Intraepidermal Blistering Disease Research Articles

Biomarkers in Pemphigus Vulgaris: A Systematic Review.

Pemphigus vulgaris (PV) is a rare intraepidermal blistering disease that is potentially life-threatening due to risk of infection and failure of skin barrier function. The identification of biomarkers has the potential to provide diagnostic utility and identify new therapeutic targets. The objective of this systematic review is to identify all potentially relevant PV biomarkers, categorize them, and identify trends to determine the involvement of T-cell-mediated, B-cell-1mediated, and innate immune-mediated pathways in PV pathogenesis. Medline and Embase databases were searched according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, resulting in the inclusion of 66 studies that reported on a total of 2463 patients and 146 unique biomarkers. Biomarkers were categorized into T-cell-mediated, B-cell-mediated, and innate immune system pathways. The most notable biomarkers trends include elevations in IL-4, IL-6, IL-17A, anti-Dsg1/3 autoantibodies, and a reduction in Treg cells and FOXP3. The results of this review support current theories of PV pathogenesis, with increased Th2 activity, increased Th17 activity, decreased Treg activity, and production of anti-Dsg1/3 autoantibodies being observed. Targeting of IL-4 and IL-6 may provide therapeutic benefit. However, more research is required to validate biomarkers for clinical utility and assess viability as therapeutic targets.

An Integrated Approach in Management of Pemphigus Vulgaris

Pemphigus refers to a group of autoantibody-mediated intra-epidermal blistering diseases characterized by loss of cohesion between epidermal cells (a process termed acantholysis). Applying pressure to the skin of these patients may elicit the separation of the epidermis which is known as Nikolsky’s sign. Pemphigus vulgaris can be compared with Agnivisarpa based on similar manifestation. The mainstay of treatment is systemic glucocorticoids in allopathy science. The current mortality is around 5% with glucocorticoids treatment. Case History: This case report is of 40 years old male patient who presented with blisters formation on whole over body, perspiration, itching and burning since last 6 months. He was treated in indoor department with Snehana Cikitsa mainly along with oral glucocorticoids for 25 days. The dose of oral glucocorticoids was tapered with improvement in patient’s condition. Result: At the time discharge, patient was prescribed 10mg prednisolone and oral Ayurvedic medicines. After 25 days of treatment patient had more than 90% relief and glucorticoids was stopped. On the 2nd follow of treatment patient was kept only on Ayurvedic medicines. During first two follow-ups, patient had significant relief.

Autoimmune Pemphigus: Latest Advances and Emerging Therapies.

Pemphigus represents a group of rare and severe autoimmune intra-epidermal blistering diseases affecting the skin and mucous membranes. These painful and debilitating diseases are driven by the production of autoantibodies that are mainly directed against the desmosomal adhesion proteins, desmoglein 3 (Dsg3) and desmoglein 1 (Dsg1). The search to define underlying triggers for anti-Dsg-antibody production has revealed genetic, environmental, and possible vaccine-driven factors, but our knowledge of the processes underlying disease initiation and pathology remains incomplete. Recent studies point to an important role of T cells in supporting auto-antibody production; yet the involvement of the myeloid compartment remains unexplored. Clinical management of pemphigus is beginning to move away from broad-spectrum immunosuppression and towards B-cell-targeted therapies, which reduce many patients’ symptoms but can have significant side effects. Here, we review the latest developments in our understanding of the predisposing factors/conditions of pemphigus, the underlying pathogenic mechanisms, and new and emerging therapies to treat these devastating diseases.

Clinical verification of individualized homoeopathic medicine Belladonna in pemphigus: A case study

Pemphigus refers to a group of autoantibody-mediated intra-epidermal blistering diseases characterized by loss of cohesion between epidermal cells [1]. It causes restlessness in patient [2]. In such cases homoeopathic medicines are always helpful when given after individualization of the patient and prescribed medicine must be similimum in order to cure the patient [3]. This case represents a case of pemphigus treated with homoeopathic remedy Belladonna. A 3 year old female child patient visited OPD on 10 Aug 2019. She was complaining of vesicular eruption all over body since last 10 days. This patient improved with Belladonna 200, single dose.

