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Timo Reunala - One of the best experts on this subject based on the ideXlab platform.
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risk of fractures in Dermatitis Herpetiformis and coeliac disease a register based study
WOS, 2019Co-Authors: Camilla Pasternack, Timo Reunala, Katri Kaukinen, Kaisa Hervonen, P Collin, Inka Koskinen, Jutta Jarvelin, Heini Huhtala, Ville M Mattila, Teea SalmiAbstract:AbstractObjectives: Dermatitis Herpetiformis (DH) is a cutaneous manifestation of coeliac disease. Bone fracture risk is increased in coeliac disease, but little knowledge exists about bone complic...
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Dermatitis Herpetiformis a common extraintestinal manifestation of coeliac disease
Nutrients, 2018Co-Authors: Timo Reunala, Katri Kaukinen, Kaisa Hervonen, Teea Salmi, Pekka CollinAbstract:Dermatitis Herpetiformis (DH) is a common extraintestinal manifestation of coeliac disease presenting with itchy papules and vesicles on the elbows, knees, and buttocks. Overt gastrointestinal symptoms are rare. Diagnosis of DH is easily confirmed by immunofluorescence biopsy showing pathognomonic granular immunoglobulin A (IgA) deposits in the papillary dermis. A valid hypothesis for the immunopathogenesis of DH is that it starts from latent or manifest coeliac disease in the gut and evolves into an immune complex deposition of high avidity IgA epidermal transglutaminase (TG3) antibodies, together with the TG3 enzyme, in the papillary dermis. The mean age at DH diagnosis has increased significantly in recent decades and presently is 40–50 years. The DH to coeliac disease prevalence ratio is 1:8 in Finland and the United Kingdom (U.K.). The annual DH incidence rate, currently 2.7 per 100,000 in Finland and 0.8 per 100,000 in the U.K., is decreasing, whereas the reverse is true for coeliac disease. The long-term prognosis of DH patients on a gluten-free diet is excellent, with the mortality rate being even lower than for the general population.
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Self-Reported Fractures in Dermatitis Herpetiformis Compared to Coeliac Disease
MDPI AG, 2018Co-Authors: Camilla Pasternack, Timo Reunala, Katri Kaukinen, Kaisa Hervonen, Pekka Collin, Heini Huhtala, Ville M Mattila, Eriika Mansikka, Teea SalmiAbstract:Dermatitis Herpetiformis (DH) is a cutaneous manifestation of coeliac disease. Increased bone fracture risk is known to associate with coeliac disease, but this has been only scantly studied in DH. In this study, self-reported fractures and fracture-associated factors in DH were investigated and compared to coeliac disease. Altogether, 222 DH patients and 129 coeliac disease-suffering controls were enrolled in this study. The Disease Related Questionnaire and the Gastrointestinal Symptom Rating Scale and Psychological General Well-Being questionnaires were mailed to participants; 45 out of 222 (20%) DH patients and 35 out of 129 (27%) of the coeliac disease controls had experienced at least one fracture (p = 0.140). The cumulative lifetime fracture incidence did not differ between DH and coeliac disease patients, but the cumulative incidence of fractures after diagnosis was statistically significantly higher in females with coeliac disease compared to females with DH. The DH patients and the coeliac disease controls with fractures reported more severe reflux symptoms compared to those without, and they also more frequently used proton-pump inhibitor medication. To conclude, the self-reported lifetime bone fracture risk is equal for DH and coeliac disease. After diagnosis, females with coeliac disease have a higher fracture risk than females with DH
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diagnostic delay in Dermatitis Herpetiformis in a high prevalence area
Acta Dermato-venereologica, 2017Co-Authors: Eriika Mansikka, Timo Reunala, Katri Kaukinen, Pekka Collin, Teea Salmi, Heini Huhtala, Kaisa HervonenAbstract:Dermatitis Herpetiformis (DH) is an extra-intestinal manifestation of coeliac disease. The highest currently reported prevalence of DH is in Finland, but knowledge of diagnostic delay is limited. This study investigated the duration of rash prior to diagnosis in 446 patients with DH, analysing the results in 3 periods of 15 years. The diagnosis was considered delayed when the duration of rash before diagnosis was 2 years or longer. Factors associated with delayed diagnosis were analysed. Within the 45 years, the median duration of rash before diagnosis decreased significantly, from 12.0 to 8.0 months (p?=?0.002) and the occurrence of a delayed diagnosis decreased from 47% to 25% (p?=?0.002). Female sex, the presence of villous atrophy, and a diagnosis of DH before the year 2000 were significantly associated with delayed diagnosis. In conclusion, the present study showed that one-quarter of patients currently have a diagnostic delay of 2 years or more, which is far from ideal.
