Pardeep Brar

Body mass index in celiac disease: beneficial effect of a gluten-free diet.

Background There is concern about celiac disease patients being overweight and gaining more weight while on a gluten-free diet (GFD). Aim To investigate body mass index (BMI) and effect of GFD on BMI of celiac disease patients in the United States where obesity is a systematic problem. Methods BMI at diagnosis and after 2.8 years (mean) on a GFD were compared with national data. Results Among our patients (n=369, 67.2% female), 17.3% were underweight, 60.7% normal, 15.2% overweight, and 6.8% obese. All patients were followed by a dietitian. Compared with national data, females had lower BMI (21.9 vs. 24.2, P<0.0001) and fewer were overweight (11% vs. 21%, P<0.0001); more males had a normal BMI (59.5% vs. 34%, P<0.0001) and fewer were underweight (9.1% vs. 26.7%, P<0.0001). Factors associated with low BMI were female sex, Marsh IIIb/c histology, and presentation with diarrhea. On GFD, 66% of those who were underweight gained weight, whereas 54% of overweight and 47% of obese patients lost weight. Conclusions A GFD had a beneficial impact on BMI, underweight patients gained weight and overweight/obese patients lost weight. The improvement in BMI adds to the impetus to diagnose celiac disease. Expert dietary counseling may be a major factor in the beneficial effects we noted.

Effect of gender on the manifestations of celiac disease: Evidence for greater malabsorption in men

Objective Because celiac disease is a female-predominant disease we investigated the influence of gender on clinical manifestations of the disease in the United States. Material and methods Data were obtained on biopsy-proven adult patients with celiac disease from a database of patients seen between 1981 and 2001 in a University-based referral center. Z scores were calculated to adjust for age, ethnicity and gender using the National Health and Nutrition Examination Survey database as controls. Results The cohort consisted of 323 patients (211 F, 112 M). Men had a shorter duration of symptoms than women (p=0.006). There was no gender difference in the age at diagnosis or mode of presentation. Body mass index (BMI), mean hemoglobin and ferritin values were lower in women than in men, but the Z scores for these values were not significantly different, indicating that the differences are physiological. All lipid values were low (negative Z scores). Men had lower total cholesterol (162.0±46.5mg/dl) compared to women (181.0±40.0mg/dl), p=0.02 and lower Z scores (−1.10±1.1) compared to women (−0.71±0.9), p=0.04. Men had lower bone density T scores at the radius (p=0.07). Autoimmune diseases were present in 30.7% with a female to male ratio of 1:1, compared to the general population in which 3.2% have autoimmune diseases with a female predominance. Conclusions Most gender differences in celiac disease are physiological. However, men have indirect evidence of greater malabsorption than females and have female-predominant associated diseases when they present with celiac disease.

Budesonide in the Treatment of Refractory Celiac Disease

OBJECTIVE:Corticosteroids are used in patients with refractory celiac disease. In order to minimize their systemic side effects, we assessed the role of a locally active sustained release corticosteroid with minimal systemic bioavailability in patients with refractory celiac disease in an open labeled noncontrolled study.METHODS:Patients who received budesonide for refractory celiac disease were classified according to whether they were primarily or secondarily unresponsive to the diet, and whether they had a polyclonal (type I) or clonal (type II) expansion of intraepithelial lymphocytes. The response to budesonide was assessed globally and by reduction in bowel movements.RESULTS:Patients (N = 29, 72% female) received budesonide for a mean of 6.7 ± 8.5 months, 5 patients (18%) had type II disease (clonal T-cell population); 76% responded to the medication, 55% completely. Response occurred when budesonide was used alone or with oral corticosteroids and/or azathioprine. There was an objective improvement in the number of bowel movements in those that responded. Response occurred in those with either primary or secondary refractory disease and in those with type II disease, irrespective of the presence of microscopic colitis (N = 7). There was no improvement in the duodenal biopsy over the study period and there were no side effects of budesonide.CONCLUSIONS:Budesonide may be of value in the management of refractory celiac disease.

The association between celiac disease, dental enamel defects, and aphthous ulcers in a United States cohort.

