The risk of renal comorbidities in celiac disease patients depends on the phenotype of celiac disease.

BACKGROUND: An increased risk of kidney disease in patients with celiac disease has been reported, but the association has remained obscure. Only few studies have investigated the association between renal comorbidities and dermatitis herpetiformis, a cutaneous manifestation of celiac disease. OBJECTIVES: We investigated whether patients with different phenotypes of celiac disease are at higher risk of kidney diseases than age- and sex-matched references. METHODS: The diagnoses of glomerulonephritis, diabetic nephropathy, interstitial nephritis, and end-stage renal disease obtained from the National Hospital Discharge Register between 1970 and 2015 were identified in celiac disease (Marsh III, n = 1072) and dermatitis herpetiformis (n = 368) patients diagnosed at Tampere University Hospital catchment region and in 4296 reference subjects. Using the Cox proportional hazards model, we compared the risk of kidney diseases between patients and references. The study protocol was approved by the Regional Ethics Committee of Tampere University Hospital (R16090). As the study was register based, no consent from patients was required. RESULTS: Even after adjusting for type 1 diabetes, celiac disease was associated with an elevated risk of kidney disease (hazard ratio [HR] 1.85, 95% confidence interval [CI] 1.12-3.03), glomerulonephritis (HR 3.37, 95% CI 1.64-6.95), and IgA nephropathy (IgAN) (HR 18.98, 95% CI 2.29-157.63). No similarly elevated risk was found among dermatitis herpetiformis patients (HR 1.50, 95% CI 0.63-3.55; HR 2.21, 95% CI 0.77-6.38; and HR 5.87, 95% CI 0.53-64.79, respectively). CONCLUSION: Celiac disease patients were at increased risk of kidney diseases, notably IgAN. The risk was dependent on the celiac disease phenotype and was not seen in patients with dermatitis herpetiformis. Awareness of possible renal manifestations is recommended when treating celiac disease patients.

Long-term outcome of patients with acute ulcerative colitis after first course of intravenous corticosteroids.

BACKGROUND AND AIMS: Every fifth patient with ulcerative colitis (UC) experiences severe acute flare at some point in the course of the disease. Corticosteroids (Cs) remain the treatment of choice in acute flare. Data on the efficacy of first intravenous Cs in the long-term prognosis of UC are scarce and were investigated here. MATERIALS AND METHODS: All episodes of patients with acute UC admitted to Tampere University Hospital and treated with intravenous Cs between January 2007 and January 2016 were identified from patient records and reviewed. The risks for colectomy and for continuous use of Cs were evaluated. Predictive factors were analysed. RESULTS: The study comprised 217 patients of whom 184 (85%) responded to intravenous Cs at index flare. Of the 33 non-responders, 31 (94%) were treated with intravenous cyclosporine A and 28 responded. Five (2.3%) patients needed emergency colectomy. Twenty-six (12%) patients underwent colectomy within 1 year of index flare. Overall colectomy rate was 56 (26%) during follow-up (median 7.5 years, range 0.1-10.5). Six months after index flare 66 (30%) patients were still on steroids. In this series 149 (69%) required further Cstherapy and 104 (48%) needed rehospitalization for new flare at some point during follow-up. Overall 155 patients were treated with thiopurines, of whom 72% within the first year after admission. A total of 36 patients had infliximab as a first-line biological treatment, nine needed second-line therapy with adalimumab or vedolizumab after infliximab failed. CONCLUSION: Although intravenous Cs were efficient in inducing clinical response in patients with severe acute UC, only one fifth maintained remission in the long term. Two-thirds of patients required further Cs and the overall colectomy rate remained at 26%. High relapse rate indicates the need for closer monitoring of these patients. Enhancement of maintenance therapy should be considered at early stage after acute flare.

Persistent Skin Symptoms after Diagnosis and on a Long-term Gluten-free Diet in Dermatitis Herpetiformis.

