An Unusual Case of Pemphigus Vulgaris

<b><i>Introduction:</i></b> Pemphigus is a potential life-threatening skin disorder belonging to the group of the autoimmune bullous diseases affecting the skin and mucosa. The most common subtypes are pemphigus foliaceus (PF) and pemphigus vulgaris. <b><i>Case Presentation:</i></b> We present the case of a young woman with scalp manifestations diagnosed as seborrhiasis who came to our office where a more careful history and clinical examination directed us toward another diagnostic suspicion. The histological examination confirmed our suspicion of pemphigus and therefore we believe it is important to report our experience to avoid misdiagnosis. <b><i>Discussion/Conclusion:</i></b> Our case may be useful in the literature to identify cases of PF with atypical manifestations that may mimic other diseases.

An Updated Review of Pemphigus Diseases

Clinicians may encounter a variety of skin conditions that present with vesiculobullous lesions in their everyday practice. Pemphigus vulgaris, pemphigus foliaceus, IgA pemphigus, and paraneoplastic pemphigus represent the spectrum of autoimmune bullous dermatoses of the pemphigus family. The pemphigus family of diseases is characterized by significant morbidity and mortality. Considering the risks associated with a delayed diagnosis or misdiagnosis and the potential for overlap in clinical features and treatment, evaluation for suspected pemphigus disease often requires thorough clinical assessment and laboratory testing. Diagnosis is focused on individual biopsies for histopathology and direct immunofluorescence. Additional laboratory methods used for diagnosis include indirect immunofluorescence and enzyme-linked immunosorbent assay. Recent advancements, including anti-CD20 therapy, have improved the efficacy and reduced the morbidity of pemphigus treatment. This contribution presents updates on the pathophysiology, clinical features, diagnostic work-up, and medical management of pemphigus. Improved strategies for diagnosis and clinical assessment are reviewed, and newer treatment options are discussed.

IgM Deficiency in Autoimmune Blistering Mucocutaneous Diseases Following Various Treatments: Long Term Follow-Up and Relevant Observations

IgM deficiency has been reported in patients with many autoimmune diseases treated with Rituximab (RTX). It has not been studied, in detail, in autoimmune mucocutaneous blistering diseases (AIMBD). Our objectives were: (i) Examine the dynamics of IgM levels in patients with and without RTX. (ii) Influence of reduced serum IgM levels on clinical and laboratory parameters. (iii) Explore the possible molecular and cellular basis for reduced serum IgM levels. This retrospective study that was conducted in a single-center from 2000 to 2020. Serial IgM levels were studied in 348 patients with five AIMBD (pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid, mucous membrane pemphigoid, and ocular cicatricial pemphigoid) and found decreased in 55 patients treated with RTX, IVIG, and conventional immunosuppressive therapy (CIST). Hence the incidence of decreased serum IgM is low. The incidence of decreased IgM in patients treated with RTX was 19.6%, in patients treated with IVIG and CIST, it was 52.8% amongst the 55 patients. IgM levels in the post-RTX group were statistically significantly different from the IVIG group (p&lt;0.018) and CIST group (p&lt;0.001). There were no statistically significant differences between the groups in other clinical and laboratory measures. Decreased serum IgM did not affect depletion or repopulation of CD19+ B cells. Patients in the three groups achieved clinical and serological remission, in spite of decreased IgM levels. Decrease in IgM was isolated, since IgG and IgA were normal throughout the study period. Decreased IgM persisted at the same level, while the patients were in clinical remission, for several years. In spite of persistent decreased IgM levels, the patients did not develop infections, tumors, other autoimmune diseases, or warrant hospitalization. Studies on IgM deficiency in knockout mice provided valuable insights. There is no universally accepted mechanism that defines decreased IgM levels in AIMBD. The data is complex, multifactorial, sometimes contradictory, and not well understood. Nonetheless, data in this study provides novel information that enhances our understanding of the biology of IgM in health and disease.

Regional Differences in the Permeability Barrier of the Skin—Implications in Acantholytic Skin Diseases

The chemical milieu, microbiota composition, and immune activity show prominent differences in distinct healthy skin areas. The objective of the current study was to compare the major permeability barrier components (stratum corneum and tight junction (TJ)), investigate the distribution of (corneo)desmosomes and TJs, and measure barrier function in healthy sebaceous gland-rich (SGR), apocrine gland-rich (AGR), and gland-poor (GP) skin regions. Molecules involved in cornified envelope (CE) formation, desquamation, and (corneo)desmosome and TJ organization were investigated at the mRNA and protein levels using qRT-PCR and immunohistochemistry. The distribution of junction structures was visualized using confocal microscopy. Transepidermal water loss (TEWL) functional measurements were also performed. CE intracellular structural components were similarly expressed in gland-rich (SGR and AGR) and GP areas. In contrast, significantly lower extracellular protein levels of (corneo)desmosomes (DSG1 and CDSN) and TJs (OCLN and CLDN1) were detected in SGR/AGR areas compared to GP areas. In parallel, kallikrein proteases were significantly higher in gland-rich regions. Moreover, gland-rich areas were characterized by prominently disorganized junction structures ((corneo)desmosomes and TJs) and significantly higher TEWL levels compared to GP skin, which exhibited a regular distribution of junction structures. According to our findings, the permeability barrier of our skin is not uniform. Gland-rich areas are characterized by weaker permeability barrier features compared with GP regions. These findings have important clinical relevance and may explain the preferred localization of acantholytic skin diseases on gland-rich skin regions (e.g., Pemphigus foliaceus, Darier’s disease, and Hailey–Hailey disease).