Subepidermal Autoimmune Bullous Diseases Research Articles

Isolation and analysis of the exosomal membrane proteins in bullous pemphigoid

ABSTRACT Background Bullous pemphigoid (BP) is a severe autoimmune sub-epidermal bullous disease. Exosomes are small extracellular vesicles secreted by most cell types. The exosomal membrane proteins are implicated in various biological and pathological pathways. This study aims to explore the potential roles of exosomes in BP pathomechanism. Research design We collected plasma samples from 30 BP patients and 31 healthy controls. Nanoparticle tracking analysis (NTA) was used to analyze the size and concentration of exosomes. The immunogold labelling experiment and extracellular vesicle (EV) array were performed to detect the content and distribution of exosomes. Results The exosomes from both the BP and control groups’ plasma were successfully extracted. EV Array showed that CD63 and CD9 levels were significantly higher in the BP group than in the control group (p < 0.05). Expression levels of the BP180 NC16A and intracellular domain (ICD) were higher in the anti-BP180 positive group versus the controls (p < 0.05). The active BP group exhibits higher CD63 and BP180 ICD protein concentrations than the control or inactive BP groups (p < 0.05). Conclusion BP180 autoantigen fragments were expressed on the exosomal membrane in BP patients. The BP180 ICD and CD63 on exosomes could potentially be novel biomarkers for monitoring disease activity.

S2k guidelines on diagnosis and treatment of linear IgA dermatosis initiated by the European Academy of Dermatology and Venereology.

Linear IgA dermatosis (LAD) is a rare subepidermal autoimmune bullous disease (AIBD) defined by predominant or exclusive immune deposits of immunoglobulin A at the basement membrane zone of skin or mucous membranes. This disorder is a rare, clinically and immunologically heterogeneous disease occurring both in children and in adults. The aim of this project is to present the main clinical features of LAD, to propose a diagnostic algorithm and provide management guidelines based primarily on experts' opinion because of the lack of large methodologically sound clinical studies. These guidelines were initiated by the European Academy of Dermatology and Venereology (EADV) Task Force Autoimmune Bullous Diseases (AIBD). To achieve a broad consensus for these S2k consensus-based guidelines, a total of 29 experts from different countries, both European and non-European, including dermatologists, paediatric dermatologists and paediatricians were invited. All members of the guidelines committee agreed to develop consensus-based (S2k) guidelines. Prior to a first virtual consensus meeting, each of the invited authors elaborated a section of the present guidelines focusing on a selected topic, based on the relevant literature. All drafts were circulated among members of the writing group, and recommendations were discussed and voted during two hybrid consensus meetings. The guidelines summarizes evidence-based and expert opinion-based recommendations (S2 level) on the diagnosis and treatment of LAD. These guidelines will support dermatologists to improve their knowledge on the diagnosis and management of LAD.

Biological treatment for bullous pemphigoid.

Bullous pemphigoid (BP) is the most common autoimmune subepidermal bullous disease. Topical or systemic corticosteroids are often used as the first-line treatment. However, long-term corticosteroid use may lead to significant side effects. Therefore, various adjuvant immunosuppressant therapies are used as steroid-sparing agents, with accumulating reports of biological treatments for severely recalcitrant BP. To describe the clinical and immunological features of a series of patients with recalcitrant BP treated with immunobiological therapies. To assess the efficacy and safety of their therapies. Patients receiving biological treatment for BP from two centers were assessed. Here, we described the clinical, immunopathological, and immunofluorescence findings of adult patients with BP and analyzed the clinical response and adverse events associated with various biological therapies. We identified nine eligible patients treated with rituximab (seven), omalizumab (three), or dupilumab (one). The mean age at diagnosis was 60.4 years, the average BP duration before biologic initiation was 1.9 years, and the average previous treatment failure was 2.11 therapies. The mean follow-up period from the first biological treatment to the last visit was 29.3 months. Satisfactory response, defined as clinical improvement, was achieved in 78% (7) of the patients, and total BP clearance was achieved in 55% (5) of the patients at the last follow-up visit. Additional rituximab courses improved the disease outcomes. No adverse events were reported. Efficient and safe novel therapies can be considered in recalcitrant steroid-dependent BP non-responsive to conventional immunosuppressant therapies.

Potential contribution of anti-p200 autoantibodies to mucosal lesions in anti-p200 pemphigoid.

