Autoimmune Bullous Disorders Research Articles

Autoimmunologiczne choroby pęcherzowe skóry — analiza retrospektywna

Introduction: Autoimmune bullous disorders is a group of chronic diseases. Bullous pemphigoid is the most common autoimmune bullous disease of all, affecting mainly elderly people in the 8th decade of life, without gender predilection. Pemphigus manifests usually between 45 and 65 years of age, with a female predilection reported in most epidemiological studies. Aim of the study was assessing the prevalence of bullous diseases with respect to their types in different age groups, coexistence with neoplasms and other diseases. Material and methods: Retrospective analysis of medical histories of patients hospitalized in the Department of Dermatology, Sexually Transmitted Diseases, and Clinical Immunology at the University of Warmia and Mazury in Olsztyn with a diagnosis of bullous diseases between 2015 and 2021. Results: Seventy-two patients diagnosed with autoimmune bullous diseases were treated in the Department of Dermatology from 2015 to 2021. The mean age of patients was 76 years for pemphigoid diseases and 58 years for pemphigus. A causative agent such as drugs or consumption of bulbous plants was suspected in 10 patients (13.9%). Coexisting neoplasms were present in 12 patients (16.7%). The subjects also had comorbidities, the most common of which was hypertension (23 patients). Conclusions: The study confirmed most of the epidemiological data: bullous pemphigoid mainly affects the elderly, in the 8th decade of life, while pemphigus usually manifests itself before the age of 65. Symptoms can be provoked by external factors such as drugs, pathogens, UV light, diet, and stress. They can also coexist with other autoimmune and cardiovascular diseases.

Disease progression and response to therapy in pemphigus based on a registry.

Pemphigus diseases are potentially life-threatening and rare autoimmune bullous disorders characterized by blisters and erosions of the skin and mucous membranes. These disorders can be largely divided into two major subtypes: pemphigus vulgaris (PV) and pemphigus foliaceus (PF). The objective of this study was to evaluate the autoantibody profile and response to therapy of PV and PF patients by analyzing the clinicopathological data from a registry for bullous autoimmune dermatoses. In a retrospective study, data from 69 patients with PV and PF were included in the analysis. The Autoimmune Bullous Skin Intensity Score (ABSIS) was used to assess the clinical course, remissions, relapses and severity of the disease at first manifestation and throughout the observation period. ELISA was performed to assess levels of anti-desmoglein (Dsg)-1 and anti-Dsg3 IgG serum autoantibodies. The mean remission time in PV and PF patients was 63 weeks. PV patients with mucosal involvement showed a more favorable healing process. In PV patients with a moderate/high anti-Dsg1 IgG serum level at baseline, anti-Dsg3 IgG levels decreased during the observation period. Our study provides additional insights into the clinical course of patients with PV and PF, revealing that a mucosal phenotype is associated with a higher tendency towards remission.

Severe blistering eruptions induced by immune checkpoint inhibitors: a multicentre international study of 32 cases.

Among dermatologic adverse events induced by immune checkpoint inhibitors (ICI), bullous life-threatening reactions are rare. To better define the clinical and histological features, treatment, and prognosis of ICI-related severe blistering cutaneous eruptions. This retrospective case series was conducted between 2014/05/15 and 2021/04/15 by the dermatology departments of four international registries involved in drug reactions. Inclusion criteria were age ≥18 years old, skin eruption with blisters with detachment covering ≥1% body surface area and at least one mucous membrane involved, available pictures, and ICI as suspect drug. Autoimmune bullous disorders were excluded. Each participant medical team gave his own diagnosis conclusion: epidermal necrolysis (EN), severe lichenoid dermatosis (LD), or unclassified dermatosis (UD). After a standardized review of pictures, cases were reclassified by four experts in EN or LD/UD. Skin biopsies were blindly reviewed. Thirty-two patients were included. Median time to onset was 52 days (3-420 days). Cases were originally diagnosed as EN in 21 cases and LD/UD in 11 cases. After review by experts, 10/21 EN were reclassified as LD/UD. The following manifestations were more frequent or severe in EN: fever, purpuric macules, blisters, ocular involvement, and maximal detachment. Most patients were treated with topical with or without systemic corticosteroids. Eight patients (25%) died in the acute phase. The culprit ICI was not resumed in 92% of cases. In three patients, another ICI was given with a good tolerance. Histology did not reveal significant differences between groups. Severe blistering cutaneous drug reactions induced by ICI are often overdiagnosed as EN. Consensus for management is pending.

