Survival and prognostic factors in bullous pemphigoid: A retrospective cohort study.

Background Bullous pemphigoid is the most common subepidermal autoimmune blistering disease. Till now, the reported prognostic factors in bullous pemphigoid vary considerably. Aims The purpose of this study was to determine the overall survival rate and prognostic factors in bullous pemphigoid. Methods We conducted a retrospective cohort study on newly diagnosed bullous pemphigoid patients between July 2001 and November 2019 in a referral unit for autoimmune blistering skin diseases in Romania. Results One hundred forty-eight patients were included in the study. The Kaplan-Meier overall survival rates at 1, 3, 5 and 10 years were respectively 74.2% (95% confidence interval, 67.5-81.6%), 53.4% (45.7-62.2%), 43.6% (35.9-53%) and 31.3% (23.5-41.7%). The median follow-up among survivors was 48 months (interquartile range: 11-150). Ninety (60.8%) patients died during the follow-up period; of them, 38 (42.2%) had active disease at the time of death. Advanced age, neurological diseases, valvular heart disease, malignancies, use of statins, skin infections and extensive cutaneous involvement were linked to poorer outcomes, while the use of topical corticosteroids was associated with increased overall survival. Limitations This study lacks a control cohort to validate the obtained results. It was conducted in a retrospective manner in a single centre. In addition, indirect immunofluorescence microscopy was not performed in all patients. Conclusion Beyond ageing and neurological comorbidities, the prognosis of bullous pemphigoid patients was significantly influenced by the presence of skin infections, valvular heart disease, use of statins and extensive cutaneous involvement. Topical corticosteroid treatment was associated with increased survival in these patients.

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.

Anti-P 200 pemphigoid - The most common floor binding subepidermal autoimmune bullous disease in a tertiary care center in south India.

BACKGROUND: The pemphigoid group of diseases may present clinically and immunologically in a very similar fashion. Indirect immunofluorescence microscopy with readily available salt-split human skin in a BIOCHIP™ helps to classify these conditions as those with either with roof binding or floor binding of immunoreactants. Epidermolysis bullosa acquisita, anti-laminin 332 pemphigoid and anti-p200 pemphigoid show floor binding, while in the most frequent type of pemphigoid disease, bullous pemphigoid, epidermal side staining pattern is seen on salt-split skin Aims: The aim of the study was to detect the target antigens in sub-epidermal bullous diseases. METHODS: Forty patients with bullous pemphigoid diagnosed by lesional histopathology and direct immunofluorescence microscopy were re-evaluated by a BIOCHIP™ mosaic containing both tissue substrates and recombinant target antigens. Sera with floor pattern staining on salt-split skin were further evaluated by immunoblotting with dermal extract. RESULTS: Five patients with floor staining had anti-p200 pemphigoid. LIMITATIONS: We could not perform serration pattern analysis of direct immunofluorescence in our patients. CONCLUSION: Histopathology and direct immunofluorescence microscopy cannot differentiate between various entities of pemphigoid diseases. A multivariant approach using a BIOCHIP™ mosaic including salt-split skin followed by immunoblotting with dermal extract helps to identify the target antigen.

Nail changes in autoimmune blistering disorders: A case-control study.

BACKGROUND: Pemphigus and pemphigoid disorders produce blistering cutaneous lesions. Earlier case reports state that nail involvement is uncommon in these autoimmune blistering disorders. AIMS AND OBJECTIVES: To study nail changes in autoimmune blistering disorders. METHODS: A case-control study was conducted where 40 cases and 40 controls were evaluated for nail changes. RESULTS: Nail changes were seen in 72.5% of cases and 17.5% of controls. The most common nail findings were paronychia and onychorrhexis. LIMITATIONS: Small sample size; short study duration; nail biopsy could not be done. CONCLUSION: Our findings indicate that the inflammatory nature of the blistering cutaneous disease is often reflected conspicuously in the nails.