Anti-p200 pemphigoid is a relatively rare subepidermal autoimmune bullous disease (AIBD), which was firstly reported by Detlef Zillikens, Takashi Hashimoto and others in 1996. Skin lesions are considered as the major clinical features of this disease, with occasional involvement of mucosal lesions. The mechanism of mucosal lesions involved in anti-p200 pemphigoid is still unclear. In the present study, we aimed to analyze published data on cases and case series of anti-p200 pemphigoid with mucosal lesions and explored the potential contribution of anti-p200 autoantibodies to mucosal lesions. A total of 32 papers that comprised 52 anti-p200 pemphigoid patients with various mucosal lesions were included in this review. Oral lesions were involved in 75.0% patients, followed by genital lesions (26.9%) and ocular lesions (11.54%). Only one patient had psoriasis, 26.9% patients had multiple mucosal lesions, and 30.8% cases had comorbidity of other AIBDs, particularly anti-laminin (LM) 332-type mucous membrane pemphigoid (MMP). In comparison with anti-LM332-type MMP, anti-BP180-type MMP and epidermolysis bullosa acquisita, higher frequency of genital lesions was identified as a unique character of anti-p200 pemphigoid with mucosal lesions. These results indicated that anti-p200 autoantibodies might contribute to mucosal lesions in a pattern different from other MMP-related autoantibodies, although its pathogenetic mechanisms are still unclear.

The Intriguing Links between Psoriasis and Bullous Pemphigoid.

The coexistence of psoriasis with autoimmune bullous diseases (AIBDs), particularly bullous pemphigoid (BP), has been documented in case reports and series, as well as in epidemiological studies. The onset of psoriasis precedes that of BP in the majority of cases. Patients with concomitant BP and psoriasis are generally younger at the onset of BP and present with fewer erosions and blisters as compared with patients suffering from isolated BP. Intriguingly, it has been speculated that some BP cases with comorbid psoriasis can actually correspond to anti-laminin gamma-1 pemphigoid, a rare form that was recently recognized as a distinct entity and which can mimic BP and/or other subepidermal AIBDs. The pathomechanisms underlying the BP-psoriasis association have not yet been identified, although several hypotheses have been proposed. The most credited among such hypotheses involves the so-called "epitope spreading" phenomenon, with tissue injury secondary to a primary inflammatory process (i.e., psoriasis) leading to the exposure of sequestered antigens evoking a secondary autoimmune disease (i.e., bullous pemphigoid). This narrative review aims to give a brief overview of the association between psoriasis and BP, examining epidemiological, clinical, and immunopathological features, the pathomechanisms underlying this association, the treatments for psoriasis incriminated as potential triggers of BP, and the therapeutic management of patients with psoriasis and BP.

Therapeutic effects of Fc gamma RIV inhibition are mediated by selectively blocking immune complex-induced neutrophil activation in epidermolysis bullosa acquisita.

Epidermolysis bullosa acquisita (EBA) is a subepidermal autoimmune bullous disease caused by autoantibodies targeting type VII collagen (COL7). It is characterized by inflammation and subepidermal blistering mainly through immune complex (IC)-mediated activation of neutrophils. In experimental EBA, binding of neutrophils to ICs in the skin and induction of clinical disease depends on the expression of the Fc gamma receptor (FcγR) IV. As activating FcγR mediate both neutrophil extravasation and activation, we used multiphoton imaging to obtain further insights into the mechanistic contribution of FcγRIV in the pathogenesis of EBA. First, we demonstrated that blocking FcγRIV function completely protects LysM-eGFP mice against induction of antibody transfer-induced EBA. To visualize the interactions of anti-COL7 IgG and neutrophils in vivo, fluorescently labeled anti-COL7 IgG was injected into LysM-eGFP mice. Multiphoton microscopy was sequentially performed over a period of 8 days. At all time points, we observed a significantly higher extravasation of neutrophils into the skin of mice treated with anti-FcγRIV antibody compared to controls. However, the percentage of detected neutrophils localized to the target antigen along the dermal-epidermal junction was comparable between both groups. Additionally, reactive oxygen release and migration in vitro assay data demonstrate that FcγRIV antibody treatment inhibits the activation, but not the migration, of neutrophils. Our findings underscore the importance of advanced in vivo imaging techniques to understand the complexity of IC-mediated neutrophil-dependent inflammation, and indicate that the therapeutic utility of FcγRIV blockade is achieved through impairment of IC-mediated neutrophil activation.

