Maternal celiac disease and the risk for long-term infectious morbidity of the offspring.

PROBLEM: Celiac disease is an autoimmune disease, patients with celiac have increased risk for infections, and offspring of celiac mothers have increased morbidity. The aim of the study was to assess long-term infectious morbidity among offspring of pregnant women with celiac disease. METHOD OF STUDY: A population-based cohort study was conducted, including all singleton deliveries between the years 1991-2014 at a tertiary medical center. The offsprings were subdivided into two groups: offsprings of mothers with and without celiac disease. Data on demographics, maternal, perinatal, and long-term hospitalizations for infectious morbidity were compared between the two groups. RESULTS: During the study period there were 210 (0.09%) deliveries of mothers with celiac, and they were compared to 242170 (99.91%) deliveries of non-celiac mothers. Cumulative infectious morbidity was significantly higher in offspring of mothers with celiac compared to offspring of mothers without celiac (Kaplan-Meier, log-rank p = .004). Specifically, among the offspring of mothers with celiac significantly higher rates of bacteremia was noted (1.0% vs. 0.1%; p = .001), and infections of the central nervous system (1% vs. 0.2%; p = .028). In the Cox multivariable model which accounted for confounding variables, being born to mothers with celiac disease was associated with significantly increased risk for long-term infectious morbidity of the offspring (adjusted HR = 1.6, 95% CI 1.165-2.357, p = .005). CONCLUSIONS: Maternal celiac disease is an independent risk factor for long-term infectious morbidity for the offspring.

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.

Association Between Celiac Disease and Mortality Risk in a Swedish Population.

Importance: Celiac disease may be associated with a modest but persistent increased long-term mortality risk. It is uncertain whether this risk has changed in the era of wider diagnosis rates, less severe clinical disease, and more widespread availability of gluten-free food. Objective: To evaluate the association between celiac disease and mortality risk in a population-based cohort in Sweden. Design, Setting, and Participants: All individuals in Sweden with celiac disease diagnosed between 1969 and 2017 were identified through the Epidemiology Strengthened by histoPathology Reports in Sweden (ESPRESSO) cohort. Participants (n = 49 829) were observed starting on the day of the biopsy. The final date of follow-up was December 31, 2017. Exposures: Celiac disease was defined by the presence of small intestinal villus atrophy on histopathology specimens during the years 1969-2017 from Sweden's 28 pathology departments. Each individual was matched with as many as 5 control participants in the general population by age, sex, county, and calendar period. Main Outcomes and Measures: The primary outcome was all-cause mortality, and the secondary outcome was cause-specific mortality. Patients with celiac disease were compared with controls using stratified Cox proportional modeling, stratifying by year of diagnosis. Results: There were 49 829 patients with celiac disease, including 24% who were diagnosed between the years 2010 and 2017. The mean (SD) age at diagnosis was 32.2 (25.2) years and 62.4% were women. During a median follow-up time of 12.5 years, 13.2% (n = 6596) died. Compared with controls (n = 246 426), overall mortality was increased in those with celiac disease (9.7 vs 8.6 deaths per 1000 person-years; absolute difference, 1.2 per 1000 person-years; hazard ratio [HR], 1.21 [95% CI, 1.17-1.25]). The relative increase in mortality risk was present in all age groups and was greatest in those diagnosed in the age range of 18 to 39 years (1.9 vs 1.1 per 1000 person-years; HR, 1.69 [95% CI, 1.47-1.94]; P values for heterogeneity comparing 18-39 years with 40-59 years and with ≥60 years were both <.001). Individuals with celiac disease were at increased risk of death from cardiovascular disease (3.5 vs 3.4 per 1000 person-years; HR, 1.08 [95% CI, 1.02-1.13]), cancer (2.7 vs 2.2 per 1000 person-years; HR, 1.29 [95% CI, 1.22-1.36]), and respiratory disease (0.6 vs 0.5 per 1000 person-years; HR, 1.21 [95% CI, 1.08-1.37]). When compared with controls, the overall mortality risk was greatest in the first year after diagnosis (15.3 vs 6.5 per 1000 person-years; HR, 2.34 [95% CI, 2.14-2.55]) but persisted beyond 10 years after diagnosis (10.5 vs 10.1 per 1000 person-years; HR, 1.15 [95% CI, 1.10-1.20]). The mortality risk was likewise present for patients diagnosed during the years 2010-2017 (7.5 vs 5.5 per 1000 person-years; HR, 1.35 [95% CI, 1.21-1.51]). Conclusions and Relevance: In a Swedish population studied between 1969 and 2017, a diagnosis of celiac disease compared with the general population was associated with a small but statistically significant increased mortality risk.

