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Clinical and Experimental Dermatology Dec 2023Dermatitis herpetiformis (DH) is a rare gluten-induced skin disorder characterized predominantly by IgA autoantibodies against endomysium, tissue transglutaminase...
BACKGROUND
Dermatitis herpetiformis (DH) is a rare gluten-induced skin disorder characterized predominantly by IgA autoantibodies against endomysium, tissue transglutaminase (TG2/tTG), epidermal transglutaminase (TG3/eTG) and deamidated gliadin. To date, circulating autoantibody reactivity has not been systematically described.
OBJECTIVES
Characterization of serum reactivities in DH.
METHODS
This multicentre international study analysed sera from 242 patients with DH taken at the time of initial diagnosis. DH-specific IgA and IgG serum autoantibodies were analysed by indirect immunofluorescence (IF) on monkey oesophagus, and by enzyme-linked immunosorbent assay (ELISA) based on recombinant TG2/tTG, TG3/eTG and deamidated gliadin (GAF3X).
RESULTS
IgA indirect IF microscopy on monkey oesophagus revealed the highest reactivity (84.3%; specificity 100%) followed by IgA TG2/tTG ELISA (78.5%, specificity 99.0%), IgA TG3/eTG ELISA (72.7%, specificity 95.0%) and IgA GAF3X ELISA (69.0%, specificity 98.5%).
CONCLUSIONS
Serum IgA and IgG autoantibodies against endomysium, TG2/tTG, TG3/eTG and deamidated gliadin are highly prevalent in DH. Indirect IF microscopy on monkey oesophagus (IgA) provides the highest diagnostic accuracy that can be further enhanced by 4.5% when combined with IgA TG2/tTG ELISA.
Topics: Humans; Animals; Dermatitis Herpetiformis; Gliadin; Immunoglobulin A; Autoantibodies; Transglutaminases; Enzyme-Linked Immunosorbent Assay; Immunoglobulin G; Haplorhini
PubMed: 37793183
DOI: 10.1093/ced/llad319 -
Digestive Diseases (Basel, Switzerland) 2015Case finding for celiac disease (CD) is becoming increasingly common practice and is conducted in a wide range of clinical situations ranging from the presence of... (Review)
Review
Case finding for celiac disease (CD) is becoming increasingly common practice and is conducted in a wide range of clinical situations ranging from the presence of gastrointestinal symptoms to failure to thrive in children, prolonged fatigue, unexpected weight loss and anemia. Case finding is also performed in associated conditions, such as autoimmune thyroid disease, dermatitis herpetiformis and type 1 diabetes, as well as in patients with irritable bowel syndrome, unexplained neuropsychiatric disorders and first-degree relatives of patients with diagnosed CD. This aggressive active case finding has dramatically changed the clinical characteristics of newly diagnosed patients. For instance, higher numbers of patients who present with extraintestinal symptoms are now being diagnosed with CD. Current recommendations state that due to a high risk for complications if the disease remains undiagnosed, patients with extraintestinal symptoms due to CD require appropriate diagnosis and treatment. Despite criticism regarding the cost-effectiveness of case finding in CD, such an aggressive approach has been considered cost-effective for high-risk patients. The diagnosis of CD among patients with extraintestinal symptoms requires a high degree of awareness of the clinical conditions that carry a high risk for underlying CD. Also, understanding the correct use of specific serology and duodenal histology is key for an appropriate diagnostic approach. Both procedures combined are able to confirm diagnosis in the vast majority of cases. However, in certain circumstances, serology and even duodenal histology cannot confirm or rule out CD. A common cause of negative IgA serology is IgA deficiency. For such eventuality, IgG-based serological tests can help confirm the diagnosis. Importantly, some histologically diagnosed cases still remain seronegative despite exclusion of IgA deficiency. On the other hand, duodenal histology may be normal despite the presence of CD-specific antibodies and active CD. This has been clearly demonstrated in some cases of untreated dermatitis herpetiformis, but may also be due to the patchy condition of CD or lesions that are not adequately recognized by nonexpert endoscopists and/or pathologists. The effectiveness of agluten-free diet depends on the clinical end point addressed. A good example is the outcome of bone loss. While risk for fracture normalizes after the first year of dietary treatment, bone parameters measured by densitometry may not be normalized in the long-term follow-up. Moreover, it is still unclear how far an early gluten-free diet will positively affect associated autoimmune diseases like type 1 diabetes and autoimmune thyroiditis.