Dermatitis herpetiformis is a cutaneous manifestation of coeliac disease treated with a gluten-free diet. However, the itching and blistering rash alleviates slowly after gluten withdrawal and occasionally persists despite a long-term gluten-free diet. This study investigated the prevalence and factors associated with prolonged (i.e. >2 years) and ongoing skin symptoms in 237 patients with dermatitis herpetiformis. Data were gathered from medical records and via questionnaires. Among patients with dermatitis herpetiformis, 38% had prolonged symptoms after diagnosis, and 14% had ongoing skin symptoms at follow-up (median duration of gluten-free diet 24 years). A severe rash at diagnosis was associated with both prolonged and ongoing cutaneous symptoms. In addition, patients with dermatitis herpetiformis with ongoing skin symptoms at follow-up had been on the dietary treatment for a shorter time (median duration 16 vs 25 years) and were less often on a strict diet (53% vs 78%) compared with patients with dermatitis herpetiformis without ongoing skin symptoms.

Overall and Cause-Specific Mortality in Adult Celiac Disease and Dermatitis Herpetiformis Diagnosed in the 21st Century.

INTRODUCTION: We assessed whether celiac disease-associated mortality is increased in Finland among patients diagnosed in the 21st century, given recent improvements in diagnostic and treatment facilities. METHODS: Biopsy-proven patients with celiac disease (Marsh III) and dermatitis herpetiformis aged 20-79 years (median 50 years) diagnosed 2005-2014 (n = 12,803) were identified from the national dietary grant registry. Dates and causes of death were obtained from Statistics Finland. Overall mortality and causes of death were compared with reference individuals (n = 38,384) matched for age, sex, and area of residence (at the time of celiac disease diagnosis) selected from the Population Information System. RESULTS: During a mean follow-up of 7.7 years (SD ±3.0 years), 884 (6.9%) and 2,613 (6.8%) deaths occurred among the celiac cohort and reference group, respectively. Overall mortality (hazard ratio [HR] 1.01, 95% confidence intervals [CIs] 0.94-1.09), mortality from all malignancies (HR 1.11, 95% CI 0.96-1.27), gastrointestinal tract malignancies (HR 1.21, 95% CI 0.56-1.71), or cardiovascular diseases (HR 0.91, 95% CI 0.77-1.07) were not increased among patients with celiac disease. Overall, mortality from lymphoproliferative diseases (HR 2.36, 95% CI 1.65-3.39) and nonmalignant digestive diseases (HR 2.19, 95% CI 1.40-3.43) was increased, but HRs decreased after the exclusion of the first 2 years of follow-up (HR 1.71, 95% CI 1.10-2.66 and HR 1.75, 95% CI 1.01-3.05, respectively). DISCUSSION: The overall mortality in adult celiac disease diagnosed 2005-2014 was not increased. Mortality from lymphoproliferative diseases was increased but lower than previously reported.

Pouch failures following restorative proctocolectomy in ulcerative colitis.

PURPOSE: Restorative proctocolectomy (RPC) is the most common operation in ulcerative colitis. Nevertheless, permanent ileostomy will sometimes be unavoidable. The aim was to evaluate the reasons for pouch failure and early morbidity after pouch excision. METHODS: The number and the reasons for pouch failures were analysed in patients undergoing RPC 1985-2016. RESULTS: Out of 491 RPC patients, 53 experienced pouch failure (10 women, 43 men); 52 out of 53 underwent pouch excision. The cumulative risk for excision at 5, 10 and 20 years was 5.6, 9.4 and 15.5%, respectively. The reasons for failure included septic events such as fistula in 12 (23%), chronic pouchitis in 11 (21%) and leakage in 8 (15%) patients. Functional reasons for pouch failure were recorded as poor function in 16 (30%), incontinence in 12 (23%) and stricture in 12 (23%) patients. Multiple causes for pouch failure were recorded for individual patients. Seven cases of Crohn's disease were found among the failure cases: two before pouch excision and five after. Altogether, 15 Crohn's disease diagnoses were set in the RPC cohort, giving a percentage of 47% of pouch failure in this disorder. A complication occurred in 23 (44%) patients within 30 days after surgery; 16 were mild (Clavien-Dindo grades I-II). CONCLUSIONS: Eleven percent of RPC patients suffered pouch failure: more men than women. The reasons were multiple. Crohn's disease created a risk of failure, but a half of these patients maintained the pouch. Morbidity after pouch excision was moderate, but in most cases slight.