Bullous pemphigoid in India: Review of cases registered in an autoimmune bullous disease clinic.

Background Information on bullous pemphigoid in an Indian context is scarce. Aim To report clinico-demographic profile, associated comorbidities and prescription pattern of bullous pemphigoid patients in India. Methods This was a retrospective study, where past records of all bullous pemphigoid patients diagnosed and treated between November 2013 and October 2019 were accessed and analysed. Patients having a compatible clinical presentation with either histopathological and/or direct immunofluorescence evidence of bullous pemphigoid were included. Results There were 96 bullous pemphigoid patients, with a male: female ratio of 1.6:1. The mean age at diagnosis was 62.5 ± 2.2 years, with mean duration of illness 27.5 ± 4.5 months before presentation. Comorbidities were present in 80 (83%) patients, with type 2 diabetes mellitus (38.5%), hypertension (36.4%) and neurological illness (16.7%) being the commonest ones. Clinically, blisters were the predominant presentation in 81 (84.4%) patients. The majority (87.5%) of patients showed a predominant eosinophilic infiltrate on histopathology. Direct immunofluorescence revealed immunoglobulin G deposits with complement C3 in 77 (80.2%) cases. The majority of patients (77.1%) were treated with oral prednisolone, either alone (11.5%) or in combination (65.6%) with other topical and systemic agents. Topical steroids were used in 29.1%, azathioprine in 28%, dapsone in 16.7% and omalizumab in 6.2% of patients. Limitations The study is retrospective. Immunofluorescence on salt split skin, direct immunofluorescence serration pattern analysis, and immunoblotting were not performed. Hence, there is a possibility that a few included cases were suffering from other subepidermal autoimmune bullous diseases like epidermolysis bullosa acquisita or anti-p200 pemphigoid. Conclusion Bullous pemphigoid patients in this study had a younger age of onset and showed male preponderance. Comorbidities like type 2 diabetes, hypertension and neurological disorders were frequent. Cutaneous blisters were the most frequent clinical presentation. Systemic corticosteroids comprised the mainstay of therapy.

Use of Dupilumab in Bullous Pemphigoid: Where Are We Now?

Bullous pemphigoid (BP) is the most frequent autoimmune subepidermal bullous disease. At present, the main treatment options are represented by corticosteroids and immunosuppressant drugs. Steroids often need to be administered in high doses, with subsequent adverse events and safety issues, as BP mainly affects elderly people. As dupilumab, a recombinant fully human IgG4 monoclonal antibody with binding specificity to human interleukin-4 receptor IL-4Rα has become paramount in the treatment of atopic dermatitis, its use in autoimmune bullous diseases has been theorized and it has been used to treat patients with BP. Dupilumab seems to be an effective and safe option to treat recalcitrant BP. Here, we report the results of a literature review on the use of dupilumab in BP, including a total of 30 treated patients in 9 papers.

Erratum: Anti-P 200 pemphigoid - The most common floor binding subepidermal autoimmune bullous disease in a tertiary care center in south India.

Erratum: Anti-P 200 pemphigoid - The most common floor binding subepidermal autoimmune bullous disease in a tertiary care center in south India.

Anti-P 200 pemphigoid - The most common floor binding subepidermal autoimmune bullous disease in a tertiary care center in south India.

The pemphigoid group of diseases may present clinically and immunologically in a very similar fashion. Indirect immunofluorescence microscopy with readily available salt-split human skin in a BIOCHIP™ helps to classify these conditions as those with either with roof binding or floor binding of immunoreactants. Epidermolysis bullosa acquisita, anti-laminin 332 pemphigoid and anti-p200 pemphigoid show floor binding, while in the most frequent type of pemphigoid disease, bullous pemphigoid, epidermal side staining pattern is seen on salt-split skin Aims: The aim of the study was to detect the target antigens in sub-epidermal bullous diseases. Forty patients with bullous pemphigoid diagnosed by lesional histopathology and direct immunofluorescence microscopy were re-evaluated by a BIOCHIP™ mosaic containing both tissue substrates and recombinant target antigens. Sera with floor pattern staining on salt-split skin were further evaluated by immunoblotting with dermal extract. Five patients with floor staining had anti-p200 pemphigoid. We could not perform serration pattern analysis of direct immunofluorescence in our patients. Histopathology and direct immunofluorescence microscopy cannot differentiate between various entities of pemphigoid diseases. A multivariant approach using a BIOCHIP™ mosaic including salt-split skin followed by immunoblotting with dermal extract helps to identify the target antigen.

