Scalp, Oral, and Nail Pemphigus Vulgaris: Clinical Characteristics and a Review of the Literature.

Pemphigus vulgaris (PV) is a rare disease that affects the skin and mucous membranes, causing blistering and erosions. Identifying and effectively managing atypical presentations of pemphigus vulgaris can be challenging due to its rarity. We describe a 32-year-old male patient with a medical history including prediabetes, moderate asthma, hyperlipidemia, coccidioidomycosis, and respiratory infections. He was evaluated via telehealth in the allergy and immunology clinic for uncontrolled asthma. Initially, he complained of a whitish film in the mouth while on treatment with fluticasone and salmeterol. He also noted new vesicular lesions on his scalp and body. When evaluated later in the clinic, he was found to have oral and periungual erosions as well as paronychia. After promptly referring to dermatology, histopathological examination and direct immunofluorescence testing were performed on the patient's lesions, revealing changes consistent with PV. Treatment with prednisone and rituximab resulted in the complete resolution of the patient's bullae and nail deformities over several months. This case highlights the importance of a thorough evaluation of complex medical histories and diagnostic testing in managing asthma and allergy symptoms. It also emphasizes the need for a multidisciplinary approach involving specialists such as immunologists, dermatologists, and infectious disease experts in the diagnosis and management of complex cases.

The multifactorial complexities of autoimmune development in Pemphigus vulgaris: Critical evaluation of the role of environmental and lifestyle "exposome" factors.

Pemphigus vulgaris (PV) is a potentially life-threatening blistering disorder characterized by autoantibodies directed against cell-cell adhesion molecules that serves as an excellent model to study human autoimmune development. Numerous studies have identified specific Human Leukocyte Antigen (HLA) genes, in particular DRB1*0402 and DQB1*0503, that confer disease risk. Although HLA is required, it is not sufficient for the initiation of disease. As with all autoimmune diseases, the etio-pathogenesis of PV is complex, meaning it is multifactorial. Susceptibility is polygenic, and the search for non-HLA disease-linked genes continues. Moreover, twin studies across autoimmune conditions indicate that non-genetic environmental and lifestyle factors, which can be collectively grouped under the term "exposome", are also major contributors to disease development. The literature presents evidence for the potential role of multiple triggers such as medications, infections, stress, diet, immunizations, and sleep to influence the etiology, pathophysiology, and prognosis of PV. However, a clear understanding of the degree to which specific factors impact PV is lacking. In this investigation, we comprehensively review the environmental elements listed above and consider the strength of evidence for these factors. The overall goals of this work are to provide greater insights into the factors that influence disease susceptibility, disease development and disease course and ultimately help to better guide clinicians and inform patients in the management of PV.

Epidemiology of Pemphigus.

Pemphigus is an epidemiologically heterogeneous group of autoimmune bullous diseases comprising pemphigus vulgaris (PV), pemphigus foliaceus, paraneoplastic pemphigus, IgA pemphigus, and pemphigus herpetiformis. Recently, our knowledge about the frequency of pemphigus, which is highly variable between different populations, has considerably expanded, and the first non-HLA genes associated with PV have been identified. In addition, a variety of comorbidities, including other autoimmune diseases, hematological malignancies, and psoriasis, have been described in this variant. Here, initial data about the impact of COVID-19 on this fragile patient population are discussed and perspectives for future epidemiological studies are outlined.

First reported case of parvovirus triggering painful widespread livedoid vasculopathy: another virus causing hypercoagulability?

