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Background: Ocular predominant mucous membrane pemphigoid (oMMP) is a severe subtype of autoimmune blistering disease (AIBD), which can result in scarring and vision loss. The diagnosis of oMMP is challenging as patients often have undetectable levels of circulating autoantibodies by conventional assays. Likewise, the principal autoantigen in oMMP has been an area of debate. Methods: In this preliminary experiment, we performed Phage Immunoprecipitation Sequencing (PhIP-seq) on sera from patients with oMMP, as well as non-ocular MMP, bullous pemphigoid, and mucocutaneous-type pemphigus vulgaris. Results: We identified several autoantigens unique to oMMP relative to other AIBDs. We then cross-referenced these antigens against previously published single-nuclei datasets, as well as the International Mouse Phenotyping Consortium Database. Several protein hits identified in our study demonstrated enriched expression on the anterior surface epithelia, including TNKS1BP1, SEC16B, FNBP4, CASZ1, GOLGB1, DOT1L, PRDM 15, LARP4B, and RPL6. Likewise, a previous study of mouse knockout models of murine analogs CASZ1, HIP1, and ELOA2 reported that these mice showed abnormalities in terms of the ocular surface and development in the eyes. Notably, PhIP-seq failed to identify the canonical markers of AIBDs such as BP180, BP230, desmogleins 1 and 3, or integrin β4, indicating that the patient autoantibodies react with conformational epitopes rather than linear epitopes. Conclusions: oMMP patients demonstrate a unique autoantibody repertoire relative to the other AIBDs. Further validation of the identified autoantibodies will shed light on their potentially pathogenic role. [ABSTRACT FROM AUTHOR]

Pemphigus vulgaris (PV) is a rare immunobullous disease. Although it classically presents as generalized flaccid blisters affecting the skin and mucosae, atypical cases of PV can be diagnostically challenging. Herein, we report an underrecognized non-blistering manifestation of pemphigus vulgaris, which we call mounded and refractory keratoses (MARK). MARK presents as exuberant scaling plaques on the scalp, often in the skin of color. When MARK features are present, pemphigus vulgaris is prone to misdiagnosis, clinically and histopathologically, leading to delays in appropriate treatment. Specifically, biopsies from these patients may resemble acantholytic dyskeratosis, resulting in initial misdiagnosis. Thus, recognizing this presentation may aid physicians in diagnosing and monitoring the recurrence of pemphigus vulgaris.

Background: Although rituximab is known to be effective in the treatment of pemphigus, its role in subepidermal autoimmune blistering diseases is unclear and currently limited to off-label use. Summary: This is a meta-analysis of case reports, case series, and retrospective studies on the effectiveness and safety of rituximab in bullous pemphigoid, mucous membrane pemphigoid, ocular pemphigoid, and epidermolysis bullosa acquisita. We compared remission and relapse rates in patients who received rituximab with those who only received conventional medical therapy. Comparisons were also made among disease subgroups. Key Message: The present analysis suggests that patients with subepidermal autoimmune blistering diseases treated with rituximab achieve a higher rate of complete remission and encounter their first relapse after a longer time interval. However, time to remission and total relapse rates were similar between groups. Adverse events and mortality rates were no more common in patients who received rituximab. This analysis was limited by the absence of randomized controlled trials and the observation that rituximab was used as a late rescue therapy in most reports. In conclusion, rituximab may be effective in subepidermal blistering disease, but randomized controlled studies are required for the validation of current observational data. [ABSTRACT FROM AUTHOR]

Pemphigus vulgaris (PV) is a rare immunobullous disease. Although it classically presents as generalized flaccid blisters affecting the skin and mucosae, atypical cases of PV can be diagnostically challenging. Herein, we report an underrecognized non-blistering manifestation of pemphigus vulgaris, which we call mounded and refractory keratoses (MARK). MARK presents as exuberant scaling plaques on the scalp, often in the skin of color. When MARK features are present, pemphigus vulgaris is prone to misdiagnosis, clinically and histopathologically, leading to delays in appropriate treatment. Specifically, biopsies from these patients may resemble acantholytic dyskeratosis, resulting in initial misdiagnosis. Thus, recognizing this presentation may aid physicians in diagnosing and monitoring the recurrence of pemphigus vulgaris.