Subepidermal Autoimmune Bullous Disease Associated With Monoclonal Gammopathy of Unknown Significance and Unexpected Positive Direct Nikolsky Phenomenon: A Case Report

Abstract Introduction: Numerous dermatoses associated with monoclonal gammopathy have been reported in the literature. Subepidermal autoimmune bullous diseases (SABD) are one of them which were not common. Here we report a case of SABD associated with MGUS who had a severe mucosal involvement and unexpected positive direct Nikolsky phenomenon. Case presentation: A 68-year-old male patient was admitted to our clinic with erosions on the oral mucosa, tense blisters, erosions, and ulcers on the trunk and extremities. Subepidermal vesicle formation was detected in the skin biopsy. Clinical examination revealed positivity for the Nikolsky phenomenon. The disease was unresponsive to conventional treatments and dysphagia and hoarseness occurred. The patient was screened for malignancy due to his unresponsiveness to the treatments and his severe oral mucosal involvement. Ig-G MGUS was detected in the patient. Discussion: The Nikolsky sign is an indicator of acantholysis and is known as a specific finding for pemphigus. However, when we look at gammopathy-associated autoimmune bullous dermatoses, skin fragility has been reported in cases. However, the meaning of fragility is not explained. The diagnosis of all these patients was Ig-M MGUS. Our patient was presented because of non-IgM MGUS, direct Nikolsky positivity, and severe mucosal involvement. Conclusion: Nikolsky positivity may be a clue for gammopathy-related subepidermal autoimmune bullous diseases.

Diagnosis of autoimmune subepidermal bullous diseases with mucous membrane involvement based on laser-scanning confocal microscopy.

Mucosal involvement in autoimmune subepidermal blistering disorders (ASBD) may represent the only or predominant localization. Circulating autoantibodies are detected in 50% cases. The aim of this study was to evaluate the usefulness of fluorescence overlay antigen mapping by laser-scanning confocal microscopy (FOAM-LSCM) to identify ASBD with mucosal involvement in oral mucosa specimens. Thirty-two ASBD patients, diagnosed based on direct immunofluorescence between 2006 and 2016, were enrolled. Localization of IgG deposits bound at the basement membrane zone, relative to laminin-332 and collagen IV localization, was assessed in vivo. FOAM-LSCM disclosed four different immunofluorescence patterns. IgG deposits were located above laminin-332, as in bullous pemphigoid (BP-type), in 19% cases and co-localized with laminin-332 (anti-laminin-332-type) in 6% cases. IgG deposits were found below laminin-332 and above collagen IV (mucous membrane pemphigoid-type) in 59% cases, and below collagen IV (epidermolysis bullosa acquisita-type) in 16%. Circulating antibodies were found in 56% cases. The FOAM-LSCM method should be used in order to obtain a definitive diagnosis of ASBD with mucosal involvement, particularly in the presence of negative circulating antibodies.

Penfigoide ampolloso Parte 2

Es una enfermedad ampollosa subepidérmica autoinmune de presentación infrecuente, originada por la pre­sencia de autoanticuerpos que se dirigen contra componentes de la membrana basal epidérmica, conocidos como BPAG1 y BPAG2. Se presenta principalmente en adultos mayores y está asociado a una alta morbilidad y morta­lidad. Clínicamente se caracteriza por la aparición de ampollas tensas sobre placas eritematosas, edematosas y pruriginosas. Para el diagnóstico, es importante la correlación de la clínica, evaluación histopatológica y el estudio por medio de inmunofluorescencia. En caso de presentaciones atípicas, el diagnóstico puede convertirse en un reto médico. El tratamiento se basa en el uso de inmunosupresores, principalmente los esteroidesm.

Epidermolysis Bullosa Acquisita Occuring In A Patient With Systemic Lupus Erythematosus