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Dermatitis Herpetiformis a cutaneous manifestation of coeliac disease
Annals of Medicine, 2017Co-Authors: Pekka Collin, Kaisa Hervonen, Katri Kaukinen, Teea Salmi, Timo ReunalaAbstract:Dermatitis Herpetiformis (DH) is an itchy blistering skin disease with predilection sites on elbows, knees, and buttocks. Diagnosis is confirmed by showing granular immunoglobulin A deposits in perilesional skin. DH is one manifestation of coeliac disease; the skin symptoms heal with gluten free diet (GFD) and relapse on gluten challenge. Of the first-degree relatives, 5% may be affected by either condition. Tissue transglutaminase (TG2) is the autoantigen in coeliac disease and epidermal transglutaminase (TG3) in DH. Both diseases conditions exhibit TG2-specific autoantibodies in serum and small bowel mucosa; patients with DH have IgA-TG3 in the skin. There are some divergencies between these two phenotypes. One-fourth of DH patients do not have small bowel mucosal villous atrophy, but virtually all have coeliac-type inflammatory changes. The skin symptoms respond slowly to GFD. The incidence of coeliac disease is increasing, whereas the opposite is true for DH. A female predominance is evident in coeliac disease, while DH may be more common in males. Coeliac disease carries the risk of small intestinal T-cell lymphoma; in DH B-cell lymphomas at any site may prevail. Adult coeliac disease carries a slightly increased elevated mortality risk, whereas in DH, the relative mortality rate is significantly decreased. Key messages Dermatitis Herpetiformis is a cutaneous manifestation of coeliac disease; both conditions are genetically determined and gluten-dependent. Gastrointestinal symptoms and the degree of villous atrophy are less obvious in Dermatitis Herpetiformis than in coeliac disease. Both show tissue transglutaminase (TG2) specific autoantibodies in serum and small bowel mucosa. In addition, TG3-targeted IgA antibodies are found in the skin of DH patients Both conditions carry an increased elevated risk of lymphoma, in coeliac disease small intestinal T-cell lymphoma, in Dermatitis Herpetiformis mainly B-cell lymphoma at various sites. Coeliac disease is currently eight times more common that DH; the incidence of DH is decreasing in contrast to that of coeliac disease, where it is increasing.
Pekka Collin - One of the best experts on this subject based on the ideXlab platform.
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Dermatitis Herpetiformis a common extraintestinal manifestation of coeliac disease
Nutrients, 2018Co-Authors: Timo Reunala, Katri Kaukinen, Kaisa Hervonen, Teea Salmi, Pekka CollinAbstract:Dermatitis Herpetiformis (DH) is a common extraintestinal manifestation of coeliac disease presenting with itchy papules and vesicles on the elbows, knees, and buttocks. Overt gastrointestinal symptoms are rare. Diagnosis of DH is easily confirmed by immunofluorescence biopsy showing pathognomonic granular immunoglobulin A (IgA) deposits in the papillary dermis. A valid hypothesis for the immunopathogenesis of DH is that it starts from latent or manifest coeliac disease in the gut and evolves into an immune complex deposition of high avidity IgA epidermal transglutaminase (TG3) antibodies, together with the TG3 enzyme, in the papillary dermis. The mean age at DH diagnosis has increased significantly in recent decades and presently is 40–50 years. The DH to coeliac disease prevalence ratio is 1:8 in Finland and the United Kingdom (U.K.). The annual DH incidence rate, currently 2.7 per 100,000 in Finland and 0.8 per 100,000 in the U.K., is decreasing, whereas the reverse is true for coeliac disease. The long-term prognosis of DH patients on a gluten-free diet is excellent, with the mortality rate being even lower than for the general population.