Livedoid vasculopathy (LV) is a noninflammatory thrombotic disease caused by occlusion of dermal small vessels associated with systemic autoimmune disorders and coagulopathies. However, LV is often reported as being 'idiopathic', despite extensive investigation. We report a case of severe LV in an otherwise healthy 27-year-old woman, associated with parvovirus infection. The patient presented with a short history of a livedoid rash initially covering her torso, which spread to acral sites. Burning pains in the lower limb caused reduced mobility;systemically, she remained well and stable throughout. Examination revealed generalized acral skin pallor, livedoid patches of violet erythema and purpura with deep serpiginous ulcerations over extensor aspects of upper and lower limbs with a more broken/racemosa nonulcerated livedoid appearance on the trunk. On admission a transaminitisareas continued to ulcerate. Codeine was present with a creatine kinase of 1569 U L.1, but other blood test results were unremarkable including erythrocyte sedimentation rate, complement, cryoglobulins, antinuclear antibodies, antineutrophil cytoplasmic antibodies, extractable nuclear antigen, rheumatoid factor, myositis screen, antiphospholipid screen and thrombophilia screen. Parvovirus IgG and IgM were both positive and tested for, as the patient's young daughter had recently been diagnosed with 'slapped cheek disease'. Magnetic resonance imaging of the thighs showed a diffuse mild myositis;electromyography, nerve-conduction studies, barium swallow and computed tomography of the chest, abdomen and pelvis were all normal. An incisional skin biopsy was performed, which revealed a blood vessel with organizing (Solimani F, Mansour Y, Didona D et al. Development of severe pemphigus vulgaris following SARS-CoV-2 vaccination with BNT162b2. J Eur Acad Dermatol Venereol 2021;35: e649- 51) have been reported. The main proposed mechanisms for AstraZeneca vaccine-induced pemphigus could be a hyperimmune reaction in genetically predisposed individuals, with eventual formation of anti-desmoglein antibodies. An alternative hypothesis is that vaccine components could act as foreign antigens resulting in a cross-reaction with pemphigus antigens. The close association of COVID-19 vaccination with the acute onset of pemphigus in our patient, as well as exacerbations after subsequent vaccine administration, is more than coincidental. Considering the recent pandemic with COVID-19 and the widespread administration of the COVID-19 vaccine, continued observation and documentation of true adverse events is essential.

Abstracts for the British Association of Dermatologists 101st Annual Meeting

The proceedings contain 331 papers. The topics discussed include: barriers to and facilitators of implementation of the dermatology curriculum across UK medical schools: results of a national survey and recommendations;what has been the impact of COVID-19 redeployment on dermatology trainees professional identity? an interpretative phenomenological study;diversifying educational resources during the COVID-19 pandemic: delivering educational dermatology podcasts and webinars for healthcare professionals;pandemic placement: delivering the dermatology undergraduate curriculum at a UK medical school during the COVID-19 crisis;skin of color representation in dermatology and undergraduate medical textbook images: a meta- analysis;the impact of the COVID-19 pandemic on dermatology ST3 application preparation: a national survey of junior doctors in the UK;Pemphix to pemphigus vulgaris: the journey to classifying blisters;scleroderma or scleroedema? The complex classification of systemic sclerosis;lessons from Sushruta revealing the Ayurvedic ancestry of dermatology;and PS02: experiences and understanding of body image dissatisfaction in individuals with a chronic dermatological condition: an interpretative phenomenological analysis.

New-onset pemphigus foliaceus following COVID-19 vaccine

Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are a rare group of immunobullous disorders that can lead to high morbidity and mortality. The produced antibodies, via the aberrant B cells, are considered to be the culprits responsible for the disease development. We present a patient with PF whose disease developed after administration of the first dose of ChAdOx1 nCoV-19 (AstraZeneca) vaccination and exacerbated following the second dose of this vaccine. A 62-year-old female, with no previous history of skin diseases, received the first dose of AstraZeneca COVID-19 vaccine on 26 February 2021. She developed a generalized erythematous itchy rash in early March 2021, a few days after her vaccination. She received the second dose of the AstraZeneca COVID-19 vaccine on 14 May 2021, which resulted in significant worsening of her skin in just a couple of days, with extensive scaling and erythema. Physical examination demonstrated large erosive annular erythematous plaques on her face, trunk and limbs. No mucosal involvement was present. Histology demonstrated subcorneal pustules containing few acantholytic keratinocytes and a large number of neutrophils. Direct immunofluorescence revealed fishnet-like positivity for IgG and C3 at the intercellular epidermal spaces. Based on the characteristic clinical and histological findings, the diagnosis was confirmed as new-onset PF following COVID-19 AstraZeneca vaccination. Two patients with PV flare-up following COVID-19 Moderna and Pfizer vaccine administration (Damiani G, Pacifico A, Pelloni F, Iorizzo M. The first dose of COVID-19 vaccine may trigger pemphigus and bullous pemphigoid flares: is the second dose therefore contraindicated? J Eur Acad Dermatol Venereol 2021;35: e645-7), and a single patient with new-onset PV occurring after vaccination with COVID-19 Pfizer vaccine (Solimani F, Mansour Y, Didona D et al. Development of severe pemphigus vulgaris following SARS-CoV-2 vaccination with BNT162b2. J Eur Acad Dermatol Venereol 2021;35: e649- 51) have been reported. The main proposed mechanisms for AstraZeneca vaccine-induced pemphigus could be a hyperimmune reaction in genetically predisposed individuals, with eventual formation of anti-desmoglein antibodies. An alternative hypothesis is that vaccine components could act as foreign antigens resulting in a cross-reaction with pemphigus antigens. The close association of COVID-19 vaccination with the acute onset of pemphigus in our patient, as well as exacerbations after subsequent vaccine administration, is more than coincidental. Considering the recent pandemic with COVID-19 and the widespread administration of the COVID-19 vaccine, continued observation and documentation of true adverse events is essential.