A Case Series of Recalcitrant Pemphigus

Pemphigus consists of a group of life threatening autoimmune bullous disorders characterised by flaccid blisters and erosions of the skin and mucosal membranes of oral, laryngeal, conjunctival, pharyngeal, anal, vaginal etc. Pemphigus vulgaris involves mucosa in 50- 70% of the patients. Pemphigus is associated with other autoimmune disorders like myasthenia gravis and thymoma. Primary subsets of pemphigus include pemphigus vulgaris, pemphigus foliaceus and paraneoplastic pemphigus. Pemphigus vulgaris constitutes nearly 70% of cases of pemphigus, with its antigens desmoglein 1 and 3, which are calcium dependent calmodulins, being the crucial targets for IgG1 and IgG4 classes of antibodies. If left untreated at an early stage, pemphigus vulgaris is associated with significant morbidity and mortality. The authors present a case series of recalcitrant pemphigus with focus on the various factors that affect the disease outcomes, morbidity and mortality

European recommendations for management of immune checkpoint inhibitors-derived dermatologic adverse events. The EADV task force 'Dermatology for cancer patients' position statement.

The introduction of immune checkpoint inhibitors (ICIs) opened a new era in oncologic therapy. The favourable profile of ICIs in terms of efficacy and safety can be overshadowed by the development of immune-related adverse events (irAEs). Dermatologic irAEs (dirAEs) appear in about 40% of patients undergoing immunotherapy and mainly include maculopapular, psoriasiform, lichenoid and eczematous rashes, auto-immune bullous disorders, pigmentary disorders, pruritus, oral mucosal lesions, hair and nail changes, as well as a few rare and potentially life-threatening toxicities. The EADV task force Dermatology for Cancer Patients merged the clinical experience of the so-far published data, incorporated the quantitative and qualitative characteristics of each specific dirAEs, and released dermatology-derived, phenotype-specific treatment recommendations for cutaneous toxicities (including levels of evidence and grades of recommendation). The basic principle of management is that the interventions should be tailored to serve the equilibrium between patients' relief from the symptoms and signs of skin toxicity and the preservation of an unimpeded oncologic treatment.

An unusual presentation of pemphigus foliaceus following COVID‐19 vaccination

An unusual presentation of pemphigus foliaceus following COVID‐19 vaccination

Dermatologic immune-related adverse events: The toxicity spectrum and recommendations for management.

Immune checkpoint inhibitors are a new class of oncologic drugs that act via the inhibition of checkpoints, thereby unlocking the immune system to attack cancer cells. Their emergence has radically changed the concept of therapy in oncologic patients. However, despite their overall favorable profile, their use has been associated with specific toxicities that may potentially affect treatment. The so-called immune-related adverse events (irAEs) mostly correspond to dysimmune reactions that can affect nearly every organ system, in theory, notably with the development of colitis, hepatitis, pneumonitis, or thyroiditis. Dermatologic irAEs are also among the most common, reaching a rate of approximately 40%. They are characterized by a wide phenotypic range, including mainly eczematous or lichenoid rashes, psoriasis, or autoimmune bullous disorders. Pruritus may accompany the aforementioned rashes or develop as an isolated symptom without the presence of skin changes. Depigmentation and hair/nail changes can be also observed in association with immune checkpoint inhibitor treatment. In the current article, we present an overview of the clinical spectrum of irAEs and provide tips for early recognition and management of dermatologic irAEs. We highlight the role that dermatologists can play in relieving patients and allowing for oncologic treatment to be maintained and administered more safely.