Risk of venous thromboembolism in patients with bullous pemphigoid: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Increased risk of venous thromboembolism is observed in several autoimmune inflammatory disorders. However, data on bullous pemphigoid, one of the most common autoimmune blistering disorders, is limited. This systematic review and meta-analysis was conducted to summarize all available evidence. METHODS: Two investigators independently searched published studies indexed in MEDLINE and EMBASE from inception to July 2016 using the terms for bullous pemphigoid and venous thromboembolism. The inclusion criteria were as follows: (1) cohort or case-control study evaluated the association between bullous pemphigoid and risk of venous thromboembolism, (2) effect estimates were provided as odds ratios, relative risk, hazard ratio, standardized incidence ratio with 95% confidence intervals, and (3) subjects without bullous pemphigoid were used as comparators for cohort studies, while subjects without venous thromboembolism were used as comparators for case-control studies. Point estimates and 95% confidence intervals were extracted from each study and were pooled together using the random-effect model, generic inverse variance method of DerSimonian and Laird. Cochran's Q test and the I2 statistic were used to evaluate the statistical heterogeneity. RESULTS: Two retrospective cohort studies, one prospective cohort study, and one case-control study met the eligibility criteria and were included in the meta-analysis. The pooled odds ratio was 2.69 (95% confidence interval, 1.79-4.05). Statistical heterogeneity was high with I2 of 77%. LIMITATION: Limited accuracy of diagnosis of primary studies and high between-study heterogeneity. CONCLUSION: This meta-analysis demonstrated that patients with bullous pemphigoid have a significantly increased risk of venous thromboembolism.

Epidermolysis bullosa acquisita and anti-p200 pemphigoid as major subepidermal autoimmune bullous diseases diagnosed by floor binding on indirect immunofluorescence microscopy using human salt-split skin.

BACKGROUND: Subepidermal autoimmune bullous diseases are a diverse group of diseases with overlapping clinical and immunopathological features. Indirect immunofluorescence microscopy on artificially split skin helps to classify these conditions into those with staining on the epidermal side of the split ("roof-binding") and those with staining on the dermal side ("floor-binding"). Epidermolysis bullosa acquisita is the prototype of "floor-binding" subepidermal autoimmune bullous diseases. However, not all floor-binding sera are associated with epidermolysis bullosa acquisita. AIM: The aim of this study was to evaluate the clinical and immunological profile of patients with floor-binding subepidermal autoimmune bullous disease by indirect immunofluorescence microscopy and to identify the target antigens in them. METHODS: Ten patients who showed a floor-binding pattern were studied with regard to their clinical and immunopathological characteristics. Target antigens were identified by modified indirect immunofluorescence microscopy using recessive dystrophic epidermolysis bullosa skin, enzyme linked immunosorbent assay, and immunoblotting. RESULTS: Diagnosis of epidermolysis bullosa acquisita was confirmed in six patients. Three patients with an inflammatory subepidermal autoimmune bullous disease mimicking bullous pemphigoid reacted with a 200 kDa protein on immunoblotting with dermal extract, as is characteristic of anti-p200 pemphigoid. One serum showed both roof and floor binding, and reacted with the BP180 antigen. LIMITATION: We could not perform serration pattern analysis in our patients. CONCLUSION: In this study, we report three cases of anti-p200 pemphigoid from India. These cases, though indistinguishable clinically from bullous pemphigoid, revealed a floor-binding pattern on indirect immunofluorescence using salt-split skin.

Bullous pemphigoid and antecedent neurological diseases: An association with dementia.

BACKGROUND: Bullous pemphigoid is the most common subepidermal immunobullous disorder. Studies have reported the association between bullous pemphigoid and various neurological diseases. AIMS: The aim of this study was to evaluate whether bullous pemphigoid is associated with pre-existent neurological diseases and whether specific diseases exhibit this association. METHODS: All dermatology inpatients from January 2010 to May 2015 were analyzed. Bullous pemphigoid cases were identified based on clinical features and consistent histopathologic and direct immunofluorescence findings. Patients with other autoimmune bullous skin disorders were excluded. An equal number of inpatients with other skin conditions were selected randomly as age- and sex- matched controls. RESULTS: Out of 3015 inpatients, 103 cases of bullous pemphigoid and 103 age- and sex-matched controls were included. Seventy six patients with bullous pemphigoid had a history of at least one neurological disease. After adjusting for age, gender, race, functional status and neuro-psychiatric medications, patients with bullous pemphigoid were found to be approximately thrice as likely to have a history of at least one neurological disease than were controls (odds ratio: 2.88; 95% confidence interval: 1.32-6.26; P = 0.008). Amongst the pre-existing neurological diseases, only dementia was statistically more prevalent in bullous pemphigoid cases compared to controls (adjusted odds ratio: 2.61; 95% confidence interval: 1.19-5.75; P = 0.017). Parkinson disease and psychiatric disorders demonstrated a higher adjusted risk among bullous pemphigoid patients but the difference was not statistically significant. LIMITATIONS: The limitations were potential referral and selection bias, as the patients were inpatients. There is a possible misclassification as the diagnosis of neurological diseases was performed using medical records. The duration from the diagnosis of neurological diseases to bullous pemphigoid could not be accurately determined as it was a retrospective review of records and most neurological diseases have a prolonged course. CONCLUSIONS: Pre-existent neurological disease, specifically dementia, was found to be associated with bullous pemphigoid.