Mortality in people with coeliac disease: Long-term follow-up from a Scottish cohort.

Background: Few studies have determined the very long-term mortality risks in adult and childhood-diagnosed coeliac disease. Objective: We quantified mortality risks in coeliac disease and determined whether age at diagnosis, or time following diagnosis, modified these risks. Methods: Standardised mortality ratios were determined using data from a cohort of 602 coeliac patients assembled between 1979-1983 from Lothian, Scotland, and followed up from 1970-2016. Results: All-cause mortality was 43% higher than in the general population. Excess deaths were primarily from haematological malignancies (standardised mortality ratio, 4.77) and external causes (standardised mortality ratio, 2.62) in adult and childhood-diagnosed cases respectively. Mortality risks declined steadily with time in adult-diagnosed cases (standardised mortality ratio, 4.85 in first year compared to 0.97, 25 years post-diagnosis). Beyond 15 years, this group had a significantly reduced risk of any malignancy (standardised mortality ratio, 0.57 (95% confidence interval: 0.33-0.92)). In contrast, for childhood-diagnosed cases an increased risk existed beyond 25 years (standardised mortality ratio, 2.24). Conclusions: Adult-diagnosed coeliac patients have a temporarily increased mortality risk mainly from malignant lymphomas and a decreased risk of any malignancy beyond 15 years post-diagnosis. In contrast, childhood-diagnosed cases are at an increased risk of mortality mainly from external causes, and have long-term mortality risks that requires further investigation.

Celiac disease and non-celiac gluten or wheat sensitivity and health in later life: A review.

Celiac disease (CD) and non-gluten (or wheat) sensitivity (NCGS) are two gluten-related disorders, the treatment of which relies on dietary withdrawal of gluten (absolute and lifelong in the case of CD patients). However, these conditions differ in their pathophysiology and impact on health. CD is an autoimmune disorder of the intestine, and is associated with a wide range of disorders, pre- and post-diagnosis. Its autoimmune and inflammatory nature raises concerns about its potential effects on mortality and morbidity. Here we review the data on the health impact CD or NCGS may have prospectively, and report on the role of a gluten-free diet (GFD) in this respect. Since study designs have been heterogeneous, we focus on studies of treated patients with a biopsy-proven diagnosis of CD, to eliminate possible bias from misdiagnosis. The review revealed a moderately increased mortality risk among CD patients, mainly attributed to cardiovascular disease and malignancy. Other long-term morbidities of CD include autoimmune disorders, nutritional deficiencies, impaired bone health, reproductive abnormalities, and neurologic and neuropsychiatric disorders, which are substantially improved, and some of them even completely treated, after strict adherence to a GFD. For NCGS, the literature is too limited and its long-term complications are unknown.

Risk of complications in coeliac patients depends on age at diagnosis and type of clinical presentation.

BACKGROUND: Coeliac disease is characterised by an increased mortality mostly due to its complications. AIMS: To study the risk of developing complications according to clinical presentation and age at diagnosis, a combined retrospective-prospective longitudinal study was performed in three Italian centres. METHODS: Incidence of complications and mortality rates were calculated using type and age at diagnosis of coeliac disease, sex, and centre of diagnosis as predictors. Patients referred after being found to suffer from coeliac disease elsewhere were excluded. RESULTS: Between 01/1999 and 06/2015, 2225 adult coeliac patients were directly diagnosed in our centres. 17 of them developed a complication and 29 died. In patients older than 60 years at diagnosis of coeliac disease, the risk of complication is 18 times higher than in patients diagnosed at 18-40 years and 9 times higher than in patients diagnosed at 40-60 years. Classical presentation increases the risk of complications by 7 times compared to non-classical presentation; in asymptomatic patients the risk of complication is virtually absent. CONCLUSIONS: The risk of developing complications in coeliac patients is linked to age at diagnosis of coeliac disease and type of clinical presentation. Follow-up methods of coeliac patients should be tailored according to these parameters.

The Relationship Between Child Mortality Rates and Prevalence of Celiac Disease.

