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MedRxiv : the Preprint Server For... Jan 2024To examine whether genetically predicted susceptibility to ten autoimmune diseases (Behçet's disease, coeliac disease, dermatitis herpetiformis, lupus, psoriasis,...
OBJECTIVE
To examine whether genetically predicted susceptibility to ten autoimmune diseases (Behçet's disease, coeliac disease, dermatitis herpetiformis, lupus, psoriasis, rheumatoid arthritis, sarcoidosis, Sjögren's syndrome, systemic sclerosis, and type 1 diabetes) is associated with risk of non-Hodgkin lymphoma (NHL).
DESIGN
Two sample Mendelian randomization (MR) study.
SETTING
Genome wide association studies (GWASs) of ten autoimmune diseases, NHL, and four NHL subtypes (i.e., follicular lymphoma, mature T/natural killer-cell lymphomas, non-follicular lymphoma, and other and unspecified types of NHL).
ANALYSIS
We used data from the largest publicly available GWASs of European ancestry for each autoimmune disease, NHL, and NHL subtypes. For each autoimmune disease, we extracted single nucleotide polymorphisms (SNPs) strongly associated ( < 5×10) with that disease and that were independent of one another (R < 1×10) as genetic instruments. SNPs within the human leukocyte antigen region were not considered due to potential pleiotropy. Our primary MR analysis was the inverse-variance weighted analysis. Additionally, we conducted MR-Egger, weighted mode, and weighted median regression to address potential bias due to pleiotropy, and robust adjusted profile scores to address weak instrument bias. We carried out sensitivity analysis limited to the non-immune pathway for nominally significant findings. To account for multiple testing, we set the thresholds for statistical significance at < 5×10.
PARTICIPANTS
The number of cases and controls identified in the relevant GWASs were 437 and 3,325 for Behçet's disease, 4,918 and 5,684 for coeliac disease, 435 and 341,188 for dermatitis herpetiformis, 4,576 and 8,039 for lupus, 11,988 and 275,335 for psoriasis, 22,350 and 74,823 for rheumatoid arthritis, 3,597 and 337,121 for sarcoidosis, 2,735 and 332,115 for Sjögren's syndrome, 9,095 and 17,584 for systemic sclerosis, 18,942 and 501,638 for type 1 diabetes, 2,400 and 410,350 for NHL; and 296 to 2,340 cases and 271,463 controls for NHL subtypes.
EXPOSURES
Genetic variants predicting ten autoimmune diseases: Behçet's disease, coeliac disease, dermatitis herpetiformis, lupus, psoriasis, rheumatoid arthritis, sarcoidosis, Sjögren's syndrome, systemic sclerosis, and type 1 diabetes.
MAIN OUTCOME MEASURES
Estimated associations between genetically predicted susceptibility to ten autoimmune diseases and the risk of NHL.
RESULTS
The variance of each autoimmune disease explained by the SNPs ranged from 0.3% to 3.1%. Negative associations between type 1 diabetes and sarcoidosis and the risk of NHL were observed (odds ratio [OR] 0.95, 95% confidence interval [CI]: 0.92 to 0.98, = 5×10, and OR 0.92, 95% CI: 0.85 to 0.99, = 2.8×10, respectively). These findings were supported by the sensitivity analyses accounting for potential pleiotropy and weak instrument bias. No significant associations were found between the other eight autoimmune diseases and NHL risk. Of the NHL subtypes, type 1 diabetes was most strongly associated with follicular lymphoma (OR 0.91, 95% CI: 0.86 to 0.96, = 1×10), while sarcoidosis was most strongly associated with other and unspecified NHL (OR 0.86, 95% CI: 0.75 to 0.97, = 1.8×10).
CONCLUSIONS
These findings suggest that genetically predicted susceptibility to type 1 diabetes, and to some extent sarcoidosis, might reduce the risk of NHL. However, future studies with different datasets, approaches, and populations are warranted to further examine the potential associations between these autoimmune diseases and the risk of NHL.
