Horacio Vázquez

Body composition and bone mineral density in untreated and treated patients with celiac disease

Body composition and bone mineral density (BMD) were studied by X-ray absorptiometry in 20 untreated and 12 treated women with celiac disease, as well as in 85 age-matched control women. Untreated patients had a significantly lower body weight, fat mass, lean tissue mass and BMD at the lumbar spine and total skeleton compared to controls (p < 0.001 for all parameters). Treated patients had also a significantly lower body weight (p < 0.01) fat mass (p < 0.05) and bone mineral density at lumbar spine and total skeleton (p < 0.05) compared with controls, but lean tissue mass was not diminished. However, treated patients had a significantly higher body weight, fat mass and BMD of the total skeleton compared with untreated celiac patients (p < 0.01 for all parameters). Serum alkaline phosphatase levels were increased in untreated patients but serum 250HD was normal. In conclusion, celiac disease causes a global and almost universal reduction of fat mass and BMD. The results of this cross-sectional study suggest that osteopenia does not seem to be completely restored by adequate treatment. Alteration of vitamin D metabolism was not the cause of osteopenia in the majority of patients.

Low-Dose Aspirin Affects the Small Bowel Mucosa: Results of a Pilot Study With a Multidimensional Assessment

BACKGROUND & AIMS Whether low-dose aspirin (acetylsalicylic acid [ASA]) produces intestinal damage is controversial. Our aim was to determine whether the small bowel is damaged by low-dose ASA on a short-term basis. METHODS Twenty healthy volunteers (age range, 19-64 years) underwent video capsule endoscopy (VCE), fecal calprotectin, and permeability tests (sucrose and lactulose/mannitol [lac/man] ratio) before and after ingestion of 100 mg of enteric-coated ASA daily for 14 days. Video capsule images were assessed by 2 independent expert endoscopists, fully blinded to the treatment group, by using an endoscopic scale. RESULTS Post-ASA VCE detected 10 cases (50%) with mucosal damage not apparent in baseline studies (6 cases had petechiae, 3 had erosions, and 1 had bleeding stigmata in 2 ulcers). The median baseline lac/man ratio (0.021; range, 0.011-0.045) increased after ASA use (0.036; range, 0.007-0.258; P = .08), and the post-ASA lac/man ratio was above the upper end of normal (>0.025) in 10 of 20 volunteers (vs baseline, P < .02). The median baseline fecal calprotectin concentration (6.05 microg/g; range, 1.9-79.2) also increased significantly after ASA use (23.9 microg/g; range, 3.1-75.3; P < .0005), with 3 patients having values above the cutoff (>50 microg/g). Five of 10 subjects with abnormal findings at VCE also had lac/man ratios above the cutoff. Median baseline sucrose urinary excretion (70.0 mg; range, 11.8-151.3) increased significantly after ASA administration (107.0 mg; range, 22.9-411.3; P < .05). CONCLUSIONS The short-term administration of low-dose ASA is associated with mucosal abnormalities of the small bowel mucosa, which might have implications in clinical practice.

Gynaecological and obstetric disorders in coeliac disease: frequent clinical onset during pregnancy or the puerperium.

Background and aim While gynaecological and obstetric disorders have been reported among women with coeliac sprue, their true prevalence and relationship to the coeliac disease process has not been completely elucidated. Our aims were to determine: (1) the prevalence of gynaecological and obstetric problems in patients with coeliac disease and the influence of strict gluten restriction on their occurrence, (2) the effect of pregnancy on the clinical course of coeliac disease and (3) the clinical features of those patients with onset of coeliac disease during pregnancy and the puerperium. Patients and methods The gynaecological and obstetric history of 130 coeliac patients and 130 age-matched healthy female controls were compared in a case-control study. Results In comparison to the controls, untreated coeliac disease patients exhibited significantly later menarche, an earlier menopause, an increased prevalence of secondary amenorrhoea and a greater incidence of spontaneous abortions. Patients who had adhered, in the long term, to a gluten-free diet had gynaecological and obstetric history indistinguishable from controls. Clinical deterioration of coeliac disease was observed in untreated patients during 17% of their pregnancies. In 14% of those untreated patients who were pregnant symptoms related to coeliac disease were manifested for the first time during either pregnancy (n = 7) or the puerperium (n = 4). Nine of these patients had underestimated features suggestive of coeliac disease. Conclusion The early diagnosis and treatment of coeliac disease may avoid significant gynaecological and obstetric complications in affected women. Celiac sprue must always be borne in mind among patients who develop diarrhoea and weight loss during pregnancy and/or the puerperium.