OBJECTIVES: Some evidence suggests that prevalence of celiac disease in the general population is increasing over time. Because the prognosis of celiac disease was a dismal one before discovering the role of gluten, our aim was to investigate a possible relationship between children under-5 mortality rates and prevalence rates of celiac disease. METHODS: Thanks to a literature review, we found 27 studies performed in 17 different countries describing the prevalence of celiac disease in schoolchildren; between 1995 and 2011, 4 studies were performed in Italy. A meta-analysis of prevalence rates was performed. Prevalence was compared between specific country under-5 mortality groups, publication year, and age. RESULTS: In the last decades, under-5 mortality rates have been decreasing all over the world. This reduction is paralleled by an increase of the prevalence of celiac disease. The Spearman correlation coefficient was -63%, 95% confidence interval -82% to -33% (P < 0.001). So, the higher the mortality rate, the lower the prevalence of CD. This finding is confirmed by the meta-analysis of the 4 studies conducted in Italy over time. CONCLUSIONS: The under-5 mortality rate seems to influence the prevalence of celiac disease in the general population. In the near future, the number of patients with celiac disease will increase, thanks to the better environmental conditions that nowadays allow a better survival of children with celiac disease.

Short article: Mortality and differential diagnoses of villous atrophy without coeliac antibodies.

OBJECTIVE: Villous atrophy (VA) of the small bowel is mainly related to coeliac disease (CD), whose diagnosis is made on the basis of positive endomysial/tissue transglutaminase antibodies while on a gluten-containing diet in the vast majority of patients. However, VA can also occur in other conditions whose epidemiology is little known. Our aim was to study the epidemiology and clinical features of these rare enteropathies. PATIENTS AND METHODS: Clinical and laboratory data of all the patients with VA directly diagnosed in our centre in the last 15 years were collected and statistically analysed. RESULTS: Between September 1999 and June 2015, 274 patients were diagnosed with VA. A total of 260 patients were also positive to coeliac antibodies; the other 14 had VA, but no IgA endomysial antibodies: five had common variable immunodeficiency, three had dermatitis herpetiformis, two had IgA deficiency associated with CD, one had abdominal lymphoma, one had unclassified sprue, one had olmesartan-associated enteropathy and one had seronegative CD. Mortality was 6.0 deaths per 100 person years (95% confidence interval: 2.2-16) in patients with VA but negative coeliac antibodies, whereas only 0.2 deaths per 100 person years (95% confidence interval: 0.1-0.6) occurred in coeliac patients. CONCLUSION: Patients with VA and negative endomysial antibodies are rare. However, these forms of VA identify specific causes that can be diagnosed. These patients are affected by a very high mortality.

Increased mortality among men aged 50 years old or above with elevated IgA anti-transglutaminase antibodies: NHANES III.

BACKGROUND: Immunoglobulin A (IgA) antibodies to tissue transglutaminase (tTG) are the serologic test of choice for diagnosing celiac disease (CD). Our aim was to determine if elevated IgA anti-tTG were associated with increased mortality risk. METHODS: Stored serum samples of National Health and Nutrition Examination Survey (NHANES) III (1988-1992) were available for 6032 individuals aged 50 years old or above, which were screened for IgA anti-tTG, and if positive, for IgA endomysial antibodies. Mortality was determined from the National Death Index records through 2006. Hazard ratios were calculated through Cox proportional hazards regression. RESULTS: From a total of 6032, 85 participants tested positive for IgA anti-tTG (1.4 %) and 5947 tested negative. After a median follow-up of 13 years, IgA anti-tTG positive participants were at increased risk of death in both crude (HR = 1.68; 95 % CI = 1.30-2.18) and adjusted analyses (adjusted hazard ratio = 1.43; 95 % CI = 1.10-1.85) as compared to IgA anti-tTG negative participants. The excess mortality was restricted to IgA anti-tTG positive males (adjusted hazard ratio = 1.69 (95 % CI = 1.26-2.29), as opposed to a hazard ratio of 0.96 (95 % CI = 0.57-1.62) among IgA anti-tTG positive females. Although the most common cause of death in IgA anti-tTG positive participants was cardiovascular disease (36 %), the increased hazard ratio was only observed in respiratory cause of death as compared to IgA anti-tTG negative participants (adjusted hazard ratio = 5.11; 2.76-9.46). CONCLUSION: Men aged 50 years old or above participants of NHANES III with elevated IgA anti-tTG antibodies had increased mortality risk. Elevated IgA anti-tTG antibodies could be a nonspecific marker of serious disease in older men.

Creation of a model to predict survival in patients with refractory coeliac disease using a multinational registry.