Natural disease course of Crohn's disease during the first 5 years after diagnosis in a European population-based inception cohort: an Epi-IBD study.

OBJECTIVE: The Epi-IBD cohort is a prospective population-based inception cohort of unselected patients with inflammatory bowel disease from 29 European centres covering a background population of almost 10 million people. The aim of this study was to assess the 5-year outcome and disease course of patients with Crohn's disease (CD). DESIGN: Patients were followed up prospectively from the time of diagnosis, including collection of their clinical data, demographics, disease activity, medical therapy, surgery, cancers and deaths. Associations between outcomes and multiple covariates were analysed by Cox regression analysis. RESULTS: In total, 488 patients were included in the study. During follow-up, 107 (22%) patients received surgery, while 176 (36%) patients were hospitalised because of CD. A total of 49 (14%) patients diagnosed with non-stricturing, non-penetrating disease progressed to either stricturing and/or penetrating disease. These rates did not differ between patients from Western and Eastern Europe. However, significant geographic differences were noted regarding treatment: more patients in Western Europe received biological therapy (33%) and immunomodulators (66%) than did those in Eastern Europe (14% and 54%, respectively, P<0.01), while more Eastern European patients received 5-aminosalicylates (90% vs 56%, P<0.05). Treatment with immunomodulators reduced the risk of surgery (HR: 0.4, 95% CI 0.2 to 0.6) and hospitalisation (HR: 0.3, 95% CI 0.2 to 0.5). CONCLUSION: Despite patients being treated early and frequently with immunomodulators and biological therapy in Western Europe, 5-year outcomes including surgery and phenotype progression in this cohort were comparable across Western and Eastern Europe. Differences in treatment strategies between Western and Eastern European centres did not affect the disease course. Treatment with immunomodulators reduced the risk of surgery and hospitalisation.

Risk of fractures in dermatitis herpetiformis and coeliac disease: a register-based study.

Objectives: Dermatitis herpetiformis (DH) is a cutaneous manifestation of coeliac disease. Bone fracture risk is increased in coeliac disease, but little knowledge exists about bone complications in DH. This study aimed to evaluate the risk of hip and other hospital-treated fractures in DH and coeliac disease in a high prevalence area with good adherence to a gluten-free diet. Materials and methods: Hip, proximal humerus, wrist and ankle fractures in 368 treated DH and 1076 coeliac disease patients between 1970 and 2015 were reviewed from the National Hospital Discharge Register. Hip fracture incidence rates for DH and coeliac disease patients were compared to those for the general population. The overall fracture risk for DH was compared to coeliac disease. Results: The hip fracture incidence rates for DH and coeliac disease patients did not differ from the general population. In females aged 80-89, the hip fracture incidence was higher in DH than in coeliac disease, but the risk for any hospital-treated fracture was lower in DH compared to coeliac disease (adjusted HR 0.620, 95% CI 0.429-0.949). The DH and coeliac disease patients with hospital-treated fractures were diagnosed at an older age, but the degree of small bowel mucosal damage did not significantly differ between patients with and without fractures. Conclusion: The incidence of hip fracture is not increased in treated DH or coeliac disease in an area with high awareness and dietary compliance rates. However, patients with DH seem to have a lower risk for fractures overall compared to coeliac disease.

Disease course of inflammatory bowel disease unclassified in a European population-based inception cohort: An Epi-IBD study.

