BMJ open gastroenterology · 2017
Clinical and genetic profile of patients with seronegative coeliac disease: the natural history and response to gluten-free diet.
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Dore Maria Pina, Pes Giovanni Mario, Dettori Ivana, Villanacci Vincenzo, Manca Alessandra, Realdi Giuseppe
Аннотация
OBJECTIVES: Patients with clinical, genetic and histological features of coeliac disease (CD), but negative for serological markers, pose a significant clinical problem. The aim of this study was to outline a specific profile, and to evaluate the natural history and response to gluten-free diet (GFD) of patients with seronegative CD.
METHODS: patients with duodenal mucosa damage Marsh I, II and III stages, HLA DQ2/DQ8 haplotype and clinical features suggestive of CD, but negative for CD serology, were defined as seronegative CD patients. Other common causes of duodenal mucosa damage were excluded. HLA-DR and DQ genotype/haplotype between all Marsh stages of patients with seronegative and seropositive CD were compared. Clinical features, laboratory testing and histological findings were evaluated after a GFD and a gluten rechallenge. A long follow-up period was available.
RESULTS: 48 patients fulfilled diagnostic criteria over a 4-year period. Clinical phenotype and HLA-DR and DQ frequencies between patients with seronegative and seropositive CD was similar. However, Marsh I stage was more prevalent in seronegative patients (42% vs 22%; p<0.05). After a 1-year GFD trial, clinical symptoms, histological features and laboratory testing improved in 40 patients and worsened in those who underwent a 6-months gluten challenge. Five patients with seronegative CD (25%) experienced the occurrence of autoimmune diseases during a median follow-up of 133 months (range 72-192).
CONCLUSIONS: Patients with seronegative CD did not display a specific profile. They benefitted from GFD as patients with seropositive CD. Waiting for more sensitive serological markers, the diagnosis of seronegative CD remains a diagnosis of exclusion.
METHODS: patients with duodenal mucosa damage Marsh I, II and III stages, HLA DQ2/DQ8 haplotype and clinical features suggestive of CD, but negative for CD serology, were defined as seronegative CD patients. Other common causes of duodenal mucosa damage were excluded. HLA-DR and DQ genotype/haplotype between all Marsh stages of patients with seronegative and seropositive CD were compared. Clinical features, laboratory testing and histological findings were evaluated after a GFD and a gluten rechallenge. A long follow-up period was available.
RESULTS: 48 patients fulfilled diagnostic criteria over a 4-year period. Clinical phenotype and HLA-DR and DQ frequencies between patients with seronegative and seropositive CD was similar. However, Marsh I stage was more prevalent in seronegative patients (42% vs 22%; p<0.05). After a 1-year GFD trial, clinical symptoms, histological features and laboratory testing improved in 40 patients and worsened in those who underwent a 6-months gluten challenge. Five patients with seronegative CD (25%) experienced the occurrence of autoimmune diseases during a median follow-up of 133 months (range 72-192).
CONCLUSIONS: Patients with seronegative CD did not display a specific profile. They benefitted from GFD as patients with seropositive CD. Waiting for more sensitive serological markers, the diagnosis of seronegative CD remains a diagnosis of exclusion.