PubMed: 38343812
DOI: 10.1101/2024.01.20.24301459 -
JAAD Case Reports Apr 2024
PubMed: 38510834
DOI: 10.1016/j.jdcr.2024.01.004 -
Italian Journal of Dermatology and... Oct 2023The oral mucosa can be involved in a wide variety of mucocutaneous conditions that may present primarily in the mouth or affect other cutaneous or mucosal sites. Many of... (Review)
Review
The oral mucosa can be involved in a wide variety of mucocutaneous conditions that may present primarily in the mouth or affect other cutaneous or mucosal sites. Many of these conditions are immune mediated and typically present as inflammatory mucosal pathology. Patients experiencing such conditions usually seek medical evaluation and treatment due to the associated pain and discomfort and occasionally taste disturbance or dysphagia and the overall deterioration in the oral health-related quality of life. These conditions share some common features and there could be some overlapping in their clinical presentation, which can lead to delays in diagnosis and proper management of patients. Clinicians dealing with such disorders, including dermatologists, need to be aware of the oral manifestations of mucocutaneous conditions, their clinical features, underlying mechanisms, diagnostic approaches, and treatment options, as well as the recent advances in the research on these conditions. This review provides a comprehensive, evidence-based reference for clinicians, with updated insights into a group of immune mediated conditions known to cause oral mucosal pathology. Part one will cover oral lichen planus, erythema multiforme and systemic lupus erythematosus, while part two will cover pemphigus vulgaris and mucous membrane pemphigoid, recurrent aphthous stomatitis, in addition to the less common disorders linear IgA disease, dermatitis herpetiformis and epidermolysis bullosa.
Topics: Humans; Mouth Mucosa; Mouth Diseases; Quality of Life; Stomatitis, Aphthous; Pemphigus
PubMed: 37916401
DOI: 10.23736/S2784-8671.23.07676-4 -
Medicina (Kaunas, Lithuania) Nov 2023HLA class II molecules are key factors determining susceptibility to autoimmune disorders, and their role in immune-mediated skin conditions such as psoriasis has been... (Review)
Review
HLA class II molecules are key factors determining susceptibility to autoimmune disorders, and their role in immune-mediated skin conditions such as psoriasis has been extensively investigated. However, there is currently little understanding of their role in antibody-mediated skin diseases such as autoimmune blistering disorders. We researched the available literature using PubMed to narratively review the current knowledge on HLA associations in antibody-mediated blistering skin pathologies. Our results summarized the risk alleles that are identified in the literature, together with certain known protective alleles: in the pemphigus group, alleles HLA-DQB1*0503 and HLA-DRB1*0402 are most commonly associated with disease; in the pemphigoid group, the most studied allele is HLA-DQB1*0301; in epidermolysis bullosa acquisita, few genetic studies are available; in dermatitis herpetiformis, the association with haplotypes HLA-DQ2 and HLA-DQ8 is strongly established; finally, in linear IgA bullous disease, specific HLA alleles may be responsible for pediatric presentations. Our current pathogenic understanding of this group of disorders assigns a key role to predisposing HLA class II alleles that are able to bind disease autoantigens and therefore stimulate antigen-specific autoreactive T cells. The latter engage B lymphocytes that will produce pathogenic autoantibodies. The distribution of HLA alleles and their disease associations are variable across demographics, and an in-depth pathogenetic understanding is needed to support associations between HLA alleles and disease phenotypes. Additionally, in a personalized medicine approach, the identification of HLA alleles associated with the risk of disease may become clinically relevant in identifying susceptible subjects that should avoid exposure to known triggers, such as medication, when possible.
Topics: Humans; Child; Pemphigus; Autoimmune Diseases; Pemphigoid, Bullous; Skin; HLA Antigens; Alleles; Genetic Predisposition to Disease; HLA-DRB1 Chains; Gene Frequency
PubMed: 38003999
DOI: 10.3390/medicina59111950 -
Acta Dermato-venereologica Nov 2023Dermatitis herpetiformis has been investigated in the past; however, only a limited number of studies have reported its incidence based on validated nationwide...
Dermatitis herpetiformis has been investigated in the past; however, only a limited number of studies have reported its incidence based on validated nationwide population-based registries. To address this gap, the aims of this study are to estimate the incidence of dermatitis herpetiformis in Sweden and to validate the National Patient Register (NPR) for diagnosis of dermatitis herpetiformis. A population-based open cohort study was conducted, including all patients diagnosed with dermatitis herpetiformis (International Classification of Diseases 10th revision; ICD-10 code L13.0) in Sweden from 2005 to 2018 (n = 1,724), identified from the NPR. The diagnosis of dermatitis herpetiformis in the NPR was validated using medical records, histopathological and immunopathological data, yielding a positive predictive value (PPV) of 62.5%. The mean annual incidence of dermatitis herpetiformis was 0.93/100,000 (95% confidence interval 0.79-1.08), female to male ratio 1:1, and mean age at diagnosis 60.9 years. In conclusion, this large nationwide cohort study showed a low validity for diagnosis of dermatitis herpetiformis in the NPR, and the adjusted incidence rate of dermatitis herpetiformis in Sweden was estimated to be 0.93/100,000, which is lower than that in previous Swedish studies.
