Autoimmune Bullous Dermatoses Research Articles

Computer-aided classification of indirect immunofluorescence patterns on esophagus and split skin for the detection of autoimmune dermatoses.

Autoimmune bullous dermatoses (AIBD) are rare diseases that affect human skin and mucous membranes. Clinically, they are characterized by blister formation and/or erosions. Depending on the structures involved and the depth of blister formation, they are grouped into pemphigus diseases, pemphigoid diseases, and dermatitis herpetiformis. Classification of AIBD into their sub-entities is crucial to guide treatment decisions. One of the most sensitive screening methods for initial differentiation of AIBD is the indirect immunofluorescence (IIF) microscopy on tissue sections of monkey esophagus and primate salt-split skin, which are used to detect disease-specific autoantibodies. Interpretation of IIF patterns requires a detailed examination of the image by trained professionals automating this process is a challenging task with these highly complex tissue substrates, but offers the great advantage of an objective result. Here, we present computer-aided classification of esophagus and salt-split skin IIF images. We show how deep networks can be adapted to the specifics and challenges of IIF image analysis by incorporating segmentation of relevant regions into the prediction process, and demonstrate their high accuracy. Using this semi-automatic extension can reduce the workload of professionals when reading tissue sections in IIF testing. Furthermore, these results on highly complex tissue sections show that further integration of semi-automated workflows into the daily workflow of diagnostic laboratories is promising.

Use of Complementary and Alternative Medicine in Patients with Autoimmune Bullous Dermatoses: A Cohort Study Analysis of a Rare Disease Group

Introduction: Autoimmune bullous diseases (AIBD) are a heterogeneous group of rare autoantibody-mediated blistering dermatoses of the skin and/or mucous membranes. Their incidence is around 20 new cases per million inhabitants per year in Germany. Patients with chronic, oncological, or rare diseases often urge for a holistic therapeutic approach that includes complementary and alternative medicine (CAM). So far, only few contradictory reports on CAM in pemphigoid or pemphigus disease exist. The purpose of this study was to determine the frequency, motives, and satisfaction with the use of alternative treatments in patients with AIBD and to provide a basis for further investigation. Methods: We used a structured online questionnaire, consisting of 20 questions to survey patients with AIBD and their relatives. The German pemphigus and pemphigoid self-help groups were responsible for distributing anonymized questionnaires. In total, we recovered 97 questionnaires, 63 of which met full inclusion criteria (24 males and 39 females). Results: Of the included participants, more than half had a currently active disease. Of all patients, 58.7% stated that they had used CAM at least once. Women were more likely to use CAM, whereas age and education showed no association to CAM use. The main motives for using CAM were “doing something for oneself” and “opportunity to contribute to treatment” (38.1% each). The internet (23.8%) was the most common source of information, and vitamins were the most frequently used therapy (49.2%). Conclusion: Our results provide new insights into the demand for CAM within this rare disease patient group. Physicians should be aware of these methods to meet patient needs but also be able to identify potential barriers such as risks and interactions.

Concordance of Clinical, Histologic and Direct Immunofluorescence Findings in Patients with Autoimmune Bullous Dermatoses in Vietnam.

