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.

Reduced mortality in dermatitis herpetiformis: a population-based study of 476 patients.

BACKGROUND: Dermatitis herpetiformis (DH) is an extra-intestinal manifestation of coeliac disease and most patients adhere to a life-long gluten free diet (GFD). Increased mortality rates have been reported in coeliac disease but knowledge in DH is scanty. OBJECTIVES: To survey the mortality rate and causes of death in a large cohort of patients with DH. MATERIAL AND METHODS: Patients with DH (n = 476 consecutive patients) diagnosed from 1970 onwards at the Tampere University Hospital were analysed for causes of death during 1971-2010. A questionnaire survey on key aspects of health behaviour was performed in patients with DH and comparisons were made with the Finnish population. RESULTS: The total number of deaths during 9079 person years followed up was 77 whereas 110 were expected. The standardized mortality rate (SMR) for all causes of death was significantly reduced, being 0·70 (95% CI 0·55-0·87), and similar in both sexes. The SMR was equal in the patients with DH with (0·73) and without (0·77) small bowel villous atrophy. The SMR was significantly reduced (0·38) for deaths due to cerebrovascular diseases. The SMR due to lymphoproliferative malignancies was significantly increased (6·86) in the first 5 years of follow-up but not thereafter. The questionnaire survey documented that 97·7% of the patients with DH adhered to a GFD. The patients reported significantly less hypercholesterolaemia and there were fewer current and past smokers compared with the age- and sex-matched control population. CONCLUSIONS: The present long-term follow-up study of DH documented significantly reduced all-cause and cerebrovascular disease mortality. Strict adherence to a GFD, less smoking and hypercholesterolaemia may play a role in the observed health benefit.

No increase in risk of fracture, malignancy or mortality in dermatitis herpetiformis: a cohort study.

BACKGROUND: Dermatitis herpetiformis forms part of the same spectrum of gluten-sensitive disorders as coeliac disease yet may have different risks of morbidity and mortality. AIMS: To quantify the risks of fracture, malignancy and mortality in people with dermatitis herpetiformis compared with the general population. METHODS: Using the General Practice Research Database, we identified 846 people with dermatitis herpetiformis and 4225 age-, gender- and practice-matched controls. We used Cox regression to estimate hazard ratios. RESULTS: Comparing people with dermatitis herpetiformis to the general population, the overall hazard ratio for any fracture was 1.1 (95% CI: 0.77-1.52). The overall hazard ratio for any malignancy was 1.0 (95% CI: 0.73-1.49); there was no increased risk of gastrointestinal (HR: 1.6; 95% CI: 0.67-3.67) or lymphoproliferative cancers (HR: 1.6; 95% CI: 0.44-6.06). A reduction in risk of breast cancer was not statistically significant (HR: 0.19; 95% CI: 0.03-1.39). The hazard ratio for all-cause mortality was 0.93 (95% CI: 0.70-1.23). CONCLUSIONS: Unlike the fivefold increase in risk seen in coeliac disease, we found no increased risk of lymphoproliferative cancer and no increase in fracture, malignancy or mortality in people with dermatitis herpetiformis compared with the general population. It is not clear whether differences in degree of intestinal inflammation or other reasons account for this. Like coeliac disease, dermatitis herpetiformis may protect against breast cancer.

Malignancies and mortality in patients with coeliac disease and dermatitis herpetiformis: 30-year population-based study.

BACKGROUND AND AIM: To assess the long-term risks of malignant diseases and mortality in patients with coeliac disease and dermatitis herpetiformis in a centre, where the prevalence of these diseases is high. The risks have probably been overestimated, as patients with subtle forms have earlier remained undetected. PATIENTS: The study comprised 17,245 person-years of follow-up in 1147 patients. METHODS: The observed numbers of malignancies and causes of deaths were assessed, and compared to those expected, and standardised incidence ratio and standardised mortality ratio given. RESULTS: The occurrence of all malignant conditions was equal to that in the population both in coeliac disease and dermatitis herpetiformis: standardised incidence ratios of 1.2 (95% confidence intervals 0.9-1.5) and 1.0 (0.6-1.5), respectively. Five patients with coeliac disease and seven with dermatitis herpetiformis had developed non-Hodgkin lymphoma; standardised incidence ratios of 3.2 (1.0-7.5) and 6.0 (2.4-12.4), respectively. Four patients with coeliac disease and one with dermatitis herpetiformis had enteropathy-associated T-cell lymphoma, associated with inadequate dietary compliance. Mortality was increased (standardised mortality ratio 1.26; 1.00-1.55) in coeliac disease, but decreased in dermatitis herpetiformis (standardised mortality ratio 0.52; 0.36-0.72). CONCLUSION: The overall prognosis in our patients was good. Non-Hodgkin lymphoma emerged in patients with undiagnosed or poorly treated coeliac disease. The mortality rate in dermatitis herpetiformis was even lower than in the population. Our data support the early diagnosis and dietary treatment of these conditions.

