Meritxell Mariné

Spectrum of gluten-sensitive enteropathy in first-degree relatives of patients with coeliac disease: clinical relevance of lymphocytic enteritis.

Background: Limited data on a short series of patients suggest that lymphocytic enteritis (classically considered as latent coeliac disease) may produce symptoms of malabsorption, although the true prevalence of this situation is unknown. Serological markers of coeliac disease are of little diagnostic value in identifying these patients. Aims: To evaluate the usefulness of human leucocyte antigen-DQ2 genotyping followed by duodenal biopsy for the detection of gluten-sensitive enteropathy in first-degree relatives of patients with coeliac disease and to assess the clinical relevance of lymphocytic enteritis diagnosed with this screening strategy. Patients and methods: 221 first-degree relatives of 82 DQ2+ patients with coeliac disease were consecutively included. Duodenal biopsy (for histological examination and tissue transglutaminase antibody assay in culture supernatant) was carried out on all DQ2+ relatives. Clinical features, biochemical parameters and bone mineral density were recorded. Results: 130 relatives (58.8%) were DQ2+, showing the following histological stages: 64 (49.2%) Marsh 0; 32 (24.6%) Marsh I; 1 (0.8%) Marsh II; 13 (10.0%) Marsh III; 15.4% refused the biopsy. 49 relatives showed gluten sensitive enteropathy, 46 with histological abnormalities and 3 with Marsh 0 but positive tissue transglutaminase antibody in culture supernatant. Only 17 of 221 relatives had positive serological markers. Differences in the diagnostic yield between the proposed strategy and serology were significant (22.2% v 7.2%, p<0.001). Relatives with Marsh I and Marsh II–III were more often symptomatic (56.3% and 53.8%, respectively) than relatives with normal mucosa (21.1%; p = 0.002). Marsh I relatives had more severe abdominal pain (p = 0.006), severe distension (p = 0.047) and anaemia (p = 0.038) than those with Marsh 0. The prevalence of abnormal bone mineral density was similar in relatives with Marsh I (37%) and Marsh III (44.4%). Conclusions: The high number of symptomatic patients with lymphocytic enteritis (Marsh I) supports the need for a strategy based on human leucocyte antigen-DQ2 genotyping followed by duodenal biopsy in relatives of patients with coeliac disease and modifies the current concept that villous atrophy is required to prescribe a gluten-free diet.

Intestinal spirochetosis and chronic watery diarrhea: Clinical and histological response to treatment and long-term follow up

Background:  The clinical significance of intestinal spirochetosis is uncertain, therefore the aim of the present paper was to assess the prevalence of histological intestinal spirochetosis in patients with and without chronic watery diarrhea and to evaluate its clinical relevance.

The prevalence of coeliac disease is significantly higher in children compared with adults.

Background  Some limited studies of coeliac disease have shown higher frequency of coeliac disease in infancy and adolescence than in adulthood. This finding has remained unnoticed and not adequately demonstrated.

Diagnostic value of duodenal antitissue transglutaminase antibodies in gluten-sensitive enteropathy

Background  In gluten‐sensitive enteropathy, antitissue transglutaminase antibodies are synthesized in the duodenum.

Mild enteropathy as a cause of iron-deficiency anaemia of previously unknown origin

BACKGROUND AND AIMS We assessed whether mild enteropathy with negative coeliac serology may be gluten-dependent, and a cause of iron-deficiency anaemia. In cases not responding to gluten-free diet, the role of Helicobacter pylori infection was evaluated. METHODS 55 consecutive unexplained iron-deficiency anaemia patients were included. In all of them we performed: HLA-DQ2/DQ8 coeliac genetic study, distal duodenum biopsies, and tests to assess H. pylori infection. A gluten-free diet or H. pylori eradication was used as indicated. Final diagnosis was established based on response to specific therapy after a 12-month follow-up period. RESULTS Histological findings were: (1) group A (positive genetics): 21 Marsh I, 2 Marsh IIIA, 12 normal; (2) group B (negative genetics): 16 Marsh I, 4 normal. Final diagnosis of anaemia in patients with enteropathy were: group A, gluten-sensitive enteropathy, 45%; H. pylori infection, 20%; gluten-sensitive enteropathy plus H. pylori, 10%; other, 10%; unknown, 15%; group B, gluten-sensitive enteropathy, 10%; H. pylori infection, 0% (1 non-eradicated case, 10%); non-steroidal anti-inflammatory drug intake, 20%; other, 20%; unknown, 40% (p=0.033). CONCLUSIONS Mild enteropathy is frequent in patients with unexplained iron-deficiency anaemia and negative coeliac serology. Most cases are secondary to either gluten-sensitive enteropathy or H. pylori infection, or both; however, there is also a substantial number of patients without a definitive diagnosis.

