New entity of adult ultra-short coeliac disease: the first international cohort and case-control study.

BACKGROUND: Ultra-short coeliac disease (USCD) is defined as villous atrophy only present in the duodenal bulb (D1) with concurrent positive coeliac serology. We present the first, multicentre, international study of patients with USCD. METHODS: Patients with USCD were identified from 10 tertiary hospitals (6 from Europe, 2 from Asia, 1 from North America and 1 from Australasia) and compared with age-matched and sex-matched patients with conventional coeliac disease. FINDINGS: Patients with USCD (n=137, median age 27 years, IQR 21-43 years; 73% female) were younger than those with conventional coeliac disease (27 vs 38 years, respectively, p<0.001). Immunoglobulin A-tissue transglutaminase (IgA-tTG) titres at index gastroscopy were lower in patients with USCD versus conventional coeliac disease (1.8×upper limit of normal (ULN) (IQR 1.1-5.9) vs 12.6×ULN (IQR 3.3-18.3), p<0.001).Patients with USCD had the same number of symptoms overall (median 3 (IQR 2-4) vs 3 (IQR 1-4), p=0.875). Patients with USCD experienced less iron deficiency (41.8% vs 22.4%, p=0.006).Both USCD and conventional coeliac disease had the same intraepithelial lymphocytes immunophenotype staining pattern; positive for CD3 and CD8, but not CD4.At follow-up having commenced a gluten-free diet (GFD) (median of 1181 days IQR: 440-2160 days) both USCD and the age-matched and sex-matched controls experienced a similar reduction in IgA-tTG titres (0.5 ULN (IQR 0.2-1.4) vs 0.7 ULN (IQR 0.2-2.6), p=0.312). 95.7% of patients with USCD reported a clinical improvement in their symptoms. INTERPRETATION: Patients with USCD are younger, have a similar symptomatic burden and benefit from a GFD. This study endorses the recommendation of D1 sampling as part of the endoscopic coeliac disease diagnostic workup.

Ultra-short celiac disease exhibits differential genetic and immunophenotypic features compared to conventional celiac disease.

BACKGROUND: Ultra-short coeliac disease (USCD) is a novel celiac disease (CD) subtype limited to the duodenal bulb (D1). HLA haplotypes and flow cytometry have not been assessed yet. AIMS: To compare genetic, clinical, serologic, histopathologic and inmmunophenotypic parameters between USCD and conventional celiac disease (CCD) patients. METHODS: Prospective single-center study in children and adult patients undergoing duodenal biopsies on a gluten-containing diet. Biopsies for histology and flow cytometry were taken separately from D1 and distal duodenum. Biopsies in seronegative patients with celiac lymphogram were repeated after 2 years on a gluten-free diet. RESULTS: Among 505 included patients, 127 were diagnosed with CD, of whom 7 (5.5%) showed USCD. HLADQ2 was significantly less common in USCD compared to CCD (71% vs. 95%, p 0.003). Likewise, USCD patients showed more frequent non-significant seronegativity (28% vs. 8%, p 0.07) and significantly lower titrations (7-15IU/ml) of tissue transglutaminase antibodies (tTG-IgA) (60% vs. 13%, p<0.001). Biopsies from D1 revealed significant less NK cells down-expression in USCD patients (1.4 vs. 5, p 0.04). CONCLUSIONS: Up to 5.5% of CD patients showed USCD. A lower frequency of HLADQ2, along with less serum tTG-IgA titration and duodenal NK cell suppression, were differential features of USCD.

Endoscopic ultrasound-guided fine-needle biopsy in patients with unexplained diffuse gastrointestinal wall thickening.

Background and study aims Endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) is recommended after non-diagnostic biopsy in gastrointestinal wall thickening, although the performance of currently available FNB needles in this setting is unknown. We aimed to assess the diagnostic accuracy and safety of EUS-FNB and to evaluate the "T" wall staging in malignant pathology. Patients and methods This was a single center retrospective study that included all consecutive patients undergoing EUS-FNB for diffuse gastrointestinal wall thickening with at least one previous negative conventional endoscopic biopsy between January 2016 and November 2019. EUS-FNB was performed using linear-array echoendoscopes with slow-pull/fanning technique. Tissue acquisition was done with 19- or 22-gauge biopsy needles. Samples were included in formalin without rapid on-site evaluation and submitted for histopathological processing. The final diagnosis was based on conclusive histology or absence of evidence of disease progression after follow-up at least 6 months. Results Twenty-nine patients (21 men), with a median age of 68 (IQR: 56-77), were included. EUS-FNB was technically feasible and the sample quality was adequate for full histological assessment in all patients (100 %). Sensitivity, specificity, positive and negative predictive values, and overall accuracy for diagnosis of malignancy were 95.5 %, 100 %, 100 %, 83.3 %, and 96.3 %, respectively. In patients with malignant disease, the samples obtained allowed detection of signs of deep layer infiltration ("histological staging") in 17 of 21 cases (81 %). No adverse events were noted. Conclusions The EUS-FNB technique demonstrated excellent diagnostic performance and safety in the study of unexplained diffuse gastrointestinal wall thickening. Histological staging was obtained in a high percentage of samples.