Topics: Bone Diseases; Celiac Disease; Female; Genital Diseases, Female; Hematologic Diseases; Humans; Liver; Skin Diseases
PubMed: 25925916
DOI: 10.1159/000369541 -
Nutrients Dec 2020Wheat is one of the most consumed cereal grains worldwide and represents an important part of the human diet [...].
Wheat is one of the most consumed cereal grains worldwide and represents an important part of the human diet [...].
Topics: Ataxia; Celiac Disease; Dermatitis Herpetiformis; Diet; Diet, Gluten-Free; Edible Grain; Glutens; Health Status; Humans; Triticum; Wheat Hypersensitivity; Whole Grains
PubMed: 33291526
DOI: 10.3390/nu12123733 -
Minerva Medica Apr 2018Celiac disease, an inflammatory disease of small bowel caused by sensitivity to dietary gluten and related protein, affects approximately 0.5-1% of the population in the... (Review)
Review
Celiac disease, an inflammatory disease of small bowel caused by sensitivity to dietary gluten and related protein, affects approximately 0.5-1% of the population in the Western world. Extra-intestinal symptoms and associated diseases are increasingly recognized including diabetes mellitus type 1, thyroid disease, dermatitis herpetiformis and ataxia. There have also been a number of reports of various types of renal involvement in patients with celiac disease including diabetes nephropathy, IgA nephropathy, membranous nephropathy, membranoproliferative glomerulonephritis, nephrotic syndrome related to malabsorption, oxalate nephropathy, and associations of celiac disease with chronic kidney disease and end-stage kidney disease. This review aims to present the current literature on possible pathologic mechanisms underlying renal disease in patients with celiac disease.
Topics: Celiac Disease; Diabetic Nephropathies; Endothelium, Vascular; Glomerulonephritis; Glomerulonephritis, IGA; Humans; Inflammation; Kidney Diseases; Malabsorption Syndromes; Malnutrition; Vascular Diseases
PubMed: 28974086
DOI: 10.23736/S0026-4806.17.05403-9 -
Expert Opinion on Drug Metabolism &... May 2019In their 70-year history, dapsone and other sulfones have been used as both antibacterial and anti-inflammatory agents. Dapsone has been the main active principle in the... (Review)
Review
In their 70-year history, dapsone and other sulfones have been used as both antibacterial and anti-inflammatory agents. Dapsone has been the main active principle in the multidrug regimen recommended by the World Health Organization for the treatment of leprosy. In addition, dapsone has been successfully used to treat a wide range of dermatological and systemic disorders, mostly characterized by neutrophilic and eosinophilic accumulation and infiltration. Areas covered: The PubMed database was searched using combinations of the following keywords: dapsone, sulfones, pharmacodynamics, pharmacology, adverse events, pharmacokinetics, drug interaction, dermatologic uses, and antimicrobial uses. This article reviews and updates the chemistry, pharmacokinetics, mechanism of action, adverse effects, drug interactions, and clinical application of sulfones. Expert opinion: Dapsone exhibits clinical efficacy in several cutaneous and systemic conditions and is now generally accepted as the therapy of choice for leprosy and for rare dermatosis, as dermatitis herpetiformis. Careful patient selection and close monitoring during treatment are mandatory to provide safe and effective use of dapsone. Familiarity with sulfones and dapsone is crucial because of this agent retains its niche in the clinician's therapeutic armamentarium.