Prevalence and clinical relevance of enteropathy associated with systemic autoimmune diseases

OBJECTIVE To assess whether systemic autoimmune diseases are a risk group for coeliac disease and if there is a systemic autoimmune diseases-associated enteropathy. METHODS 183 patients with systemic autoimmune diseases were included. Duodenal biopsy was carried out on patients with positive coeliac genetics (HLA-DQ2-DQ8) and/or serology and/or symptoms of the coeliac disease spectrum. When enteropathy was found, causes, including gluten sensitivity, were investigated and categorized according to a sequentially applied treatment. Results were analysed with Chi-square or Fisher exact tests. RESULTS The prevalence of coeliac disease with atrophy was 0.55% (1 of 183 patients). Thirty-eight of the 109 patients (34.8%) who underwent duodenal biopsy had lymphocytic enteropathy (8 infectious, 5 due to gluten sensitive enteropathy, 5 HLA-DQ2/DQ8 who did not accept gluten-free diet and 20 of unknown aetiology). Lymphocytic enteropathy was unrelated to disease activity or immunosuppressants. HLA-DQ2 was more frequent in connective tissue disease (41.5%) compared with systemic vasculitis and autoinflammatory diseases (17.9%) (p=0.02), whereas a lower percentage of lymphocytic enteropathy was observed in the former (20.2% vs. 41.6%). Lymphocytic enteropathy was clinically irrelevant in cases with no definite aetiology. DISCUSSION One third of systemic autoimmune diseases patients had enteropathy of uncertain clinical meaning in the majority of cases, which was rarely due to gluten sensitive enteropathy.

Palliative care and prognosis in COPD: a systematic review with a validation cohort

Current recommendations to consider initiation of palliative care (PC) in COPD patients are often based on an expected poor prognosis. However, this approach is not evidence-based, and which and when COPD patients should start PC is controversial. We aimed to assess whether current suggested recommendations for initiating PC were sufficiently reliable. We identified prognostic variables proposed in the literature for initiating PC; then, we ascertained their relationship with 1-year mortality, and finally, we validated their utility in our cohort of 697 patients hospitalized for COPD exacerbation. From 24 articles of 499 screened, we selected 20 variables and retrieved 48 original articles in which we were able to calculate the relationship between each of them and 1-year mortality. The number of studies where 1-year mortality was detailed for these variables ranged from 9 for previous hospitalizations or FEV1 ≤30% to none for albumin ≤25 mg/dL. The percentage of 1-year mortality in the literature for these variables ranged from 5% to 60%. In the validation cohort study, the prevalence of these proposed variables ranged from 8% to 64%; only 10 of the 18 variables analyzed in our cohort reached statistical significance with Cox regression analysis, and none overcame an area under the curve ≥0.7. We conclude that none of the suggested criteria for initiating PC based on an expected poor vital prognosis in COPD patients in the short or medium term offers sufficient reliability, and consequently, they should be avoided as exclusive criteria for considering PC or at least critically appraised.

Case-finding in primary care for coeliac disease: Accuracy and cost-effectiveness of a rapid point-of-care test:

Background An on-site, rapid, fingertip, whole-blood point-of-care test (POCT) is attractive for active case-finding of coeliac disease (CD) in primary care because of its simplicity. Aim The aim of this article is to assess the usefulness and cost-effectiveness of adult case-finding using a POCT based on deamidated gliadin peptide antibodies (IgA/IgG-DGP) in primary care for CD diagnosis. Methods A case-finding study for CD was conducted by using an easy-to-use, on-site, whole-blood for IgA/IgG-DGP-based fingertip POCT compared with tTG2 in 350 individuals. Sample size was calculated based on 0.28% prevalence in the reference population. Duodenal biopsies for histology, intraepithelial lymphocytes and in situ deposition of tTG2 were obtained if tTG2 and/or POCT were positive. Accuracy and cost-effectiveness of strategies using serology or POCT were calculated. Results Prevalence of CD was 1.14% (95% CI, 0.3–3.4), almost double what was previously observed. Four patients were diagnosed with CD. tTG2 was positive in three (0.85%) and POCT in 29 (8.2%). Sensitivity of POCT for CD was 100%, specificity 93%, PPV 14%, and NPV 100%. POCT followed by duodenal biopsy was the most cost-effective approach in our setting (standard diagnosis: €13,033/case; POCT + duodenal biopsy: €7360/case). Conclusions A negative POCT allows ruling out CD in primary care, making it suitable for case-finding. POCT strategy was the most cost effective.