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Advanced Science (Weinheim,... Sep 2023Dermatitis herpetiformis (DH) is an inflammatory skin disorder often considered as an extra intestinal manifestation of celiac disease (CeD). Hallmarks of CeD and DH are...
Dermatitis herpetiformis (DH) is an inflammatory skin disorder often considered as an extra intestinal manifestation of celiac disease (CeD). Hallmarks of CeD and DH are auto-antibodies to transglutaminase 2 (TG2) and transglutaminase 3 (TG3), respectively. DH patients have auto-antibodies reactive with both transglutaminase enzymes. Here it is reported that in DH both gut plasma cells and serum auto-antibodies are specific for either TG2 or TG3 with no TG2-TG3 cross reactivity. By generating monoclonal antibodies from TG3-specific duodenal plasma cells of DH patients, three conformational epitope groups are defined. Both TG2-specific and TG3-specific gut plasma cells have few immunoglobulin (Ig) mutations, and the two transglutaminase-reactive populations show distinct selection of certain heavy and light chain V-genes. Mass spectrometry analysis of TG3-specific serum IgA corroborates preferential usage of IGHV2-5 in combination with IGKV4-1. Collectively, these results demonstrate parallel induction of anti-TG2 and anti-TG3 auto-antibody responses involving separate B-cell populations in DH patients.
Topics: Humans; Celiac Disease; Dermatitis Herpetiformis; Immunoglobulin A; Plasma Cells; Protein Glutamine gamma Glutamyltransferase 2; Transglutaminases
PubMed: 37424036
DOI: 10.1002/advs.202300401 -
Annals of Medicine Dec 2023Dermatitis herpetiformis (DH) is a cutaneous manifestation of coeliac disease. Increased cardiovascular morbidity has been reported in coeliac disease, but in DH only...
INTRODUCTION
Dermatitis herpetiformis (DH) is a cutaneous manifestation of coeliac disease. Increased cardiovascular morbidity has been reported in coeliac disease, but in DH only little is known about this. In this cohort study with a long-term follow-up, the risk for vascular diseases in patients with dermatitis herpetiformis (DH) and coeliac disease was assessed.
METHODS
The study consisted of 368 DH and 1072 coeliac disease patients with biopsy-proven diagnosis performed between 1966 and 2000. For each DH and coeliac disease patient three matched reference individuals were obtained from the population register. Data regarding all outpatient and inpatient treatment periods between 1970 and 2015 were reviewed for diagnostic codes of vascular diseases from the Care Register for Health Care. Cox proportional hazard model was used to assess the risks for the diseases studied and the HRs were adjusted for diabetes mellitus (aHR).
RESULTS
The median follow-up time of DH and coeliac disease patients was 46 years. The risk for cardiovascular diseases did not differ between DH patients and their references (aHR 1.16, 95% CI 0.91-1.47), but among coeliac disease patients, the risk was increased (aHR 1.36, 95% CI 1.16-1.59). The risk for cerebrovascular diseases was found to be decreased in DH patients when compared with references (aHR 0.68, 95% CI 0.47-0.99) and increased in coeliac disease patients (aHR 1.33, 95% CI 1.07-1.66). The risk for venous thrombosis was increased in coeliac disease patients (aHR 1.62, 95% CI 1.22-2.16) but not in DH.
CONCLUSIONS
The risk for vascular complications appears to differ between DH and coeliac disease. In DH the risk for cerebrovascular diseases seems to be decreased, while in coeliac disease an elevated risk for cerebrovascular and cardiovascular diseases was observed. These differing vascular risk profiles between the two manifestations of the same disease merit further investigation.
Topics: Humans; Celiac Disease; Dermatitis Herpetiformis; Cohort Studies; Cardiovascular Diseases; Vascular Diseases
PubMed: 37378421
DOI: 10.1080/07853890.2023.2227423 -
Frontiers in Medicine 2023The term gluten-related disorders (GRD) refer to a spectrum of different clinical manifestations triggered by the ingestion of gluten in genetically susceptible... (Review)
Review
The term gluten-related disorders (GRD) refer to a spectrum of different clinical manifestations triggered by the ingestion of gluten in genetically susceptible individuals, including coeliac disease (CD), wheat allergy and non-celiac gluten sensitivity (NCGS). GRD are characterized by a large variety of clinical presentations with both intestinal and extra-intestinal manifestations. The latter may affect almost every organ of the body, including the skin. Besides the well-known association between CD and dermatitis herpetiformis, considered as the cutaneous specific manifestation of CD, many other muco-cutaneous disorders have been associated to GRD. In this review, we analyzed the main features of dermatological diseases with a proven association with GRD and those that improve after a gluten-free diet, focusing on the newly described cutaneous manifestations associated with NCGS. Our main hypothesis is that a "cutaneous-gluten sensitivity," as specific cutaneous manifestation of NCGS, may exist and could represent a diagnostic marker of NCGS.
