A Case of an Autoimmune Blistering Disease: Pemphigus Vulgaris.

Pemphigus vulgaris is a rare autoimmune disorder characterized by the formation of intraepithelial blisters that clinically appear as erosions and flaccid bullae on the skin and mucus membranes. Herein, we report a case of pemphigus vulgaris in an elderly male. He was initially misdiagnosed by his primary care provider and given topical lidocaine and acetaminophen with hydrocodone, without improvement in symptoms. This delay in treatment caused a worsening of his condition. The patient presented to our dermatology office two months after his primary care visit and reported worsening blisters and pain. Clinically he presented with flaccid bullae, crusted erosions, and erythematous plaques on the chest, back, abdomen, arms, and legs, and a tender oral ulcer. Two punch biopsies were obtained and sent for direct immunofluorescence and routine histology. The biopsy results confirmed the diagnosis of pemphigus vulgaris. Our patient achieved clearance after four weeks of oral prednisone and maintained clearance after a slow prednisone taper and the addition of mycophenolate mofetil 1g twice daily. We aim to bring awareness of the clinical presentation and treatment regimen of pemphigus vulgaris to prevent misdiagnosis and delayed care.

A Rare Case of Pertuzumab-Induced Toxic Epidermal Necrolysis.

Pertuzumab is a targeted therapy drug that is employed in the management of human epidermal growth factor receptor 2 (HER2)-positive breast cancer and works by blocking the ability of cancer cells to receive growth and proliferation signals. Toxic epidermal necrolysis (TEN) is a severe cutaneous manifestation characterized by widespread erythema, necrosis, and bullous detachment of the skin involving more than 10% of the body surface area (BSA) and may be precipitated by an immunologic response to the administration of certain medications. However, TEN development as a consequence of HER2 inhibitor therapy has not been described in the existing literature. A 44-year-old female with a history of metastatic breast cancer to the liver presented with a diffuse blistering rash following a first-time administration of pertuzumab three days prior. Her rash began as painful and pruritic blisters 12 hours after the last infusion of pertuzumab and progressed to involve her arms, chest, groin, and thighs with a positive Nikolsky sign. She was managed supportively with high-dose steroids and antihistamines, and although her hospital course was complicated by hypotension requiring pressor support, she gradually made a full recovery and was released to a rehabilitation facility.

A Patient Develops Bullous Rash After Receiving the Second Dose of COVID-19 Vaccine.

Our knowledge about the clinical spectrum of COVID-19 has continued to evolve. The clinical features of the infection and vaccine are continuously updated. We present a case of bullous pemphigoid after receiving a second dose of the COVID-19 vaccine. This case highlights autoimmune skin findings seen in a patient after COVID-19 vaccination. A 70-year-old male presented with the chief complaint of blistering skin rash. He received his second dose of Pfizer COVID-19 vaccine two days before developing a painful pruritic maculopapular rash that started on his hands and extended proximally to his trunk. Physical exam was remarkable for tense bullae with negative Nikolsky sign. Biopsy and direct immunofluorescence lead to the diagnosis of bullous pemphigoid. The lesions improved significantly with steroids. Various cutaneous eruptions have been reported with Moderna and Pfizer COVID-19 vaccines, including the new onset of bullous pemphigoid. Based on our case, we suggest that bullous pemphigoid after COVID-19 vaccination is responsive to steroids and the prognosis is excellent. Understanding the clinical course and prognosis of bullous pemphigoid from the COVID-19 vaccine is of significant importance as we strive to keep our patients and communities safe. More data is needed to better guide recommendations, but so far looking at the example from our case, the benefits of COVID-19 vaccination seem to outweigh the risks. Therefore, patients should be advised to continue with future vaccinations.

Emerging treatments for bullous pemphigoid.

Bullous pemphigoid (BP) is the most common autoimmune blistering disease. It is characterized by an immune response against the hemidesmosomal anchoring proteins BP180 and BP230. BP mainly affects elderly patients, with an increasing incidence over the past two decades. High potency topical and/or systemic corticosteroids as well as immunosuppressants are the current mainstay of treatment. However, long-term systemic immunosuppression may result in significant morbidity and mortality. Recent advances in the understanding of the pathogenesis of BP have enabled the investigation of newer therapies that specifically work against a variety of pro-inflammatory mediators associated with BP. These new treatments hold promise to be highly efficient and safer alternatives and are expected to be shortly available for the treatment of BP. This review discusses current evidence on the use of novel targeted therapeutic approaches in the treatment of BP.

Pemphigus Foliaceus and Pemphigus Erythematosus are the Most Common Subtypes of Pemphigus in Northern Finland.

Pemphigus is an autoimmune skin disease characterized by blistering and erosions of the skin and mucous membranes. Pemphigus is rare in Northern and Western Europe but its incidence is higher around the Mediterranean Sea. The most common type worldwide is pemphigus vulgaris. The aim of this study was to investigate the incidence of pemphigus subtypes in Northern Finland between 1985 and 2017. A total of 46 patients diagnosed with pemphigus at the Department of Dermatology of Oulu University Hospital were found the female/male ratio was 1.7. In contrast to many other countries it was found that in Northern Finland the superficial pemphigus subtypes were the most common: erythematosus or foliaceus (65%) followed by pemphigus vulgaris (26%). Over the past 4 decades the annual incidence of pemphigus in Finland has increased from 0.76 to 2.8 cases per million persons.