BACKGROUND: Refractory coeliac disease is a severe complication of coeliac disease with heterogeneous outcome. AIM: To create a prognostic model to estimate survival of patients with refractory coeliac disease. METHODS: We evaluated predictors of 5-year mortality using Cox proportional hazards regression on subjects from a multinational registry. Bootstrap resampling was used to internally validate the individual factors and overall model performance. The mean of the estimated regression coefficients from 400 bootstrap models was used to derive a risk score for 5-year mortality. RESULTS: The multinational cohort was composed of 232 patients diagnosed with refractory coeliac disease across seven centres (range of 11-63 cases per centre). The median age was 53 years and 150 (64%) were women. A total of 51 subjects died during a 5-year follow-up (cumulative 5-year all-cause mortality = 30%). From a multiple variable Cox proportional hazards model, the following variables were significantly associated with 5-year mortality: age at refractory coeliac disease diagnosis (per 20 year increase, hazard ratio = 2.21; 95% confidence interval, CI: 1.38-3.55), abnormal intraepithelial lymphocytes (hazard ratio = 2.85; 95% CI: 1.22-6.62), and albumin (per 0.5 unit increase, hazard ratio = 0.72; 95% CI: 0.61-0.85). A simple weighted three-factor risk score was created to estimate 5-year survival. CONCLUSIONS: Using data from a multinational registry and previously reported risk factors, we create a prognostic model to predict 5-year mortality among patients with refractory coeliac disease. This new model may help clinicians to guide treatment and follow-up.

No increased mortality in 109,000 first-degree relatives of celiac individuals.

BACKGROUND: Several studies have shown an excess mortality in individuals with celiac disease (CD). However, it is unknown if also first-degree relatives (FDRs) to celiac patients are at increased risk of death. AIM: We aimed to assess mortality in FDRs to celiac patients. METHODS: Individuals with CD were identified through biopsy reports (equal to Marsh grade III). Each celiac individual was matched on sex, age, county and calendar year with up to five control individuals. Through Swedish healthcare registries we identified all FDRs (father, mother, sibling, offspring) of CD individuals and controls. Through Cox regression we calculated hazard ratios (HRs) for mortality (all-cause death, circulatory, cancer and other). RESULTS: We identified 109,309 FDRs of celiac individuals and 549,098 FDRs of controls. Overall mortality was increased in FDRs to celiac individuals (HR=1.02, 95%CI=1.00-1.04, p=0.03). This corresponded to an excess risk of 5.9 deaths per 100,000 person-years of follow-up. When limiting follow-up to time since celiac diagnosis in the index individual, we found no increased risk of death (HR=1.01; 95%CI=0.98-1.03). CONCLUSION: FDRs to individuals with CD are at increased risk of death. This excess risk is however minimal and unlikely to be of any clinical importance to the individual.

Surgery in (pre)malignant celiac disease.

AIM: To report the outcome of surgery in patients with (pre)malignant conditions of celiac disease (CD) and the impact on survival. METHODS: A total of 40 patients with (pre)malignant conditions of CD, ulcerative jejunitis (n = 5) and enteropathy associated T-cell lymphoma (EATL) (n = 35), who underwent surgery between 2002 and 2013 were retrospectively evaluated. Data on indications, operative procedure, post-operative morbidity and mortality, adjuvant therapy and overall survival (OS) were collected. Eleven patients with EATL who underwent chemotherapy without resection were included as a control group for survival analysis. Patients were followed-up every three months during the first year and at 6-mo intervals thereafter. RESULTS: Mean age at resection was 62 years. The majority of patients (63%) underwent elective laparotomy. Functional stenosis (n = 13) and perforation (n = 12) were the major indications for surgery. In 70% of patients radical resection was performed. Early postoperative complications, mainly due to leakage or sepsis, occurred in 14/40 (35%) of patients. Eight patients required reoperation. More patients who underwent resection in the acute setting (n = 3, 20%) died compared to patients treated in the elective setting. With a median follow-up of 20 mo, seven patients (18%) required reoperation due to long-term complications. Significantly more patients who underwent acute surgery could not be treated with adjuvant chemotherapy. Patients who first underwent surgical resection showed significantly better OS than patients who received chemotherapy without resection. CONCLUSION: Although the complication rate is high, the preferred first step of treatment in (pre)malignant CD consists of local resection as early as possible to improve survival.

Treatment response in enteropathy associated T-cell lymphoma; survival in a large multicenter cohort.