Introduction: Autoimmune bullous dermatoses (ABD) represent a heterogeneous group of blistering disorders that may be debilitating with high morbidity. Clinical, histological, and direct immunofluorescence (DIF) studies are essential in establishing an accurate diagnosis of ABD, which is essential for its clinical management. Our study objective was to perform a systematic evaluation of ABD cases in a patient population at an academic medical center in Ho Chi Minh City, Vietnam, and determine the degree of concordance of clinical, histological, and DIF findings in ABD. Methodology: A systematic retrospective cross-sectional study was performed on 92 patients diagnosed with ABD by clinical, histological, and DIF studies at the University of Medicine and Pharmacy in Ho Chi Minh City, Vietnam, between September 2019 and September 2021. The clinical histories, H and E stained tissue sections, and DIF stains were evaluated by pathologists at the University of Medicine and Pharmacy. Results: ABD was evaluated as a whole and subdivided into an intraepidermal blister subgroup and a subepidermal blister subgroup. The analysis of paired diagnostic methods (clinical, histological, and DIF) for concordance with the final diagnosis was performed and showed that there were no statistically significant differences between the paired methods (McNemar’s test, p > 0.05). There was moderate concordance between the clinical, histological, and DIF diagnoses among all ABD cases (Brennan-Prediger coefficient Kappa test, κBP = 0.522, CI = 0.95). In the intraepidermal blister subgroup, the diagnostic accuracies of the histology and DIF stains were comparable to each other, and both were more accurate than a clinical diagnosis alone. In the subepidermal blister subgroup, there was no statistically significant difference in each pair of the three diagnostic methods (clinical, histological, and DIF) (McNemar’s test, p > 0.05). The concordance between the clinical, histological, and DIF diagnoses was high for the intraepidermal blister subgroup (Kappa test, κBP = 0.758, CI = 0.95). However, the concordance between the clinical, histological, and DIF diagnoses was slight for the subepidermal blister subgroup (Kappa test, κBP = 0.171, CI = 0.95). Conclusion: Histological evaluation is highly accurate in the diagnosis of the intraepidermal blister subgroup, but it is not as accurate in the diagnosis of the subepidermal blister subgroup in the Vietnamese patient cohort in which clinical, histological, and DIF studies were performed. DIF stains are a crucial diagnostic tool for ABD in this patient population.

Rituximab in the Management of a Child with Pemphigus Vulgaris: Case Study

Background. Pemphigus vulgaris is an autoimmune bullous dermatosis. Its management generally involves lifelong administration of maintenance dose of systemic glucocorticosteroids, that leading to serious adverse effects especially in children.Clinical case description. Patient is the 16 years old boy with severe course of pemphigus vulgaris. The diagnosis was confirmed by the results of cell smear study from fresh erosions (> 50 acantholytic cells were revealed), histological examination of the skin biopsy from the lesion with the vesicle element (suprabasal vesicle was localized in the center, it included fibrin, neutrophil granulocytes, and acantholytic cells), skin biopsy from the area near the lesion (visually healthy skin), via direct immunofluorescence methods (IgG deposition was detected on keratinocytes’ surface throughout the epidermis), and enzyme-linked immunosorbent assay (desmoglein 1 IgG autoantibodies — 121 U/mL (reference value < 20 U/mL) and desmoglein 3 — > 200 U/mL (reference value < 20 U/mL)). Genetically engineered biologic drug, rituximab, and systemic glucocorticosteroid, methylprednisolone, were prescribed as first-line therapy with gradual dose reduction to permanent discontinuation in 8 months. Complete remission maintained after the completion of therapy course and discontinuation of systemic glucocorticosteroid.Conclusion. Combined therapy with systemic glucocorticosteroids and rituximab can be considered as first-line therapy in pediatric patients with pemphigus vulgaris due to relatively low risk of recurrence after rather rapid and complete drugs’ discontinuation.

In-hospital mortality in a dermatology department

Background: Far from popular belief making dermatological conditions benign and harmless, we know that some dermatoses may be life-threatening. The aim of our study was to evaluate the overall mortality resulting from dermatological disorders in our department because of the rarity of similar studies. Materials and Methods: We conducted a retrospective, observational study on all patients who died in the Ibn Sina Hospital of Rabat between January 2017 and December 2021 (a period of five years), after they were initially admitted to the dermatology department. Results: Among 1731 patients hospitalized during this period, 45 died, corresponding to an average of 2.6%. The male-to-female ratio was 1.9 and the mean age at death was 63.2 years. The mean number of comorbidities per patient was 1.2, dominated by diabetes. The reasons for hospitalization were as follows: twenty-three cases of extensive bullous dermatoses (60.5% of the cases), four cases of severe toxidermia (10.5%), three cases of erythroderma (7.8%), one case of acro-lentiginous melanoma, one case of squamous cell carcinoma, and one case of pyoderma gangrenosum. In twenty patients (52.6%), the cause of death was directly related to the dermatosis. In sixteen, the cause of death was septic shock of cutaneous origin. Sixteen patients (42.1%) died of causes unrelated to dermatosis. Conclusion: This study showed that life-threatening dermatoses are not uncommon. Among these conditions, autoimmune bullous dermatoses and severe toxidermia, such as TEN and DRESS syndrome, were found to be the most lethal. An advanced age, a surface area of skin involvement, mucosal involvement, associated comorbidities, and the development of sepsis may be considered poor prognostic factors.