Comprehensive review on the pathophysiology, clinical variants and management of pemphigus (Review).

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.

A Case of IgA Pemphigus in a Five-Year-Old Child

Immunoglobulin A (IgA) pemphigus is a group of autoimmune intraepidermal blistering diseases presenting with vesiculopustular eruptions, neutrophilic infiltration of the skin, and in vivo bound and circulating IgA autoantibodies against the cell surface of keratinocytes. It usually occurs in middle-aged or elderly persons. We report a case of childhood IgA pemphigus in a 5-year-old male child, with direct immunofluorescence confirmation, which is an uncommon occurrence.

Genetics and Omics Analysis of Autoimmune Skin Blistering Diseases.

Autoimmune blistering diseases (AIBDs) of the skin are characterized by autoantibodies against different intra-/extracellular structures within the epidermis and at the basement membrane zone (BMZ). Binding of the antibodies to their target antigen leads to inflammation at the respective binding site and degradation of these structures, resulting in the separation of the affected skin layers. Clinically, blistering, erythema and lesions of the skin and/or mucous membranes can be observed. Based on the localization of the autoantigen, AIBDs can be divided into pemphigus (intra-epidermal blistering diseases) and pemphigoid diseases (sub-epidermal blistering diseases), respectively. Although autoantigens have been extensively characterized, the underlying causes that trigger the diseases are still poorly understood. Besides the environment, genetic factors seem to play an important role in a predisposition to AIBDs. Here, we review currently known genetic and immunological mechanisms that contribute to the pathogenesis of AIBDs. Among the most commonly encountered genetic predispositions for AIBDs are the HLA gene region, and deleterious mutations of key genes for the immune system. Particularly, HLA class II genes such as the HLA-DR and HLA-DQ alleles have been shown to be prevalent in patients. This has prompted further epidemiological studies as well as unbiased Omics approaches on the transcriptome, microbiome, and proteome level to elucidate common and individual genetic risk factors as well as the molecular pathways that lead to the pathogenesis of AIBDs.

Bullous autoimmune dermatoses.

Pathophysiologically, bullous autoimmune dermatoses are caused by autoantibodies directed against adhesion molecules or structural proteins of the skin and mucous membranes, clinically resulting in blister formation. Depending on the respective target proteins of the autoimmune response and their location in the skin, a distinction is made between intraepidermal (pemphigus disorders), junctional (pemphigoid disorders), and subepidermal (epidermolysis bullosa acquisita, dermatitis herpetiformis) autoimmune blistering diseases. The most common bullous autoimmune dermatosis, bullous pemphigoid is characterized by marked clinical variability and intense pruritus. Predominantly affecting elderly individuals, there has been a significant increase in its incidence in recent years. While mucosal lesions occur in less than 30% of bullous pemphigoid patients, the second most common bullous autoimmune dermatosis, pemphigus vulgaris, typically presents with oral erosions as the predominant and - frequently - initial symptom. Its onset is usually in the 4th to 6th decade of life. Scarring is typically found in subepidermal blistering disorders such as epidermolysis bullosa acquisita or mucous membrane pemphigoid. Diagnosis is based on clinical and histological findings as well as direct and indirect immunofluorescence and detection of circulating autoantibodies. Although a number of controlled clinical trials have been conducted in recent years, treatment of bullous autoimmune disorders is still primarily based on clinical experience. Therapeutic options include topical and systemic corticosteroids as well as adjuvant immunosuppressants. Recalcitrant cases may require treatment with immunoadsorption, intravenous immunoglobulins, or the monoclonal anti-CD20 antibody rituximab.

Efficacy of Triaging Direct Immunofluorescence in Intraepidermal Bullous Dermatoses.