Pemphigus Vulgaris Possibly Associated with COVID-19 Infection.

Pemphigus vulgaris (PV) represents damage to epidermal keratinocytes, resulting in acantholysis due to the production of autoantibodies against desmoglein-1 and desmoglein-3. Autoimmune blistering disorders such as pemphigus vulgaris or bullous pemphigoid that develop following coronavirus disease 2019 (COVID-19) have been reported in several studies. Herein, we report a case of PV onset following COVID-19 infection in a 17-year-old female, demonstrating --the potential pathogenic capacity of SARS-CoV-2 to develop PV.

Five cases of new-onset pemphigus following vaccinations against coronavirus disease 2019.

Pemphigus is a group of blistering disorders characterized by the formation of intraepithelial blisters in skin and mucous membranes induced by the binding of circulating autoantibodies to intercellular adhesion molecules. The pathogenesis is complex and not fully understood; however, genetic predisposition and various triggers are widely accepted as key factors in pemphigus development. A few cases of new-onset pemphigus following coronavirus disease 2019 (COVID-19) vaccination have already been published. The present paper reports a total of two cases of pemphigus foliaceous and three cases of pemphigus vulgaris that occurred following vaccinations against COVID-19, with anamnestic, clinical, and diagnostic data collection suggesting assumptions over a possible causal correlation.

COVID 19 and Pemphigus vulgaris: a potential correlation

Autoimmune blistering diseases have been associated with exposure to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition, oropharyngeal Pemphigus vulgaris appears to be associated with the coronavirus. In order to understand the molecular basis linking SARS-CoV-2 and Pemphigus vulgaris, this study explores the molecular mimicry hypothesis and analyzes the peptide sharing between the Pemphigus vulgaris autoantigen, i.e., Desmoglein 3 (Dsg-3), and the SARS-CoV-2 proteome. Results indicate a low molecular mimicry level, still immunologically significant, between SARS-CoV-2 and Dsg-3.

Desquamative Gingivitis in the Context of Autoimmune Bullous Dermatoses and Lichen Planus-Challenges in the Diagnosis and Treatment.

Desquamative gingivitis (DG) is a clinical term that describes erythema, desquamation and erosions of the gingiva, of various etiologies. Although the clinical aspect is not specific for a certain disease, an accurate diagnosis of the underlying disorder is necessary because the disease course, prognosis and treatment vary according to the cause. DG may inflict significant oral discomfort, which is why patients typically present to the dentist for a first consultation, rendering it important for these specialists to be informed about this condition. Our paper aims to review the ethiopatogenesis and diagnostic approach of DG, focusing on the most common underlying disorders (autoimmune bullous dermatoses and lichen planus) and on the management of these patients. Potential etiological agents leading to an inflammatory immune response in the oral mucosa and DG appearance include genetic predisposition, metabolic, neuropsychiatric, infectious factors, medication, dental materials, graft-versus-host reaction and autoimmunity. A thorough anamnesis, a careful clinical examination, paraclinical explorations including histopathological exam and direct immunofluorescence are necessary to formulate an appropriate diagnosis. Proper and prompt management of these patients lead to a better prognosis and improved quality of life, and must include management in the dental office with sanitizing the oral cavity, instructing the patient for rigorous oral hygiene, periodic follow-up for bacterial plaque detection and removal, as well as topical and systemic therapy depending on the underlying disorder, based on treatment algorithms. A multidisciplinary approach for the diagnosis and follow-up of DG in the context of pemphigus vulgaris, bullous pemphigoid, cicatricial pemhigoid or lichen planus is necessary, including consultations with dermatologists, oral medicine specialists and dentists.