Epidermolysis Bullosa Acquisita (EBA) is a rare, chronic autoimmune subepidermal bullous disease and has been noted to be associated with systemic lupus erythematosus (SLE). The incidence of EBA and SLE in one patient within the period of 1980-1990 found only 7 published case reports. A 23 years old woman with exfoliate skin since 12 years ago. Initially itchy on her buttock then appeared small blister. Blister spread almost the entire body and rupture. This complaint got worsening in a year accompanied with hair loss, weight loss, and oral ulcer. Dermatological examination showed patch eritematosa, hyperpigmentation, hypopigmentation, erotion with erythematous base, yellow brownish crust. Also obtained sclerodactyli toes and nail fingers. Laboratory examination anemia gravis, hypoalbuminemia, Coombs test +2, ANA Test negatif, dsDNA IgG 32,80. Histopathology examination showed blister subepidermal, no vacuolar degeneration, no superficial and deep infiltrat, and minimal lymphocyte. Patient had diagnosed SLE from Internal Department based on MEX-SLEDAI score. The patient was treated with metylprednisolone intravenous pulse dose 500 mg on 3 days then tappering off and wound care. Epidermolysis Bullosa Acquisita immunogenetically related with MHC class II haplotype in particular HLA-DR2. This factor suggest playing role in the development of EBA to express more aggresive SLE.

New Insights Into the Pathogenesis of Bullous Pemphigoid: 2019 Update.

There are several lines of evidence indicating that the physiopathological bases of bullous pemphigoid (BP), the most common subepidermal autoimmune bullous disease, are hallmarked by the production of autoantibodies directed against the hemidesmosomal anchoring proteins BP180 and BP230. In contrast to the robustness of the latter assumption, the multifaceted complexity of upstream and downstream mechanisms implied in the pathogenesis of BP remains an area of intense speculation. So far, an imbalance between T regulatory cells and autoreactive T helper (Th) cells has been regarded as the main pathogenic factor triggering the autoimmune response in BP patients. However, the contributory role of signaling pathways fostering the B cell stimulation, such as Toll-like receptor activation, as well as that of ancillary inflammatory mechanisms responsible for blister formation, such as Th17 axis stimulation and the activation of the coagulation cascade, are still a matter of debate. In the same way, the pathomechanisms implied in the loss of dermal-epidermal adhesion secondary to autoantibodies binding are not fully understood. Herein, we review in detail the current concepts and controversies on the complex pathogenesis of BP, shedding light on the most recent theories emerging from the literature.

Actualización en dermatosis autoinmunes en caninos caracterizadas por pústulas, vesículas y ampollas: anatomopatología y diagnóstico

El objetivo de la presente revisión fue realizar una actualización sobre los aspectos clínicos, histopatológicos y patogenia de las dermatosis autoinmunes que afectan a los caninos y que se caracterizan por pústulas, vesículas y ampollas como lesión primaria. Se consideran los aspectos clínicos y las características histopatológicas de las enfermedades que componen el complejo pénfigo y las enfermedades ampollares subepidérmicas autoinmunes. Además, se describen las técnicas inmunológicas utilizadas en el diagnóstico y la caracterización de este grupo de enfermedades.

Evaluation of the value of indirect immunofluorescence on different substrates in the diagnosis of autoimmune subepidermal bullous diseases

Objective To evaluate the value of indirect immunofluorescence (IIF) on three different substrates including normal human skin (NS) , monkey esophagus (ME) and salt-split human skin (SS) in the diagnosis of autoimmune subepidermal bullous diseases. Methods A total of 56 patients with autoimmune subepidermal bullous diseases, including 47 with bullous pemphigoid (BP) , 6 with epidermolysis bullosa acquisita (EBA) , 2 with linear IgA bullous dermatosis, and 1 with anti-P200 pemphigoid, were diagnosed in and enrolled from Department of Dermatology, Institute of Dermatology, Chinese Academy of Medical Sciences between January 2015 and December 2016. Seventy patients with pemphigus, 15 patients with chronic eczema and 15 healthy adults served as controls. Blood samples collected from these patients and controls were subjected to IIF on three different substrates including NS, ME and SS, and the fluorescence deposition was observed. The sensitivities and specificities of IIF in the diagnosis of different subepidermal bullous diseases were compared. Statistical analysis was carried out with SPSS 13.0 software by using chi-square test for the comparison of enumeration data. Results IIF on NS or ME in the serum of patients with BP showed linear deposition of fluorescent material along the basement membrane zone. IIF on SS showed linear deposition of fluorescent material in the epidermis in the patients with BP, but in the dermis in the patients with EBA and anti-P200 pemphigoid. The sensitivities of IIF on NS, ME or SS in the diagnosis of subepidermal bullous diseases were 73.2%, 60.7% and 94.6% respectively, and the specificities were 98.0%, 100% and 97.1% respectively. There were significant differences among the sensitivities (χ2 = 18.2, P 0.05) . The diagnostic sensitivity of IIF on SS was significantly higher than that of IIF on NS or ME (χ2 = 8.0, 16.7, both P < 0.05) . Conclusion In the diagnosis of autoimmune subepidermal bullous diseases, IIF on SS is superior to IIF on ME or NS. Key words: Fluorescent antibody technique, indirect; Pemphigoid, bullous; Autoimmune subepidermal bullous disease; Diagnosis; Sensitivity; Specificity

The Usefulness of Indirect Immunofluorescence in Pemphigus and the Natural History of Patients With Initial False-Positive Results: A Retrospective Cohort Study.