Malignancy and survival in dermatitis herpetiformis: a comparison with coeliac disease.

BACKGROUND: Dermatitis herpetiformis is a lifelong, gluten sensitive skin disease. Patients with dermatitis herpetiformis, similar to patients with coeliac disease not adhering to a gluten free diet, seem to have increased risk for lymphoma. AIMS: This study looked at the occurrence of malignancy and survival of patients with dermatitis herpetiformis and compared the results with those seen in patients with coeliac disease or in the general population. PATIENTS: A total of 305 adult patients with dermatitis herpetiformis diagnosed at the University Hospital of Tampere in 1970-1992 were studied. Most patients started a gluten free diet and at the end of the study 93% of the patients were adhering to the diet. A control group comprised 383 adult patients with coeliac disease, 81% of them adhered to a gluten free diet, 6% had a normal diet, and in 13% the diet history remained unknown. METHODS: The occurrence of malignant diseases and survival of the patients were assessed up to the end of 1993. Standardised incidence ratios (SIR) with 95% confidence intervals were used for the malignant diseases. The survival of the patients was compared with that of the general population. RESULTS: Thirteen (4.3%) patients with dermatitis herpetiformis developed 14 malignant disorders during the follow up (SIR 1.25; 95% confidence intervals 0.68 to 2.09). A non-Hodgkin's lymphoma occurred in four patients with dermatitis herpetiformis, significantly more than expected (SIR 10.3; 2.8-26.3). Thirteen (4.3%) patients with dermatitis herpetiformis died during the follow up but there was no increased general mortality. In coeliac disease, 13 (3.4%) patients developed malignancy (SIR 1.16; 0.62 to 1.97), 31 (8.1%) patients died but the survival rate did not differ from that in the general population. CONCLUSIONS: The incidence of non-Hodgkin's lymphoma was significantly increased in patients with dermatitis herpetiformis. The results also confirm that the patients with dermatitis herpetiformis treated mainly with a gluten free diet have no increased general mortality.

Mortality and cancer incidence in patients with dermatitis herpetiformis: a cohort study.

One hundred and fifty-two patients in whom a diagnosis of dermatitis herpetiformis was made at St John's Hospital for Diseases of the Skin, London, during 1950-85, were followed from the date of diagnosis to the end of 1989 for mortality, and from 1971, or the date of diagnosis if later, to 1986 for cancer incidence. Thirty-eight deaths occurred under the age of 85, slightly fewer than expected on the basis of national general population rates [standardized mortality ratio (SMR) = 87; 95% confidence interval (CI) 61-119]. All-cause mortality was somewhat lower in patients who had followed a gluten-free diet (SMR = 51; 17-120) than in those who had not (SMR = 97; 66-136), but the difference in SMRs was not significant (P = 0.3). Cancer mortality was non-significantly below expectations from national rates (SMR = 72; 31-142), but cancer incidence was significantly increased [standardized registration ratio (SRR) = 394; 180-749]. No particular cancer site accounted for the cancer incidence excess. One death occurred from cancer of the small intestine (SMR = 4953, P = 0.04), and one lymphoma was incident (SRR = 1555, P = 0.12). Increased risks of these malignancies have previously been found to be associated with coeliac disease (which is present in many patients with dermatitis herpetiformis), and with dermatitis herpetiformis, respectively. Mortality from ischaemic heart disease (IHD) was significantly below national rates (SMR = 37; 95% CI 12-86), and was similar in patients who had followed a gluten-free diet and those who had not.(ABSTRACT TRUNCATED AT 250 WORDS)

International mortality from bullous diseases since 1950.

National mortality figures hold information about our overall success in treating bullous disorders which cannot be found elsewhere. The official data, since 1950, for England and Wales, the Unites States, France, Japan, Scotland, Ireland and Denmark have been analysed after corrections for changes in the population structure and in the International Classification of Disease. A steep fall in deaths occurred in England and Wales between 1952 (121 deaths) and 1955 (55 deaths). The low rate persisted from 1955 to 1962 (40 deaths) when it fell to a steady even lower level lasting until the present. The United States figures showed a sharp drop in mortality starting about 2 years earlier (from 283 deaths in 1950 to 150 deaths in 1954), followed by a gradual fall to the present. Mortality in Scotland, Ireland and Denmark has followed the same general pattern but the figures from France, after a steady fall between 1951 (68 deaths) and 1965 (29 deaths), have risen again until 1971 (62 deaths). The number of deaths has not fallen in Japan but the data are difficult to interpret. The timing of the improvement in mortality in England and Wales, and in the United States, fits well with the introduction of systemic steroids into general use. A fall to about one-third of the presteroid level is in general agreement with the improvement recorded in smaller personal series from several centres.