Reactive infectious mucocutaneous eruption (RIME) associated with COVID-19 infection

A 24-year-old man presented with a 7-day history of oral ulceration and 3-day history of erythema at the urethral meatus with one erythematous papule on the scrotum. The patient had tested positive for COVID-19 on polymerase chain reaction test. The patient had not eaten for 6 days, managing only sips of water. There were no new medications and no recent vaccinations. On examination his lips were ulcerated with haemorrhagic crust. His tongue had significant swelling and ulceration. There was erythema and superficial ulceration surrounding the urethral meatus. Thus, the patient had mucosal involvement only, with no target lesions, blisters or epidermal detachment. Inflammatory markers were raised. The initial impression was that of reactive infectious mucocutaneous eruption (RIME) associated with COVID-19 infection, given the likely viral cause, in a systemically well, young patient. The differential included erythema multiforme major, Stevens-Johnson syndrome and pemphigus vulgaris. Bacterial and viral swabs, septic screen, sexually transmitted infection screen including HIV, circulating skin antibodies were all negative. The patient was treated with topical and systemic steroids, with a catheter to prevent urethral stenosis, intravenous Pabrinex®, oral nutritional supplements, analgesia, Difflam™ mouthwash, betamethasone mouth rinse and lidocaine mouth spray. The patient's symptoms had resolved after 6 weeks. This case demonstrates the multispecialty management of a patient presenting acutely with RIME secondary to COVID-19, who was treated successfully with oral and topical steroids.

Acute localized deterioration in pemphigoid gestationis following COVID-19 vaccination

Pemphigoid gestationis is a rare autoimmune blistering disorder which typically presents in the second and third trimester of pregnancy. We present an interesting case of a localized flare of the condition following COVID-19 vaccination. A 33- year-old woman presented 2 weeks post partum with an acute onset bullous rash. This had started at week 35 of gestation, one day prior to the onset of labour. A pruritic rash developed on her right arm before becoming widespread, with urticated erythematous plaques and tense bullae. There was no mucous membrane involvement and the infant was unaffected. Skin biopsy showed a prominent perivascular infiltrate with numerous eosinophils, suggestive of pemphigoid gestationis. Uncharacteristically, direct immunofluorescence was negative. Her symptoms improved with 30 mg oral prednisolone and topical clobetasol propionate ointment. She received the first dose of the Pfizer SARS-CoV-2 vaccine 5 weeks after the onset of the rash and within days developed a flare of her rash around the inoculation site. To our knowledge, this is the first report of a flare of pemphigoid gestationis following COVID-19 vaccination. There are case reports of other autoimmune bullous disorders (bullous pemphigoid and pemphigus vulgaris) flaring and occurring de novo following mRNA COVID-19 vaccinations. COVID -19 vaccination has been rapidly rolled out and side-effects in patients with rare conditions are only becoming apparent as these patients are exposed to the vaccine. Knowledge of this side effect will enable us to anticipate it, counsel and treat our patients more effectively, and could help maintain vaccine uptake in this vulnerable patient group. (Figure Presented) .

COVID vaccination associated immunological cutaneous reactions

While our knowledge about the short-term side-effects of COVID-19 vaccination in adults has rapidly evolved, data about the long-term systemic side-effects and potential new onset autoimmune disorders has been limited. Here we present a case series of patients with new onset autoimmune skin conditions between 10 days and 4 weeks post mRNA COVID-19 vaccination and discuss the underlying pathophysiological changes contributing to these side-effects. Exclusions included any patients who have previously tested positive for COVID-19 or had COVID-19 symptoms. Our cases include new onset discoid lupus, localized cutaneous lupus, dermatomyositis, linear IgA bullous disease, pemphigus vulgaris, bullous pemphigoid, lichen planus pemphigoides, erosive lichen planus, psoriasis and vitiligo. In addition, we are reporting significant flare-up of pre-existing autoimmune skin conditions after a long period of remission. These include three cases of psoriasis, two cases of systemic lupus, one pemphigus vulgaris koebnerizing within a previous shingles site, and a case of pyoderma gangrenosum flare. The BNT162b2 vaccine is a potent activator of the T- and B-cell pathways. The production of interleukin (IL)-17 and IL- 21 seems to play an important role in vaccine-induced immunological protection, which is also linked to germinal centre activation linked to autoimmune disorders. This report improves our knowledge regarding some rarer potential sideeffects associated with these new vaccines and highlights the importance of further studies.