Direct immunofluorescence (DIF) is considered pivotal in diagnosing autoimmune blistering diseases. Our goal was to examine the necessity of DIF in intraepidermal bullous cases, of which pemphigus vulgaris (PV) is the prototype. Sixty-six cases from 2010 to 2014 submitted for DIF with an intraepidermal blistering disease listed in the differential diagnosis were reviewed by 2 board-certified dermatopathologists to see if they would order DIF based on routine histologic findings. If either pathologist requested DIF, it was considered required. DIF was "required" in 29% (19/66) (94% intraobserver concordance) and was positive in 16% (3/19) of those "required," leading to a diagnosis of PV (2/3) or pemphigus foliaceus [(PF) 1/3]. DIF was "not required" in 71% (47/66). Of these, 37/47 had negative/nonspecific DIF findings (79%). Of the 10 DIF+ cases, 8 were accurately diagnosed as PV based solely on the hematoxylin and eosin (H&E) findings. Three of 47 "not required" cases were misdiagnosed. Two (2/10 DIF+) were called "spongiotic dermatitis" by H&E interpretation yet had DIF consistent with PF. One case of acantholytic pityriasis rubra pilaris was diagnosed as PV on H&E, an error that may have been avoided with real-time clinical correlation. H&E diagnosis was 80% sensitive and 97% specific for intraepidermal blistering diseases. Positive predictive value was 89%; negative predictive value was 95%. H&E triaging could significantly reduce the need for DIF, especially in PV. If PF is in the differential diagnosis, DIF is necessary. In certain settings, triaging by H&E can obviate the need for DIF, resulting in significant savings.

Counseling in Pemphigus.

Pemphigus is a chronic, potentially life threatening, autoimmune intraepidermal blistering disease affecting the skin and the mucous membrane. Pemphigus may have profound impact on the quality of life in the affected patients. Counselling and adjuvant psychotherapy may be beneficial at least in few patients and should be considered as a part of multidisciplinary approach.

Immunofluorescence testing in the diagnosis of autoimmune blistering diseases: overview of 10-year experience.

BACKGROUNDImmunofluorescence testing is an important tool for diagnosing blistering diseases.OBJECTIVETo characterize the immunofluorescence findings in patients diagnosed with autoimmune blistering skin diseases.METHODSWe retrospectively analyzed immunofluorescence results encompassing a 10-year period.RESULTS421 patients were included and divided into 2 groups: group 1- intraepidermal blistering diseases (n=277) and 2- subepidermal blistering diseases (n=144). For group 1, positive DIF findings demonstrated: predominance of IgG intercellular staining (ICS) and C3 for pemphigus foliaceus-PF (94% and 73% respectively), pemphigus vulgaris-PV (91.5%-79.5%) and paraneoplastic pemphigus-PNP (66%-33%); ICS IgA in 100% of IgA pemphigus cases, and IgG deposits in the basement membrane zone (BMZ) along with ICS in one Hailey-Hailey patient. The IIF findings revealed mean titers of 1:2.560 for PV and 1:1.280 for PF. For paraneoplastic pemphigus, IIF was positive in 2 out of 3 cases with rat bladder substrate. In group 2, positive DIF findings included multiple deposits at basement membrane zone for epidermolysis bullosa acquisita-EBA (C3-89%,IgG-79%,IgA-47%,IgM-21%) mucous membrane pemphigoid-MMP (C3,IgG,IgA,IgM-80%) and bullous pemphigoid-BP (C3-91%,IgG-39%,IgA-11%,IgM-6%), and IgA at basement membrane zone for IgA linear disease (99%) and dermatitis herpetiformis-DH (dermal papillae in 84.6%). For lichen planus pemphigoides, there was C3 (100%) and IgG (50%) deposition at basement membrane zone. indirect immunofluorescence positive findings revealed basement membrane zone IgG deposits in 46% of BP patients, 50% for EBA, 15% for IgA linear dermatosis and 50% for LPP. Indirect immunofluorescence positive results were higher for BP and EBA with Salt-Split skin substrate.CONCLUSIONOur results confirmed the importance of immunofluorescence assays in diagnosing autoimmune blistering diseases, and higher sensitivity for indirect immunofluorescence when Salt-split skin technique is performed.

