Seronegative Celiac Disease; Frequently Encountered Yet Undiagnosed Clinical Entity

Abstract

BACKGROUND There are limited studies on the seronegative celiac disease from the Indian subcontinent. The aim of this study was to assess the prevalence, pathological, genetic, and clinical profile of patients with seronegative celiac disease. METHODS This prospective observational study was conducted in the Department of Gastroenterology, SMS Hospital, Jaipur, between October 2017 to March 2019. Consecutive patients with seronegative celiac disease with age ≥ 3 years were enrolled for the assessment of demography, clinical features, histological findings, celiac serology, genetic analysis, and response to gluten-free diet. RESULTS Out of total of 312 patients with celiac disease, 13 (4.16 %) patients (median age 25 years [range 5-46 years], 10 female) were diagnosed as having seronegative celiac disease. Presenting symptoms were chronic diarrhea in nine (69.23%), abdominal pain in six (46.15%), weight loss in five (38.46%), and short stature in two (15.38 %) patients. On histological analysis, Marsh stage 2 was seen in five (38.46%), Marsh 3c in two (15.38%), Marsh 3a in three (23.07%), and Marsh 3b in three (23.07%) patients. On HLA analysis, HLA-DQ2.5 was seen in six (46.15%) patients, HLA-DQ2.2 in five (38.46%), and HLA-DQ8 in two (15.38%) patients. CONCLUSION The prevalence of seronegative celiac disease in our study was 4.16%. The most common symptoms were chronic diarrhea and abdominal pain, and the histological grade was Marsh stage 2.

Clinical Features of Children With Serology Negative, Biopsy Positive Celiac Disease

“…Compared to pediatrics there have been more studies of SNCD in adults and prevalence has varied widely (9.1%–38.5%) depending on the cohort and the criteria applied (9,10). There are fewer pediatric studies examining the prevalence of SNCD, although overall our findings do seem consistent with the reported prevalence range from 3%–6.25% (11,13,14). In contrast, Gustafsson et al (15) identified no SNCD patients in 2 cohorts of 307 Finnish and 83 Romanian children with CD.…”

“…This may be given the very small sample size of the SNCD patients, a major limitation of this study. All SNCD patients were referred for symptoms and gastrointestinal symptoms were the most common, similar to what is reported by Dhingra et al (14). Case series and reports suggest abdominal distention may be a common sign, but again this information was not available for our population (18,19).…”

Description of a clinical case of seronegative celiac disease in a 5-year-old girl

“…По данным индийских исследователей, частота встречаемости СНЦ составляет 4,16% случаев (13 из 312 пациентов) [10]. Итальянские ученые определяли СНЦ у 2% детей от общего количества больных [16,18,19].…”

“…Повышение анти-tTG IgА выявляется у подавляющего большинства пациентов (чувствительность от 95 до 98%), однако небольшая часть пациентов с целиакией может иметь отрицательную серологию, и в этих случаях диагноз зависит от типичной гистопатологии тонкой кишки наряду с HLA-DQ2 и (или) HLA-DQ8 и исключения других причин энтеральной атрофии, что является обязательным требованием при подозрении на диагноз серонегативной целиакии (СНЦ) (рис. 1) 1 [8][9][10][11][12].…”