Prescrire's ratings of new drugs in 2021: A brief review

Three new drugs, all based on messenger RNA or small interfering RNA technology, represented a major therapeutic advance in 2021. But the bigger picture is that most of the new authorisations that advanced patient care were adaptations of existing drugs. And that more than half of this year's new authorisations were not advances, and in fact about one-tenth represented a step backwards compared to existing options.

Epidemiology of Pemphigus: A Single Center Experience in Morocco

Objective: Pemphigus is a life threatening autoimmune bullous disease which involves the skin and mucous membranes of the stratified squamous epithelium. The global distribution of Pemphigus varies according to genetic, ethnic, socioeconomic, and cultural backgrounds. The purpose of our study is to evaluate the epidemiological features of pemphigus a single center in Morocco and compare our results with those reported elsewhere. Methods: A retrospective analysis was conducted of 302 pemphigus patients seen between 1990 and 2020 in the Dermatology Department of Ibn Sina Hospital (Rabat, Morocco). We further collected all the Moroccan scientific researches published by now to compare. Results: The average annual incidence was 0.32/100,000 inhabitants. The incidence doubled to 0.72 in 2020. The most common variant was pemphigus vulgaris (125 cases) followed by pemphigus erythematosus (99 cases), pemphigus foliaceous (40 cases), and vegetans (27 cases). The female to male ratio was 0.75, the average age at onset was 53years old and the mean duration of the disease before diagnosis was 13.36months. Conclusion: This study joins the main characteristics of pemphigus in the Maghreb and around the world (pemphigus vulgaris most frequent subtype). In 2020, an epidemiological peak occurred during the coronavirus disease 2019 pandemic;probably related to stress and delayed time consultation for fear of contracting the severe acute respiratory syndrome coronavirus 2.

Development of severe pemphigus vulgaris following ChAdOx1 nCoV-19 vaccination and review of literature.

Vaccines are indeed a boon for tackling the present COVID-19 pandemic. In India, ChAdOx1 nCoV-19 (Covishield) is the most commonly used vaccine in the government vaccination program for adults more than 18 years of age. It is a recombinant vaccine developed by Oxford-Astra Zeneca and manufactured in India by Serum Institute of India (SSI). Here, we report a case of severe pemphigus vulgaris following the second dose of ChAdOx1 nCoV-19 vaccination in an adult male. The patient developed septicemia during the course of hospital stay, and he was managed with systemic steroids, parenteral antibiotics, and intravenous immunoglobulins (IVIg) along with proper wound care. Patient started improving within 1 month of therapy. This case is being reported in view of the rarity of pemphigus vulgaris following ChAdOx1 nCoV-19 vaccine.

Diagnosis and Treatment Challenges of an Atypical Case of Pemphigus vulgaris During the COVID-19 Pandemic.

Pemphigus defines a group of rare autoimmune blistering diseases that affect the skin and mucous membranes, with pemphigus vulgaris being the most common form that has increased morbidity and mortality in the absence of an early diagnosis and treatment. We report the case of a 24-year-old male with an atypical form of pemphigus vulgaris with cutaneous onset and subsequent involvement of the oral cavity. The management of the patient initially consisted of long-term systemic corticosteroid therapy. Following a mild form of SARS-CoV-2 infection and a flare-up of the disease in this context, which was not controlled with high doses of systemic corticosteroids, targeted therapy with rituximab was initiated but immediately stopped due to the manifestations of urticaria and angioedema. Considering the magnitude of these reactions, dapsone systemic therapy i.e., a steroid-sparing agent with minimal risk of infections, was started and managed to control the underlying disease. The management of this case of pemphigus vulgaris was challenging for both the patient and his physician, as the patient developed COVID-19 which caused disease complications and implied additional costs. This case highlights the importance of an accurate diagnosis given the atypical onset of the disease and the financial limitations with the impossibility of performing all confirmatory diagnostic tests.