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Self-Reported Fractures in Dermatitis Herpetiformis Compared to Coeliac Disease
MDPI AG, 2018Co-Authors: Camilla Pasternack, Timo Reunala, Katri Kaukinen, Kaisa Hervonen, Pekka Collin, Heini Huhtala, Ville M Mattila, Eriika Mansikka, Teea SalmiAbstract:Dermatitis Herpetiformis (DH) is a cutaneous manifestation of coeliac disease. Increased bone fracture risk is known to associate with coeliac disease, but this has been only scantly studied in DH. In this study, self-reported fractures and fracture-associated factors in DH were investigated and compared to coeliac disease. Altogether, 222 DH patients and 129 coeliac disease-suffering controls were enrolled in this study. The Disease Related Questionnaire and the Gastrointestinal Symptom Rating Scale and Psychological General Well-Being questionnaires were mailed to participants; 45 out of 222 (20%) DH patients and 35 out of 129 (27%) of the coeliac disease controls had experienced at least one fracture (p = 0.140). The cumulative lifetime fracture incidence did not differ between DH and coeliac disease patients, but the cumulative incidence of fractures after diagnosis was statistically significantly higher in females with coeliac disease compared to females with DH. The DH patients and the coeliac disease controls with fractures reported more severe reflux symptoms compared to those without, and they also more frequently used proton-pump inhibitor medication. To conclude, the self-reported lifetime bone fracture risk is equal for DH and coeliac disease. After diagnosis, females with coeliac disease have a higher fracture risk than females with DH
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diagnostic delay in Dermatitis Herpetiformis in a high prevalence area
Acta Dermato-venereologica, 2017Co-Authors: Eriika Mansikka, Timo Reunala, Katri Kaukinen, Pekka Collin, Teea Salmi, Heini Huhtala, Kaisa HervonenAbstract:Dermatitis Herpetiformis (DH) is an extra-intestinal manifestation of coeliac disease. The highest currently reported prevalence of DH is in Finland, but knowledge of diagnostic delay is limited. This study investigated the duration of rash prior to diagnosis in 446 patients with DH, analysing the results in 3 periods of 15 years. The diagnosis was considered delayed when the duration of rash before diagnosis was 2 years or longer. Factors associated with delayed diagnosis were analysed. Within the 45 years, the median duration of rash before diagnosis decreased significantly, from 12.0 to 8.0 months (p?=?0.002) and the occurrence of a delayed diagnosis decreased from 47% to 25% (p?=?0.002). Female sex, the presence of villous atrophy, and a diagnosis of DH before the year 2000 were significantly associated with delayed diagnosis. In conclusion, the present study showed that one-quarter of patients currently have a diagnostic delay of 2 years or more, which is far from ideal.
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Dermatitis Herpetiformis a cutaneous manifestation of coeliac disease
Annals of Medicine, 2017Co-Authors: Pekka Collin, Kaisa Hervonen, Katri Kaukinen, Teea Salmi, Timo ReunalaAbstract:Dermatitis Herpetiformis (DH) is an itchy blistering skin disease with predilection sites on elbows, knees, and buttocks. Diagnosis is confirmed by showing granular immunoglobulin A deposits in perilesional skin. DH is one manifestation of coeliac disease; the skin symptoms heal with gluten free diet (GFD) and relapse on gluten challenge. Of the first-degree relatives, 5% may be affected by either condition. Tissue transglutaminase (TG2) is the autoantigen in coeliac disease and epidermal transglutaminase (TG3) in DH. Both diseases conditions exhibit TG2-specific autoantibodies in serum and small bowel mucosa; patients with DH have IgA-TG3 in the skin. There are some divergencies between these two phenotypes. One-fourth of DH patients do not have small bowel mucosal villous atrophy, but virtually all have coeliac-type inflammatory changes. The skin symptoms respond slowly to GFD. The incidence of coeliac disease is increasing, whereas the opposite is true for DH. A female predominance is evident in coeliac disease, while DH may be more common in males. Coeliac disease carries the risk of small intestinal T-cell lymphoma; in DH B-cell lymphomas at any site may prevail. Adult coeliac disease carries a slightly increased elevated mortality risk, whereas in DH, the relative mortality rate is significantly decreased. Key messages Dermatitis Herpetiformis is a cutaneous manifestation of coeliac disease; both conditions are genetically determined and gluten-dependent. Gastrointestinal symptoms and the degree of villous atrophy are less obvious in Dermatitis Herpetiformis than in coeliac disease. Both show tissue transglutaminase (TG2) specific autoantibodies in serum and small bowel mucosa. In addition, TG3-targeted IgA antibodies are found in the skin of DH patients Both conditions carry an increased elevated risk of lymphoma, in coeliac disease small intestinal T-cell lymphoma, in Dermatitis Herpetiformis mainly B-cell lymphoma at various sites. Coeliac disease is currently eight times more common that DH; the incidence of DH is decreasing in contrast to that of coeliac disease, where it is increasing.
