Less, but not gone-gluten-free diet effects on fatigue in celiac disease: a prospective controlled study.

Introduction: Fatigue is a frequent complaint in patients with celiac disease. A gluten-free diet is the only established treatment for celiac disease, but how this diet influences fatigue is uncertain. We aimed to investigate fatigue prevalence, severity, and associated factors in patients with celiac disease, at diagnosis and at 1 year after commencing a gluten-free diet. Methods: 78 patients with serologically and histologically verified celiac disease, 78 age- and sex-matched healthy subjects. Primary endpoints were Fatigue Visual Analog Scale (fVAS), Fatigue Severity Scale (FSS), and inverted Vitality subscale of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36vs). Clinically relevant fatigue was defined as: FSS score ≥ 4, fVAS score ≥ 50 mm, or inverted SF-36vs score ≥ 65. Higher scores represented more fatigue. Results: Fatigue was reduced after a 12-month gluten-free diet. Median scores changed from 3.8 (interquartile range [IQR]: 2.2 to 4.8) to 1.9 (IQR: 1.4 to 3.5) for FSS, from 44.5 (IQR: 18.8 to 66.0) to 15.5 (IQR: 7.8 to 43.3) for fVAS, and from 65 (IQR: 40 to 75) to 35 (IQR: 25 to 55) for inverted SF-36vs (p < 0.001 for all). Fatigue prevalence also declined after treatment. However, scores were significantly higher in patients compared to control subjects. Higher fatigue scores were associated with depression and pain, but not with signs of disease activity or nutritional deficiency. Conclusion: At diagnosis, patients with celiac disease frequently had severe fatigue. Fatigue declined after a gluten-free diet, but it remained higher than that observed in healthy subjects. Clinical trial registration: ClinicalTrials.gov, Identifier NCT01551563.

Fatigue: a frequent and biologically based phenomenon in newly diagnosed celiac disease.

Fatigue is increasingly recognized as a major complaint in patients with chronic inflammatory and autoimmune diseases. Although fatigue is assumed to represent a significant problem in celiac disease, existing knowledge is scarce, and opinions are conflicting. This study aimed to investigate the prevalence and severity of fatigue in patients with newly diagnosed celiac disease and compare it with healthy control subjects. Ninety patients with newly diagnosed celiac disease were compared with 90 age- and sex-matched healthy subjects. The primary endpoints were fatigue severity as measured by: the fatigue Visual Analog Scale (fVAS), the Fatigue Severity Scale (FSS), and the inverted Vitality subscale of the MOS36 (SF-36vs). Higher scores indicate more severe fatigue. Clinically relevant fatigue was determined using predefined cut-off values. Secondary endpoints were the associations between fatigue, and sex, age, depression, pain, and selected biochemical variables. The median (IQR) fVAS-scores were 43.0 (18.0-64.5) in patients, and 9.0 (2.0-16.0) in the control group (p < 0.001); and the FSS scores 3.8 (2.0-4.8) in patients, and 1.4 (1.0-1.9) in control subjects (p < 0.001). Inverted SF-36vs scores had a mean (SD) value of 58.8 (23.6) in patients, and 29.7 (14.3) in healthy subjects (p < 0.001). The presence of clinically relevant fatigue ranged from 41 to 50% in patients. Increased fatigue severity was associated with female sex, younger age, and elevated pain and depression scores, but not with levels of selected biochemical variables, including hemoglobin. Fatigue is a severe and frequent phenomenon in patients with untreated celiac disease.

Subtherapeutic concentrations of infliximab and adalimumab are associated with increased disease activity in Crohn's disease.