Topics: Humans; Male; Female; Middle Aged; Cohort Studies; Sweden; Incidence; Dermatitis Herpetiformis; Retrospective Studies
PubMed: 37971253
DOI: 10.2340/actadv.v103.13210 -
Cureus Mar 2024Food allergy is a major health concern worldwide, encompassing both immunologic and non-immunologic reactions. This review thoroughly examines the pathophysiology,... (Review)
Review
Food allergy is a major health concern worldwide, encompassing both immunologic and non-immunologic reactions. This review thoroughly examines the pathophysiology, clinical manifestations, and treatment options for various types of food allergies. Immunologic food allergies, including IgE-mediated reactions such as oral allergy syndrome and systemic anaphylaxis, pose various diagnostic and management challenges. Non-IgE-mediated reactions such as food protein-induced enterocolitis syndrome, dermatitis herpetiformis, and proctocolitis necessitate individualized patient care. In addition, mixed reactions such as eosinophilic esophagitis and atopic dermatitis complicate the clinical picture. Skin prick tests, serum-specific IgE tests, and oral food challenges are all necessary for accurate food allergy diagnosis. The primary therapeutic options are allergen avoidance, epinephrine-based emergency management, and emerging treatments like immunotherapy. Our review emphasizes the importance of multidisciplinary collaboration and ongoing research in improving our understanding and managing food allergies, promising a brighter future for those affected.
PubMed: 38654770
DOI: 10.7759/cureus.56823 -
Cureus Oct 2023Objectives The aim of this study was to describe the clinical, serological, and histopathological features of patients with dermatitis herpetiformis (DH) in Saudi...
Objectives The aim of this study was to describe the clinical, serological, and histopathological features of patients with dermatitis herpetiformis (DH) in Saudi Arabia. Methods We retrospectively reviewed the medical charts of all patients diagnosed with DH in the dermatology departments of National Guard Health Affairs (NGHA) hospitals in five different cities, from 2016 to 2022. We included patients who had been diagnosed by a dermatologist and had a combination of typical DH skin lesions, positive immunoglobulin A (IgA) on direct immunofluorescence (DIF), and/or positive tissue transglutaminase (tTG) IgA. Results A total of 11 patients were included. Their average age was 43.6 ± 12.5 years, and the ratio of females: males was 2.7: 1. Among the eight skin biopsies performed, IgA was detected on DIF in five patients. Seven out of nine patients (77.8%) had positive tTG IgA. Nine patients were managed with dapsone and a gluten-free diet (GFD); they had excellent responses within months. Conclusion The profiles of Saudi patients with DH were similar to those of Caucasian patients, but DH appears to be less common in Saudi Arabia. The high positive rates of tTG IgA make it an important tool for diagnosis in unclear cases. Dermatitis herpetiformis is likely associated with underlying gluten-sensitive enteropathy in Saudi patients.
PubMed: 38034235
DOI: 10.7759/cureus.48045 -
Nutrients Jan 2024Dermatitis herpetiformis is a cutaneous manifestation of celiac disease. Phenotyping of intraepithelial lymphocytes in the small bowel mucosa can strengthen the...
Dermatitis herpetiformis is a cutaneous manifestation of celiac disease. Phenotyping of intraepithelial lymphocytes in the small bowel mucosa can strengthen the diagnosis of celiac disease when it is not clear-cut. We aim to evaluate the usefulness of the intraepithelial lymphogram to confirm dermatitis herpetiformis in equivocal cases. We performed a retrospective multicenter study on patients diagnosed with dermatitis herpetiformis and collected data from the intraepithelial lymphogram assessed by flow cytometry. A total of 36 patients were analyzed in relation to the severity of intestinal damage (18 had non-atrophic mucosa) at baseline (N = 28) and/or after the adoption of a gluten-free diet (median follow-up of three years, N = 16). We observed that patients with atrophy more often had positive celiac serology ( = 0.019), celiac clinical symptoms ( = 0.018), and iron-deficiency anemia ( = 0.018), but the severity of skin damage was similar in both groups ( = 0.79). At baseline, increased TCRγδ cells were present in 94% of patients with atrophy and 67% with non-atrophic lesions ( = 0.13). After a gluten-free diet, increased TCRγδ cells persisted in 100% and 63% of cases, respectively ( = 0.21). We concluded that increased TCRγδ cells may be helpful in confirming the diagnosis of dermatitis herpetiformis in equivocal cases, even in patients who were started on a gluten-free diet.