BI14: Multiple autoimmune bullous disorders arising secondary to immune checkpoint blockade

BI14: Multiple autoimmune bullous disorders arising secondary to immune checkpoint blockade

Histomorphological spectrum of noninfectious vesiculobullous lesions of skin: A rural area based study

Background: Vesiculobullous lesions are the major contribution of various skin disorders. They are primary morphological representation of various pathological stimuli. Histopathology plays major role in the initial phase of diagnosis helps in further evaluation to identify the underlying etiology. Aim and Objective: To study the prevalence of various morphological types of vesiculobullous skin lesions in different age groups in a rural area. Methodology: A Retrospective study conducted from May 2018 to May 2021, at Katuri Medical College & Hospital, Guntur. A study of vesiculobullous lesions of the skin biopsies of 90 cases was received to the department of pathology, at Katuri Medical College & Hospital, for 3 years. Complete clinical and relevant history was recorded. The specimens were routinely processed and H&E-stained slides were studied. Results: Out of 454 skin biopsies, of which 90 cases (19.8%) were diagnosed as vesiculobullous lesions by histopathologically. Pemphigous vulgaris comprised 38 cases (42.23%) followed by Bullous pemphigoid 24 cases (26.67%), in clinically suspected Autoimmune Bullous Disorders. Conclusion: Clinical examination has greater significance in diagnosis still histopathological examination plays vital role, helps to arrive at a definitive diagnosis in the majority of vesiculobullous disorders. Skin biopsy is inexpensive, carried out as OPD procedure with minimal discomfort to the patient.

Utility of Direct Immunofluorescence in Cutaneous Autoimmune Bullous Disorders.

BackgroundAutoimmune bullous disorders (AIBD) are a heterogeneous group of disorders with substantial clinical overlap associated with blistering of skin or mucosa.AimsThe present study aimed to study the histopathological spectrum and evaluate the utility of direct immunofluorescence (DIF) on snap-frozen and paraffin-embedded sections in resolving the differential diagnosis of AIBD and connective tissue disorders of the skin. We also compared the efficacy of DIF on paraffin versus the snap-frozen sections in diagnosing AIBD.MethodsThe present study was conducted for three years (2017-2019) and included 27 biopsies. We also included a retrospective analysis that included 25 biopsies collected over three years (2014-2017). Histopathological examination and DIF were conducted on all samples.ResultsPemphigus vulgaris was the most common autoimmune cutaneous disorder constituting 37% (n = 10) in prospective and 36% (n = 9) in the retrospective study. DIF showed a specificity of 81.25% in our prospective study. While on the paraffin-embedded sections, it showed a specificity of 66.6% in our retrospective study. In the prospective study, DIF on paraffin-embedded sections had a positivity rate of 43.75% as compared to 81.25% in DIF done on snap-frozen sections.ConclusionDIF is a sensitive tool for the diagnosis as well as distinguishing immune-mediated bullous disorders from other lesions primarily when performed on snap-frozen sections. The diagnostic yield is enhanced by DIF in cases that pose a diagnostic dilemma both clinically and histologically. The final diagnosis depends on all clinical, histopathological and immunofluorescence findings.

A retrospective cohort study reporting rituximab treatment for 33 patients with immunobullous disease.

Autoimmune bullous disorders, encompassing pemphigus and pemphigoid diseases, are associated with significant morbidity and mortality. This is in part due to high cumulative doses of corticosteroids in combination with immunosuppressant agents used in traditional treatment regimes. Rituximab is an antiCD20 monoclonal antibody which can induce complete remission, but it is currently unlicensed in the UK and approved only after other treatments have failed. We report a retrospective cohort study of 33 patients with pemphigus and pemphigoid diseases treated with rituximab from a single tertiary centre from 2013 to 2019. "Complete remission off therapy" was achieved by 27.3% (n=9), and a further 27.3% (n=9) had complete remission on minimal therapy. Twenty-one per cent (n=7) had "partial remission on minimal therapy"; 9.1% (n=3) patients were in the "consolidation phase," and 12.1% (n=4) had a "relapse/flare." A steady reduction in prednisolone doses was observed post-Rituximab infusion. Pre-Rituximab the median dose of prednisolone was 20mg (range 10-35, IQR 25), 15mg (range 9.5-22.5, IQR 13) at 1month, 9mg (range 5-10, IQR 5) at 6months, 4mg (range 0-5mg, IQR 5) at 12months and 0 (0-4.35, IQR 4.25) at 18months. Twelve per cent (n=4) of patients had documented infusion reaction symptoms. Twelve per cent (n=4) had later infective complications. This real clinic data adds to the evidence that Rituximab is a safe and effective treatment for both pemphigus and pemphigoid autoimmune blistering conditions. Significantly, we were able to demonstrate a substantial reduction in corticosteroid dosage in our cohort of patients following rituximab treatment.

