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Postepy Dermatologii I Alergologii Feb 2022Dermatitis herpetiformis is a rare chronic, autoimmune bullous disease linked to gluten sensitivity with intense pruritus and characteristic skin eruptions.... (Review)
Review
Dermatitis herpetiformis is a rare chronic, autoimmune bullous disease linked to gluten sensitivity with intense pruritus and characteristic skin eruptions. Etiopathogenesis is complex and not fully understood. It is currently considered to be a specific cutaneous manifestation of celiac disease. Genetic, environmental and immunological factors influence both conditions. Exposure to gluten is the starting point of an inflammatory cascade leading to the formation of circulating IgA antibodies against tissue transglutaminase and skin immune IgA deposition followed by skin lesions. Binding of the immune complex deposits of IgA transglutaminases and epidermal antibodies with enzymes in the papillary dermis stimulates complement activation, neutrophil influx, proinflammatory cytokine release and overproduction of matrix metalloproteinases. We have collected current knowledge of the pathogenesis of dermatitis herpetiformis.
PubMed: 35369614
DOI: 10.5114/ada.2020.101637 -
Clinics in Dermatology 2022Although relatively uncommon, autoimmune bullous diseases carry the risk of increased mortality and can significantly impact quality of life. This group of diseases is... (Review)
Review
Although relatively uncommon, autoimmune bullous diseases carry the risk of increased mortality and can significantly impact quality of life. This group of diseases is broad and encompasses subepidermal conditions such as bullous pemphigoid, cicatricial pemphigoid, epidermolysis bullosa acquisita, dermatitis herpetiformis, and linear IgA bullous dermatosis, as well as intraepidermal conditions such as pemphigus and its variants. The pathophysiology of each condition is incompletely understood but broadly involves the formation of autoantibodies targeting skin adhesion proteins, a process that relies on a complex interplay between a dysregulated immune system, genetic predisposition, and environmental factors. We review the impact of nutrition on pathogenesis, clinical course, and treatment of various autoimmune bullous diseases.
Topics: Autoimmune Diseases; Epidermolysis Bullosa Acquisita; Humans; Pemphigoid, Bullous; Pemphigus; Quality of Life; Skin Diseases, Vesiculobullous
PubMed: 34808244
DOI: 10.1016/j.clindermatol.2021.10.009 -
Der Hautarzt; Zeitschrift Fur... Apr 2019Dermatitis herpetiformis (DH) is a genetically determined, gluten sensitive autoimmune bullous dermatosis related to celiac disease in which granular, insoluble... (Review)
Review
Dermatitis herpetiformis (DH) is a genetically determined, gluten sensitive autoimmune bullous dermatosis related to celiac disease in which granular, insoluble aggregates in the papillary dermis of epidermal transglutaminase (TG3), immunoglobulin A (IgA), and fibrinogen are present. Detection of the dermal IgA-TG3 immune complex is the gold standard of diagnosis. DH develops in a subpopulation of patients with gluten sensitive enteropathy, characterized by itching, erythematous, excoriated papules showing characteristic distribution over the knees, elbows and buttocks; vesicles are rarely seen. The primary therapy of DH is a strict, lifelong gluten-free diet, and it may be necessary to temporarily give dapsone in case of severe symptoms.
Topics: Celiac Disease; Dermatitis Herpetiformis; Diet, Gluten-Free; Glutens; Humans; Transglutaminases
PubMed: 30868254
DOI: 10.1007/s00105-019-4378-8 -
Frontiers in Immunology 2019Dermatitis herpetiformis (DH) is an inflammatory disease of the skin, considered the specific cutaneous manifestation of celiac disease (CD). Both DH and CD occur in... (Review)
Review
Dermatitis herpetiformis (DH) is an inflammatory disease of the skin, considered the specific cutaneous manifestation of celiac disease (CD). Both DH and CD occur in gluten-sensitive individuals, share the same Human Leukocyte Antigen (HLA) haplotypes (DQ2 and DQ8), and improve following the administration of a gluten-free diet. Moreover, almost all DH patients show typical CD alterations at the small bowel biopsy, ranging from villous atrophy to augmented presence of intraepithelial lymphocytes, as well as the generation of circulating autoantibodies against tissue transglutaminase (tTG). Clinically, DH presents with polymorphic lesions, including papules, vesicles, and small blisters, symmetrically distributed in typical anatomical sites including the extensor aspects of the limbs, the elbows, the sacral regions, and the buttocks. Intense pruritus is almost the rule. However, many atypical presentations of DH have also been reported. Moreover, recent evidence suggested that DH is changing. Firstly, some studies reported a reduced incidence of DH, probably due to early recognition of CD, so that there is not enough time for DH to develop. Moreover, data from Japanese literature highlighted the absence of intestinal involvement as well as of the typical serological markers of CD (i.e., anti-tTG antibodies) in Japanese patients with DH. Similar cases may also occur in Caucasian patients, complicating DH diagnosis. The latter relies on the combination of clinical, histopathologic, and immunopathologic findings. Detecting granular IgA deposits at the dermal-epidermal junction by direct immunofluorescence (DIF) from perilesional skin represents the most specific diagnostic tool. Further, assessing serum titers of autoantibodies against epidermal transglutaminase (eTG), the supposed autoantigen of DH, may also serve as a clue for the diagnosis. However, a study from our group has recently demonstrated that granular IgA deposits may also occur in celiac patients with non-DH inflammatory skin diseases, raising questions about the effective role of eTG IgA autoantibodies in DH and suggesting the need of revising diagnostic criteria, conceivably emphasizing clinical aspects of the disease along with DIF. DH usually responds to the gluten-free diet. Topical clobetasol ointment or dapsone may be also applied to favor rapid disease control. Our review will focus on novel pathogenic insights, controversies, and management aspects of DH.