Since the concurrence of bullous pemphigoid (BP) and psoriasis was first reported in 1929, an increasing number of studies has been published to analyse their relationship in recent years. However, the pathogenesis of the concurrence is not yet well understood, and the coexistence of the two conditions imposes a difficult therapeutic challenge. This case report demonstrates the first case of secukinumab achieving a dramatic clinical improvement of both chronic psoriasis and active BP. [ABSTRACT FROM AUTHOR]

Competing Interests: None disclosed.

Background: Leprosy disease in the community is usually mistaken as a cursed disease. Leprosy disease is a chronic granulomatous infection caused by Mycobacterium leprae. Quality of life in leprosy patients with neuropathic pain in every region is varied. Objective: To determine the quality of life in leprosy patients with neuropathic pain by using the SALSA Scale and VAS. Methods: The research used analytic observational, a cross-sectional design and an interview technic. 37 subjects of 19 to 59 years age had leprosy with neuropathic pain at Donorojo Hospital. Results: SALSA score explains that 62.2% of the research subject has limitation of activity and has a correlation with leprosy disease with p 0.012. There is no correlation between VAS score and leprosy disease with p 0.034. SALSA score and VAS score in this research explain there is no correlation with p 0.458. The number of other medical conditions with limitation activity has a correlation score of 0.870 which has a very good correlation power. The number of used tools with limitation activity has a correlation score of 0.716 which has a good correlation power. Conclusion: There is activity limitation in leprosy patients with neuropathic pain at Donorojo Hospital Jepara District. The other aspect that affect activity limitation is the number of other medical conditions. Multibacillary type has more limitation than a Paucibacillary type. [ABSTRACT FROM AUTHOR]

Background: Autoimmune bullous disorders, encompassing pemphigus and pemphigoid diseases, are associated with significant morbidity and mortality. This is in part due to high cumulative doses of corticosteroids in combination with immunosuppressant agents used in traditional treatment regimes. Rituximab is an antiCD20 monoclonal antibody which can induce complete remission, but it is currently unlicensed in the UK and approved only after other treatments have failed. Methods: We report a retrospective cohort study of 33 patients with pemphigus and pemphigoid diseases treated with rituximab from a single tertiary centre from 2013 to 2019. Results: "Complete remission off therapy" was achieved by 27.3% (n = 9), and a further 27.3% (n = 9) had complete remission on minimal therapy. Twenty‐one per cent (n = 7) had "partial remission on minimal therapy"; 9.1% (n = 3) patients were in the "consolidation phase," and 12.1% (n = 4) had a "relapse/flare." A steady reduction in prednisolone doses was observed post‐Rituximab infusion. Pre‐Rituximab the median dose of prednisolone was 20mg (range 10‐35, IQR 25), 15mg (range 9.5‐22.5, IQR 13) at 1 month, 9mg (range 5‐10, IQR 5) at 6 months, 4mg (range 0‐5mg, IQR 5) at 12 months and 0 (0‐4.35, IQR 4.25) at 18 months. Twelve per cent (n = 4) of patients had documented infusion reaction symptoms. Twelve per cent (n = 4) had later infective complications. Conclusion: This real clinic data adds to the evidence that Rituximab is a safe and effective treatment for both pemphigus and pemphigoid autoimmune blistering conditions. Significantly, we were able to demonstrate a substantial reduction in corticosteroid dosage in our cohort of patients following rituximab treatment. [ABSTRACT FROM AUTHOR]