BACKGROUND AND AIM: A definitive diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) is not always possible, and a proportion of patients will be diagnosed as inflammatory bowel disease unclassified (IBDU). The aim of the study was to investigate the prognosis of patients initially diagnosed with IBDU and the disease course during the following 5 years. METHODS: The Epi-IBD study is a prospective population-based cohort of 1289 IBD patients diagnosed in centers across Europe. Clinical data were captured prospectively throughout the follow-up period. RESULTS: Overall, 476 (37%) patients were initially diagnosed with CD, 701 (54%) with UC, and 112 (9%) with IBDU. During follow-up, 28 (25%) IBDU patients were changed diagnoses to either UC (n = 20, 71%) or CD (n = 8, 29%) after a median of 6 months (interquartile range: 4-12), while 84 (7% of the total cohort) remained IBDU. A total of 17 (15%) IBDU patients were hospitalized for their IBD during follow-up, while 8 (7%) patients underwent surgery. Most surgeries (n = 6, 75%) were performed on patients whose diagnosis was later changed to UC; three of these colectomies led to a definitive diagnosis of UC. Most patients (n = 107, 96%) received 5-aminosalicylic acid, while 11 (10%) patients received biologicals, of whom five remained classified as IBDU. CONCLUSIONS: In a population-based inception cohort, 7% of IBD patients were not given a definitive diagnosis of IBD after 5 years of follow-up. One in four patients with IBDU eventually was classified as CD or UC. Overall, the disease course and medication burden in IBDU patients were mild.

Long-term functional outcome after restorative proctocolectomy: a cross-sectional study.

OBJECTIVE: Restorative proctocolectomy is the procedure of choice in the surgical treatment of ulcerative colitis. Functional outcome is the key result of surgery. The aim of this study was to evaluate the long term-functional outcome after the procedure. MATERIAL AND METHODS: The study comprised 282 ulcerative colitis patients over 18 years of age who underwent restorative proctocolectomy between1985 and 2009. The median follow-up time was 13 years (range 4-28). Functional outcome of the pouch was evaluated by the disease-specific Öresland questionnaire with a score 0-15; 15 being the worst, and score <8 considered well-functioning. RESULTS: The mean functional score was 5.5 (men 5.6, women 5.0). Seventy per cent of the patients had a well-functioning pouch. Those with poor function had had significantly more pouchitis than the patients with well-functioning pouches, 51.0 vs. 25.6% respectively (p = .001). No association was found between functional score and the time since the operation. In multiple regression analysis only the occurrence of pouchitis was associated with poor functional results. CONCLUSIONS: The functional results were good and remained stable in the majority of the patients. Pouchitis seemed to have a negative impact on the functional results. Elderly patients especially need careful planning and counselling before restorative proctocolectomy.

Diagnostic Delay in Dermatitis Herpetiformis in a High-prevalence Area.

Dermatitis herpetiformis (DH) is an extra-intestinal manifestation of coeliac disease. The highest currently reported prevalence of DH is in Finland, but knowledge of diagnostic delay is limited. This study investigated the duration of rash prior to diagnosis in 446 patients with DH, analysing the results in 3 periods of 15 years. The diagnosis was considered delayed when the duration of rash before diagnosis was 2 years or longer. Factors associated with delayed diagnosis were analysed. Within the 45 years, the median duration of rash before diagnosis decreased significantly, from 12.0 to 8.0 months (p?=?0.002) and the occurrence of a delayed diagnosis decreased from 47% to 25% (p?=?0.002). Female sex, the presence of villous atrophy, and a diagnosis of DH before the year 2000 were significantly associated with delayed diagnosis. In conclusion, the present study showed that one-quarter of patients currently have a diagnostic delay of 2 years or more, which is far from ideal.

Clinical Characteristics and the Dietary Response in Celiac Disease Patients Presenting With or Without Anemia.