Topics: Administration, Topical; Autoantibodies; Celiac Disease; Clobetasol; Dapsone; Dermatitis Herpetiformis; Diet, Gluten-Free; GTP-Binding Proteins; HLA-DQ Antigens; Humans; Immunoglobulin A; Protein Glutamine gamma Glutamyltransferase 2; Transglutaminases
PubMed: 31244841
DOI: 10.3389/fimmu.2019.01290 -
Acta Dermato-venereologica Feb 2020Dermatitis herpetiformis (DH) is an autoimmune skin disease that causes itchy, blistering rash, typically on the elbows, knees and buttocks. DH and coeliac disease share... (Review)
Review
Dermatitis herpetiformis (DH) is an autoimmune skin disease that causes itchy, blistering rash, typically on the elbows, knees and buttocks. DH and coeliac disease share the same genetic background, gluten-dependent enteropathy and antibody response against tissue transglutaminase. DH is currently considered a cutaneous manifestation of coeliac disease, and the prevailing hypothesis is that DH develops as a late manifestation of subclinical coeliac disease. The incidence of DH is decreasing contemporarily with the increasing incidence of coeliac disease. The IgA immune response in DH skin is directed against epidermal transglutaminase, while the autoantigen in the gut is tissue transglutaminase. Granular IgA deposition in the papillary dermis is pathognomonic for DH, and is a finding used to confirm the diagnosis. The treatment of choice for DH is a life-long gluten-free diet, which resolves the rash and enteropathy, increases quality of life, and offers a good long-term prognosis.
Topics: Autoimmune Diseases; Celiac Disease; Combined Modality Therapy; Comorbidity; Dapsone; Dermatitis Herpetiformis; Diet, Gluten-Free; Female; Humans; Incidence; Male; Prognosis; Risk Assessment; Transglutaminases; Treatment Outcome
PubMed: 32039457
DOI: 10.2340/00015555-3401 -
Revista Medica de Chile Sep 2021Dermatitis herpetiformis is an autoimmune chronic blistering disease, considered a skin manifestation of celiac disease. Being both conditions multifactorial, they share... (Review)
Review
Dermatitis herpetiformis is an autoimmune chronic blistering disease, considered a skin manifestation of celiac disease. Being both conditions multifactorial, they share some genetic traits and pathogenic mechanisms, which are responsible for the typical skin and gastrointestinal manifestations. In dermatitis herpetiformis, skin and other lesions heal after gluten-free diet and reappear shortly after its reintroduction to complete diet. Prevalence of celiac disease is 1% in the population, and approximately 13% of patients with the disease develop dermatitis herpetiformis. Diagnosis of celiac disease has progressively increased in recent decades, while clinical manifestations become more and more diverse. Given the current high frequency of skin lesions in celiac patients, in this review we update relevant aspects of the epidemiology, pathogenesis, clinical presentations, treatment and follow up of dermatitis herpetiformis, as a contribution to improve the management of both conditions.
Topics: Celiac Disease; Dermatitis Herpetiformis; Humans; Skin
PubMed: 35319687
DOI: 10.4067/S0034-98872021000901330 -
Frontiers in Immunology 2021
Topics: Animals; Celiac Disease; Humans; T-Lymphocytes
PubMed: 34539679
DOI: 10.3389/fimmu.2021.756087 -
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 -
Frontiers in Immunology 2024Autoimmune blistering disorders (AIBDs) are a heterogeneous group of approximately a dozen entities comprising pemphigus and pemphigoid disorders and dermatitis... (Review)
Review
Autoimmune blistering disorders (AIBDs) are a heterogeneous group of approximately a dozen entities comprising pemphigus and pemphigoid disorders and dermatitis herpetiformis. The exact diagnosis of AIBDs is critical for both prognosis and treatment and is based on the clinical appearance combined with the detection of tissue-bound and circulating autoantibodies. While blisters and erosions on the skin and/or inspectable mucosal surfaces are typical, lesions may be highly variable with erythematous, urticarial, prurigo-like, or eczematous manifestations. While direct immunofluorescence microscopy (IFM) of a perilesional biopsy is still the diagnostic gold standard, the molecular identification of the major target antigens opened novel therapeutic avenues. At present, most AIBDs can be diagnosed by the detection of autoantigen-specific serum antibodies by enzyme-linked immunosorbent assay (ELISA) or indirect IFM when the clinical picture is known. This is achieved by easily available and highly specific and sensitive assays employing recombinant immunodominant fragments of the major target antigens, i.e., desmoglein 1 (for pemphigus foliaceus), desmoglein 3 (for pemphigus vulgaris), envoplakin (for paraneoplastic pemphigus), BP180/type XVII collagen (for bullous pemphigoid, pemphigoid gestationis, and mucous membrane pemphigoid), laminin 332 (for mucous membrane pemphigoid), laminin β4 (for anti-p200 pemphigoid), type VII collagen (for epidermolysis bullosa acquisita and mucous membrane pemphigoid), and transglutaminase 3 (for dermatitis herpetiformis). Indirect IFM on tissue substrates and in-house ELISA and immunoblot tests are required to detect autoantibodies in some AIBD patients including those with linear IgA disease. Here, a straightforward modern approach to diagnosing AIBDs is presented including diagnostic criteria according to national and international guidelines supplemented by long-term in-house expertise.
Topics: Humans; Autoantibodies; Autoimmune Diseases; Autoantigens; Skin Diseases, Vesiculobullous; Enzyme-Linked Immunosorbent Assay
PubMed: 38903493
DOI: 10.3389/fimmu.2024.1363032