Enteropathy-associated T-cell lymphoma (EATL) is a T-cell Non-Hodgkin Lymphoma which is highly associated with celiac disease. The prognosis of EATL has been considered poor and there are no standardized treatment protocols. Here, we evaluate treatment response and survival of EATL patients in a large multicenter cohort. A total of 61 patients diagnosed with EATL were analyzed. Various treatment regimens were applied in EATL during the past fifteen years including either monotherapy consisting of chemotherapy or resection, or combination therapy with both aforementioned regimens whether or not combined with stem-cell transplantation (SCT). Overall, 50/61 patients (82%) died after a median of 7.4 months. One- and five-year overall survival was 40 and 11%, respectively. Median follow-up in the survivors was 26 months. Patients treated with the most aggressive treatment, that is, resection, chemotherapy and autologous SCT, showed the most favourable outcome with complete remission in all patients, the lowest relapse rate and one- and five-year overall survival of 100 and 33%, respectively, although overall survival in this group was not significantly better as compared to patients treated with surgery and chemotherapy. This study indicates that combination treatment is superior compared to monotherapy. Whether or not consolidation therapy with autologous SCT may improve survival needs to be substantiated in a larger randomized international trial.

Follow-up of ischaemic heart disease in patients with coeliac disease.

Patients with coeliac disease and myocardial infarction have a more favourable atherosclerotic risk factor profile than controls with myocardial infarction (MI). Therefore, MI prognosis and treatment may differ according to coeliac status. This paper reports on the study of Swedish MI patients with and without coeliac disease (equal to villous atrophy; Marsh histopathology stage 3) based on duodenal or jejunal biopsy data. We used the Swedish Quality Register (SWEDEHEART) to identify individuals with a record of MI from 2005 to 2008 and to obtain data on medication, coronary interventions, and clinical and laboratory parameters at 6-10 weeks and one year after first MI. One-year mortality and coronary interventions were assessed for 430 coeliac patients and 1988 controls. For other outcome variables, we compared 42 coeliac patients with MI and 201 general population controls with MI. Odds ratios (ORs) were calculated by logistic regression. The results showed that compared with controls with MI, coeliac individuals with MI had significantly higher one-year all-cause mortality (OR = 1.43; 95% confidence interval (CI) = 1.04-1.95) but less often underwent a percutaneous coronary intervention (OR = 0.77; 95% CI = 0.61-0.96). Coeliac patients were more often prescribed warfarin but less often aspirin and statins. The readmission rate due to cardiac events in coeliac patients was 15.2% vs. 12.6% in controls (p-value = 0.69). Other clinical and laboratory parameters were similar. We conclude that the follow up of MI does not seem to differ between coeliac patients and controls, and is unlikely to explain the excess mortality from cardiovascular disease noted in Swedish patients with CD.

Causes of death in people with coeliac disease in England compared with the general population: a competing risk analysis.

INTRODUCTION: Quantifying excess cause-specific mortality among people with coeliac disease (CD) compared with the general population accounting for competing risks will allow accurate information to be given on risk of death from specific causes. METHOD: We identified from the Clinical Practice Research Datalink all patients with CD linked to Office for National Statistics between 1998 and 2012. We selected controls by frequency matching from the registered general practice population within 10-year age bands. We calculated the adjusted cumulative incidence (including adjustment for competing risks) and excess cumulative incidence for different causes of death up to 10 years from diagnosis. RESULTS: Of the 10 825 patients with CD, 773 died within the study period. The overall mortality rate among patients with CD was 128/10 000 person years compared with 153/10 000 in controls (HR=0.94 95% CI 0.84 to 1.01). We found no overall difference in the cumulative incidence of respiratory disease, digestive disease or cancer related death among cases and controls. The adjusted cumulative incidence of death from cardiovascular deaths was slightly lower compared with those without CD diagnosis (CD 0.32% vs controls 0.41%) with a corresponding excess cumulative incidence of -0.08% (95% CI -0.13 to -0.04). However, patients with CD had 0.15% excess risk (95% CI 0.03 to 0.27) of deaths from non-Hodgkin's lymphoma from the general population baseline risk. CONCLUSIONS: Overall, people with CD have no major excess risk of cancer, digestive disease or respiratory disease related or cardiovascular mortality compared with the general population. These findings should be reassuring to patients with CD and clinicians managing their care.

A multicentre case control study on complicated coeliac disease: two different patterns of natural history, two different prognoses.

