Preferred Label : Dermatitis herpetiformis, familial;
CISMeF acronym : DH;
Type : Other, mainly phenotypes with suspected mendelian basis;
Alternative titles and symbols : DH;
Description : Dermatitis herpetiformis (DH) and celiac disease (CD; 212750) are gluten-sensitive
diseases. In classic CD the small intestine is predominantly affected, whereas in
DH the skin is also affected, showing typical rash and IgA deposits. Reunala (1996)
reported on the familial incidence of DH in a prospective study started in 1969 in
Finland. A total of 1,018 patients with DH were diagnosed and questioned for positive
family histories. Of the 999 unrelated DH patients, 105 (10.5%) had 1 or several affected
first-degree relatives. Disease in the relatives was either DH (4.4%) or CD (6.1%).
Analysis of the 105 families showed that 13.6% of parents, 18.7% of sibs, and 14%
of children were affected, a segregation pattern that fitted well to a mendelian dominant
mode of inheritance. Gender may also be important because the first-degree relatives
affected with DH were more often females and those affected with CD twice as often
females as males. DH and CD have a common immunogenetic background; both disorders
are associated with HLA alleles DQA1*0501 (see 146880) and B1*0201 (see 142857). Karell
et al. (2002) evaluated the role of the HLA-DQ locus in 25 families in which both
classic CD and DH occurred in sibs. By using a family-based approach, they assumed
that within each family, variation in environmental factors was substantially lower
than in the standard case-control setting, and that the problems related to population
stratification could be avoided. Results from Finnish family material comprising 25
discordant and 85 concordant sib pairs, and from case-control material comprising
71 unrelated Hungarian DH and 68 classic CD patients, together indicated that the
HLA-DQ locus did not differ between the 2 major outcomes of gluten-sensitive enteropathy.
The authors concluded that non-HLA-DR;DQ factors are crucial for the different clinical
manifestations of gluten sensitivity. Using ELISA, Sardy et al. (2002) found that
sera from both CD and DH reacted with tissue transglutaminase (TGM2; 190196) and epidermal
transglutaminase (TGM3; 600238), but the DH antibodies had a markedly higher avidity
for TGM3. Immunofluorescence and confocal microscopy demonstrated that IgA precipitates
in the papillary dermis of DH patients contained TGM3, but not keratinocyte transglutaminase
(TGM1; 190195) or TGM2. Sardy et al. (2002) concluded that TGM3 is the dominant autoantigen
in DH, explaining why skin symptoms rather than intestinal symptoms appear in a proportion
of patients with gluten-sensitive disease.;
Inheritance : Autosomal dominant;
Prefixed ID : 601230;
Origin ID : 601230;
UMLS CUI : C1832586;
Automatic exact mappings (from CISMeF team)
- Currated CISMeF NLP mapping
- HPO term(s)
- ORDO concept(s)
- Semantic type(s)
- UMLS correspondences (same concept)