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Dermatitis Herpetiformis refractory to gluten free dietary treatment
Acta Dermato-venereologica, 2016Co-Authors: Kaisa Hervonen, Teea Salmi, Tuire Ilus, Kaija Paasikivi, Martine Vornanen, Kaija Laurila, Katri Lindfors, Keijo Viiri, Paivi Saavalainen, Pekka CollinAbstract:Dermatitis Herpetiformis (DH) is a blistering skin disease, which is regarded as an extra-intestinal manifestation of coeliac disease. Refractory cases of coeliac disease, that do not respond to a gluten-free diet and which carry an increased risk of lymphoma, are well-known in coeliac disease. To determine whether refractory cases of DH with active rash and persistent small bowel atrophy occur we analysed our series of 403 patients with DH. Seven (1.7%) patients, who had been on a gluten-free diet for a mean of 16 years, but who still required dapsone to treat the symptoms of DH, were identified. Of these, one patient died from mucinous adenocarcinoma before re-examination. At re-examination skin immunoglobulin A (IgA) deposits were found in 5/6 refractory and 3/16 control DH patients with good dietary response. Small bowel mucosa was studied at re-examination from 5 refractory and 8 control DH patients and was normal in all 5 refractory and 7/8 control DH patients. One refractory DH patient died from adenocarcinoma, but no lymphoma developed in any of the patients. This study
Marzia Caproni - One of the best experts on this subject based on the ideXlab platform.
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Dermatitis Herpetiformis novel perspectives
Frontiers in Immunology, 2019Co-Authors: Emiliano Antiga, Veronica Bonciolini, Diletta Bonciani, Alice Verdelli, Roberto Maglie, Lavinia Quintarelli, Marzia CaproniAbstract: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.
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granular iga deposits in the skin of patients with coeliac disease is it always Dermatitis Herpetiformis
Acta Dermato-venereologica, 2018Co-Authors: Veronica Bonciolini, Emiliano Antiga, Beatrice Bianchi, Elena Del Bianco, Alessandra Ninci, Vincenza Maio, Nicola Pimpinelli, Marzia CaproniAbstract:Coeliac disease is an immune-mediated enteropathy driven by gluten, which can be associated with Dermatitis Herpetiformis. The presence of granular IgA deposits, detected by direct immunofluorescence, is the hallmark of Dermatitis Herpetiformis; nevertheless, IgA deposits have also been demonstrated in healthy skin of patients with coeliac disease. The main objective of this study was to investigate whether IgA deposits could be found in the skin of patients with coeliac disease who have non-Dermatitis Herpetiformis inflammatory skin diseases. Direct immunofluorescence was performed on perilesional skin biopsies of 6 patients with coeliac disease with non-Dermatitis Herpetiformis inflammatory skin diseases and, as control, on 12 non-coeliac patients with inflammatory skin diseases. IgA deposits were found in all of the patients with coeliac disease, but were absent in the control group. In conclusion, IgA deposits may be considered an immunopathological marker for coeliac disease; therefore, patients with coeliac disease showing skin manifestations with positive direct immunofluorescence should be investigated carefully in order to make a differential diagnosis between Dermatitis Herpetiformis and other non-Dermatitis Herpetiformis inflammatory skin diseases.