BACKGROUND: Low anti-tumor necrosis factor α (TNFα) serum concentrations may result in lack of treatment response in patients with inflammatory bowel disease. We determined the anti-TNFα drug concentrations in patients with inflammatory bowel disease and investigated whether or not subtherapeutic drug concentrations were associated with increased levels of disease activity. METHODS: In a single-center cross-sectional study, we included patients with ulcerative colitis or Crohn's disease who were receiving infliximab or adalimumab maintenance therapy. Demographic data, disease activity symptom scores (Partial Mayo Score, Harvey Bradshaw Index), inflammatory markers [C-reactive protein (CRP), fecal calprotectin], antidrug antibodies and serum drug concentrations were recorded. Therapeutic drug concentrations were defined as 3-8 mg/liter for infliximab and 5-12 mg/liter for adalimumab. RESULTS: Of 210 patients included, 137 (65.2%) had Crohn's disease. In the adalimumab group, subtherapeutic drug concentrations were measured in 16.7% of patients with ulcerative colitis and in 27.7% of patients with Crohn's disease. In the infliximab group, subtherapeutic drug concentrations were found in 23% (ulcerative colitis) and 30.3% (Crohn's disease) of patients. In Crohn's disease, subtherapeutic adalimumab concentrations were associated with higher fecal calprotectin and CRP concentrations compared with therapeutic concentrations. Subtherapeutic infliximab concentrations in patients with Crohn's disease were also associated with higher CRP concentrations compared with therapeutic concentrations. CONCLUSIONS: The prevalence of subtherapeutic drug levels ranged from 17% to 30%. In patients with Crohn's disease, subtherapeutic serum drug concentrations were associated with significantly higher disease activity with both anti-TNFα agents. These findings were not observed in patients with ulcerative colitis. Clinicaltrials.gov identifier [NCT02134054].

Follow-up of coeliac disease with the novel one-hour 13C-sorbitol breath test versus the H2-sorbitol breath test.

BACKGROUND: We recently developed a (13)C-sorbitol breath test ((13)C-SBT) as an alternative to the H(2)-sorbitol breath test (H(2)-SBT) for coeliac disease. In this study we compared the diagnostic properties of the H(2)-SBT and the (13)C-SBT in follow-up of coeliac disease. MATERIAL AND METHODS: Twenty-seven coeliac patients on a gluten-free diet (GFD) performed the breath tests. All had been tested before treatment in the initial study of the (13)C-SBT, in which 39 untreated coeliac patients, 40 patient controls, and 26 healthy volunteers participated. Five gram sorbitol and 100 mg (13)C-sorbitol were dissolved in 250 ml tap water and given orally. H(2), CH(4) and (13)CO(2) were measured in end-expiratory breath samples every 30 min for 4 h. Increased H(2) concentration ≥20 ppm from basal values was used as cut-off for the H(2)-SBT. Sixty minutes values were used as diagnostic index in the (13)C-SBT. RESULTS: (13)CO(2) levels at 60 min increased in 20/26 treated coeliac patients (77%) after GFD, but were significantly lower than in control groups. Out of 20 patients who had a positive H(2)-SBT before GFD, 12 had a negative H(2)-SBT after GFD. Peak H(2) concentrations were not correlated with (13)C-SBT results. CONCLUSION: The study confirms the sensitivity of a one-hour (13)C-SBT for small intestinal malabsorption. The (13)C-SBT has superior diagnostic properties compared with the H(2)-SBT in follow-up of coeliac disease.

A novel one-hour 13C-sorbitol breath test versus the H2-sorbitol breath test for assessment of coeliac disease.

OBJECTIVE: The H(2)-sorbitol breath test (H(2)-SBT) has previously been suggested as a screening tool for coeliac disease. We developed an alternative (13)C-sorbitol breath test ((13)C-SBT). The aim of the study was to compare the diagnostic properties of the H(2)-SBT and the (13)C-SBT in a clinical setting. MATERIAL AND METHODS: Thirty-nine coeliac patients, 40 patient controls (mainly patients with irritable bowel syndrome) and 26 healthy volunteers underwent the breath tests. The patients were given an oral load of 5 g sorbitol and 100 mg (13)C-sorbitol dissolved in 250 ml tap-water. H(2), CH(4) and (13)CO(2) concentrations were measured in end-expiratory breath samples every 30 min for 4 h. Increased H(2) concentration > or =20 ppm from basal values was used as the cut-off for the H(2)-SBT. RESULTS: The H(2)-SBT had a sensitivity of 71%, a specificity of 46% versus healthy controls, and a specificity of 25% versus patient controls. Individuals with methane-producing intestinal flora had significantly lower peak H(2) concentrations than non-methane producers. The (13)C-SBT reached maximal combined sensitivity/specificity (74%/85%) for both control groups after 1 h. A diagnostic algorithm which stratified patients into high-, moderate- and low risk for coeliac disease was proposed. Following the algorithm, 62% of coeliac patients were detected with 100% specificity. The (13)C-SBT, but not the H(2)-SBT, correlated with age and serum IgA tissue-transglutaminase antibody levels in coeliac patients. CONCLUSIONS: The novel (13)C-SBT has superior diagnostic properties compared to the H(2)-SBT, which has unsatisfactory specificity in clinical practice. The 1-h (13)C-SBT may be a useful supplemental test when investigating for coeliac disease.