Prevalence of Skin-specific Autoantibodies in HIV-infected Patients and Uninfected Controls.

Various autoantibodies are detected more frequently in HIV-infected individuals than in HIV-negative controls; however, limited data exist regarding autoimmune blistering skin diseases. Using enzyme-linked immunoassay (ELISA) and indirect immunofluore-scence, no difference in the frequency and magnitude of autoantibodies against BP180, BP230, desmoglein 1 and 3 was found between 594 HIV-infected patients and 248 uninfected controls in this cross-sectional study (16.0% vs. 11.7%, respectively, for at least one positive ELISA, p = 0.11). Interestingly, reactive syphilis serology in both HIV-infected individuals and uninfected controls was associated with positive anti-BP180 ELISA results (adjusted odds ratio (OR) 2.14, 95% confidence interval (CI) 1.07-4.29, p = 0.03 and OR 4.70, CI 1.3-16.86; p = 0.0180). Our study shows a comparably low prevalence of cutaneous autoantibodies in both HIV-infected patients and uninfected controls lacking signs of autoimmune blistering skin disease. Positive BP180 ELISA in the absence of clinical signs of bullous pemphigoid should prompt further evaluation for syphilis antibodies.

Current Clinical Trials in Pemphigus and Pemphigoid.

Autoimmune bullous dermatoses (AIBDs) are a group of rare chronic inflammatory skin diseases, which clinically manifest as blisters and erosions of the skin and/or mucosa. Immunologically, AIBDs are characterized and caused by autoantibodies targeting adhesion molecules in the skin and mucosa. According to the histological location of the blistering, AIBDs are classified into the following two main subtypes: pemphigus (intraepidermal blistering) and pemphigoid (subepidermal blistering). Most AIBDs were potentially life-threatening diseases before the advent of immunosuppressive drugs, especially systemic steroid therapies, which suppress pathogenic immunological activity. Although there have been recent advancements in the understanding of the pathogenesis of AIBDs, glucocorticosteroids and/or adjuvant immunosuppressive drugs are still needed to control disease activity. However, the long-term use of systemic immunosuppression is associated with major adverse events, including death. Based on the growing understanding of AIBD pathogenesis, novel treatment targets have emerged, some of which are currently being evaluated in clinical trials. Within this article, we review the current clinical trials involving pemphigus and pemphigoid and discuss the rationale that lead to these trials. Overall, we aim to foster insights into translational research in AIBDs to improve patient care.

The Immunometabolomic Interface Receptor Hydroxycarboxylic Acid Receptor 2 Mediates the Therapeutic Effects of Dimethyl Fumarate in Autoantibody-Induced Skin Inflammation.

The drug dimethyl fumarate (DMF) is in clinical use for the treatment of psoriasis and multiple sclerosis. In addition, it has recently been demonstrated to ameliorate skin pathology in mouse models of pemphigoid diseases, a group of autoimmune blistering diseases of the skin and mucous membranes. However, the mode of action of DMF in inflammatory skin diseases has remained elusive. Therefore, we have investigated here the mechanisms by which DMF improves skin pathology, using the antibody transfer model of bullous pemphigoid-like epidermolysis bullosa acquisita (EBA). Experimental EBA was induced by transfer of antibodies against collagen VII that triggered the infiltration of immune cells into the skin and led to inflammatory skin lesions. DMF treatment reduced the infiltration of neutrophils and monocytes into the skin explaining the improved disease outcome in DMF-treated animals. Upon ingestion, DMF is converted to monomethyl fumarate that activates the hydroxycarboxylic acid receptor 2 (HCA2). Interestingly, neutrophils and monocytes expressed Hca2. To investigate whether the therapeutic effect of DMF in EBA is mediated by HCA2, we administered oral DMF to Hca2-deficient mice (Hca2-/-) and wild-type littermates (Hca2+/+) and induced EBA. DMF treatment ameliorated skin lesions in Hca2+/+ but not in Hca2-/- animals. These findings demonstrate that HCA2 is a molecular target of DMF treatment in EBA and suggest that HCA2 activation limits skin pathology by inhibiting the infiltration of neutrophils and monocytes into the skin.

Peptide mimetics of immunoglobulin A (IgA) and FcαRI block IgA-induced human neutrophil activation and migration.

The cross-linking of the IgA Fc receptor (FcαRI) by IgA induces release of the chemoattractant LTB4, thereby recruiting neutrophils in a positive feedback loop. IgA autoantibodies of patients with autoimmune blistering skin diseases therefore induce massive recruitment of neutrophils, resulting in severe tissue damage. To interfere with neutrophil mobilization and reduce disease morbidity, we developed a panel of specific peptides mimicking either IgA or FcαRI sequences. CLIPS technology was used to stabilize three-dimensional structures and to increase peptides' half-life. IgA and FcαRI peptides reduced phagocytosis of IgA-coated beads, as well as IgA-induced ROS production and neutrophil migration in in vitro and ex vivo (human skin) experiments. Since topical application would be the preferential route of administration, Cetomacrogol cream containing an IgA CLIPS peptide was developed. In the presence of a skin permeation enhancer, peptides in this cream were shown to penetrate the skin, while not diffusing systemically. Finally, epitope mapping was used to discover sequences important for binding between IgA and FcαRI. In conclusion, a cream containing IgA or FcαRI peptide mimetics, which block IgA-induced neutrophil activation and migration in the skin may have therapeutic potential for patients with IgA-mediated blistering skin diseases.