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the diagnosis and treatment of Dermatitis Herpetiformis
Clinical Cosmetic and Investigational Dermatology, 2015Co-Authors: Emiliano Antiga, Marzia CaproniAbstract:Dermatitis Herpetiformis (DH) is an inflammatory cutaneous disease with a chronic relapsing course, pruritic polymorphic lesions, and typical histopathological and immunopathological findings. According to several evidences, DH is considered the specific cutaneous manifestation of celiac disease, and the most recent guidelines of celiac disease have stated that, in celiac patients with a proven DH, a duodenal biopsy is unnecessary for the diagnosis. In this review, the most recent data about the diagnosis and the management of DH have been reported and discussed. In particular, in patients with clinical and/or histopathological findings suggestive for DH, the finding of granular IgA deposits along the dermal–epidermal junction or at the papillary tips by direct immunofluorescence (DIF) assay, together with positive results for anti-tissue transglutaminase antibody testing, allows the diagnosis. Thereafter, a gluten-free diet should be started in association with drugs, such as dapsone, that are able to control the skin manifestations during the first phases of the diet. In conclusion, although DH is a rare autoimmune disease with specific immunopathological alterations at the skin level, its importance goes beyond the skin itself and may have a big impact on the general health status and the quality of life of the patients.
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Dermatitis Herpetiformis from the genetics to the development of skin lesions
Clinical & Developmental Immunology, 2012Co-Authors: Diletta Bonciani, Emiliano Antiga, P Fabbri, Veronica Bonciolini, Alice Verdelli, Antonietta Derrico, Marzia CaproniAbstract:Dermatitis Herpetiformis (DH) is a rare autoimmune disease linked to gluten sensitivity with a chronic-relapsing course. It is currently considered to be the specific cutaneous manifestation of celiac disease (CD). Both conditions are mediated by the IgA class of autoantibodies, and the diagnosis of DH is dependent on the detection of granular deposits of IgA in the skin. There is an underlying genetic predisposition to the development of DH, but environmental factors are also important. This paper describes these different factors and discusses the known mechanism that lead to the development of skin lesions.
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newly described clinical and immunopathological feature of Dermatitis Herpetiformis
Clinical & Developmental Immunology, 2012Co-Authors: Veronica Bonciolini, Emiliano Antiga, P Fabbri, Diletta Bonciani, Alice Verdelli, Antonietta Derrico, Marzia CaproniAbstract:Dermatitis Herpetiformis (DH) is an inflammatory cutaneous disease with typical histopathological and immunopathological findings clinically characterized by intensely pruritic polymorphic lesions with a chronic-relapsing course. In addition to classic clinical manifestations of DH, atypical variants are more and more frequently reported and histological and immunological are added to them, whereas the impact on quality of life of patients with DH is increasingly important to a certain diagnosis. The aim of this paper is to describe all the possible clinical, histological, and immunological variants of DH in order to facilitate the diagnosis of a rare disease and, therefore, little known.
Sarolta Kárpáti - One of the best experts on this subject based on the ideXlab platform.
