310.9, P = 0.03). LIMITATIONS: Limited sample size, short follow-up duration, and inability to perform anti-Dsg enzyme linked immunosorbent assay for all the patients at all the time points of assessment are limitations of this study. CONCLUSION: Immunological relapse can be determined before clinical relapse, so that treatment can be restarted/modified and clinical remission can be maintained.

Clinical and pathological characterization of oral mucosal 'lichen planus-like lesions' in patients with pemphigus vulgaris: An observational study.

BACKGROUND: Lichen planus-like lesions on oral mucosa occasionally occur in Indian patients with pemphigus vulgaris. Its significance, both clinical and pathological, is yet to be elucidated. AIMS AND OBJECTIVES: To study the clinical and pathological characteristics of clinically apparent oral mucosal lichen planus-like lesions in pemphigus patients and to assess their relation with pemphigus disease activity. MATERIALS AND METHODS: A total of 32 patients with pemphigus vulgaris who had oral lichen planus-like lesions were included and classified as 'cases,' and eight diagnosed cases of pemphigus vulgaris without lichenoid 'hue' were included as controls. The biopsy specimens were subjected to routine histopathologic examination, immunohistochemistry with FasL, and caspase-3 and direct immunofluorescence. RESULTS: On histopathologic examination, the diagnosis of pemphigus vulgaris, lichen planus, 'overlap' and 'nonspecific' were rendered in 19 (59.4%), 4 (12.5%), 5 (15.6%) and 4 (12.5%) cases, respectively. On immunohistochemistry, FasL was positive in epithelial cells in 16 (50%) cases and 4 (12.5%) controls (P = 0.066). Caspase-3 stained positively in 18 (56.2%) cases and 20 (62.5%) controls (P = 0.77). Direct immunofluorescence was positive in 77.8% (21/27) of the cases. LIMITATIONS: Relatively small number of controls is the limitation of this study. CONCLUSION: Lichen planus-like lesions in pemphigus should not be labeled as inactive disease or postinflammatory hyperpigmentation. Apoptosis followed by pigment incontinence seems to explain such lesions with 'lichen planus-like appearance' in oral pemphigus vulgaris. Active pemphigus smoulders in a majority of these lesions.

Role of dental restoration materials in oral mucosal lichenoid lesions.

BACKGROUND: Dental restorative materials containing silver-mercury compounds have been known to induce oral lichenoid lesions. OBJECTIVES: To determine the frequency of contact allergy to dental restoration materials in patients with oral lichenoid lesions and to study the effect of removal of the materials on the lesions. RESULTS: Forty-five patients were recruited in three groups of 15 each: Group A (lesions in close contact with dental materials), Group B (lesions extending 1 cm beyond the area of contact) and Group C (no topographic relationship). Thirty controls were recruited in two groups of 15 individuals each: Group D (oral lichenoid lesions but no dental material) and Group E (dental material but no oral lichenoid lesions). Patch tests were positive in 20 (44.5%) patients. Mercury was the most common allergen to elicit a positive reaction in eight patients, followed by nickel (7), palladium (5), potassium dichromate (3), balsam of Peru, gold sodium thiosulphate 2 and tinuvin (2) and eugenol (1), cobalt chloride (1) and carvone (1). Seven patients elicited positive response to more than one allergen. In 13 of 20 patients who consented to removal of the dental material, complete healing was observed in 6 (30%), marked improvement in 7 (35%) and no improvement in 7 (35%) patients. Relief of symptoms was usually observed 3 months after removal. LIMITATIONS: Limited number of study subjects and short follow up after removal/replacement of dental restoration materials are the main limitations of this study. CONCLUSION: Contact allergy to amalgam is an important etiologic factor in oral lichenoid lesions and removal of restorative material should be offered to patients who have lesions in close proximity to the dental material.

Clinical characteristics and outcome in multibacillary (MB) leprosy patients treated with 12 months WHO MDT-MBR: a retrospective analysis of 730 patients from a leprosy clinic at a tertiary care hospital of Northern India.

BACKGROUND: Shortened (12 months) multidrug multibacillary regimen (MDT MBR) was implemented in India in 1998, however there is yet a paucity of crucial data on its long-term outcome. OBJECTIVE: To assess the efficacy of 12 months MDT MBR in multibacillary (MB) patients at our centre. DESIGN: This was a retrospective study undertaken analysing the clinic records of 1210 patients registered at the leprosy clinic of our institute from 1999 to 2010. RESULTS: 730 MB patients were treated with 12 months MDT MBR over this period. High bacillary index (BI) > or = 3 + was observed in 313 patients at the time of registration. Four hundred and one (54.9%) patients experienced lepra reactions. Recurrent ENL was observed in only 14 patients which manifested even after 5 years of stopping treatment. Clinico-histological correlation was noted in 361 (49.5%) patients. During follow up period ranging from 9 months to 10 years, nearly all patients had clearance of skin lesions including histopathological/bacteriological improvement. Only 13 (1.7%) patients relapsed. CONCLUSIONS: All patients responded well with 12 months MDT MBR without significant side effects. The overall relapse rate was only 1.7%. Thus, the recommendation for 12 months MDT MBR for all MB patients is robust and operationally practical, a decision which seems logical.

Cutaneous vasculitides: clinico-pathological correlation.

