Clinicopathological Study of Seronegative Celiac Disease in Adults in Pakistan: A Pilot Study

Abstract

BACKGROUND Celiac disease (CD) is usually missed, if the serology is negative. We aimed to evaluate the clinicopathological characteristics of seronegative CD (SNCD) and its response to gluten-free diet (GFD) in adult patients. METHODS This observational study was carried out at the Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation, Karachi, Pakistan from 2009 to 2015. All consecutive adult patients (≥17 years) with features of marked villous atrophy (Marsh class≥III) on duodenal biopsy, negative tissue transglutaminase IgA and IgG antibodies (anti-tTg IgA and IgG) and human leukocyte antigen (HLA) DQ2 or DQ8 serotypes were studied. Clinical characteristics, laboratory parameters, and response to GFD were analyzed by SPSS software version 20. Median and interquartile range (IQR) were used for summarizing quantitative data. Frequency (percentages) was used for qualitative data. RESULTS A total of 12 patients with median age of 31.5 years (IQR: 19.75-46.75 years), of whom five (41.6%) were men were studied. The presenting complaints were: weight loss in 11 (91.6%) and abdominal pain in 9 (75%) patients. Anemia was observed in 10 (83.3%) patients with median hemoglobin of 9.5 g/dL (IQR: 6.3-13.25 g/dL). Median alanine transaminase (ALT) was 21 U/L (IQR: 13–27 U/L) and median albumin was 3 g/dL (IQR: 2.4-3.6 g/dL). Anti-tTg IgA and IgG were negative in all patients. HLA DQ serotyping showed homozygous DQ2 and DQ8 in four and one patients, respectively; while heterozygous DQ2 and DQ8 in five and two patients, respectively. All patients were advised to receive GFD. Nine (75%) patients showed complete clinical response. Two patients were non-compliant and one with non-alcoholic fatty liver disease (NAFLD)-related cirrhosis had partial clinical response. Out of the nine responders, two patients showed response within 6 months while the remaining showed improvement over a year period. CONCLUSION The diagnosis of SNCD is rewarding as it responds favorably to GFD in most patients. HLA serology provides an important tool for diagnosis of this entity.

Seronegative Celiac Disease; Frequently Encountered Yet Undiagnosed Clinical Entity

“…This finding is compatible with previous studies in which the reported positivity for HLA DQ2 was 85.71% and 75%. 27,28 We found that patients with SNCD had a milder degree of villous atrophy with five (38.46%) patients showed Marsh 2, three (23.07%) Marsh 3a, three (23.07%) Marsh 3b, and only two (15.38%) patients had Marsh 3c stage. These results are similar to published studies that showed seropositive patients have a proportionately greater degree of villous atrophy than seronegative patients in various studies.…”

“…27 At the end of 6 months, 10 patients were available for follow-up, and all responded to GFD, which is similar to earlier studies. 28,30 The classical clinical features, including diarrhea, abdominal pain, anemia, and weight loss, were more common in patients with SNCD compared with seropositive patients. These results are in concordance with a previous study.…”

Classical celiac disease is more frequent with a double dose of HLA-DQB1*02: A systematic review with meta-analysis

“…Five studies [24, 26, 28, 40, 44] reported on the presence of diarrhea at diagnosis, all were included in the analysis of double vs. single dose of HLA-DQB1*02 and that of double vs. zero dose of the allele, as well. We failed to detect a significant gene dose effect, nor in the subgroups of children and adults in a homogeneous dataset (I 2 = 0.0%) (Table 2, S1 and S2 Figs).…”

“…Regarding the severity of villous atrophy, seven [12, 24, 25, 41–44] and eight studies [12, 24, 25, 41–45] were eligible for inclusion in the analysis of double vs. single dose of HLA-DQB1*02 and that of double vs. zero dose of the allele. Marsh 3c at diagnosis was not more frequent in patients with a double dose of HLA-DQB1*02, as compared to single and zero doses of the allele (OR = 0.870, CI: 0.514 to 1.470, p = 0.602 [I 2 = 39.7%, p = 0.127] and OR = 0.822, CI: 0.333 to 2.032, p = 0.671 [I 2 = 46.8%, p = 0.068], respectively).…”

Clinical classification and long‐term outcomes of seronegative coeliac disease: a 20‐year multicentre follow‐up study

“…This is due to the different study designs and diagnostic criteria adopted, endpoints and limited sample sizes of the populations under investigation in previous studies. 4,10,11,[13][14][15][16][17][18][19][20][21][22][23][24] Sensitivity and specificity of serological markers for coeliac disease have improved over the last few years, 25 thus making it more difficult to define the real prevalence of this condition. Indeed, debate exists on whether to consider positive coeliac IgG based serology in the context of IgA deficiency as seronegative coeliac disease, 9,10 or instead as a conventional form of coeliac disease associated with IgA deficiency.…”