Topics: Animals; Anti-Infective Agents; Dapsone; Drug Interactions; Humans; Leprostatic Agents; Leprosy; Skin Diseases
PubMed: 30943794
DOI: 10.1080/17425255.2019.1600670 -
Journal Der Deutschen Dermatologischen... Sep 2018Blasenbildende Autoimmundermatosen (BAIDs) sind eine heterogene Gruppe seltener Erkrankungen, die klinisch durch Erosionen und/oder Blasen an Haut und Schleimhäuten... (Review)
Review
Blasenbildende Autoimmundermatosen (BAIDs) sind eine heterogene Gruppe seltener Erkrankungen, die klinisch durch Erosionen und/oder Blasen an Haut und Schleimhäuten charakterisiert sind. BAIDs können in zwei Gruppen eingeteilt werden: Pemphigus-Erkrankungen, die durch intraepidermale Blasenbildung und Autoantikörper gegen desmosomale Proteine wie Desmoglein (Dsg) 1, Dsg3 und Mitglieder der Plakin-Familie charakterisiert sind, sowie subepidermale BAIDs, die Pemphigoid-Erkrankungen und die Dermatitis herpetiformis umfassen. Bei der Dermatitis herpetiformis greifen die Autoantikörper die Transglutaminasen 2 und 3 an, während sie bei Pemphigoid-Erkrankungen gegen Strukturproteine der dermoepidermalen Junktionszone gerichtet sind. Die Analyse einer periläsionalen Biopsie mittels direkter Immunfluoreszenzmikroskopie (IF-Mikroskopie) stellt zwar nach wie vor den diagnostischen Goldstandard dar, mittlerweile sind jedoch verschiedene Tests allgemein verfügbar, die eine serologische Diagnosefindung für den Großteil der Patienten ermöglichen. Zur serologischen Standarddiagnostik gehört die indirekte IF auf Affenösophagus und NaCl-separierter Spalthaut. Die Spezifität der Autoantikörper kann mit ELISA-Systemen, die auf rekombinanten Formen der immundominanten Regionen der Zielantigene basieren, sowie indirekter IF-Mikroskopie anhand multivarianter Tests mit mehreren multivariate näher charakterisiert werden. Diese serologischen Tests werden durch verschiedene hauseigene Immunoblotting- und ELISA-Systeme ergänzt, die nur in spezialisierten Laboratorien verfügbar sind. In diesem Review geben wir einen Überblick über neue Entwicklungen bei der Diagnose von BAIDs und beschreiben moderne Diagnoseverfahren für diese Krankheitsgruppe.
PubMed: 30179341
DOI: 10.1111/ddg.13637_g -
Frontiers in Immunology 2021Dermatitis herpetiformis is a cutaneous form of celiac disease manifesting as an itching rash typically on the elbows, knees and buttocks. It is driven by the ingestion... (Review)
Review
Dermatitis herpetiformis is a cutaneous form of celiac disease manifesting as an itching rash typically on the elbows, knees and buttocks. It is driven by the ingestion of gluten-containing cereals and characterized by granular deposits of immunoglobulin A in the papillary dermis. These antibodies target transglutaminase (TG) 3 and in the majority of patients they are also found in circulation. The circulating antibodies disappear and skin symptoms resolve as a result of gluten-free diet but the cutaneous anti-TG3 IgA deposits may persist for several years. In dermatitis herpetiformis, plasma cells secreting antibodies against TG3 are located in the intestinal mucosa similarly to those producing TG2 antibodies characteristic for celiac disease. In fact, both TG2- and TG3-specific plasma cells and gluten responsive T cells are found in dermatitis herpetiformis patients but the interplay between these cell populations is unknown. The small bowel mucosal damage in celiac disease is believed to be mediated by co-operation of cytotoxic intraepithelial T cells and the inflammatory milieu contributed by gluten-reactive CD4+ T cells, whereas the skin lesions in dermatitis herpetiformis appear to be devoid of gluten reactive T cells. Thus, how celiac disease-type intestinal T and B cell responses develop into an autoimmune condition affecting the skin is still incompletely understood. Finally, the skin and small bowel lesions may reappear upon reintroduction of gluten in patients treated with gluten-free diet but virtually nothing is known about the long-lived B cell and memory T cell populations activating in response to dietary gluten in dermatitis herpetiformis.
