Complications and associated conditions of celiac disease

The aim of this thesis was to explore possible complications and associated conditions of celiac disease (CD) in order to shed new light on the burden of illness related to CD and to identify groups at high risk of CD, where screening for CD may be considered. We also assessed the effects of a gluten-free diet on the risk of lymphoma, an important complication of CD. Throughout the thesis, Swedish population-based registers have been used.

To investigate the risk of urinary tract infections (UTI) in CD we linked the Swedish Hospital discharge register and the Medical Birth Register. We studied the risk of UTI in 829 women who had received a diagnosis of CD before they had UTI and in 895 pregnancies to women diagnosed with CD after they had UTI and compared them with 1.7 million women without a diagnosis of CD. We found a moderately increased (but not statistically significant) risk of UTI (Adjusted Odds Ratio (AOR) = 1.37; 95% CI = 0.78-2.43; p= 0.276) in women with undiagnosed CD and no increased risk of UTI in women with diagnosed CD (AOR = 1.02; 95% CI = 0.79-1.32; p = 0.864).

To assess the risk of Immune Thrombocytopenic Purpura (ITP) in CD and vice versa we used the Swedish national Inpatient Register to identify 14,347 individuals with CD (1964-2003) and 69,967 matched reference individuals. We found that individuals with CD were at increased risk of both subsequent ITP of any type (Hazard ratio (HR) = 1.91; 95% = 1.19-3.11; p = 0.008) and subsequent chronic ITP (HR 2.77; 1.09-7.04; p = 0.033). There was also a positive association between CD and prior ITP of any type (Odds ratio (OR) = 2.96; 95% CI = 1.60-5.50; p = 0.001) or with prior chronic ITP (OR = 6.00; 95% CI = 1.83 -19.66; p = 0.003).

To examine the risk of subsequent sepsis in individuals with CD we used the Swedish Inpatient register to identify 15,325 individuals with a diagnosis of CD (1964-2003) and 75,249 matched reference individuals from the general population. This study showed a modestly increased risk of sepsis in patients with CD (HR = 2.6; 95% CI = 2.1-3.0; p <0.001) with the highest risk for pneumococcal sepsis (HR = 3.9; 95% CI = 2.2-7.0; p <0.001).

To study the relationship between body mass index (BMI) and CD we identified all individuals with diagnosed or undiagnosed (at time of BMI measurement) CD in the Swedish Medical Birth register and the Swedish Conscript register. In some 800,000 women and 8000 men we found that underweight was associated with undiagnosed CD (future diagnosis of CD) in both women (HR = 2.5; 95% CI = 1.6-3.7) and men (OR = 2.4; 95% CI = 1.2- 4.9). But we also found that many individuals with undiagnosed CD are overweight (9.2% of women, 14.3% of men).

In the last study we assessed the relationship between compliance to a gluten free diet and risk of lymphoma in individuals with CD. We linked the Swedish national inpatient register with the Swedish Cancer Registry and thus identified 59 cases of CD and of incident malignant lymphomas. In a nested case-control design, 137 controls with CD, but without lymphoma were matched to the cases by sex, age at diagnosis (± 3 years), follow up time and calendar year of diagnosis (± 3 years). We studied the medical records of all cases and controls, blinded to the case-control status and found that poor compliance was associated with a marked increase in risk of B-cell lymphoma (OR 4.74, CI 0.89-25.33) and extraintestinal lymphoma (OR 2.85, CI 0.68-11.91), whereas risk of T-cell lymphoma (OR 1.01, CI 0.32-3.15) and intestinal lymphoma (OR 0.66, CI 0.17-2.56) remained unelevated.

List of scientific papers

I. Olén O, Montgomery SM, Ekbom A, Bollgren I, Ludvigsson JF (2007). Urinary tract infections in pregnant women with coeliac disease. Scand J Gastroenterol. 42(2): 186-93.
https://pubmed.ncbi.nlm.nih.gov/17327938

II. Olén O, Montgomery SM, Elinder G, Ekbom A, Ludvigsson JF (2008). Increased risk of immune thrombocytopenic purpura among inpatients with coeliac disease. Scand J Gastroenterol. 43(4): 416-22.
https://pubmed.ncbi.nlm.nih.gov/18365906

III. Ludvigsson JF, Olén O, Bell M, Ekbom A, Montgomery SM (2008). Coeliac disease and risk of sepsis. Gut. 57(8): 1074-80. Epub 2008 Feb 12
https://pubmed.ncbi.nlm.nih.gov/18270242

IV. Olén O, Montgomery SM, Marcus C, Ekbom A, Ludvigsson JF (2008). Celiac disease and Body Mass Index: A study of two Swedish general population based registers. [Submitted]

V. Olén O, Askling J, Ludvigsson JF, Hildebrand H, Ekbom A, Ekstrom Smedby K (2008). Celiac disease, compliance to a gluten free diet and risk of lymphoma by subtype. [Submitted]