BACKGROUND: Cases of autoimmune bullous dermatosis (AIBD) have been reported following COVID-19 vaccination.
OBJECTIVE: We aimed to provide an overview of clinical characteristics, treatments, and outcomes of AIBDs following COVID-19 vaccination.
METHODS: We conducted a systematic review and searched the Embase, Cochrane Library, and Medline databases from their inception to 27 March 2024. We included all studies reporting ≥ 1 patient who developed new-onset AIBD or experienced flare of AIBD following at least one dose of any COVID-19 vaccine.
RESULTS: We included 98 studies with 229 patients in the new-onset group and 216 in the flare group. Among the new-onset cases, bullous pemphigoid (BP) was the most frequently reported subtype. Notably, mRNA vaccines were commonly associated with the development of AIBD. Regarding the flare group, pemphigus was the most frequently reported subtype, with the mRNA vaccines being the predominant vaccine type. The onset of AIBD ranged from 1 to 123 days post-vaccination, with most patients displaying favorable outcomes and showing improvement or resolution from 1 week to 8 months after treatment initiation.
CONCLUSIONS: Both new-onset AIBD and exacerbation of pre-existing AIBD may occur following COVID-19 vaccination. Healthcare practitioners should be alert, and post-vaccination monitoring may be essential.

Pemphigus foliaceus (PF) differs from pemphigus vulgaris (PV) in that it affects only the skin and mucous membranes are not involved. Pemphigus is commonly treated with systemic corticosteroids and immunosuppressive agents (ISAs). More recently, biologics have been used. The current literature on biologic therapy often combines treatment of PF with PV, hence it is often difficult for clinicians to isolate the treatment of PF from PV. The purpose of this review was to provide information regarding the use of current biological therapy, specifically in PF.
A search of PubMed, Embase, and other databases was conducted using keywords pemphigus foliaceus (PF), rituximab (RTX), intravenous immunoglobulin (IVIg), and biologics. Forty-one studies were included in this review, which produced 105 patients with PF, treated with RTX, IVIg, or a combination of both. Eighty-five patients were treated with RTX, eight patients with IVIg, and 12 received both RTX and IVIg.
Most patients in this review had PF that was nonresponsive to conventional immunosuppressive therapies (CIST), and had significant side effects from their use. RTX treatment resulted in complete remission (CR) in 63.2%, a relapse rate of 39.5%, an infection rate of 19.7%, and a mortality rate of 3.9%. Relapse was greater in the lymphoma (LP) protocol than the rheumatoid arthritis (RA) protocol (p<0.0001). IVIg led to CR in 62.5% of patients, with no relapses or infections. Patients receiving both biologics experienced better outcomes when RTX was first administered, then followed by IVIg. Follow-up durations for patients receiving RTX, IVIg, and both were 22.1, 24.8, and 35.7 months, respectively.
In pemphigus foliaceus patients nonresponsive to conventional immunosuppressive therapy or in those with significant side effects from CIST, RTX and IVIg appear to be useful agents. Profile of clinical response, as well as relapse, infection, and mortality rates in PF patients treated with RTX were similar to those observed in PV patients. The data suggests that protocols specific for PF may produce better outcomes, less adverse effects, and improved quality of life.

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.

Pemphigus represents a group of chronic inflammatory disorders characterized by autoantibodies that target components of desmosomes, leading to the loss of intercellular adhesion between keratinocytes and causing intraepithelial blistering. The pemphigus group consists of four main clinical types with several variants: pemphigus vulgaris (with pemphigus vegetans and pemphigus herpetiformis as variants), pemphigus foliaceus, paraneoplastic pemphigus and IgA pemphigus (with two clinical variants: intraepidermal neutrophilic IgA dermatosis and subcorneal pustular dermatosis). Genetic factors are involved in the pathogenesis, with HLA-DR4 (DRB1*0402) and HLA-DRw6 (DQB1*0503) allele more common in patients with pemphigus vulgaris, HLA class II DRB1*0344 and HLA Cw*1445 correlated with paraneoplastic pemphigus, and HLA-DRB1*04:01, HLA-DRB1*04:06, HLA-DRB1*01:01, HLA-DRB1*14, associated with a higher risk of developing pemphigus foliaceus. Autoantibodies are conducted against structural desmosomal proteins in the skin and mucous membranes, mainly desmogleins, desmocollins and plakins. Cell-mediated immunity may also play a role, especially in paraneoplastic pemphigus. Patients may present erythema, blisters, erosions, and ulcers that may affect the skin, as well as mucosal surfaces of the oral cavity, eyes, nose, leading to severe complaints including pain, dysphagia, and fetor. Oral mucosal postbullous erosive lesions are frequently the first sign of disease in pemphigus vulgaris and in paraneoplastic pemphigus, without skin involvement, making the diagnosis difficult. Treatment options classically include immunosuppressive agents, such as corticosteroids and corticosteroid-sparing agents such as azathioprine, mycophenolate mofetil, cyclophosphamide, methotrexate or dapsone. Newer therapies focus on blocking cell signaling events induced by pathogenic autoantibodies and/or targeting specific autoantibodies. The disease evolution is conditioned by the treatment with maximum doses of corticosteroids and the side effects associated with long-term immunosuppressive therapy, which is why patients need a multidisciplinary approach in following the treatment. In this review, we provide a comprehensive overview of the epidemiology, pathophysiology, clinical aspect, diagnosis and management of the main intraepidermal blistering diseases from the pemphigus group.