Non-classical forms of pemphigus: pemphigus herpetiformis, IgA pemphigus, paraneoplastic pemphigus and IgG/IgA pemphigus

The pemphigus group comprises the autoimmune intraepidermal blistering diseases classically divided into two major types: pemphigus vulgaris and pemphigus foliaceous. Pemphigus herpetiformis, IgA pemphigus, paraneoplastic pemphigus and IgG/IgA pemphigus are rarer forms that present some clinical, histological and immunopathological characteristics that are different from the classical types. These are reviewed in this article. Future research may help definitively to locate the position of these forms in the pemphigus group, especially with regard to pemphigus herpetiformis and the IgG/ IgA pemphigus.

Infliximab therapy failure in two patients with pemphigus vulgaris

To the Editor: Pemphigus vulgaris (PV) is a severe autoimmune intraepidermal blistering disease associated with autoantibodies against desmoglein-1 and -3; its treatment is generally challenging. High-dose corticosteroids, along with other immunosuppressants, is the mainstay of therapy.1 We report the cases of two patients with refractory PV unsuccessfully treated with the tumor necrosis factor (TNF)–alpha antagonist infliximab.

Radiotherapy‐induced pemphigus vulgaris with autoantibodies targeting a 110 kDa epidermal antigen

Pemphigus is an autoimmune intraepidermal blistering disease mediated by autoantibodies targeting desmosomes. It can be induced by many triggers, such as ionizing radiation. We report a case of radiotherapy-induced pemphigus (RIP) with a review of the published cases in the English and French literature. A 61-year old man was diagnosed to have epidermoid carcinoma of the piriform sinus and then received a 70 Gy radiation therapy. One month after the treatment completion, multiple blisters and erosions occurred initially on the site of irradiation, then in other skin areas. Histological examination showed an intraepidermal blister with acantholysis and necrosis of individual keratinocytes. Direct immunofluorescence and indirect immunofluorescence were typical of pemphigus. Immunoblot revealed antibodies reacting with a 110 kDa antigen. This feature was consistent with the diagnosis of RIP. Less than 20 cases of RIP have been reported previously. Mean age at diagnosis was 64.2 years, and there is a slight female preponderance. RIP occurred, in most cases, initially within the area of irradiation. Our patient showed some distinctive findings never reported previously in RIP: a histological focal keratinocyte necrosis, and the presence of autoantibodies reacting with a 110 kDa keratinocytic protein in immunoblot analysis. Because of a different prognosis, it is important to differentiate RIP and paraneoplastic pemphigus (PNP), although cases of ionizing radiation-induced PNP had also been described. As in our patient, RIP seems to respond well to systemic corticosteroids and immunosuppressive therapy, which induce remission within a few months.

Pathophysiology of Autoimmune Bullous Diseases

In immunobullous disease, the host immune system disrupts adhesive interactions in the skin, typically leading to clinical blister formation. The pathophysiology of these diseases has been an active area of investigation. The mechanisms by which these disorders lead to loss of adhesion are variable and disease dependent; however, general principles have been described. The term ‘‘subepidermal blistering disease’’ applies to several disorders that share the clinical appearance of vesicles and bulla, the histologic finding of subepidermal blistering, and in situ deposition of autoantibodies at the dermal–epidermal junction. This group of diseases includes bullous pemphigoid (BP), cicatricial pemphigoid, herpes gestationis, dermatitis herpetiformis, linear IgA disease, lichen planus pemphigoides, epidermolysis bullosa acquisita (EBA), and bullous systemic lupus erythematosus. Intraepidermal blistering diseases are characterized by acantholysis, loss of adhesion between adjacent epidermal keratinocytes, and deposition of immunoreactants at the keratinocyte cell membrane. The protypical intraepidermal autoimmune blistering diseases are pemphigus vulgaris (PV) and pemphigus foliaceus (PF). The autoimmune nature of these disorders began to be appreciated in the late 1960s when Jordon and Beutner used immunofluorescent techniques to demonstrate that BP patients have circulating and tissue-bound autoantibodies directed against antigens of the basement membrane zone. Use of these autoantibodies as a screening tool facilitated the identification of the target autoantigens. Using such an approach, Stanley et al. (1981, 1988) first characterized BP antigens at the molecular level and cloned the BP230 cDNA. Subsequently, cDNAs encoding BP180 (the autoantigen for BP, cicatricial pemphigoid, herpes gestationis, lichen planus pemphigoides, and linear IgA disease), laminin 5 (the autoantigen for cicatricial pemphigoid), and type VII collagen (the autoantigen for EBA and bullous systemic lupus erythematosus) were also cloned and characterized.