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Dermatitis Herpetiformis close to unravelling a disease
Journal of Dermatological Science, 2004Co-Authors: Sarolta KárpátiAbstract:Abstract Dermatitis Herpetiformis is characterised by granular IgA precipitates in the papillary dermis. In contrast to other autoimmune blistering diseases, where tissue-deposited and circulating autoantibodies recognise the same target within the skin, in Dermatitis Herpetiformis a serum IgA reacting with a component of the healthy papillary dermis has not been detected. Recently, the antigenic specificity of pathognomic skin-bound IgA has been clarified: the immune precipitates contain epidermal transglutaminase, an enzyme not previously detected in the papillary region of normal skin. Furthermore, serum IgA in Dermatitis Herpetiformis has been found to bind epidermal transglutaminase. These findings may relate to the fact, that Dermatitis Herpetiformis is associated with gluten sensitive enteropathy, coeliac disease, which is characterised by IgA type autoantibodies to a closely related enzyme, tissue transglutaminase. The two transglutaminases are highly homologous, and therefore, cross reactivity of the two antibodies might explain why patients with gluten sensitive enteropathy, with or without skin disease, generally have serum autoantibodies to both enzymes. There is growing evidence that Dermatitis Herpetiformis should be considered as the skin manifestation of gluten sensitivity developing in those patients with mild coeliac disease, who produce epidermal transglutaminase autoantibodies of high avidity and affinity. Both the skin and the small bowel diseases are gluten dependent and are strongly associated with HLA DQ with no genetic differences to explain the two phenotypes. The question should be asked whether the rash in Dermatitis Herpetiformis is a classic autoimmune blistering disease or whether it has an immune complex basis, which is the most likely alternative.
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epidermal transglutaminase tgase 3 is the autoantigen of Dermatitis Herpetiformis
Journal of Experimental Medicine, 2002Co-Authors: Miklos Sardy, Sarolta Kárpáti, Barbara Merkl, Mats Paulsson, Neil SmythAbstract:Gluten sensitivity typically presents as celiac disease, a common chronic small intestinal disorder. However, in certain individuals it is associated with Dermatitis Herpetiformis, a blistering skin disease characterized by granular IgA deposits in the papillary dermis. While tissue transglutaminase has been implicated as the major autoantigen of gluten sensitive disease, there has been no explanation as to why this condition appears in two distinct forms. Here we show that while sera from patients with either form of gluten sensitive disease react both with tissue transglutaminase and the related enzyme epidermal (type 3) transglutaminase, antibodies in patients having Dermatitis Herpetiformis show a markedly higher avidity for epidermal transglutaminase. Further, these patients have an antibody population specific for this enzyme. We also show that the IgA precipitates in the papillary dermis of patients with Dermatitis Herpetiformis, the defining signs of the disease, contain epidermal transglutaminase, but not tissue transglutaminase or keratinocyte transglutaminase. These findings demonstrate that epidermal transglutaminase, rather than tissue transglutaminase, is the dominant autoantigen in Dermatitis Herpetiformis and explain why skin symptoms appear in a proportion of patients having gluten sensitive disease.
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antibodies to tissue transglutaminase as serologic markers in patients with Dermatitis Herpetiformis
Journal of Investigative Dermatology, 1999Co-Authors: Walburga Dieterich, Eberhardt Laag, T Zagoni, Sarolta Kárpáti, Ernst-otto Riecken, Leena Brucknertuderman, Timo Reunala, Detlef SchuppanAbstract:Dermatitis Herpetiformis is a gluten-sensitive disease with a symmetrically distributed blistering over extensor surfaces. The association with celiac disease is further supported by the high rate of immunoglobulin A autoantibodies to endomysium in patients with Dermatitis Herpetiformis, which are highly specific and sensitive indicators of celiac disease. Therefore, we determined immunoglobulin A antibodies to tissue transglutaminase, the recently discovered endomysial autoantigen in celiac disease, in patients with Dermatitis Herpetiformis and controls. Sera of 61 patients with Dermatitis Herpetiformis, as characterized by granular immunoglobulin A deposits in the subepidermal basement membrane and known endomysial antibody titers (determined by indirect immunofluorescence) as well as 84 control sera of patients with dermal or intestinal diseases unrelated to Dermatitis Herpetiformis, were analyzed for circulating immunoglobulin A antibodies to tissue transglutaminase by enzyme-linked immunosorbent assay. Immunoglobulin A anti-tissue transglutaminase titers in patients with Dermatitis Herpetiformis were significantly elevated above the controls. Furthermore, the immunoglobulin A anti-tTG titers showed a positive correlation with semiquantitative endomysial antibody data. Compared with endomysial antibodies, determination of immunoglobulin A anti-tissue transglutaminase reached a specificity and sensitivity of 97.6% and 89.1%. Patients with Dermatitis Herpetiformis have elevated immunoglobulin A autoantibodies to tissue transglutaminase, confirming its pathogenic relation with celiac disease and further supporting the usefulness of this novel assay for screening and therapy control.