PubMed: 37265490
DOI: 10.3389/fmed.2023.1155288 -
Biomolecules Mar 2023Autoimmune bullous skin diseases (AIBDs), such as bullous pemphigoid (BP) and pemphigus, are characterized and caused by autoantibodies targeting structural proteins. In...
Autoimmune bullous skin diseases (AIBDs), such as bullous pemphigoid (BP) and pemphigus, are characterized and caused by autoantibodies targeting structural proteins. In BP, clinical experience and recent systematic evaluation identified pruritus to be common and an important cause of impaired quality of life. Furthermore, chronic pruritus may be the sole clinical symptom of BP. In pemphigus, a retrospective study recently documented a high prevalence of pruritus. The temporal relation between pruritus and BP/pemphigus are, however, unknown. Likewise, the presence of pruritus in AIBDs other than BP and pemphigus is unknown. To address this, we performed propensity-matched retrospective cohort studies using TriNetX, providing real-world patient data to (i) assess the risk to develop AIBDs following the diagnosis of pruritus and (ii) vice versa. We assessed this in eight AIBDs: BP, mucous membrane pemphigoid (MMP), epidermolysis bullosa acquisita, dermatitis herpetiformis, lichen planus pemphigoides (LPP), pemphigus vulgaris, pemphigus foliaceous, and paraneoplastic pemphigus (PNP). For all AIBDs, pruritus was associated with an increased risk for the subsequent diagnosis of each of the eight investigated AIBDs in 1,717,744 cases (pruritus) compared with 1,717,744 controls. The observed hazard ratios ranged from 4.2 (CI 3.2-5.5; < 0.0001) in MMP to 28.7 (CI 3.9-211.3; < 0.0001) in LPP. Results were confirmed in two subgroup analyses. When restricting the observation time to 6 months after pruritus onset, most HRs noticeably increased, e.g., from 6.9 (CI 6.2-7.9; < 0.0001) to 23.3 (CI 17.0-31.8; < 0.0001) in BP. Moreover, pruritus frequently developed following the diagnosis of any of the eight AIBDs, except for PNP. Thus, all AIBDs should be considered as differential diagnosis in patients with chronic pruritus.
Topics: Humans; Pemphigus; Retrospective Studies; Quality of Life; Autoimmune Diseases; Pemphigoid, Bullous; Skin Diseases, Vesiculobullous; Pruritus
PubMed: 36979421
DOI: 10.3390/biom13030485 -
Frontiers in Immunology 2023Autoimmune bullous dermatoses (AIBD) are rare diseases that affect human skin and mucous membranes. Clinically, they are characterized by blister formation and/or...
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.
Topics: Animals; Humans; Fluorescent Antibody Technique, Indirect; Blister; Autoimmune Diseases; Pemphigus; Pemphigoid, Bullous; Skin Diseases, Vesiculobullous
PubMed: 36926325
DOI: 10.3389/fimmu.2023.1111172 -
International Medical Case Reports... 2023Dermatitis herpetiformis (DH) is an autoimmune vesiculobullous disease associated with celiac enteropathy. The clinical manifestation of DH is the occurrence of a...
INTRODUCTION
Dermatitis herpetiformis (DH) is an autoimmune vesiculobullous disease associated with celiac enteropathy. The clinical manifestation of DH is the occurrence of a papulovesicular rash on the skin. Oral mucosal involvement in DH is very rare. This study aimed to describe the impact of COVID-19 on the acute exacerbation of oral dermatitis herpetiformis.