HLA‐DRB1*0402 haplotypes without DQB1*0302 in Venezuelan patients with pemphigus vulgaris

The two basic forms of autoimmune intraepidermal blistering diseases, pemphigus vulgaris (PV) and pemphigus foliaceus (PF), affect different layers of the skin, have different symptoms and target different antigens. We have defined human leukocyte antigen (HLA)-DRB1-DQB1 alleles and haplotypes in a case-control study of 66 non-Jewish patients attending a public reference Hospital over the past 10 years. The control group consisted of 101 matched individuals tested also by medium to high-resolution polymerase chain reaction-sequence-specific oligonucleotide with primers and probes from the 12th and 13th International Histocompatibility Workshop. Patients and controls were descendants of three-generation individuals born in the country. Among the patients, 49 had PV, 50% showed predominantly mucosal involvement, 50% showed predominantly the cutaneous clinical phenotype and 17 had PF. Statistically significant HLA-DR frequency differences between patients with PV and controls were found only for DRB1*0402 and DRB1*1401 [odds ratio (OR) = 27.22, confidence interval (CI) 94.7-7.82, P= 1.1 x 10(-14) and OR = 46.56, CI 801.4-2.70 P= 7.5 x 10(-6), respectively]. Both alleles were also increased in the patients with PF compared with the controls (OR = 7.0, P= 0.038 and OR = 21.64, P= 0.009, respectively), but the significance of the difference did not resist Bonferroni correction. Haplotype analysis showed that DRB1*0402 was always present with DQB1*0302 and DRB1*1401 with DQB1*0503, but no independent effect of the DQB1*0302 in the former haplotype was evident. Our results support the hypothesis that the DRB1*0402 without DQB1*0302 is the most relevant HLA-DRB1 allele responsible for the pathogenesis of pemphigus in Venezuelan patients with PV and discard the DQB1*0302 influence observed in other populations.

Using Desmoglein 1 and 3 Enzyme-linked Immunosorbent Assay as an Adjunct Diagnostic Tool for Pemphigus

Pemphigus is an acquired autoimmune intraepidermal blistering disease that is divided into 2 major subtypes: pemphigus vulgaris (PV) and pemphigus foliaceus (PF). Patients with pemphigus have circulating anti-desmoglein (Dsg)1 and/or anti-Dsg3 IgG autoantibodies. Recently, a novel commercial enzyme-linked immunosorbent assay (ELISA) against Dsg1 and Dsg3 has been established and found to be extremely sensitive and specific. To date, the usefulness of Dsg1 and Dsg3 ELISA in the diagnosis of pemphigus in the Taiwanese population has never been reported. Serum samples were obtained from 143 patients, including 20 patients with PV, 9 patients with PF, 72 patients with bullous pemphigoid, 1 patient with dermatitis herpetiformis and 41 patients with non-autoimmune blistering diseases. They were tested for anti-Dsg1 and anti-Dsg3 reactivity by ELISA. Seventeen of 20 PV sera (85%) exceeded the cut-off value of Dsg3 ELISA, and 9 of 9 PF sera (100%) exceeded the cut-off value of Dsg1 ELISA, while only 1 (0.88%) and 3 (2.6%) of 114 non-pemphigus sera exceeded the cut-off values of Dsg3 and Dsg1 ELISAs, respectively. Thus, the sensitivity and specificity of Dsg3 ELISA were 85% and 99.1%, while the sensitivity and specificity of Dsg1 ELISA were 100% and 97.4%, respectively. The correlation between ELISA scores and disease activity along the time course was examined in 6 PV patients and 1 PF patient, and the result was equivocal. Dsg1 and Dsg3 ELISAs provide a simple, highly sensitive and specific method that can serve as a useful adjunct tool for the initial diagnosis of pemphigus.