COVID‐19 had a great impact on medical approaches among dermatologist. This systematic review focuses on all skin problems related to COVID‐19, including primary and secondary COVID‐related cutaneous presentations and the experts recommendations about dermatological managements especially immunomodulators usage issues. Search was performed on PubMed, Scopus, Embase and ScienceDirect. Other additional resources were searched included Cochrane, WHO, Medscape and coronavirus dermatology resource of Nottingham university. The search completed on May 3, 2020. Three hundred seventy‐seven articles assigned to the inclusion and exclusion groups. Eighty‐nine articles entered the review. Primary mucocutaneous and appendageal presentations could be the initial or evolving signs of COVID‐19. It could be manifest most commonly as a maculopapular exanthamatous or morbiliform eruption, generalized urticaria or pseudo chilblains recognized as "COVID toes" (pernio‐like acral lesions or vasculopathic rashes). During pandemic, Non‐infected non‐at risk patients with immune‐medicated dermatologic disorders under treatment with immunosuppressive immunomodulators do not need to alter their regimen or discontinue their therapies. At‐risk o suspected patients may need dose reduction, interval increase or temporary drug discontinuation (at least 2 weeks). Patients with an active COVID‐19 infection should hold the biologic or non‐biologic immunosuppressives until the complete recovery occur (at least 4 weeks). [ABSTRACT FROM AUTHOR]

In patients with specific dermatologic disorders who are affected by new corona virus, we know little about disease course (underlying disease and new onset infection), and the most proper management strategies include both issues that are what this systematic review targets. Databases of PubMed, Scopus, Google Scholar, Medscape, and Centre of Evidence‐Based Dermatology, coronavirus dermatology resource of Nottingham University searched completely up to May 15, 2020, and initial 237 articles were selected to further review and finally 9 articles (including 12 patients) entered to this study. From 12 patients with chronic underlying dermatologic disease treated with systemic therapies, only 1 patient required Intensive Care Unit admission, the others have been treated for mild‐moderate symptoms with conventional therapies. The biologic or immunosuppressive/immunomodulator agents have been ceased during the course of disease. The course of coronovirus diseases 2019 (COVID‐19) and its management was as similar as normal populations. Their underlying dermatologic disease were exacerbating from mild to moderate. Their treatment has been continued as before, after the symptoms improved. Exacerbation of patients underlying dermatologic disease was mild to moderate. Discontinuing the treatment in the acute period of COVID and the restart after recovery may prevent severe recurrence and disturbing cytokine storms in these patients. [ABSTRACT FROM AUTHOR]

Neonatal pemphigus is a transient, self-limiting entity featuring appearance of evanescent blisters in a neonate born to mother diagnosed with immuno-bullous blistering disorders. A case report of neonatal pemphigus born to a 30-year-old female with Pemphigus Vulgaris is being reported. Higher maternal antibody titre causing clinically evident blistering in neonate is not commonly reported. This report, thus, emphasises the need for diagnostic considerations and vigilant surveillance of neonatal pemphigus in neonates born to mothers with immunobullous disorders. Since the cases reported in the literature and the references assessed revealed that neonatal pemphigus is infrequent, but the understanding about the disease permits for an early diagnosis to be made.

Objectives: Oral autoimmune bullous disorders show clinical overlap with diseases such as lichen planus and others that may cause desquamative gingivitis. As direct immunofluorescence is expensive, we sought to determine if routine histology alone would be sufficient to distinguish between oral autoimmune bullous disorders and mimics. Methods: We searched the records for patients with a suspected oral autoimmune bullous disorder who underwent biopsies for concurrent routine histologic evaluation and direct immunofluorescence and who had at least one follow‐up visit. Cases were separated into high and low suspicion subgroups based on clinical findings. Results: Within 148 cases, the sensitivity of routine histology alone was 0.810, with a negative predictive value of 0.889. However, the specificity was 0.989 with a positive predictive value of 0.979. Of the high suspicion cases, 57 (47.1%) were found to be consistent with an oral autoimmune bullous disorder, with a total of 11 histologic false negatives. 8 cases, all in the high suspicion subgroup, showed indeterminate direct immunofluorescence results. There were no histologic false negatives or inconclusive direct immunofluorescence results in the low suspicion subgroup. Conclusions: In patients with a low clinical suspicion for an oral autoimmune bullous disorder, it is reasonable and more cost‐effective to evaluate the lesion with routine histology alone. [ABSTRACT FROM AUTHOR]