Detecting Lesional Granulysin Levels for Rapid Diagnosis of Cytotoxic T lymphocyte–Mediated Bullous Skin Disorders

Bullous skin disorders are induced by different pathomechanisms and several are emergent, including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Rapid diagnostic methods for SJS/TEN or cytotoxic T-lymphocyte (CTL)-mediated bullous disorders are crucial for early treatment. Granulysin, primarily expressed by CTLs, is a specific cytotoxic protein responsible for SJS/TEN and similar skin reactions. To assess granulysin levels in blister fluids to differentiate SJS/TEN and similar CTL-mediated bullous reactions from other autoimmune bullous disorders. Using ELISA, we measured granulysin in blister fluids from patients with bullous skin disorders, including SJS/TEN, erythema multiforme major, bullous fixed-drug eruption, bullous lupus erythematosus, paraneoplastic pemphigus, pemphigus vulgaris, bullous pemphigoid, purpura fulminans-related bullae, and hand-foot syndrome/hand-foot-skin reactions. We compared serum and blister granulysin levels in patients with SJS/TEN presenting varying severity, monitoring serial granulysin levels from acute to late stages. Overall, 144 patients presenting with bullous skin disorders were enrolled. Blister granulysin levels (mean ± SD) in CTL-mediated disorders, including TEN (n= 28; 3938.7 ± 3475.7), SJS-TEN overlapping (n= 22; 1440.4 ± 1179.6), SJS (n= 14; 542.0 ± 503.2), erythema multiforme major (n= 7; 766.3 ± 1073.7), generalized bullous fixed-drug eruption (n= 10; 720.4 ± 858.3), and localized bullous fixed-drug eruption (n= 16; 69.0 ± 56.4), were significantly higher than in non-CTL-mediated bullous disorders (P < .0001), including bullous lupus erythematosus (n= 3; 22.7 ± 20.1), paraneoplastic pemphigus (n= 3; 20.3 ± 8.6), pemphigus vulgaris (n= 3; 4.4 ± 2.8), bullous pemphigoid (n= 18; 4.0 ± 2.7), purpura fulminans (n= 4; 5.9 ± 5.5), and hand-foot syndrome/hand-foot-skin reactions (n= 6; 4.6 ± 3.5). Blister granulysin levels correlated with clinical severity of SJS/TEN (P < .0001). Determination of blister granulysin levels is a noninvasive and useful tool for rapid differential diagnosis of SJS/TEN and other similar CTL-mediated bullous skin disorders for treatment selection.

Pemphigus Vulgaris and Bullous Pemphigoid: Update on Diagnosis and Treatment.

Autoimmune bullous disorders are a heterogeneous spectrum of skin disorders characterized by the production of autoantibodies against adhesion molecules of the skin. The 2 major groups of diseases are "pemphigus diseases" and "autoimmune bullous diseases of the pemphigoid type." Pemphigus diseases are a group of autoimmune blistering diseases of the skin and mucous membranes characterized by intraepithelial cleft and acantholysis. The main subtypes of pemphigus include pemphigus vulgaris, pemphigus foliaceus, and paraneoplastic pemphigus. Diagnosis is based on clinical manifestations and confirmed with histological, immunofluorescence, and serological testing. Recently multivariant enzyme-linked immunosorbent assay systems have been developed as practical screening tools for patients with suspected autoimmune bullous dermatoses. The current first-line treatment of pemphigus is based on systemic corticosteroids that are often combined with immunosuppressive adjuvants, such as azathioprine, mycophenolate mofetil, and the anti-CD20 monoclonal antibody rituximab, usually at initiation of treatment. Rituximab efficacy is higher when it is administered early in the course of the disease. Therefore, it should be used as first-line treatment to improve efficacy and reduce cumulative doses of corticosteroids and their side effects. Treatment of bullous pemphigoid is based on disease extension. Localized and mild forms can be treated with superpotent topical corticosteroids or with nonimmunosuppressive agents. In patients with generalized disease or whose disease is resistant to the treatments described above, systemic corticosteroids are preferred and effective. Adjuvant immunosuppressants are often combined with steroids for their steroid-sparing effect.

