Celiac Disease Linked to Modestly Increased Mortality

by Laurie Barclay, MD
September 15, 2009 — Mortality risk is modestly increased in patients with celiac disease, inflammation, or latent celiac disease, according to the results of a retrospective cohort study reported in the September 16 issue of the Journal of the American Medical Association.




"Studies of mortality in celiac disease have not taken small-intestinal pathology into account," write Jonas F. Ludvigsson, MD, PhD, from Karolinska Institutet in Stockholm, Sweden, and colleagues. "We used nationwide histopathology data to examine the overall risk of death in individuals with celiac disease and inflammation. Through regional data linkage, we were also able to examine mortality in latent celiac disease."



The investigators studied duodenal/jejunal biopsies performed at all 28 pathology departments in Sweden between July 1969 and February 2008 on celiac disease (Marsh stage III: villous atrophy; n = 29,096 individuals) and inflammation (Marsh stage I - II; n = 13,306).



A third cohort of 3719 individuals with latent celiac disease, defined as positive celiac disease serology results in individuals with normal-appearing mucosa (Marsh stage 0), was obtained from 8 university hospitals. All-cause mortality risk through August 31, 2008, vs age- and sex-matched control subjects from the general population, was estimated through linkage with the Swedish Total Population Register.



There were 3049 deaths among patients with celiac disease (hazard ratio [HR], 1.39; 95% confidence interval [CI], 1.33 - 1.45; median follow-up, 8.8 years), 2967 among patients with inflammation (HR, 1.72; 95% CI, 1.64 - 1.79; median follow-up, 7.2 years), and 183 deaths among patients with latent celiac disease (HR, 1.35; 95% CI, 1.14 - 1.58; median follow-up, 6.7 years).



Absolute mortality rate was 10.4 (95% CI, 10.0 - 10.8) per 1000 person-years in celiac disease, 25.9 (95% CI, 25.0 - 26.8) in inflammation, and 6.7 (95% CI, 5.7 - 7.6) in latent celiac disease; excess mortality rate was 2.9, 10.8, and 1.7, respectively. Similar risk increases also occurred in children. When the first year of follow-up was excluded, HRs were somewhat decreased.



"Risk of death among patients with celiac disease, inflammation, or latent celiac disease is modestly increased," the study authors write.



Limitations of this study include possible misclassification of some pathologic features, the possibility that some patients with inflammation did not have celiac disease, lack of adjustment for smoking, and lack of weight and height data.



"Individuals undergoing small-intestinal biopsy in childhood had increased HRs for death," the study authors conclude. "Cardiovascular disease and malignancy were the main causes of death in celiac disease."



In an accompanying editorial, Peter H.R. Green, MD, notes the increasing evidence for the presence of celiac disease in patients with various neurologic and psychiatric disorders.



"The study by Ludvigsson and colleagues reinforces the importance of celiac disease as a diagnosis that should be sought by physicians," Dr. Green writes. "It also suggests that more attention should be given to the lesser degrees of intestinal inflammation and gluten sensitivity."



The Swedish Society of Medicine, the Swedish Research Council, the Sven Jerring Foundation, the Örebro Society of Medicine, the Karolinska Institutet, the Clas Groschinsky Foundation, the Juhlin Foundation, the Majblomman Foundation, Uppsala-Örebro Regional Research Council, and the Swedish Celiac Society supported this study. The study authors and Dr. Green have disclosed no relevant financial relationships.



JAMA. 2009;302:1171-1178, 1225-1226.