Background: Bullous pemphigoid (BP) autoantibody levels are generally elevated in patients with BP but can be present nonspecifically in patients without BP.Objective: To analyze the clinical findings of patients with elevated BP180 or BP230 autoantibody levels and negative direct immunofluorescence (DIF) study findings.Methods: We retrospectively reviewed records of patients seen at our institution during January 1, 2005-December 31, 2015, who were positive for BP180 or BP230 autoantibodies and had a negative DIF study finding. These patients' demographic characteristics and BP180 and BP230 levels were compared with those of a BP control group who were positive for BP180 or BP230 autoantibodies and had positive DIF study findings.Results: We identified 208 patients with BP autoantibodies but without positive DIF study findings. These patients' mean age and enzyme-linked immunosorbent assay values were significantly lower than those of the control group. Dermatitis was the most common final clinical diagnosis. Of the 208 patients, 41 (19.7%) had at least 2 years' follow-up. Four patients had positive DIF results upon repeating the test and ultimately received pemphigoid diagnoses.Limitations: Retrospective design with limited follow-up.Conclusion: Patients might harbor serum BP autoantibodies in the context of a wide range of dermatoses. Low positive BP180 and BP230 autoantibody levels should not be overinterpreted as evidence for BP in the setting of a negative DIF. [ABSTRACT FROM AUTHOR]

Aims: Tzanck smear is an old but useful test for diagnosis of cutaneous dermatoses. The aim of this study was to highlight the potential usefulness and diagnostic pitfalls of Tzanck smear for diagnosis of cutaneous dermatoses and infections. Materials and Methods: This hospital based cross-sectional study was carried out on all Tzanck smears received for a period of twenty months (January 2014–August 2015). The smears were assessed to establish the utility of Tzanck smears in corroborating or excluding a diagnosis of immunobullous lesion or herpetic infection. Cases with discrepant diagnosis on histopathology were reviewed to identify additional cytomorphological features. Results: A total of 57 Tzanck smears were performed during the study period. Out of the 18 clinically suspected cases of immunobullous disorders, Tzanck smear findings corroborated the clinical diagnosis in 7/18 cases, one case was diagnosed as cutaneous candidiasis, and diagnosis of immunobullous lesions could be excluded in 5/18 cases. Out of the 19 suspected cases of herpetic infections, viral cytopathic effect was observed in 8/19 cases. Besides immunobullous lesions and herpetic infections, acantholytic cells were also observed in spongiotic dermatitis and genodermatosis. Dyskeratotic keratinocytes seen in vacuolar interface dermatitis were not easily distinguishable from acantholytic cells on Tzanck smear. Conclusions: Tzanck smear test is an inexpensive and useful diagnostic tool for certain skin diseases. It can aid in establishing a rapid clinical diagnosis and can serve as a useful adjunct to routine histological examination. We recommend the use of Tzanck smear as a first-line investigation for vesiculobullous, erosive, and pustular lesions.

Background: Immunobullous diseases are morphologically heterogeneous and the differentiation between various subtypes is essential for proper treatment and prognosis. Aim of our study was to analyze and correlate clinical, histopathological and immunofluorescence findings in autoimmune bullous diseases. Materials and Methods: A cross-sectional study was done over a period of two years (2010-2012) after approval of the ethics committee. Sixty patients, who met the inclusion criteria of immunobullous disease, were included in the study. Skin biopsy for histopathology and direct immunofluorescence (DIF) examination was taken. DIF using salt-split technique was done in few of the cases. The final diagnosis was based on clinical, histopathology and DIF findings. Pearson′s coefficient of correlation (r) was calculated. Statistical Analysis was done using Epi info version. 7.0. Results: Fifty-three cases with clinical diagnosis of autoimmune bullous diseases were evaluated. In 88.6% of cases, histopathology diagnosis was consistent with clinical diagnosis and in 75.5% of cases, DIF findings were consistent with clinical diagnosis. A positive relation was seen between clinical and DIF findings with r = 0.65 and between histopathology and DIF findings with r = 0.75. DIF positivity was seen in 100% cases of bullous pemphigoid (BP) and pemphigus foliaceous and 94.7% cases of pemphigus vulgaris, which was statistically significant with p < 0.05. In DIF salt-split test, deposition was seen on roof of blister in BP whereas on floor in epidermolysis bullosa acquisita. Conclusion: Our study provides evidence-based guidance for the diagnosis and classification of various immunobullous disorders. DIF test should be done in conjunction with histopathology for definitive diagnosis and to minimize both: False-positive and false-negative results.