Long-term deterioration of quality of life in adult patients with celiac disease is associated with treatment noncompliance

BACKGROUND Deterioration of quality of life in the long term has been suggested for celiac disease patients on a gluten-free diet. AIMS To determine long-term quality of life of celiac disease patients and to assess the benefits of gluten-free diet compliance. PATIENTS We prospectively evaluated 53 newly diagnosed adult celiac disease patients. METHODS The Short Form 36 Health Survey, the Gastrointestinal Symptoms Rating Scale and the Beck Depression Inventory were employed at the time of diagnosis, 1 year, and beyond 4 years (median: 53 months) on treatment. RESULTS At 1 year, a significant improvement from baseline in quality of life indicators was observed (p<0.001 to p<0.0001) with comparable scores to healthy subjects. At 4 years, the Short Form 36 Health Survey scores (p<0.002 to p<0.0002) and Beck Depression Inventory score (p<0.002) show significant deterioration compare with 1 year. Most scores remained significantly better than those at diagnosis (p<0.03 to p<0.0005). No changes were detected in the Gastrointestinal Symptoms Rating Scale scores. The long-term impairment of quality of life was attributable to the deterioration of most dimensions in patients who were not strictly compliant with the gluten-free diet (p<0.05 to p<0.001). CONCLUSIONS Long-term deterioration of quality of life outcomes after the first year of gluten-free diet was associated with the lack of strict compliance with the diet.

Permeability, zonulin production, and enteropathy in dermatitis herpetiformis

BACKGROUND & AIMS Dermatitis herpetiformis (DH) is characterized by variable degrees of enteropathy and increased intestinal permeability. Zonulin, a regulator of tight junctions, seems to play a key role in the altered intestinal permeability that characterizes the early phase of celiac disease. Our aim was to assess both intestinal permeability and serum zonulin levels in a group of patients with DH having variable grades of enteropathy. METHODS We studied 18 DH patients diagnosed on the basis of characteristic immunoglobulin (Ig)A granular deposits in the dermal papillae of noninvolved skin. Results were compared with those of classic celiac patients, patients with linear IgA dermatosis, and healthy controls. RESULTS According to Marshs classification, 5 patients had no evidence of enteropathy (type 0), 4 patients had type II, 2 patients had type IIIb damage, and 7 patients had a more severe lesion (type IIIc). Intestinal permeability (lactulose/mannitol ratio [lac/man]) was abnormal in all patients with DH. Patients with more severe enteropathy had significantly greater permeability ( P < .05). The serum zonulin concentration (enzyme-linked immunosorbent assay) for patients with DH was 2.1 +/- .3 ng/mg with 14 of 16 (87.5%) patients having abnormally increased values. In contrast, patients with linear IgA dermatosis had normal histology, normal intestinal permeability, and negative celiac serology. CONCLUSIONS Increased intestinal permeability and zonulin up-regulation are common and concomitant findings among patients with DH, likely involved in pathogenesis. Increased permeability can be observed even in patients with no evidence of histologic damage in biopsy specimens. Patients with linear IgA dermatosis appear to be a distinct population with no evidence of gluten sensitivity.

Successful treatment of retractile mesenteritis with oral progesterone

Retractile mesenteritis is a rare inflammatory mesenteric disorder that involves the intestine secondarily. The natural history of this process is diverse, but most patients require some empiric therapeutic measures. Up to now, pharmacological therapy has included corticosteroids, colchicine, and immunosuppressive drugs. Although these drugs are successful in most patients, some have been refractory to these therapies and, in others, the beneficial effects were counterbalanced by adverse reactions. Many patients require surgery, but most have poor results. This report describes a 42-year-old man with histologically proven retractile mesenteritis refractory to surgical intervention who had a good response to oral progesterone (10 mg/day for 6 months) with complete disappearance of tumor mass and clinical symptoms. No adverse effects were detected. Current knowledge about the mechanism by which progesterone affects fibrogenesis is scanty. It seems likely that progesterone down-regulates proliferation and metabolism of fibroblasts and fibrogenesis.

Exploratory, randomized, double-blind, placebo-controlled study on the effects of Bifidobacterium infantis natren life start strain super strain in active celiac disease.