Cyclophosphamide-induced cancers in pemphigus patients –A report of three cases

Introduction: Cyclophosphamide is an important steroid-sparing immunosuppressive drug that was found to be effective for the treatment of autoimmune bullous disorders such as pemphigus. However, cyclophosphamide (an alkylating drug) is a mutagenic drug and is associated with the risk of malignancies. Three cases of cancers developing due to cyclophosphamide use in pemphigus are presented. Case Report: A 50-year-old male patient of pemphigus vulgaris received over 50 g of cyclophosphamide over 3 years. He died of bladder cancer 9 years after stopping the treatment. A 57-year-old male patient, a known case of diabetes, received over 100 g of cyclophosphamide for over 4 years for pemphigus foliaceus diagnosed with bladder cancer 5 years after stopping treatment. A 50-year-old male received around 100 g of cyclophosphamide over 3 years for pemphigus foliaceus diagnosed with squamous cell carcinoma of oral mucosa 2 years after stopping treatment. Conclusion: Cyclophosphamide is a mutagenic drug and is associated with the risk of malignancy which can appear many years after stopping the treatment; hence, long-term follow-up is important.

IADVL Position Statement and Recommendations on Post Lockdown Dermatology Practice Amidst the Covid -19 Pandemic (IADVL Academy and IADVL Executive Committee).

IADVL Position Statement and Recommendations on Post Lockdown Dermatology Practice Amidst the Covid -19 Pandemic (IADVL Academy and IADVL Executive Committee).

Direct immunofluorescence is of limited utility in patients with low clinical suspicion for an oral autoimmune bullous disorder

Oral autoimmune bullous disorders show clinical overlap with diseases such as lichen planus and others that may cause desquamative gingivitis. As direct immunofluorescence is expensive, we sought to determine if routine histology alone would be sufficient to distinguish between oral autoimmune bullous disorders and mimics. We searched the records for patients with a suspected oral autoimmune bullous disorder who underwent biopsies for concurrent routine histologic evaluation and direct immunofluorescence and who had at least one follow-up visit. Cases were separated into high and low suspicion subgroups based on clinical findings. Within 148 cases, the sensitivity of routine histology alone was 0.810, with a negative predictive value of 0.889. However, the specificity was 0.989 with a positive predictive value of 0.979. Of the high suspicion cases, 57 (47.1%) were found to be consistent with an oral autoimmune bullous disorder, with a total of 11 histologic false negatives. 8 cases, all in the high suspicion subgroup, showed indeterminate direct immunofluorescence results. There were no histologic false negatives or inconclusive direct immunofluorescence results in the low suspicion subgroup. In patients with a low clinical suspicion for an oral autoimmune bullous disorder, it is reasonable and more cost-effective to evaluate the lesion with routine histology alone.

Advances in the diagnosis of autoimmune bullous dermatoses

Autoimmune bullous dermatoses are defined by autoantibodies directed against adhesion proteins in the epidermis or basement membrane zone, resulting in blister formation on the skin and mucosa. Diagnosis depends on lesional biopsy for histopathology and perilesional biopsy for direct immunofluorescence. Additional diagnostic methods include indirect immunofluorescence, enzyme-linked immunosorbent assay, and immunoblot (Western blot), which may be selected in specific clinical scenarios due to improved sensitivity and/or specificity. This contribution reviews the available evidence supporting the use of each method to provide a practical reference for clinicians when diagnosing autoimmune bullous disorders. Techniques and cost are reviewed, and newer diagnostic techniques with potential for clinical application are

A Clinical Profile and Co-morbidities of Pemphigus Vulgaris Patients: A Study of 35 Cases