Aims: Tzanck smear is an old but useful test for diagnosis of cutaneous dermatoses. The aim of this study was to highlight the potential usefulness and diagnostic pitfalls of Tzanck smear for diagnosis of cutaneous dermatoses and infections. Materials and Methods: This hospital based cross-sectional study was carried out on all Tzanck smears received for a period of twenty months (January 2014-August 2015). The smears were assessed to establish the utility of Tzanck smears in corroborating or excluding a diagnosis of immunobullous lesion or herpetic infection. Cases with discrepant diagnosis on histopathology were reviewed to identify additional cytomorphological features. Results: A total of 57 Tzanck smears were performed during the study period. Out of the 18 clinically suspected cases of immunobullous disorders, Tzanck smear findings corroborated the clinical diagnosis in 7/18 cases, one case was diagnosed as cutaneous candidiasis, and diagnosis of immunobullous lesions could be excluded in 5/18 cases. Out of the 19 suspected cases of herpetic infections, viral cytopathic effect was observed in 8/19 cases. Besides immunobullous lesions and herpetic infections, acantholytic cells were also observed in spongiotic dermatitis and genodermatosis. Dyskeratotic keratinocytes seen in vacuolar interface dermatitis were not easily distinguishable from acantholytic cells on Tzanck smear. Conclusions: Tzanck smear test is an inexpensive and useful diagnostic tool for certain skin diseases. It can aid in establishing a rapid clinical diagnosis and can serve as a useful adjunct to routine histological examination. We recommend the use of Tzanck smear as a first-line investigation for vesiculobullous, erosive, and pustular lesions. [ABSTRACT FROM AUTHOR]

Competing Interests: Dr Yeung has been an advisor, consultant, speaker, and/or investigator for AbbVie, Allergan, Amgen, Astellas, Bausche, Baxalta, Boehringer Ingelheim, Celgene, Centocor, Coherus, Dermira, Eli Lilly, Forward, Fresnius Kabi, Galderma, Incyte, Janssen, LEO Pharma, Lilly, Medimmune, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Sun Pharma, Takeda, UCB, and Xenon. Dr Mufti has been a speaker for AbbVie and Janssen. Author Sood has no conflicts of interest to declare.

Neonatal pemphigus is a transient, self-limiting entity featuring appearance of evanescent blisters in a neonate born to mother diagnosed with immuno-bullous blistering disorders. A case report of neonatal pemphigus born to a 30-year-old female with Pemphigus Vulgaris is being reported. Higher maternal antibody titre causing clinically evident blistering in neonate is not commonly reported. This report, thus, emphasises the need for diagnostic considerations and vigilant surveillance of neonatal pemphigus in neonates born to mothers with immunobullous disorders. Since the cases reported in the literature and the references assessed revealed that neonatal pemphigus is infrequent, but the understanding about the disease permits for an early diagnosis to be made. [ABSTRACT FROM AUTHOR]

Childhood pemphigus is a rare diasease and comprises only a minority of immunobullous diseases seen in children. Almost all variants of pemphigus in childhood have been described in literature. Pemphigus vulagaris is the most common type seen, after excluding endemic foliaceus. The clinical features are essentially similar to that of adults. Special consideration is required while treating children so as to use drugs which are less carcinogenic and do not affect fertility. We present here a review of cases of childhood pemphigus vulgaris, pemphigus foliaceus, pemphigus vegetans, pemphigus erythematosus, paraneoplastic pemphigus, IgA pemphigus and neonatal pemphigus.