Topics: Animals; Autoimmunity; B-Lymphocytes; Biomarkers; Celiac Disease; Dermatitis Herpetiformis; Diagnosis, Differential; Disease Susceptibility; Epitopes; Glutens; Humans; Immunity, Cellular; Immunity, Humoral; Phenotype; Skin; T-Lymphocytes
PubMed: 33854513
DOI: 10.3389/fimmu.2021.657280 -
Cureus Sep 2023Gluten sensitivity is defined as a chronic intolerance to gluten ingestion in genetically predisposed individuals. The etiology is thought to be immune-mediated and has... (Review)
Review
Gluten sensitivity is defined as a chronic intolerance to gluten ingestion in genetically predisposed individuals. The etiology is thought to be immune-mediated and has a variable dermatologic presentation. Celiac disease (CD) is one of the most common forms of gluten intolerance and encompasses a wide range of extra-intestinal pathology, including cutaneous, endocrine, nervous, and hematologic systems. Psoriasis, another long-term inflammatory skin condition, has been linked to significant symptomatic improvement with a gluten-free diet (GFD). Palmoplantar pustulosis (PP), a variant of psoriasis, and aphthous stomatitis, which causes recurrent oral ulcers, have also exhibited beneficial results after the dietary elimination of gluten. In addition to this, dermatitis herpetiformis (DH), another immune-mediated skin disorder, is genetically similar to CD and has, therefore, shown tremendous improvement with a GFD. Another highly prevalent long-term skin condition called atopic dermatitis (AD), however, has revealed inconsistent results with gluten elimination and would require further research in the future to yield concrete results. Hereditary angioedema (HA) has shown an association with gluten intolerance in some patients who had symptomatic benefits with a GFD. Similarly, vitiligo and linear IgA bullous dermatosis have also shown some clinical evidence of reversal with a GFD. On the contrary, rosacea enhances the risk of developing CD. This narrative review emphasizes the potential impact of gluten intolerance on different cutaneous conditions and the potential therapeutic effect of a GFD on various symptomatic manifestations. There is a need for additional clinical and observational trials to further expand on the underlying pathophysiology and provide conclusive and comprehensive recommendations for possible dietary interventions.
PubMed: 37790051
DOI: 10.7759/cureus.44549 -
Nature Communications Oct 2023Transglutaminase 3 (TG3), the autoantigen of dermatitis herpetiformis (DH), is a calcium dependent enzyme that targets glutamine residues in polypeptides for either...
Transglutaminase 3 (TG3), the autoantigen of dermatitis herpetiformis (DH), is a calcium dependent enzyme that targets glutamine residues in polypeptides for either transamidation or deamidation modifications. To become catalytically active TG3 requires proteolytic cleavage between the core domain and two C-terminal β-barrels (C1C2). Here, we report four X-ray crystal structures representing inactive and active conformations of human TG3 in complex with a TG3-specific Fab fragment of a DH patient derived antibody. We demonstrate that cleaved TG3, upon binding of a substrate-mimicking inhibitor, undergoes a large conformational change as a β-sheet in the catalytic core domain moves and C1C2 detaches. The unique enzyme-substrate conformation of TG3 without C1C2 is recognized by DH autoantibodies. The findings support a model where B-cell receptors of TG3-specific B cells bind and internalize TG3-gluten enzyme-substrate complexes thereby facilitating gluten-antigen presentation, T-cell help and autoantibody production.
Topics: Humans; Celiac Disease; Autoantibodies; Dermatitis Herpetiformis; Transglutaminases; Immunoglobulin A; Glutens
PubMed: 37798283
DOI: 10.1038/s41467-023-42004-z -
Acta Dermato-venereologica Apr 2021Dermatitis herpetiformis is a cutaneous manifestation of coeliac disease. Anaemia is a common finding in patients with untreated coeliac disease, but little is known...
Dermatitis herpetiformis is a cutaneous manifestation of coeliac disease. Anaemia is a common finding in patients with untreated coeliac disease, but little is known about the occurrence of anaemia in those with dermatitis herpetiformis. This study investigated the prevalence of anaemia and factors associated with anaemia in 250 patients with dermatitis herpetiformis, at diagnosis and one year after diagnosis. As controls, 139 patients with coeliac disease were included. Patient records were reviewed to gather baseline clinical, histological, and laboratory data. Follow-up data for patients with dermatitis herpetiformis were collected from patient records and via questionnaires or at follow-up visits. The prevalence of anaemia was 12% in patients with dermatitis herpetiformis and 17% in patients with coeliac disease at diagnosis (p = 0.257). Anaemia in patients with dermatitis herpetiformis was not associated with the severity of skin symptoms or small bowel damage. The prevalence of anaemia at a 1-year follow-up had increased to 19%, but it was associated mainly with dapsone treatment.
Topics: Anemia; Celiac Disease; Dermatitis Herpetiformis; Follow-Up Studies; Humans; Prevalence
PubMed: 33846758
DOI: 10.2340/00015555-3795