The specificity and the predictive values of indirect immunofluorescence (IIF) in real-life settings is yet to be firmly established. The natural history of patients with false-positive results has not been sufficiently elucidated. The primary aim of the current study is to evaluate the diagnostic value of IIF analysis on monkey esophagus in pemphigus, utilizing a large cohort arising from the real-life experience of a tertiary referral center. The secondary endpoint was to determine the clinical outcomes of patients with false-positive results. This was a retrospective cohort study including all patients who were tested for the presence of intercellular autoantibodies by IIF on monkey esophagus between 2000 and 2017. Overall, 770 sera from different individuals were tested by IIF microscopy. Of those, 176 patients had been diagnosed with pemphigus vulgaris (PV) and 29 patients with pemphigus foliaceus (PF). The sensitivity of this immunoassay was significantly higher for the diagnosis of PV (87.4%; 95% CI, 81.5–91.9%) as compared to PF (69.0%; 95% CI, 49.2–84.7%; P = 0.018). The specificity for the diagnosis of pemphigus was 93.5% (95% CI, 91.1–95.4%). Patients with false-positive results (n = 37) were followed for a median duration of 5.3 years contributing 280.8 person-years. Thirty patients (81.1%) were eventually diagnosed clinically and immunopathologically with subepidermal autoimmune bullous diseases, whereas the remaining patients (18.9%) were diagnosed clinically and histologically with other inflammatory dermatoses, but none of them developed pemphigus during the follow-up duration. Of note, 7.0% (n = 23) of all patients diagnosed with bullous pemphigoid (BP) in the same period (n = 328) were tested positive for IgG intercellular antibodies. Histopathological review of the biopsy specimens of these patients did not reveal acantholysis. In conclusion, the predictive value of negative test in IIF on monkey esophagus is particularly reliable to exclude a diagnosis of pemphigus. Individuals tested positive for intercellular antibodies without an initial overt pemphigus did not show an increased risk for developing pemphigus subsequently. A sizable fraction of patients with BP showed circulating intercellular autoantibodies by IIF, without a histopathological evidence for acantholysis.

The Growing Incidence of Bullous Pemphigoid: Overview and Potential Explanations.

Bullous pemphigoid (BP) is the most common type of subepidermal autoimmune bullous diseases. BP characteristically affects the elderly and is seen mainly in patients older than 70 years. While the annual incidence of BP has been estimated to be between 2.4 and 23 cases per million in the general population, it rises exponentially to 190–312 cases per million in individuals older than 80 years. In addition, a growing body of evidence reports a remarkable trend of increased incidence of BP, showing a 1.9- to 4.3-fold rise over the past two decades. This demonstrable increase warrants a higher awareness of the increased risk to develop BP. This review summarizes the current understanding of the epidemiological features of BP and sheds light on the putative explanations for its growing incidence.

Histologic characterization of cellular infiltration in autoimmune subepidermal bullous diseases in a tertiary hospital in Saudi Arabia.

BackgroundAutoimmune subepidermal bullous dermatoses have similar clinical features to those of a spectrum of immune reactants at the dermoepidermal junction (DEJ). It is difficult to obtain a precise diagnosis without an immunofluorescence assay because of their similar clinical presentations. The aim of this study was to describe the cellular cutaneous infiltration among autoimmune subepidermal bullous dermatoses.Materials and methodsThis retrospective analysis was conducted at a hospital in Riyadh, Saudi Arabia using biopsy-based data collected from 65 patients.ResultsSpongiotic changes, neutrophils, and lymphocyte infiltrations in the epidermis differed among the subepidermal bullous diseases. The DEJ showed a difference in the extent of neutrophil infiltration. The dermis showed differences in perivascular lymphocytic infiltration, neutrophilic infiltration, eosinophilic infiltration, and dermal edema.ConclusionThe dermal and DEJ showed most of the histopathologic changes in subepidermal autoimmune bullous dermatoses.