Genetic dissection between coeliac disease and dermatitis herpetiformis in sib pairs

Abstract

Gluten sensitive enteropathy has various manifestations, of which the two major forms are classical coeliac disease (cCD) and dermatitis herpetiformis (DH). In cCD predominantly the small intestine is affected, whereas in DH also the skin is affected showing typical rash and IgA deposits. The symptoms in both forms are dependent on gluten intake. The factors diversifying these two clinical outcomes are unknown. In the present report we evaluated the role of the major genetic susceptibility locus, HLA DQ, in 25 families, in which both forms of the disease, cCD and DH, occurred in siblings. By using the family-based approach it can be assumed that within each family variation in environmental factors is substantially lower than in the standard case-control setting, and also the problems related to population stratification can be avoided. Results from the Finnish family material with 25 discordant and 85 concordant sib pairs, and from additional case-control material comprising 71 unrelated Hungarian DH and 68 cCD patients, together indicated that the HLA DQ locus did not differ between the two major outcomes of gluten sensitive enteropathy. The non-HLA DR ; DQ factors are critical for the different clinical manifestations of gluten sensitivity.

Dermatitis herpetiformis

“…Despite this, the majority of patients with DH have clinically silent or mild gastrointestinal CD and show improvement of cutaneous manifestations of CD on a GFD. 12,14,18,27,35,55 In fact, isolated iron deficiency may be the only indicator of CD in a patient with DH. 14,68 Because underlying CD may cause atrophic gastritis, pernicious anemia may also be the sole finding in patients with DH.…”

“…10,11 Although DH was not considered a familial condition for many years, that view is now changing because a number of genetic studies and epidemiologic reports have recorded familial cases of DH. [12][13][14] The prevalence and presentation of DH varies geographically. Northern Europe appears to have the largest number of cases overall, but DH with onset in childhood tends to be more common in Mediterranean countries.…”

Transglutaminases as diagnostically relevant autoantigens in patients with gluten sensitivity

“…Dermatitis herpetiformis (DH; Duhring disease) and celiac disease (CD) represent the two manifestations of untreated gluten sensitivity, sharing the same genetic background, such as HLA‐B 8, HLA‐DR 3, HLA‐DQ 2 and HLA‐DQ 8 [1, 2, 3]. DH is a blistering skin disease, mainly affecting young adults.…”

IgA Nephropathy, Celiac Disease and Dermatitis Herpetiformis: A Rare Triad

“…Sardy et al proposed that the DH pathogenesis consists of immune response of low avidity for tTG, resulting initially in silent CD that with continued exposure to gliadin, leads to the development of populations of antibodies with high affinity to eTG for cross-reactivity, which manifests as DH. Moreover, as in CD, in which genetic predisposition is associated with the HLADQ2 (allelesDQA1 * 0501 and DQB1 *020) and HLA-DQ8 (DQA1 * 03 alleles and DQB1* 0302), DH presents similar genetic alterations [18,19]. Childhood DH is rare, with an uncertain incidence and prevalence.…”