IgA anti-epidermal transglutaminase autoantibodies: a sensible and sensitive marker for diagnosis of dermatitis herpetiformis in adult patients.

BACKGROUND: Dermatitis herpetiformis (DH) is a rare gluten-sensitive blistering itchy skin disease, strictly related to coeliac disease (CD). Direct immunofluorescence, demonstrating IgA granular deposits localized either in the dermal papillae or along the dermo-epidermal junction, is currently the gold standard for diagnosis of DH. It has been shown that DH immunocomplexes contain epidermal transglutaminase (eTG) and that sera from patients with DH contain antibodies specifically directed against eTG. OBJECTIVES: We studied the usefulness of serum eTG antibodies in discriminating between DH, CD and other gastrointestinal and dermatologic diseases. METHODS: eTG antibodies were tested in 308 adult patients' sera: 44 patients with untreated dermatitis herpetiformis (UDH), 99 patients with untreated coeliac disease (UCD), 70 dermatological controls and 95 gastrointestinal controls. RESULTS: In UDH eTG antibody levels were significantly higher than in DH patients on gluten-free diet, UCD, gastrointestinal controls and dermatological controls. In UCD eTG antibodies strongly correlated with tissue transglutaminase (tTG) antibodies, whereas in UDH no significant correlation was observed. CONCLUSION: Serum IgA eTG antibody determination can efficiently distinguish UDH from other dermatological itchy diseases and is highly sensitive to gluten-free diet.

Cytokine genetic profile in Whipple's disease.

Whipple's disease (WD) is a very rare chronic systemic condition characterised by a Th2/T regulatory (Treg) dysregulated immune response versus Tropheryma whipplei, a bacterium widely diffuse in the environment. To investigate whether this Th2/Treg polarised response has a genetic background, we investigated the Th1, Th2, Th17 and Treg cytokine genetic profile of 133 patients with WD. Thanks to the European Consortium on WD (QLG1-CT-2002-01049), the polymorphism of 13 cytokine genes was analysed in 111 German and 22 Italian patients using the polymerase chain reaction with sequence-specific primers (PCR-SSP) technique. The frequencies of the genotypes, haplotypes and functional phenotypes were compared with those obtained in 201 German and 140 Italian controls. Clinical heterogeneity was also considered. Functionally, WD patients may be considered as low producers of TGF-ß1, having an increased frequency of the genotype TGF-ß1+869C/C,+915C/C [12.3 % vs. 3.81 %, odds ratio (OR) = 4.131, p = 0.0002] and high secretors of IL-4, carrying the genotype IL-4-590T/T (5.34 % vs. 1.17 %, OR = 5.09, p = 0.0096). No significant association was found between cytokine polymorphism and clinical variability. Analogously to the recent cellular findings of a Th2/Treg polarised response, we showed that the cytokine genetic profile of WD patients is skewed toward a Th2 and Treg response. This was similar in both German and Italian populations. However, the significant deviations versus the controls are poorer than that expected on the basis of these recent cellular findings.

The prevalence and the causes of minimal intestinal lesions in patients complaining of symptoms suggestive of enteropathy: a follow-up study.

AIMS: Although they are non-specific, minimal intestinal lesions are at the end of the coeliac histological damage spectrum. To investigate whether minimal intestinal lesions in patients without endomysial antibodies are due to coeliac disease, their prevalence, causes and risk of evolving into frank coeliac disease were studied. METHODS: From January 2000 to December 2005, 645 duodenal biopsies were performed. In 209 patients, duodenal biopsies were performed independently of endomysial antibody results. Clinical data and HLA-typing of all the patients negative to endomysial antibodies but with minimal mucosal lesions were re-evaluated. Three years later, they were offered to be seen again, and further investigations were proposed. RESULTS: 14 out of 209 patients had minimal mucosal lesions and negative endomysial antibodies. Two patients were lost to follow-up; in 7/12 patients, symptoms and histological lesions were due to a different condition, not related to coeliac disease. In 11/12 patients, HLA-typing made diagnosis of coeliac disease very unlikely. Only one patient was on a gluten-free diet because of gluten-sensitive symptoms and was DQ2(+)/DQ8(+). CONCLUSIONS: Minimal duodenal lesions in patients negative to endomysial antibodies are rare and are likely to be due to conditions unrelated to coeliac disease.

The incidence of coeliac disease in adult first degree relatives.

BACKGROUND AND AIMS: Although prevalence of coeliac disease among first degree relatives of coeliac patients is well-known, only four studies are available about its incidence. We investigated whether first degree relatives found to be negative at a first serological screening can subsequently develop coeliac disease. PATIENTS AND METHODS: In the last 6 years, endomysial antibodies were tested in 158 adult first degree relatives referred to our coeliac out-patient clinic. After at least a year, negative subjects were offered a second testing. Sixty-three accepted. RESULTS: 130/158 first degree relatives tested negative initially. Although one of them had developed coeliac disease after the first testing, at the second testing none of the 63 endomysial antibody negative first degree relatives proved positive. Incidence of coeliac disease among first degree relatives was 1/64 in 51 months, 0.437% year (95%CI 0.05-2.62). An analysis of the sample size showed that 10,000 first degree relatives must be followed up to significantly reduce the CI. CONCLUSIONS: Although we confirmed the high prevalence of coeliac disease among first degree relatives (28/158, 17.7%), we found that the low incidence suggests that further studies are required to understand whether endomysial antibody negative first degree relatives need to be followed up.

Is a gluten-free diet necessary in patients with potential celiac disease?

Potential celiac disease is characterized by a normal duodenal mucosa despite high intraepithelial lymphocytes count and/or positive endomysial antibodies while on a gluten-containing diet. An agreement about the management of this condition is still lacking. A 68-year-old lady complaining of weight loss and epigastric pain was found to be affected by potential celiac disease. Although she maintained a gluten-containing diet, epigastric pain and weight loss disappeared. If she had started a gluten-free diet, the improvement would have been considered a demonstration of the beneficial effect of the diet. Potential celiac patients can be maintained on a gluten-containing diet providing they are closely followed up.