BACKGROUND AND AIMS: It remains unclear as to what are the clinical characteristics associated with the presence of anemia at celiac disease diagnosis, and how these are affected by a gluten-free diet. We investigated these issues in a prospective study. METHODS: Clinical and demographic data, small-bowel mucosal histology, serology, and laboratory parameters, body mass index (BMI), and bone mineral density (BMD) both at diagnosis and after 1 year on a gluten-free diet were investigated in 163 adults with celiac disease. Gastrointestinal symptoms and psychological well-being were evaluated by validated Gastrointestinal Symptom Rating Scale and Psychological General Well-Being questionnaires. All study variables were compared between participants with and without anemia at celiac disease diagnosis. RESULTS: Altogether, 23% of the patients had anemia at diagnosis. Anemic patients were more often women (P=0.001) and had more gastrointestinal symptoms (P=0.004) and were less often screen detected (P=0.009). Further, they had higher celiac antibody values (P=0.007) and a lower total iron (P<0.001), BMI (P=0.003), and density of mucosal γδ+ intraepithelial lymphocytes (P=0.033). After 1 year on a gluten-free diet, the anemia group had a lower mucosal villous height-crypt depth ratio (P=0.008) and BMI (P=0.050), and higher antibody values (P=0.012) and densities of CD3 (P=0.008) and αß+ intraepithelial lymphocytes (P=0.022). There was no significant difference between the groups in their bone mineral density, Gastrointestinal Symptom Rating Scale and Psychological General Well-Being. CONCLUSIONS: Celiac patients with anemia had more severe disease than nonanemic patients in terms of the serology and a lower BMI. Further, they evinced a slower histologic response to the dietary treatment. An early diagnosis and careful follow-up are important in these patients.

The Decreasing Prevalence of Severe Villous Atrophy in Dermatitis Herpetiformis: A 45-Year Experience in 393 Patients.

GOALS: We analyzed from our prospectively collected series of patients with dermatitis herpetiformis (DH) whether small-bowel histologic findings are changing and how serum tissue transglutaminase (TG2) IgA antibodies correlate to mucosal damage. BACKGROUND: DH is an extraintestinal manifestation of celiac disease presenting with itchy blistering rash and pathognomonic IgA deposits in the skin. Prominent gastrointestinal symptoms are rare, and small-bowel findings range from severe villous atrophy (SVA) and partial villous atrophy (PVA) to normal mucosa with inflammatory changes. METHODS: The cohort included 393 patients (214 male and 179 female) with DH having small-bowel biopsies performed at Tampere University Hospital since 1970. The small-bowel findings were calculated in the three 15-year periods, and in the last period they were correlated with serum IgA class TG2 antibody levels measured by enzyme-linked immunosorbent assay. RESULTS: The prevalence of SVA decreased significantly (P=0.032), from 42% in the first study period to 29% in the last study period. A concomitant increase was seen in PVA, from 33% to 41%, and normal villous architecture, from 25% to 30%. The patients with SVA (P<0.001) and PVA (P=0.046) had significantly higher TG2 antibody levels than those with normal villous architecture. CONCLUSIONS: This long-term study in patients with DH disclosed a significant decrease in the occurrence of SVA. Serum IgA TG2 antibody levels correlated to damage in the small bowel. The trend toward milder small-bowel histology in DH suggests that a similar pattern could occur in the pool of undiagnosed celiac disease from which DH develops.

Gastrointestinal Symptoms Increase the Burden of Illness in Dermatitis Herpetiformis: A Prospective Study.

Dermatitis herpetiformis (DH) is an extraintestinal manifestation of coeliac disease. The burden of illness in untreated coeliac disease is known to be considerable, but corresponding evidence for DH is lacking. In this study the burden of DH was evaluated prospectively in 52 patients newly diagnosed with DH using a study questionnaire and a validated Psychological General Well-Being (PGWB) questionnaire. The PGWB scores were compared with those of 110 healthy controls. Quality of life was significantly (p < 0.001) lower among patients with DH at the time of diagnosis, but after 1 year on a gluten-free diet their quality of life was at same level as that of the controls. The presence of gastrointestinal symptoms was shown to significantly increase the burden of untreated DH. We conclude that there is a significant burden related to untreated, but not to treated, DH, and the burden is even greater among DH patients with gastrointestinal symptoms.

Type 1 and type 2 diabetes in celiac disease: prevalence and effect on clinical and histological presentation.