BACKGROUND: Coeliac disease is a common enteropathy characterized by an increased mortality mainly due to its complications. The natural history of complicated coeliac disease is characterised by two different types of course: patients with a new diagnosis of coeliac disease that do not improve despite a strict gluten-free diet (type A cases) and previously diagnosed coeliac patients that initially improved on a gluten-free diet but then relapsed despite a strict diet (type B cases). Our aim was to study the prognosis and survival of A and B cases. METHODS: Clinical and laboratory data from coeliac patients who later developed complications (A and B cases) and sex- and age-matched coeliac patients who normally responded to a gluten-free diet (controls) were collected among 11 Italian centres. RESULTS: 87 cases and 136 controls were enrolled. Complications tended to occur rapidly after the diagnosis of coeliac disease and cumulative survival dropped in the first months after diagnosis of complicated coeliac disease. Thirty-seven cases died (30/59 in group A, 7/28 in group B). Type B cases presented an increased survival rate compared to A cases. CONCLUSIONS: Complicated coeliac disease is an extremely serious condition with a high mortality and a short survival. Survival depends on the type of natural history.

Refractory celiac disease.

A small subset of celiac disease (CD) patients becomes refractory to a gluten-free diet with persistent malabsorption and intestinal villous atrophy. Diagnosis of this condition defined as refractory celiac disease (RCD) is made after exclusion of other small bowel diseases with villous atrophy. RCD has been subdivided into two subgroups according to the normal or abnormal phenotype of intraepithelial lymphocytes. Whereas normal RCD is hardly distinguishable from active CD, abnormal RCD has a severe clinical presentation and a very poor prognosis. We precisely describe below the different types of RCD and propose diagnostic and therapeutic guidelines for its clinical management.

PROgnosticating COeliac patieNts SUrvivaL: the PROCONSUL score.

INTRODUCTION: It has been shown that mortality rates of coeliac patients correlate with age at diagnosis of coeliac disease, diagnostic delay for coeliac disease, pattern of clinical presentation and HLA typing. Our aim was to create a tool that identifies coeliac patients at higher risk of developing complications. METHODS: To identify predictors of complications in patients with coeliac disease, we organised an observational multicenter case-control study based on a retrospective collection of clinical data. Clinical data from 116 cases (patients with complicated coeliac disease) and 181 controls (coeliac patients without any complications) were collected from seven European centres. For each case, one or two controls, matched to cases according to the year of assessment, gender and age, were selected. Diagnostic delay, pattern of clinical presentation, HLA typing and age at diagnosis were used as predictors. RESULTS: Differences between cases and controls were detected for diagnostic delay and classical presentation. Conditional logistic models based on these statistically different predictors allowed the development of a score system. Tertiles analysis showed a relationship between score and risk of developing complications. DISCUSSION: A score that shows the risk of a newly diagnosed coeliac patient developing complications was devised for the first time. This will make it possible to set up the follow-up of coeliac patients with great benefits not only for their health but also for management of economic resources. CONCLUSIONS: We think that our results are very encouraging and represent the first attempt to build a prognostic score for coeliac patients.

Low incidence but poor prognosis of complicated coeliac disease: a retrospective multicentre study.

BACKGROUND: Coeliac disease is a chronic enteropathy characterized by an increased mortality caused by its complications, mainly refractory coeliac disease, small bowel carcinoma and abdominal lymphoma. Aim of the study was to study the epidemiology of complications in patients with coeliac disease. METHODS: Retrospective multicenter case-control study based on collection of clinical and laboratory data. The incidence of complicated coeliac disease was studied among coeliac patients directly diagnosed in four Italian centres. Patients referred to these centres after a diagnosis of coeliac disease and/or complicated coeliac disease in other hospitals were therefore excluded. RESULTS: Between 1/1999 and 10/2011, 1840 adult coeliac patients were followed up for 7364.3 person-years. Fourteen developed complications. Since five patients died, at the end of the observation period (10/2011), the prevalence of complicated coeliac disease was 9/1835 (1/204, 0.49%, 95% CI 0.2-0.9%). The annual incidence of complicated coeliac disease in the study period was 14/7364 (0.2%, 95% CI 0.1-0.31%). Although complications tend to occur soon after the diagnosis of coeliac disease, Kaplan-Meier curve analysis showed that they can actually occur at any time after the diagnosis of coeliac disease. CONCLUSIONS: Complications of coeliac disease in our cohort were quite rare, though characterised by a very high mortality.