S2442 A Rare Finding of a Common Disorder

Introduction: Esophagitis dissecans superficialis (EDS) is a rare desquamative disorder of the esophagus, characterized by sloughing of the esophageal squamous mucosa. Most cases of EDS have been associated with autoimmune bullous dermatoses, medications like bisphosphonates, chemical irritants, iatrogenic injury, and celiac disease. To our knowledge, EDS has not previously been reported with achalasia. Case Description/Methods: Our patient is a 42-year-old woman with Hashimoto’s thyroiditis and untreated achalasia type II diagnosed on high-resolution manometry 4 years ago who presented to the hospital with dysphagia to both solids and liquids and oral intake intolerance for one week. She also endorsed weight loss, nausea, and vomiting clear secretions mixed with thick white cord-like material. Physical exam was remarkable for dry mucous membranes. Laboratory tests were notable for mild leukocytosis. Given her history of achalasia and progressive symptoms, esophagogastroduodenoscopy (EGD) was performed and showed large fragments of mucosal sloughing in the distal esophagus or “tissue paper esophagus” consistent with EDS and hypertonic lower esophageal sphincter (Figure 1). Pneumatic dilation (PD) to 30 mm was successfully performed with improvement in symptoms. She was continued on a daily proton pump inhibitor and was doing well on her 4-month follow-up. Discussion: EDS can be an incidental finding on endoscopy or can present with a variety of symptoms, including dysphagia, odynophagia, coughing, or vomiting the sloughed esophageal mucosa like in our patient. The pathogenesis remains unclear. It might represent a mucosal reaction to various insults (iatrogenic, chemical, thermal, and immunological). Although EDS has been reported in association with certain dermatologic and gastrointestinal autoimmune diseases like celiac disease, it has not been reported in the setting of achalasia. Perhaps the possible autoimmune pathogenesis of achalasia related to antibodies against the enteric neurons contributes to its occurrence. Biopsies are recommended to rule out other etiologies such as candidiasis and squamous cell carcinoma (SCC). There is no specific treatment for EDS; a combination of acid suppression and discontinuation of the offending agent if present can result in healing. Prognosis is benign without lasting esophageal complications. In conclusion, endoscopists need to be aware of EDS in order not to mistake it for other conditions like esophagitis and SCC and to recognize its association with achalasia.Figure 1.: Sloughing of the esophageal mucosa described as "tissue paper esophagus" in esophagitis dissecans superficialis.

Advances in research related to heat shock protein 90 and autoimmune dermatoses

Autoimmune dermatoses result from immune imbalances due to aberrant immune responses to self-antigens. Heat shock protein 90 (HSP90), as a member of a highly conserved family of stress proteins, plays an important role in inflammation and immune responses. It has been suggested that HSP90 is related to the occurrence and development of autoimmune dermatoses, but the exact mechanisms involved remain unclear. In this report, we review the evidence indicating a potential link between HSP90 and three common autoimmune dermatoses, bullous dermatoses, psoriasis and lupus erythematosus. In addition, the progress of research involving HSP90 inhibitors as potential therapeutic targets is assessed.

Association of specific HLA alleles and haplotypes with pemphigus vulgaris in the Bulgarian population.

Pemphigus vulgaris (PV) is an autoimmune bullous dermatosis with uneven geographic distribution and higher incidence in certain populations. In previous studies, a relatively high incidence of PV was reported in Bulgaria (0.47/100,000/year) comparable to that in other countries. The genetic background was considered responsible for the disease susceptibility, and multiple reports have proven PV to be an HLA-associated condition. The aim of our study was to analyze the role of genetic factors in the development of PV in Bulgaria. HLA genotyping was performed in 56 PV patients, ethnic Bulgarians whose diagnosis was confirmed based on clinical, histological, and immunofluorescent findings. The control group consisted of 204 healthy individuals from the Bulgarian population without evidence for HLA-associated autoimmune diseases. HLA-A,-B,-DRB1,-DQB1 analysis was performed by PCR-SSP. Our results revealed predisposing associations with DRB1*14, DRB1*04:02, and B*38, B*55, while allele DRB1*03:01 and the corresponding haplotypes were significantly decreased in the PV patients. The predisposing role of these alleles has been observed in other populations. All reported predisposing DRB1 alleles have the same amino acids at key positions of the beta chain of the HLA molecules, 26 (Phe), 67 (Leu or Ileu), 70 and 71 (hydrophobic AA: Gln, Arg, Asp, or Glu), and 86 (Val), which is important for the selective presentation of desmoglein 3 peptides. Additionally, specific alleles HLA-A*01 and DRB1*11 were identified with decreased frequencies in the patients’ group, the last one being a common protective allele for autoimmune diseases in the Bulgarian population. The elucidation of the role of genetic factors for the development of pemphigus will help explain its higher incidence and clinical variability in certain populations.