Pemphigus is a rare but life-threatening autoimmune skin disease characterized by blistering on skin and/or mucous membranes. The physiological process of blister formation involves IgG antibodies against the desmogleins (Dsgs) and desmocollins (Dscs). Additional autoAbs have also been suggested to mediate the disease heterogeneity, such as anti-thyroid peroxidase (anti-TPO) and antithyroglobulin (anti-Tg) antibodies, the essential culprits of the immune system in autoimmune thyroid diseases.
To investigate the levels and antibody positivity of anti-TPO and anti-Tg antibodies in pemphigus patients.
Antibody positivity and levels of anti-TPO and anti-Tg antibodies in pemphigus patients as compared to healthy controls were examined. A meta-analysis was conducted by reviewing six similar studies.
98 Chinese pemphigus patients and 65 healthy controls were enrolled in the study. Our meta-analysis revealed a significant correlation between increased presence of positive anti-TPO and anti-Tg antibodies and pemphigus, particularly for pemphigus vulgaris (PV). Such correlation was also observed in our own hospitalized PV patients, but not in pemphigus foliaceus (PF) patients. In addition, the status of anti-TPO and anti-Tg antibodies were also compared between females and males within PV patients, PF patients or controls, as well as compared for females or males between pemphigus patients and controls. In the analysis of T cell counts, we found abnormal low CD3 + T cell counts (< 690 n/µl) were only detected in patients whose thyroid antibody levels were less than 20 IU/ml.
Pemphigus patients showed higher levels and antibody positivity of anti-TPO and anti-Tg antibodies than healthy controls. Further investigations are needed to identify the pathogenic functions of these antibodies in pemphigus, as well as to identify the potential shared susceptibility genes.

BACKGROUND: Nocardiosis is an uncommon opportunistic infection seen in immunocompromised patients or those with a dysfunctional immune system. Nocardia asteroides infection in patients with Pemphigus foliaceus (PF) has never been reported.
METHODS: We report an interesting case of nocardiosis-characterized by pulmonary intra-cavitary infection, in a 54-year-old man with PF and diabetes mellitus. The man finally recovered from the infection.
CONCLUSIONS: This is the first case reporting pulmonary nocardiosis in a patient with PF. We recommend that physicians be aware of nocardiosis in patients with pemphigus as a possible cause of underlying infectious disease to avoid misdiagnoses and mismanagement.

Pemphigus foliaceus (PF) is an autoimmune bullous disorder that has occasionally been reported to present as a polycyclic or arcuate eruption in children. We present a case of childhood PF presenting as an annular and polycyclic eruption, which initially led to a diagnostic conundrum and a delay in diagnosis but which ultimately responded well to therapy with systemic steroids and rituximab infusions. We briefly review the literature on polycyclic presentations of PF in childhood as well as the use of rituximab for pediatric pemphigus.

Pemphigus is a group of rare, potentially devastating autoimmune diseases of the skin and mucous membranes with high morbidity and potentially lethal outcome. The major clinical variant, pemphigus vulgaris (PV) is caused by a loss of intercellular adhesion of epidermal keratinocytes which is induced by IgG autoantibodies against components of desmosomes. Specifically, IgG against the desmosomal adhesion proteins, desmoglein 3 (Dsg3) and desmoglein 1 (Dsg1), preferentially target their ectodomains which are presumably critical for the transinteraction and signalling function of these adhesion molecules. There is a close immunogenetic association of PV with the human leukocyte antigen (HLA) class II alleles, HLA-DRB1*04:02 and HLA-DQB1*05:03. These have been shown to be critical for the presentation of immunodominant peptides to autoreactive CD4+ T helper cells. The importance of autoaggressive T-B cell interaction in the induction of pathogenic IgG autoantibodies which directly cause epidermal loss of adhesion has been demonstrated both clinically (by the use of the anti-CD20 monoclonal antibody rituximab) and experimentally (in PV mouse models). The strong association of clinically active pemphigus with autoantibodies of the IgG4 and IgE subclasses strongly suggests that T helper 2 cells are critical regulators of the immune pathogenesis of pemphigus. Novel therapeutic approaches target autoreactive T and B cells to specifically interfere with the T cell-dependent activation of B cells leading to the generation of autoantibody-producing plasma cells. Our improved understanding of the autoantibody-driven effector phase of pemphigus has led to the introduction of novel therapies that target pathogenic autoantibodies such as immunoadsorption and drugs that block pathogenic autoantibody-induced cell signalling events.