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ultrastructural binding sites of endomysium antibodies from sera of patients with Dermatitis Herpetiformis and coeliac disease
Gut, 1992Co-Authors: Sarolta Kárpáti, Marita Meurer, Wilhelm Stolz, A Burginwolff, Otto Braunfalco, Th KriegAbstract:The ultrastructural binding sites of endomysium antibodies, specific serological markers of gluten sensitive enteropathy, were investigated in the rabbit oesophagus using the immunogold technique. Endomysium antibodies from sera of patients with Dermatitis Herpetiformis and with coeliac disease bound in an identical manner in a non-fibrillar material closely associated with fine collagenous-reticulin fibrils and also with similar fibrils connecting smooth muscle cells and elastic tissue in the endomysial connective tissue. These observations suggest that IgA antibodies in sera from patients with Dermatitis Herpetiformis and coeliac disease recognise a common antigen in an amorphous component associated with the reticular connective tissue of oesophageal lamina muscularis mucosae and thus confirm the probable identity of IgA class endomysium and jejunal antibodies.
Kaisa Hervonen - One of the best experts on this subject based on the ideXlab platform.
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risk of fractures in Dermatitis Herpetiformis and coeliac disease a register based study
WOS, 2019Co-Authors: Camilla Pasternack, Timo Reunala, Katri Kaukinen, Kaisa Hervonen, P Collin, Inka Koskinen, Jutta Jarvelin, Heini Huhtala, Ville M Mattila, Teea SalmiAbstract:AbstractObjectives: Dermatitis Herpetiformis (DH) is a cutaneous manifestation of coeliac disease. Bone fracture risk is increased in coeliac disease, but little knowledge exists about bone complic...
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Dermatitis Herpetiformis a common extraintestinal manifestation of coeliac disease
Nutrients, 2018Co-Authors: Timo Reunala, Katri Kaukinen, Kaisa Hervonen, Teea Salmi, Pekka CollinAbstract:Dermatitis Herpetiformis (DH) is a common extraintestinal manifestation of coeliac disease presenting with itchy papules and vesicles on the elbows, knees, and buttocks. Overt gastrointestinal symptoms are rare. Diagnosis of DH is easily confirmed by immunofluorescence biopsy showing pathognomonic granular immunoglobulin A (IgA) deposits in the papillary dermis. A valid hypothesis for the immunopathogenesis of DH is that it starts from latent or manifest coeliac disease in the gut and evolves into an immune complex deposition of high avidity IgA epidermal transglutaminase (TG3) antibodies, together with the TG3 enzyme, in the papillary dermis. The mean age at DH diagnosis has increased significantly in recent decades and presently is 40–50 years. The DH to coeliac disease prevalence ratio is 1:8 in Finland and the United Kingdom (U.K.). The annual DH incidence rate, currently 2.7 per 100,000 in Finland and 0.8 per 100,000 in the U.K., is decreasing, whereas the reverse is true for coeliac disease. The long-term prognosis of DH patients on a gluten-free diet is excellent, with the mortality rate being even lower than for the general population.