BACKGROUND: Cutaneous vasculitis presents as a mosaic of clinical and histological findings. Its pathogenic mechanisms and clinical manifestations are varied. AIMS: To study the epidemiological spectrum of cutaneous vasculitides as seen in a dermatologic clinic and to determine the clinico-pathological correlation. METHODS: A cohort study was conducted on 50 consecutive patients clinically diagnosed as cutaneous vasculitis in the dermatology outdoor; irrespective of age, sex and duration of the disease. Based on the clinical presentation, vasculitis was classified according to modified Gilliam's classification. All patients were subjected to a baseline workup consisting of complete hemogram, serum-creatinine levels, serum-urea, liver function tests, chest X-ray, urine (routine and microscopic) examination besides antistreptolysin O titer, Mantoux test, cryoglobulin levels, antineutrophilic cytoplasmic antibodies and hepatitis B and C. Histopathological examination was done in all patients while immunofluorescence was done in 23 patients. RESULTS: Out of a total of 50 patients diagnosed clinically as cutaneous vasculitis, 41 were classified as leukocytoclastic vasculitis, 2 as Heinoch-Schonlein purpura, 2 as urticarial vasculitis and one each as nodular vasculitis, polyarteritis nodosa and pityriasis lichenoid et varioliforme acuta. Approximately 50% of the patients had a significant drug history, 10% were attributed to infection and 10% had positive collagen workup without any overt manifestations, while 2% each had Wegener granulomatosis and cryoglobulinemia. No cause was found in 26% cases. Histopathology showed features of vasculitis in 42 patients. Only 23 patients could undergo direct immunofluorescence (DIF), out of which 17 (73.9%) were positive for vasculitis. CONCLUSIONS: Leukocytoclastic vasculitis was the commonest type of vaculitis presenting to the dermatology outpatient department. The workup of patients with cutaneous vasculitis includes detailed history, clinical examination and investigations to rule out multisystem involvement followed by skin biopsy and DIF at appropriate stage of evolution of lesions. Follow up of these patients is very essential as cutaneous manifestations may be the forme fruste of serious systemic involvement.

Comparative evaluation of immunotherapeutic efficacy of BCG and mw vaccines in patients of borderline lepromatous and lepromatous leprosy.

BACKGROUND: Even after 12 months of multi-drug therapy (M.D.T.) multibacillary (MB) therapy patients with high bacterial index (B.I.) continue to harbor dead bacilli and viable persisters, which lead to immunological complications such as recurrent reactions and late relapses, respectively. To achieve faster killing of viable bacilli and clearance of dead bacilli, various immunotherapeutic agents (vaccines and cytokines) are being evaluated as an adjunct to M.D.T. Aims and objectives. To evaluate the role of BCG and Mw vaccines in the immunotherapy of leprosy. MATERIALS AND METHODS: Sixty untreated leprosy patients with a BI = 2 were randomly allocated to three treatment groups of twenty patients each. Group A patients received World Health Organization (W.H.O.) (12 months M.D.T.-MBR) and BCG intradermally (105 live bacilli/per dose). Group B patients were administered 12 months M.D.T.-MBR and Mycobacterium w (1 x 108) killed bacilli as first dose and 0.5 x 108 /dose in subsequent doses. Group C received 12 months M.D.T. MBR with 0.1 ml of normal saline as placebo. All the groups received 4 doses of vaccine or normal saline repeated at three monthly intervals. The patients were periodically monitored by clinical (Ramu's score), bacteriological (slit skin smear), and histopathological (skin biopsy) parameters, six monthly during and one year after completion of M.D.T. RESULTS: The mean reduction in clinical scores in BCG and Mw groups was significantly more when compared to controls. At 12 and 24 months, the patients in BCG group had significantly greater reduction in Ramu's score as compared to those in the Mw group. BI declined by 2.40 units/year in patients receiving BCG, 2.05 units/year in the Mw group and 0.85 units/year in the control group. Although the incidence of type 1 reactions was apparently more in the BCG and Mw vaccinated groups, the incidence of type 2 reactions, neuritis and development of new deformities was less as compared to the controls. CONCLUSIONS: In our study, BCG exhibited slightly better and faster effect on bacteriological clearance and clinical improvement as compared to Mw vaccine in borderline lepromatous (BL)/ polar lepromatous (LL) patients with a high initial B.I., however, their effect on histopathological (decrease in GF) improvement was comparable. Both the vaccines were well tolerated. Immunotherapy can be a useful adjunct to the shortened (12 months) M.D.T. MB regimen to decrease the risk of reactions and relapses in highly bacilliferous BL/LL patients.

Impact of combined Mycobacterium w vaccine and 1 year of MDT on multibacillary leprosy patients

A total of 20 bacteriologically positive multibacillary (MB) leprosy patients older than 18 years of age with a bacterial index (BI) of 2+ or greater were given standard World Health Organization multiple drug therapy (MDT-MB) for 12 consecutive months plus four intradermal doses of Mycobacterium w vaccine at 3 monthly intervals (Study group). Twenty age-matched MB patients were given WHO/MDT alone (Control group). The patients of both groups were followed up for 1 year. Improvements in the patients were periodically monitored by clinical (Ramu's score), bacteriological (SSS), histopathological (skin biopsy) and immunological (lepromin conversion) parameters. Study group patients showed more significant improvements in all parameters except for lepromin conversion compared to patients in the Control group. The incidence of type 1 reaction was more in the Study group (30% vs 10%), while the incidence of type 2 reaction was more in the Control group (25% vs 15%). Neuritis associated with reactions was seen more often in the Control group compared to the Study group (20% vs 10%). The addition of Mycobacterium w vaccine as an adjunct to the 1-year WHO/MDT regimen appears to be significantly more beneficial in MB leprosy patients with a high initial BI compared to WHO/MDT given alone. Studies on larger numbers of patients with extended follow up will be in order.