Background: Pemphigus vulgaris (PV), an autoimmune blistering disease involving the skin and mucosa. PV frequently begins with oral lesions and progresses to skin lesions. Autoimmune bullous skin disorders are associated with IgG or IgA auto- antibodies against distinct adhesion molecules of the epidermis and dermal epidermal basement membrane zone, respectively. These auto- antibodies lead to a loss of skin adhesion which shows up clinically as the formation of blisters or erosions.&#x0D; Objectives: To characterize the clinical parameters and co-morbidities of PV patients from a single tertiary medical centre in Bangladesh.&#x0D; Material and Methods: This observational study was done including 35 PV patients attending in the department of Dermatology and Venereology, Khwaja Yunus Ali Medical College Khawja Eunus Ali Medical College from 2010 to 2014. Thirty patients of pemphigus diagnosed clinically confirmed and treated over a 4-year period (2010-2014).&#x0D; Results: Majority of the patients 45.7% belongs to age group 41-50 years. Mean age 47.12±11.13. The male to female ratio in our study sample was 1:1.5. The youngest patient was 17 years old and the oldest 68. For both genders, the risk of onset peaked during the fifth and sixth decade of life. Out of 35 patients, 15(42.9%) was presented with mucosal lesions only, while 13 patients 37.1% had mucocutaneous lesions and 7 patients 20% had only cutaneous lesions. The most common comorbidies were hypertension 20.0%, osteoporosis 17.1%, and diabetes 8.6%, thyroid disease 8.6%, psoriasis 5.7%, rheumatoid arthritis 2.7%, rheumatic fever 2.9%, autoimmune hepatitis 2.9%, and myasthenia gravis 2.9%.&#x0D; Conclusion: The associated comorbidities of PV emphasize the need for dermatologists to keep a high index of suspicion and actively evaluate patients to determine their presence.&#x0D; KYAMC Journal Vol. 10, No.-2, July 2019, Page 106-109

Therapy of pemphigus

Pemphigus diseases are aheterogeneous group of potentially life-threatening autoimmune bullous disorders. Therefore, rapidly acting and effective therapeutic approaches are essential. In this review, current therapeutic options in line with available guidelines are presented and new therapeutic approaches are discussed. Aliterature search was performed using PubMed. Treatment of pemphigus is based on systemic glucocorticosteroids, frequently combined with potentially corticosteroid-sparing immunosuppressants such as azathioprine and mycophenolate mofetil/mycophenolic acid. Recently, the impressive efficacy of the anti-CD20 antibody rituximab has been shown in aprospective randomized trial. In severe or treatment-refractory cases, immunoadsorption or high-dose intravenous immunoglobulins (IVIG) are recommended. Adjuvant immunoadsorption also seems to be useful within the first 8-12weeks of therapy in patients with very high autoantibody levels. Avariety of new therapeutic approaches is currently evaluated in phase IIa studies. Therapy of pemphigus has been greatly improved by the employment of rituximab. The use of glucocorticosteroids, associated with ahigh number of adverse events and elevated mortality, could be reduced by the additional use of rituximab. After approval of rituximab for the treatment of pemphigus by the US Food and Drug Administration in 2018, licensing in Europe is expected in 2019.

Biochip detection of BP180 autoantibodies in blister fluid for the serodiagnosis of bullous pemphigoid: A pilot study.

Bullous pemphigoid is an autoimmune subepidermal blistering skin disease immunologically defined by autoantibodies directed against basement membrane zone antigens, the main of which is BP180. Laboratory tests are essential for diagnosis and include direct immunofluorescence and serologic assessments with indirect immunofluorescence and ELISA. Serology may be performed on blister fluid, in alternative to blood serum. This study investigated the use of a Biochip-based indirect immunofluorescence approach for the serum diagnosis of bullous pemphigoid on blister fluid. We compared the results using the Biochip-method with the ELISA detection of bullous pemphigoid-180 autoantibodies in blister fluid and observed a perfect correlation between these 2 methods in our group of 13 patients with clinical and direct immunofluorescence diagnosis of bullous pemphigoid. The Biochip is a simple, standardized and inexpensive diagnostic tool and its use on blister fluid may facilitate the diagnosis of this and other autoimmune bullous disorders. Our results suggest that the Biochip assay on serum of bullae is a non-invasive screening technique for the early diagnosis of bullous pemphigoid that is practical for fragile elderly patients and achievable even in small laboratory settings.