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Self-Reported Fractures in Dermatitis Herpetiformis Compared to Coeliac Disease
MDPI AG, 2018Co-Authors: Camilla Pasternack, Timo Reunala, Katri Kaukinen, Kaisa Hervonen, Pekka Collin, Heini Huhtala, Ville M Mattila, Eriika Mansikka, Teea SalmiAbstract:Dermatitis Herpetiformis (DH) is a cutaneous manifestation of coeliac disease. Increased bone fracture risk is known to associate with coeliac disease, but this has been only scantly studied in DH. In this study, self-reported fractures and fracture-associated factors in DH were investigated and compared to coeliac disease. Altogether, 222 DH patients and 129 coeliac disease-suffering controls were enrolled in this study. The Disease Related Questionnaire and the Gastrointestinal Symptom Rating Scale and Psychological General Well-Being questionnaires were mailed to participants; 45 out of 222 (20%) DH patients and 35 out of 129 (27%) of the coeliac disease controls had experienced at least one fracture (p = 0.140). The cumulative lifetime fracture incidence did not differ between DH and coeliac disease patients, but the cumulative incidence of fractures after diagnosis was statistically significantly higher in females with coeliac disease compared to females with DH. The DH patients and the coeliac disease controls with fractures reported more severe reflux symptoms compared to those without, and they also more frequently used proton-pump inhibitor medication. To conclude, the self-reported lifetime bone fracture risk is equal for DH and coeliac disease. After diagnosis, females with coeliac disease have a higher fracture risk than females with DH
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diagnostic delay in Dermatitis Herpetiformis in a high prevalence area
Acta Dermato-venereologica, 2017Co-Authors: Eriika Mansikka, Timo Reunala, Katri Kaukinen, Pekka Collin, Teea Salmi, Heini Huhtala, Kaisa HervonenAbstract:Dermatitis Herpetiformis (DH) is an extra-intestinal manifestation of coeliac disease. The highest currently reported prevalence of DH is in Finland, but knowledge of diagnostic delay is limited. This study investigated the duration of rash prior to diagnosis in 446 patients with DH, analysing the results in 3 periods of 15 years. The diagnosis was considered delayed when the duration of rash before diagnosis was 2 years or longer. Factors associated with delayed diagnosis were analysed. Within the 45 years, the median duration of rash before diagnosis decreased significantly, from 12.0 to 8.0 months (p?=?0.002) and the occurrence of a delayed diagnosis decreased from 47% to 25% (p?=?0.002). Female sex, the presence of villous atrophy, and a diagnosis of DH before the year 2000 were significantly associated with delayed diagnosis. In conclusion, the present study showed that one-quarter of patients currently have a diagnostic delay of 2 years or more, which is far from ideal.
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Dermatitis Herpetiformis a cutaneous manifestation of coeliac disease
Annals of Medicine, 2017Co-Authors: Pekka Collin, Kaisa Hervonen, Katri Kaukinen, Teea Salmi, Timo ReunalaAbstract:Dermatitis Herpetiformis (DH) is an itchy blistering skin disease with predilection sites on elbows, knees, and buttocks. Diagnosis is confirmed by showing granular immunoglobulin A deposits in perilesional skin. DH is one manifestation of coeliac disease; the skin symptoms heal with gluten free diet (GFD) and relapse on gluten challenge. Of the first-degree relatives, 5% may be affected by either condition. Tissue transglutaminase (TG2) is the autoantigen in coeliac disease and epidermal transglutaminase (TG3) in DH. Both diseases conditions exhibit TG2-specific autoantibodies in serum and small bowel mucosa; patients with DH have IgA-TG3 in the skin. There are some divergencies between these two phenotypes. One-fourth of DH patients do not have small bowel mucosal villous atrophy, but virtually all have coeliac-type inflammatory changes. The skin symptoms respond slowly to GFD. The incidence of coeliac disease is increasing, whereas the opposite is true for DH. A female predominance is evident in coeliac disease, while DH may be more common in males. Coeliac disease carries the risk of small intestinal T-cell lymphoma; in DH B-cell lymphomas at any site may prevail. Adult coeliac disease carries a slightly increased elevated mortality risk, whereas in DH, the relative mortality rate is significantly decreased. Key messages Dermatitis Herpetiformis is a cutaneous manifestation of coeliac disease; both conditions are genetically determined and gluten-dependent. Gastrointestinal symptoms and the degree of villous atrophy are less obvious in Dermatitis Herpetiformis than in coeliac disease. Both show tissue transglutaminase (TG2) specific autoantibodies in serum and small bowel mucosa. In addition, TG3-targeted IgA antibodies are found in the skin of DH patients Both conditions carry an increased elevated risk of lymphoma, in coeliac disease small intestinal T-cell lymphoma, in Dermatitis Herpetiformis mainly B-cell lymphoma at various sites. Coeliac disease is currently eight times more common that DH; the incidence of DH is decreasing in contrast to that of coeliac disease, where it is increasing.