BACKGROUND: Association between celiac disease and type 1 diabetes in adults is still somewhat unclear, and that between celiac disease and type 2 diabetes even less known. We studied these issues in a large cohort of adult celiac disease patients. METHODS: The prevalence of type 1 and type 2 diabetes in 1358 celiac patients was compared with the population-based values. Furthermore, patients with celiac disease and concomitant type 1 or type 2 diabetes and those with celiac disease only underwent comparisons of clinical and histological features and adherence to gluten-free diet. RESULTS: The prevalence of type 1 diabetes (men/women) was 8.0 % /1.8 % in celiac patients and 0.7 % /0.3 % in the population, and that of type 2 diabetes 4.3 % /2.5 % and 4.4 % /3.0 %, respectively. Celiac patients with concomitant type 1 diabetes were younger (45 years vs 65 years and 52 years, P < 0.001) and more often screen-detected (43 % vs 13 % and 14 %, P < 0.001), had less other gastrointestinal diseases (8 % vs 40 % and 25 %, P = 0.028), more thyroidal diseases (18 % vs 16 % and 13 %, P = 0.043) and lower dietary adherence (71 % vs 95 % and 96 %, P < 0.001) compared with celiac patients with concomitant type 2 diabetes and patients with celiac disease only. Patients with concomitant type 2 diabetes had more hypercholesterolemia than the other groups (8 % vs 6 % and 4 %, P = 0.024), and both diabetes groups more hypertension (47 % and 31 % vs 15 %, P < 0.001) and coronary artery disease (29 % and 18 % vs 3 %, P < 0.001) than the patients with celiac disease only. CONCLUSIONS: Type 1 diabetes was markedly overrepresented in celiac disease, especially in men, whereas the prevalence of type 2 diabetes was comparable with the population. Concomitant type 1 or type 2 diabetes predisposes celiac patients to severe co-morbidities and type 1 diabetes also to poor dietary adherence.

Dermatitis Herpetiformis Refractory to Gluten-free Dietary Treatment.

Dermatitis herpetiformis (DH) is a blistering skin disease, which is regarded as an extra-intestinal manifestation of coeliac disease. Refractory cases of coeliac disease, that do not respond to a gluten-free diet and which carry an increased risk of lymphoma, are well-known in coeliac disease. To determine whether refractory cases of DH with active rash and persistent small bowel atrophy occur we analysed our series of 403 patients with DH. Seven (1.7%) patients, who had been on a gluten-free diet for a mean of 16 years, but who still required dapsone to treat the symptoms of DH, were identified. Of these, one patient died from mucinous adenocarcinoma before re-examination. At re-examination skin immunoglobulin A (IgA) deposits were found in 5/6 refractory and 3/16 control DH patients with good dietary response. Small bowel mucosa was studied at re-examination from 5 refractory and 8 control DH patients and was normal in all 5 refractory and 7/8 control DH patients. One refractory DH patient died from adenocarcinoma, but no lymphoma developed in any of the patients. This study documents for the first time refractory DH, in which the rash is non-responsive to a gluten-free diet, but the small bowel mucosa heals. This differs from refractory coeliac disease, in which the small bowel mucosa does not heal on a gluten-free diet.

Antibody biomarker discovery through in vitro directed evolution of consensus recognition epitopes.

To enable discovery of serum antibodies indicative of disease and simultaneously develop reagents suitable for diagnosis, in vitro directed evolution was applied to identify consensus peptides recognized by patients' serum antibodies. Bacterial cell-displayed peptide libraries were quantitatively screened for binders to serum antibodies from patients with celiac disease (CD), using cell-sorting instrumentation to identify two distinct consensus epitope families specific to CD patients (PEQ and (E)/DxFV(Y)/FQ). Evolution of the (E)/DxFV(Y)/FQ consensus epitope identified a celiac-specific epitope, distinct from the two CD hallmark antigens tissue transglutaminase-2 and deamidated gliadin, exhibiting 71% sensitivity and 99% specificity (n = 231). Expansion of the first-generation PEQ consensus epitope via in vitro evolution yielded octapeptides QPEQAFPE and PFPEQxFP that identified ω- and γ-gliadins, and their deamidated forms, as immunodominant B-cell epitopes in wheat and related cereal proteins. The evolved octapeptides, but not first-generation peptides, discriminated one-way blinded CD and non-CD sera (n = 78) with exceptional accuracy, yielding 100% sensitivity and 98% specificity. Because this method, termed antibody diagnostics via evolution of peptides, does not require prior knowledge of pathobiology, it may be broadly useful for de novo discovery of antibody biomarkers and reagents for their detection.