Goals and Background European studies have demonstrated that dental enamel defects and oral aphthae are observed in celiac disease (CD). We investigated this association in a US population. Study Biopsy proven CD patients and controls were recruited from a private dental practice and from CD support meetings. History of aphthae was taken and dental examination was performed by a single dentist. Teeth were photographed and enamel defects graded according to the Aine classification. A second dentist reviewed all photographs. Results Among patients (n=67, mean age 34.8±21.6 y) compared with controls (n=69, mean age 28.1±15.7 y), there were significantly more enamel defects [51% vs. 30%, P=0.016, odds ratio (OR) 2.4, 95% confidence interval (CI) 1.2-4.8]. This was confined to children (87% vs. 33%, P=0.003, OR 13.3, 95% CI 3.0-58.6), but not adults (32% vs. 29%, P=0.76, OR 1.2, 95% CI 0.5-2.8). This was reflected in defects being observed in those with mixed dentition compared with those with permanent dentition (68.4% vs. 29.6%, P<0.0001). The degree of agreement between the 2 dentists was good (κ coefficient=0.53, P<0.0001), aphthous ulcers were more frequent in CD than controls (42.4% vs. 23.2%, P=0.02). Conclusions This study supports that CD is highly associated with dental enamel defects in childhood, most likely because of the onset of CD during enamel formation; no such association was found in adults. Our study also supports the association between CD and aphthous ulcer. All physicians should examine the mouth, including the teeth, which may provide an opportunity to diagnose CD. In addition, CD should be added to the differential diagnosis of dental enamel defects and aphthous ulcers.

Celiac Disease in African-Americans

Celiac disease is generally under diagnosed in the United States and it is unclear whether the disease is encountered in ethnic minorities. Our purpose is to describe a case series of African-American patients with celiac disease. Nine (1.3%) African-American patients with celiac disease were identified from a prospectively generated database of 700 patients with biopsy proven celiac disease and seen between 1981 and 2004. Females predominated, with seven, compared to two males. Diarrhea was the presentation in only two patients, while three presented with iron deficiency anemia. One third had at least one autoimmune disease. Compliance with a gluten-free diet, the only medical therapy of this disease, was poor. Only four patients adhered strictly to the diet. Celiac disease occurs in African-Americans and may well be underdiagnosed. Special attention needs to be given to methods that encourage adherence to the diet in minority groups.

Immunohistochemical and T-cell receptor gene rearrangement analyses as predictors of morbidity and mortality in refractory celiac disease.

Background: Classification of refractory celiac disease (RCD) is based on the presence or absence of monoclonal expansions of intraepithelial lymphocytes (IELs) with an aberrant immunophenotype. Goals: To investigate the contribution of IEL parameters toward mortality and morbidity in RCD. Study: IEL phenotype by immunohistochemistry and T-cell receptor (TCR) gene rearrangement by polymerase chain reaction were assessed in 73 RCD patients (type I=67, type II=6). Detection of a monoclonal TCR gene rearrangement and presence of <50% CD3+ CD8+ IELs were considered abnormal. Time to worsening of clinical symptoms and predictors of worsening were calculated by Kaplan-Meier and Cox proportional hazard analyses. Results: Fewer than 50% CD3+ CD8+ IELs were detected in 30 patients and monoclonal TCR rearrangements in 6. Three patients died and 40 suffered clinical worsening despite treatment. Estimated 5-year survival rates decreased from 100% in patients with >50% CD3+ CD8+ IELs and polyclonal TCR to 88% and 50% in patients with <50% CD3+ CD8+ IELs and monoclonal TCR, respectively. Clinical worsening was more frequent (100%) among patients harboring a monoclonal TCR gene rearrangement with <50% CD3+ CD8+ IELs. These patients also showed shorter median time to clinical worsening (11 mo) when compared to patients with <50% CD3+ CD8+ IELs alone (21 mo), polyclonal TCR (38 mo), or >50% CD3+ CD8+ IELs alone (66 mo). After adjusting for age and gender, only the presence of <50% CD3+ CD8+ IELs was associated with increased risk for clinical worsening despite negative celiac serologies (hazard ratio=4.879; 95% confidence interval, 1.785-13.336; P=0.002). Conclusions: Presence of <50% CD3+ CD8+ IELs is a risk factor for clinical worsening in RCD and combined with a monoclonal TCR gene rearrangement result is associated with increased mortality. IEL phenotype and TCR gene rearrangement analyses provide differential information regarding morbidity and mortality in RCD.