Background/Aims: The aim of this exploratory trial was to establish if the probiotic Bifidobacterium natren life start (NLS) strain strain may affect the clinical course and pathophysiological features of patients with untreated celiac disease (CD). Positive findings would be helpful in directing future studies. Methods: Twenty-two adult patients having 2 positives CD-specific tests were enrolled. Patients were randomized to receive 2 capsules before meals for 3 weeks of either Bifidobacterium infantis natren life start strain super strain (Lifestart 2) (2×109 colony-forming units per capsule) (n=12) or placebo (n=10), whereas they also consumed at least 12 g of gluten/day. A biopsy at the end of the trial confirmed CD in all cases. The primary outcome was intestinal permeability changes. Secondary endpoints were changes in symptoms and the Gastrointestinal Symptom Rating Scale, and in immunologic indicators of inflammation. Results: The abnormal baseline intestinal permeability was not significantly affected by either treatment. In contrast to patients on placebo, those randomized to B. infantis experienced a significant improvement in Gastrointestinal Symptom Rating Scale (P=0.0035 for indigestion; P=0.0483 for constipation; P=0.0586 for reflux). Final/baseline IgA tTG and IgA DGP antibody concentration ratios were lower in the B. infantis arm (P=0.055 for IgA tTG and P=0.181 for IgA DGP). Final serum macrophage inflammatory protein-1&bgr; increased significantly (P<0.04) only in patients receiving B. infantis. The administration of B. infantis was safe. Conclusions: The study suggests that B. infantis may alleviate symptoms in untreated CD. The probiotic produced some immunologic changes but did not modify abnormal intestinal permeability. Further studies are necessary to confirm and/or expand these observations.

Azathioprine in refractory sprue: results from a prospective, open-label study

OBJECTIVE:Refractory sprue is a rare and severe malabsorptive disorder that mimics celiac disease but is refractory to a gluten-free diet and is without initial evidence of overt lymphoma. Treatment is largely empiric and often ineffective, with steroids and immunosuppression being the mainstream therapeutic options. The aim of this study was to evaluate prospectively the effect of azathioprine on a group of patients diagnosed with refractory sprue.METHODS:We studied seven consecutive patients (five women and two men) with a well-defined diagnosis of refractory sprue and a lack of response to oral or parenteral steroids. At diagnosis, five patients had endoscopic evidence of ulcerative jejunitis, and five underwent exploratory laparotomy for exclusion of malignancies. The characteristic monoclonal TCRγ gene rearrangement was shown in five of six patients studied. Patients were treated for a mean of 11 months (range 8–12 months), and clinical, biochemical, molecular, and histological parameters were reassessed at the end of the trial. The study was a prospective, open-label, non-placebo-controlled study using azathioprine (2 mg/kg/day) plus oral prednisone (1 mg/kg/day). A gluten-free diet (n = 7) as well as enteral (n = 6) and parenteral nutrition (n = 5) were administered during the trial.RESULTS:After treatment, five patients had a complete clinical remission, and biochemical and nutritional parameters were significantly improved. Steroids were tapered after the onset of azathioprine, and no patient was on steroids at the end of the trial. Intestinal histology improved significantly in all cases (normal histology in three cases and minor infiltration in the lamina propria in two). Two patients did not respond to treatment at any time and died in months 10 and 9, of an irreversible ventricular fibrillation and sepsis, respectively. No overt lymphoma was demonstrated during the follow-up.CONCLUSIONS:The present study confirms earlier anecdotal reports on the efficacy of azathioprine in refractory sprue, with clear clinical and histological improvement shown in most patients. However, monoclonality persisted after treatment. We consider that a larger number of patients should be evaluated before a definitive recommendation is adopted for use of this drug in refractory sprue.

Value of a screening algorithm for celiac disease using tissue transglutaminase antibodies as first level in a population-based study.

OBJECTIVE:Serological screening for celiac disease (CD) can detect a large number of otherwise undiagnosed patients based on the sequential evaluation of serological tests and intestinal biopsy. The aim of this study was to compare the screening value for CD of two different protocols for the same community-based population.METHODS:We screened 1000 consecutive subjects (497 women, age range 16–71 yr) attending a centralized laboratory for obligatory prenuptial blood tests. Serum samples obtained from all subjects were processed using two different protocols: 1) a three-level classic screening consisting of the parallel use of IgG and IgA antigliadin antibodies as first level, followed by endomysial antibodies and total serum IgA for positive patients, and finally, intestinal biopsy of positive patients; and 2) a study screening protocol consisting of the parallel use of a commercial guinea pig antitissue transglutaminase antibody and total serum IgA as first line, endomysial antibodies (type IgA and/or IgG) for positive patients, and finally, intestinal biopsy.RESULTS:The classic screening protocol identified five subjects who were eligible for intestinal biopsy, which confirmed the presence of CD in all (prevalence 5.0 × 1000, 95% CI = 1.6–11.6). Using the study algorithm, we detected seven new patients including the five patients detected by the first protocol (prevalence 7.0 × 1000, 95% CI = 2.8–14.4). The two additional patients diagnosed using the proposed algorithm had positive IgG antigliadin antibodies and normal total serum IgA and were not detected by the classic protocol. Both patients were endomysial antibodies positive. The comparative analysis showed that the classic approach was more expensive (U.S.

New Serology Assays Can Detect Gluten Sensitivity among Enteropathy Patients Seronegative for Anti–Tissue Transglutaminase

4687 per new patient detected) compared with the proposed study algorithm (U.S.