Background Bullous pemphigoid (BP) has been associated with neurologic disorders. Objective We sought to analyze the association between BP and neurologic disorders. Methods We retrospectively identified residents of Olmsted County, Minnesota, with a first lifetime diagnosis of BP between January 1, 1960, and December 31, 2009. Three age- and sex-matched Olmsted County, Minnesota, residents without BP were selected as control subjects for each patient. We compared history of or development of neurologic disorders (dementia, Alzheimer disease, Parkinson disease, multiple sclerosis, cerebrovascular disease, and seizures) between groups using case-control and cohort designs. Results In all, 87 patients with BP were identified and matched to 261 control subjects. The odds of a previous diagnosis of any neurologic disorder or a history of dementia were significantly increased among cases compared with controls (odds ratio 6.85; 95% confidence interval [CI] 3.00-15.64; P < .001; and odds ratio 6.75; 95% CI 2.08-21.92; P = .002, respectively). Both Parkinson disease (hazard ratio 8.56; 95% CI 1.55-47.25; P = .01) and any type of neurologic disorder (hazard ratio 2.02; 95% CI 1.17-3.49; P = .01) were significantly more likely to develop during follow-up in patients with than without BP. Limitations Small geographic area and retrospective study design are limitations. Conclusion Findings confirmed an association of BP with neurologic disorders, especially dementia and Parkinson disease. [ABSTRACT FROM AUTHOR]

Background: Bullous pemphigoid (BP) is an autoimmune blistering disease characterized by autoantibodies specific for the 180-kd BP antigen-2 (BP180) (also termed “type XVII collagen”) protein. The BP180 enzyme-linked immunosorbent assay (ELISA) is specific for the immunodominant NC16A domain of the protein. However, we and others have observed patients whose reactivity to BP180 is exclusive of the NC16A domain (referred to henceforth as non-NC16A BP). Objective: We sought to determine the incidence of non-NC16A BP and identify regions of reactivity within the BP180 protein. Methods: Sera from 51 patients who met the clinical and histologic criteria for BP were screened for NC16A reactivity by ELISA. Sera that were negative by ELISA were screened for IgG reactivity to an epidermal extract, recombinant BP180 protein, and subregions of BP180, by immunoblot. Demographic and clinical data were also collected on all patients. Results: Four sera (7.8%) were negative using the BP180 ELISA but positive for IgG reactivity to the extracellular domain of BP180. Further mapping identified 4 regions outside of NC16A recognized by these sera: amino acid (AA) 1280 to 1315, AA 1080 to 1107, AA 1331 to 1404, and AA 1365 to 1413. One of these sera also had IgE specific for NC16A. One patient had an atypical presentation with lesions limited to the lower aspect of the legs and scarring of the nail beds. Limitations: The small total number of patients with non-NC16A BP limits the identification of demographic or clinical correlates. Conclusion: It is significant that 7.8% of sera from patients with new BP react to regions of BP180 exclusively outside of NC16A and, thus, would not be identified using the currently available BP180 ELISA. [ABSTRACT FROM AUTHOR]

Autoimmune bullous dermatoses are characterized by the presence of tissue-bound and often circulating pathogenic autoantibodies targeting structural components of the skin and/or mucous membranes. The diagnostic workup for this heterogeneous group of disorders consists of a multi-step process, of which the light microscopic examination is a crucial component. This review is organized following a classification scheme that is based on two main histopathologic features, namely level of intraepithelial split and composition of the inflammatory infiltrate. Overall, we aim to place emphasis on the histopathologic clues that can assist pathologists in differential diagnosis and review the updates in the literature., (Copyright © 2022 Elsevier Inc. All rights reserved.)