Anaphylatoxins spark the flame in early autoimmunity.

The complement system (CS) is an ancient and highly conserved part of the innate immune system with important functions in immune defense. The multiple fragments bind to specific receptors on innate and adaptive immune cells, the activation of which translates the initial humoral innate immune response (IR) into cellular innate and adaptive immunity. Dysregulation of the CS has been associated with the development of several autoimmune disorders such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ANCA-associated vasculitis, and autoimmune bullous dermatoses (AIBDs), where complement drives the inflammatory response in the effector phase. The role of the CS in autoimmunity is complex. On the one hand, complement deficiencies were identified as risk factors to develop autoimmune disorders. On the other hand, activation of complement can drive autoimmune responses. The anaphylatoxins C3a and C5a are potent mediators and regulators of inflammation during the effector phase of autoimmunity through engagement of specific anaphylatoxin receptors, i.e., C3aR, C5aR1, and C5aR2 either on or in immune cells. In addition to their role in innate IRs, anaphylatoxins regulate humoral and cellular adaptive IRs including B-cell and T-cell activation, differentiation, and survival. They regulate B- and T-lymphocyte responses either directly or indirectly through the activation of anaphylatoxin receptors via dendritic cells that modulate lymphocyte function. Here, we will briefly review our current understanding of the complex roles of anaphylatoxins in the regulation of immunologic tolerance and the early events driving autoimmunity and the implications of such regulation for therapeutic approaches that target the CS.

Adverse outcome and severity of COVID-19 in patients with autoimmune bullous diseases: A historical cohort study.

The ongoing COVID‐19 pandemic has raised concerns regarding the outcome of this infection in patients with autoimmune bullous dermatoses (AIBDs) due to effect of drugs used to treat these disorders. This investigation was performed from the onset of the pandemic to June 1, 2021. Patients with AIBDs who contracted COVID‐19 were evaluated. A generalized linear model was employed to find the predictors of severe COVID‐19 among patients with AIBDs. Ninety‐three patients with AIBDs with a mean age of 50.3 years were evaluated. The most COVID‐19 related symptoms were tiredness (76.3%) myalgia (69%), and cough (63.4%). During follow‐up, the rate of hospitalization and death were 45.2% and 4.3%, respectively. Previous comorbidities (β = 0.61) and mean prednisolone dosage above 10 mg/day in the last 3 months (β = 1.10) significantly increased COVID‐19 severity. Also, vaccination against SARS‐CoV‐2 (β = −1.50) and each passing month from the last rituximab dose decreased severity (β = −0.02). Notably, 19.3% of the patients developed AIBD flare‐ups following COVID‐19 infection. Higher prednisone dose and the shorter interval from the last rituximab infusion were determinants of severe COVID‐19. Physicians should assess the risk versus the benefits when prescribing the medications. Moreover, vaccination could successfully attenuate COVID‐19 severity.

Desquamative Gingivitis in the Context of Autoimmune Bullous Dermatoses and Lichen Planus-Challenges in the Diagnosis and Treatment.