Diagnosis for liver fibrosis - noninvasively.

Noninvasive tests are utilized in chronic liver diseases to assess excessive connective tissue. Blood tests such as the N-terminal peptide of procollagen (PIIINP) and APRI (ASAT/platelet count) measure the formation and degradation of connective tissue or liver function. Elastography (Fibroscan) is based on the propagation of ultrasound in liver tissue, accelerated by fibrosis: the results are more sensitive and accurate than those based on blood tests. Reliable detection of severe fibrosis and cirrhosis is possible with Fibroscan along with determining normal liver tissue.

Benefits of a gluten-free diet for asymptomatic patients with serologic markers of celiac disease.

BACKGROUND & AIMS: We investigated whether screen-detected and apparently asymptomatic adults with endomysial antibodies (EmA) benefit from a gluten-free diet (GFD). METHODS: We performed a prospective trial of 3031 individuals at risk for celiac disease based on screens for EmA. Of 148 seropositive individuals, 40 fulfilled inclusion criteria and were assigned randomly to groups placed on a GFD or gluten-containing diets. We evaluated ratios of small-bowel mucosal villous height:crypt depth, serology and laboratory test results, gastrointestinal symptom scores, physiologic well-being, perception of health by a visual analog scale, bone mineral density, and body composition at baseline and after 1 year. Thereafter, the group on the gluten-containing diet started a GFD and was evaluated a third time; subjects in the GFD group remained on this diet. RESULTS: After 1 year on the GFD, the mean mucosal villous height:crypt depth values increased (P < .001), levels of celiac-associated antibodies decreased (P < .003), and gastrointestinal symptoms improved to a greater extent than in patients on gluten-containing diets (P = .003). The GFD group also had reduced indigestion (P = .006), reflux (P = .05), and anxiety (P = .025), and better health, based on the visual analog scale (P = .017), than the gluten-containing diet group. Only social function scores improved more in the gluten-containing diet group than in the GFD group (P = .031). There were no differences between groups in laboratory test results, bone mineral density, or body composition. Most measured parameters improved when patients in the gluten-containing diet group were placed on GFDs. No subjects considered their experience to be negative and most expected to remain on GFDs. CONCLUSIONS: GFDs benefit asymptomatic EmA-positive patients. The results support active screening of patients at risk for celiac disease. Clinicaltrials.gov no: NCT01116505.

Predictors and Significance of Incomplete Mucosal Recovery in Celiac Disease After 1 Year on a Gluten-Free Diet.

OBJECTIVES: In celiac disease, a follow-up biopsy taken 1 year after diagnosis is considered important in monitoring histological recovery. In many cases, recovery is incomplete, and the clinical significance of this is poorly understood. We now investigated associated factors and the significance of imperfect histological recovery in patients in whom the follow-up had been completed. METHODS: Two hundred sixty-three biopsy-proven patients were divided into two groups: histological recovery and incomplete recovery after 1 year on gluten-free diet. Serology, laboratory values, bone mineral density, and different clinical variables were measured at diagnosis and after 1 year. Gastrointestinal symptoms and quality of life were assessed by validated questionnaires. Further, long-term follow-up data on mortality, malignancies, and other severe complications were collected. RESULTS: The incomplete recovery group had more severe mucosal damage (P=0.003), higher antibody values (P=0.017), and more signs of malabsorption (P<0.001) at diagnosis. There was no difference in gender, symptoms or quality of life, family history of celiac disease, or comorbidities. At follow-up, there was still a difference in antibodies (P=0.018) and femoral T-scores (P=0.024). Histologically recovered patients showed better dietary adherence, although it was excellent in both groups (97% vs. 87%, P<0.001). There was no difference in long-term outcomes between groups. CONCLUSIONS: The presence of more severe disease in terms of histology, serology, and signs of malabsorption was associated with histological non-response. In patients with high dietary adherence, incomplete villous recovery after 1 year does not affect the clinical response or long-term prognosis. A personalized approach is required to decide the optimal timing of the follow-up biopsy.