Topics: Humans; Anemia, Iron-Deficiency; Atrophy; Celiac Disease; Data Collection; Dermatitis Herpetiformis; Retrospective Studies
PubMed: 38257124
DOI: 10.3390/nu16020232 -
Nutrients Dec 2023Celiac disease (CD) is an immune-mediated systemic gluten-related disorder characterized by a wide spectrum of intestinal and extra-intestinal manifestations, including... (Review)
Review
Celiac disease (CD) is an immune-mediated systemic gluten-related disorder characterized by a wide spectrum of intestinal and extra-intestinal manifestations, including damage to cutaneous and connective tissue. We report a rare case of chronic severe dermatitis involving connective tissue and cutaneous vascular vessels as the main clinical presentation of undiagnosed seronegative gluten disorder. A gluten-free diet dramatically improved the intestinal and cutaneous clinical damage in the patient. Pitfalls and the steps of differential diagnosis are described. We also review the literature regarding studies of CD and connective tissue diseases to extend the knowledge of these rare associations. We propose a practical diagnostic approach in suspected CD in autoimmune cutaneous disorders.
Topics: Humans; Celiac Disease; Skin Diseases; Dermatitis; Glutens; Autoimmune Diseases
PubMed: 38201912
DOI: 10.3390/nu16010083 -
Frontiers in Immunology 2023Autoimmune bullous diseases (AIBDs) are a group of rare cutaneous disorders affecting cornified skin and mucous membranes. They are characterized by tense or flaccid...
INTRODUCTION
Autoimmune bullous diseases (AIBDs) are a group of rare cutaneous disorders affecting cornified skin and mucous membranes. They are characterized by tense or flaccid blistering and erosions due to autoantibodies against desmosomal and hemidesmosomal structural proteins of the skin. This group of disorders can be divided into those of pemphigoid and those of pemphigus diseases. If left untreated, these autoimmune diseases can cause serious or even life-threatening complications such as loss of fluid, superinfections or impaired food intake. Due to modern standardized serological assays, the diagnosis of AIBDs can usually be confirmed in combination with their clinical appearance. Whereas for a long time corticosteroids were the major players in the treatment of these diseases, with the approval of rituximab and other immunosuppressive agents, the therapy has increasingly improved.
METHODS
In this study, we aimed to investigate epidemiologic and clinical features as well as diagnostics and therapy of bullous autoimmune diseases in Middle Franconia, a governorate within the German federal state of Bavaria. Patients diagnosed or treated because of a AIBDs between 01.04.2013 and 31.03.2019 at the dermatological department of the university hospital Erlangen were included in this retrospective study (n = 242). Patients were either diagnosed for the first time (n=176) or the diagnosis has been confirmed (n=66) at the department. The respective incidence was calculated among the 176 subjects who had been diagnosed at the center in this period. Data was taken from patient records and analyzed with Microsoft® Excel. The evaluation included the diagnoses of pemphigus vulgaris (PV), pemphigus foliaceus (PF), bullous pemphigoid (BP), mucous membrane pemphigoid (MMP), linear IgA dermatosis (LAD), epidermolysis bullosa acquisita (EBA), and dermatitis herpetiformis (DH).
RESULTS
This study shows that the incidence of each AIBDs in Middle Franconia is low and comparable (PV, PF, LAD, EBA) or lower (BP, MMP, DH) than in other studies and regions. BP is the most common newly diagnosed AIBD in Middle Franconia.
DISCUSSION
Due to the chronic and sometimes severe course of AIBDs, repeated in-house treatments are often necessary. To date, mainly topically and systemically applied corticosteroids in combination with immunomodulators are used as first-line therapy.
Topics: Humans; Retrospective Studies; Pemphigoid, Bullous; Autoimmune Diseases; Skin Diseases, Vesiculobullous; Pemphigus; Linear IgA Bullous Dermatosis; Epidermolysis Bullosa Acquisita; Adrenal Cortex Hormones
PubMed: 37881435
DOI: 10.3389/fimmu.2023.1256617