Desquamative gingivitis (DG) is a clinical term that describes erythema, desquamation and erosions of the gingiva, of various etiologies. Although the clinical aspect is not specific for a certain disease, an accurate diagnosis of the underlying disorder is necessary because the disease course, prognosis and treatment vary according to the cause. DG may inflict significant oral discomfort, which is why patients typically present to the dentist for a first consultation, rendering it important for these specialists to be informed about this condition. Our paper aims to review the ethiopatogenesis and diagnostic approach of DG, focusing on the most common underlying disorders (autoimmune bullous dermatoses and lichen planus) and on the management of these patients. Potential etiological agents leading to an inflammatory immune response in the oral mucosa and DG appearance include genetic predisposition, metabolic, neuropsychiatric, infectious factors, medication, dental materials, graft-versus-host reaction and autoimmunity. A thorough anamnesis, a careful clinical examination, paraclinical explorations including histopathological exam and direct immunofluorescence are necessary to formulate an appropriate diagnosis. Proper and prompt management of these patients lead to a better prognosis and improved quality of life, and must include management in the dental office with sanitizing the oral cavity, instructing the patient for rigorous oral hygiene, periodic follow-up for bacterial plaque detection and removal, as well as topical and systemic therapy depending on the underlying disorder, based on treatment algorithms. A multidisciplinary approach for the diagnosis and follow-up of DG in the context of pemphigus vulgaris, bullous pemphigoid, cicatricial pemhigoid or lichen planus is necessary, including consultations with dermatologists, oral medicine specialists and dentists.

Current and Innovated Managements for Autoimmune Bullous Skin Disorders: An Overview.

Autoimmune bullous skin disorders are a group of disorders characterized by the formation of numerous blisters and erosions on the skin and/or the mucosal membrane, arising from autoantibodies against the intercellular adhesion molecules and the structural proteins. They can be classified into intraepithelial or subepithelial autoimmune bullous dermatoses based on the location of the targeted antigens. These dermatoses are extremely debilitating and fatal in certain cases, depending on the degree of cutaneous and mucosal involvement. Effective treatments should be implemented promptly. Glucocorticoids serve as the first-line approach due to their rapid onset of therapeutic effects and remission of the acute phase. Nonetheless, long-term applications may lead to major adverse effects that outweigh the benefits. Hence, other adjuvant therapies are mandatory to minimize the potential harm and ameliorate the quality of life. Herein, we summarize the current therapeutic strategies and introduce promising therapies for intractable autoimmune bullous diseases.

How to decrease systemic corticosteroids in pemphigus patients under rituximab.

How to decrease systemic corticosteroids in pemphigus patients under rituximab.

Autoimmune bullous dermatoses: should we treat the patient or the antibodies? A preliminary study

Autoimmune bullous dermatoses: should we treat the patient or the antibodies? A preliminary study

Unilateral bullous pemphigoid in a hemiplegic patient

Sir, Bullous pemphigoid (BP) is the most common autoimmune bullous dermatosis, mainly affecting the elderly. Its association with neurological diseases has been reported for several years in several studies, including with strokes. We report a new case of unilateral BP in a hemiplegic patient. A 78-year-old patient with a history of hypertensive and ischemic heart disease and ischemic stroke three years ago was admitted for pruriginous bullous dermatosis evolving for one month prior to admission. A general examination revealed right hemiplegia with facial involvement and aphasia. A dermatological examination found localized erosions on the paralyzed side of the body, without urticarial or bullous lesions. Nikolsky’s sign was absent and the rest of the clinical examination was without abnormality (Figs. 1a – 1c). A skin biopsy revealed a skin coating widely ulcerated on the surface without eosinophilic infiltrate. Indirect immunofluorescence was positive at 1260. The diagnosis of BP was retained and the patient was started on a strong local dermocorticoid with a good evolution and the disappearance of the lesions after two months.

PEMPHIGOID GESTATIONIS : CASE REPORT AND REVIEW OF LITTERATURE

Pemphigoid gestationis (PG) is a rare autoimmune bullous dermatosis associated with pregnancy. Its previous designation, herpes gestationis, is obsolete. PG is characterized by a subepidermic separation induced by the presence of peripheral blood autoantibodies against two hemidesmosomal antigens: BPAG1 and BPAG2. Clinical diagnosis is confirmed by histology and positive cutaneous immunofluorescence tests. The most discriminant examination for other pruritic dermatoses of pregnancy is the enzyme-linked immunosorbent assay (Elisa) NC16A BP 180. First-line treatment is local corticosteroid therapy if local treatment fails, general corticosteroid therapy should be administered. The prognosis is good for mother and child, except that there is a risk of preterm delivery and of moderate fetal growth restriction. Management in a specialized setting is therefore necessary. Recurrence is possible during subsequent pregnancies. We report a case of PG identified in our department, with a review of literature about physiopathology, diagnosis and treatment of this rare pathology.