Erfolgreiche Therapie des IgA-Pemphigus vom subkorneal pustul�sen Typ

IgA pemphigus is a rare autoimmune intraepidermal blistering disease characterized by in vivo bound, and circulating IgA autoantibodies that target cell surface components (cadherins) of epidermal keratinocytes. The average age of onset is approximately 50 years. Histological hallmarks of IgA pemphigus are epidermal acantholysis, subcorneal or intraepidermal pustulosis, and neutrophilic infiltration. The main clinical characteristics are erythematous skin lesions with vesiculopustules, erosions, crusts and desquamation, favoring the trunk, groins, auxiliaries, and proximal extremities. The drug of choice for treating IgA pemphigus is diaminodiphenylsulfone. In this case study, we describe a patient who suffered from IgA pemphigus and responded well to diaminodiphenylsulfone.

Endemic pemphigus foliaceus (fogo selvagem) and pemphigus vulgaris: immunoglobulin G heterogeneity detected by indirect immunofluorescence

Pemphigus are autoimmune intraepidermal blistering diseases in which immunoglobulin G (IgG) autoantibodies are directed against desmosomal glycoproteins. The aim of this study was to determine the IgG subclass profile of endemic pemphigus foliaceus (fogo selvagem) and pemphigus vulgaris utilizing indirect immunofluorescence. Twenty-five patients with pemphigus vulgaris, 25 with endemic pemphigus foliaceus (fogo selvagem), and 25 healthy controls were analyzed by indirect immunofluorescence for circulating autoantibodies (total IgG and its subclasses). Our data revealed a significant correlation (P <.05) of disease activity and autoantibody levels in both forms of pemphigus, i.e., negative titers related to clinical remission, whereas positive results related to active disease. Immunoglobulin G subclass analysis in fogo selvagem demonstrated that in patients in remission, 56% showed positive immunoglobulin G4; in active disease, immunoglobulin G4 was the predominant subclass (100% positive in all cases). The IgG subclass profile in pemphigus vulgaris showed that in patients in remission, only 10% were positive for immunoglobulin G4; in active disease, positivity for immunoglobulin G4 was present in 78% to 88% of the cases. Subclass characterization of immunoglobulin G autoantibodies is a useful tool for pemphigus follow-up, since immunoglobulin G4 (IgG4) is the subclass that is closely related to recognition of pathogenic epitopes, and consequently with disease activity. Careful monitoring should be performed for fogo selvagem in clinical remission with a homogeneous IgG4 response, since this may indicate more frequent relapses.

Pemphigus foliaceus autoantibodies bind both epidermis and squamous mucosal epithelium, but tissue injury is detected only in the epidermis. The Cooperative Group on Fogo Selvagem Research.

Fogo selvagem (FS) is an autoimmune intraepidermal blistering disease mediated by antidesmosomal autoantibodies. Patients with FS do not have mucosal lesions despite extensive skin involvement. Our purpose was to evaluate the epidermis and the oral epithelium of patients with FS as targets of antidesmosomal autoantibodies. Fifteen patients were studied clinically, histologically, and immunologically. Biopsy specimens from the skin and the oral mucosa were studied by light microscopy and direct immunofluorescence. The serum of each of these patients was also titrated by indirect immunofluorescence. All patients showed skin lesions and subcorneal acantholyis, but none exhibited oral blisters or erosions. Direct immunofluorescence analysis demonstrated the presence of tissue-bound autoantibodies in both the epidermis and the oral epithelium of all patients with FS. Antiepidermal autoantibodies were also found in the sera of the patients. Relevant epitopes on desmoglein 1 molecules of oral epithelium may not be available to react with pathogenic FS autoantibodies.