Neurological diseases and bullous pemphigoid: A case-control study in Iranian patients.

INTRODUCTION: Neurological diseases are important co-morbidities found in association with bullous pemphigoid. Various neurological conditions (stroke, Parkinson's disease, dementia, epilepsy and multiple sclerosis) have been reported as associations of this bullous disease; whether these are significant has not been definitely proved. However, the presence of neurological conditions is a predictor of poorer prognosis. OBJECTIVES: Our aim was to examine the association of bullous pemphigoid and neurological diseases in Iranian bullous pemphigoid patients. METHODS: The medical records of one hundred and sixty consecutive bullous pemphigoid patients who presented to the Autoimmune Bullous Diseases Research Center, Tehran, Iran, from 2006 to 2011 were examined for evidence of any neurological disease. The control group comprised of 317 age- and sex-matched subjects. RESULTS: Neurological diseases were seen in 42 (26.4%) patients with bullous pemphigoid and in 29 (9.1%) controls (odds ratio: 3.53 (2.1-5.9), P< 0.001). Comparing cases to controls, stroke was seen in 17.5% versus 4.1%, odds ratio 4.96 (2.49-9.88); dementia in 5.6% versus 1.9%, odds ratio 3.09 (1.08-8.84); Parkinson's disease in 2.5% versus 2.2%, odds ratio 1.14 (0.33-3.94); epilepsy in 2.5% versus 0.6%, odds ratio 4.04 (0.73-22.3); and multiple sclerosis in 0 versus 0.3% odds ratio 1.00 (0.98-1.01). LIMITATIONS: The main limitations of our study were referral bias, retrospective design and a rather low sample size. CONCLUSIONS: Neurological diseases in general, and stroke and dementia in particular, were significantly associated with bullous pemphigoid in our study.

Evaluation of the combination of BP180-NC16a enzyme-linked immunosorbent assay and BP230 enzyme-linked immunosorbent assay in the diagnosis of bullous pemphigoid.

BACKGROUND: Bullous pemphigoid (BP) is an acquired autoimmune subepidermal blistering disease characterized by circulating IgG autoantibodies directed against BP180 and BP230 hemidesmosomal proteins. Previous studies have demonstrated that antibodies against the NC16a domain of BP180 mediate BP pathogenesis, while antibodies against BP230 enhance the inflammatory response. Recently, commercial BP180-NC16a enzyme-linked immunosorbent assay (ELISA) and BP230 ELISA kits were developed to detect anti-BP180 and anti-BP230 autoantibodies in human BP sera. AIMS: To evaluate the efficacy of BP180-NC16a ELISA and BP230 ELISA in the initial diagnosis of BP. METHODS: Sera from 62 BP patients and 62 control subjects were tested by BP180-NC16a ELISA and BP230 ELISA and compared with findings from indirect immunofluorescence (IIF) and immunoblotting (IB) to determine the sensitivity and specificity of these assays. RESULTS: The sensitivities of BP180-NC16a ELISA and BP230 ELISA were 87.1% (54/62) and 56.5% (35/62), respectively, and the specificities of both were 100% (62/62). Using both ELISAs for diagnosis increased the sensitivity to 95.2% (59/62) and was statistically comparable with IB sensitivity. CONCLUSIONS: ELISA is a convenient, effective, and reliable method for serodiagnosis of BP, and combined use of BP180-NC16a ELISA and BP230 ELISA can increase the sensitivity of this diagnostic approach.