Acrodermatitis enteropathica-like eruption

Acrodermatitis enteropathica-like eruption

Dermatological emergencies: a Moroccan retrospective case series over a period of two years.

Introductiona dermatological emergency is defined as an acute dermatosis evolving since less than 5 days and being life or functional threatening. The main objective of this study was to describe the epidemiological and clinical profile of patients seen for a dermatological emergency.Methodsthis is a retrospective case series, carried out over a period of two years [May 2018 - May 2020], including all the patients seen in the Dermatology Department for a true dermatological emergency. The descriptive analysis was carried out using Excel software.Resultsa total of 843 patients were collected. The mean age was 46.95 years, with a standard deviation of 15.69 and a slight male predominance (n=448). There were 709 adults and 134 children. The majority of patients came from central emergencies (n=451). The pathologies seen were in order of frequency: Infectious dermatoses (n=469) dominated by erysipelas in adults (n=302) and viral dermatoses in children (n=47); drug-induced skin reactions (n=160); inflammatory dermatoses (n=113) including erythroderma (n=36), urticaria (n=32), vasculitis (n=25), and erythema multiform (n=20); autoimmune bullous dermatoses (n=74); and physical skin diseases (n=27). Other specialists´ advice was needed for 231 patients. Biological involvement and imaging were required in respectively 536 and 421 cases. Only 235 required hospital admission, while the others needed an ambulatory care.Conclusionthe pathologies seen in the dermatological emergency unit were dominated by infectious dermatoses, suggesting elaborating a medical program to improve the non-dermatologist physicians' knowledge about them.

Bullous Dermatoses and Quality of Life: A Summary of Tools to Assess Psychosocial Health.

Autoimmune bullous dermatoses (ABDs), such as pemphigus and bullous pemphigoid (BP), cause cutaneous lesions that are painful and disfiguring. These conditions affect a patient's ability to perform everyday tasks, and individual lesions can take years to heal. Multiple small studies have examined how these conditions affect a patient's lifestyle. We systematically reviewed the trials that have evaluated the mental health of patients with bullous dermatoses. Of the 13 studies assessed, 2 domains of interest were primarily evaluated: quality of life (QOL) and psychological state. Quality of life predominantly was analyzed using the Dermatology Life Quality Index (DLQI). To evaluate psychological state, the General Health Questionnaire (GHQ) primarily was utilized. This review informs providers and summarizes the various ways that ABDs affect mental health.

Epidemiologija i komorbiditeti kod buloznog pemfigoida u periodu od januara 2019. do januara 2021. godine

Introduction: Bullous pemphigoid is an autoimmune bullous dermatosis that most commonly occurs in elderly patients. Due to its pathogenesis and treatment of the disease, it can also affect the development of comorbidities. Aim: Determination of comorbidities and their frequency in patients with bullous pemphigoid, as well as their distribution by sex and the estimation of the duration of dermatosis from the onset of symptoms to data collection. Material and methods: In the period from January 2019 to January 2021, a number of 80 patients was analyzed. Basic patient data (age, sex, time of illness) and data on accompanying comorbidities were obtained. Data were categorized based on the ICD-10 classification into groups of diseases, as well as individual diseases that occurred frequently in the population. Results: Of the total number of respondents, 41.3% were male and 58.8% female. The average age of the respondents was 75.8 years, 76.45 years for men and 75.36 years for women. The period from the onset of symptoms to data collection was 3 months, while the average age of the disease in all subjects was 74.4 years. The most common comorbidities were hypertension 73.75%, psychiatric diseases 25%, type 2 diabetes mellitus 25%, other skin diseases 21.25%, urinary tract disorders 18.75%, ischemic heart disease 12.5%, type 1 diabetes mellitus 10%, kidney disease 8.75%, neurological disease 6.25%. Comorbidities were statistically more common in female patients: hypertension, ischemic heart disease, skin diseases and type 2 diabetes mellitus. Conclusion: In our study, bullous pemphigoid is confirmed the disease is of the elderly, predominantly female. Female patients suffer from some comorbidities more often. The period from the onset of symptoms to the collection of data is about 3 months. It is also showed that there are a number of comorbidities in the studied pemphigoid population, however, a large number of studies are needed to determine their association.