CASE REPORT
A 74-year-old woman was referred to the Oral Medicine Department with a chief complaint of the blisters on the skin for a week and ulcers in the oral cavity appeared two days ago. Extraoral examination revealed crusts on the neck and extremities. The lips appeared dry and desquamative. Intraoral examination revealed erosive lesions covered with a white-yellowish plaques on the right and left sides of the buccal mucosa, an ulcer with a diameter of 0.5 cm, and purpura hemorrhagic on left buccal mucosa and right lateral border of the tongue. Histopathological examination of the skin lesion revealed a subepithelial blister with eosinophils and neutrophil cells. The definitive diagnosis of dermatitis herpetiformis was made. She was given 5 mg intravenous dexamethasone, cetirizine 10 mg, and clindamycin 300 mg by the dermatologist. We gave hyaluronic acid 0.025% mouthwash for oral ulcers and petroleum jelly for the lips. The oral lesions had significant improvement after 4 weeks of treatment. Two months later, the patient experienced acute exacerbation after being infected with COVID-19 (anti-SARS-CoV-2 IgG S-RBD >40,000 AU/mL). The oral lesions healed after a month of treatment.
CONCLUSION
COVID-19 can trigger the acute exacerbation of dermatitis herpetiformis. SARS-CoV-2 causes an immune dysregulation and hypersensitivity reaction.
PubMed: 36923800
DOI: 10.2147/IMCRJ.S401775 -
Frontiers in Immunology 2023Dermatitis herpetiformis (DH) is a rare autoimmune, polymorphous blistering disorder, characterized by severe itch or burning sensation, which represents the cutaneous...
INTRODUCTION
Dermatitis herpetiformis (DH) is a rare autoimmune, polymorphous blistering disorder, characterized by severe itch or burning sensation, which represents the cutaneous manifestation of celiac disease (CD). The current estimation of DH versus CD is around 1:8 and the affected individuals have a genetic predisposition. Pathogenetically, IgA autoantibodies against the epidermal transglutaminase, an essential constituent of the epidermis, cause DH and are reported to develop through cross-reaction with the tissue transglutaminase, with IgA auto-antibodies causing CD. Immunofluorescence techniques allow for a rapid diagnostics of the disease using patient sera. Evaluation of IgA endomysial deposition with indirect immunofluorescence on monkey oesophagus is highly specific, but moderately sensitive, with some operator-dependent variability. Recently, indirect immunofluorescence with monkey liver as a substrate has been proposed as an alternative, well-functioning diagnostic approach with higher sensitivity in CD.
METHODS
The objective of our study was to evaluate whether monkey oesophagus or liver tissue shows advantage for diagnostics in patients with DH, compared to CD. To that end, sera of 103 patients with DH (n=16), CD (n=67) and 20 controls ere compared by 4 blinded experienced raters.
RESULTS
For DH, we found a sensitivity of 94.2% for monkey liver (ML) compared to 96.2% in monkey oesophagus (ME), while specificity in ML was superior (91.6% versus 75%) to ME. In CD, ML had a sensitivity of 76.9% (ME 89.1%) and specificity of 98.3% (ME 94.1%).
DISCUSSION
Our data show that ML substrate is well suitable for DH diagnostics.
Topics: Animals; Fluorescent Antibody Technique, Indirect; Celiac Disease; Dermatitis Herpetiformis; Primates; Liver; Autoimmune Diseases; Immunoglobulin A; Haplorhini
PubMed: 36875085
DOI: 10.3389/fimmu.2023.1104360 -
Cureus Feb 2023Adalimumab is a blocker of tumor necrosis factor (TNF)-alpha with established efficacy in the treatment of ulcerative colitis. However, literature indicated that...
Adalimumab is a blocker of tumor necrosis factor (TNF)-alpha with established efficacy in the treatment of ulcerative colitis. However, literature indicated that adalimumab can, occasionally, induce paradoxical psoriasis reactions and, very rarely, dermatitis herpetiformis. We present a unique case of a 26-year-old female patient who developed a combination of dermatitis herpetiformis and scalp psoriasis paradoxically as a result of adalimumab treatment for ulcerative colitis. To the best of our knowledge, this is the first case of such a combination within the context of adalimumab therapy. The etiopathological underpinning of such a reaction remains elusive but is speculated to be complex and involves the interaction of several immunological and dermatological mechanisms. Adalimumab therapy is associated with a genuine risk for the development of paradoxical psoriasis and dermatitis herpetiformis. We, through this case report, added to the evidence confirming such an association. Clinicians should follow these potential adverse effects and make every effort to warn patients of their likelihood.
PubMed: 36846641
DOI: 10.7759/cureus.35317