Increased Risk of Systemic Lupus Erythematosus in 29,000 Patients with Biopsy-verified Celiac Disease

Department of Pediatrics, Örebro University Hospital, Örebro University, Örebro, Sweden
The Journal of Rheumatology (Impact Factor: 3.19). 08/2012; 39(10):1964-70. DOI: 10.3899/jrheum.120493
Source: PubMed


To investigate a possible association between celiac disease (CD) and systemic lupus erythematosus (SLE). Case series have indicated a possible association, but population-based studies are lacking.
We compared the risk of SLE in 29,048 individuals with biopsy-verified CD (villous atrophy, Marsh 3) from Sweden's 28 pathology departments with that in 144,352 matched individuals from the general population identified through the Swedish Total Population Register. SLE was defined as having at least 2 records of SLE in the Swedish Patient Register. We used Cox regression to estimate hazard ratios (HR) for SLE.
During followup, 54 individuals with CD had an incident SLE. This corresponded to an HR of 3.49 (95% CI 2.48-4.90), with an absolute risk of 17/100,000 person-years and an excess risk of 12/100,000. Beyond 5 years of followup, the HR for SLE was 2.54 (95% CI 1.57-4.10). While SLE was predominantly female, we found similar risk estimates in men and women. When we restricted our outcome to individuals who also had a dispensation for a medication used in SLE, the HR was 2.43 (95% CI 1.22-4.87). The HR for having 2 records of SLE diagnoses, out of which at least 1 had occurred in a department of rheumatology, nephrology/dialysis, internal medicine, or pediatrics, was 2.87 (95% CI 1.97-4.17).
Individuals with CD were at a 3-fold increased risk of SLE compared to the general population. Although this excess risk remained more than 5 years after CD diagnosis, absolute risks were low.

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Available from: Jonas Ludvigsson, Mar 05, 2014
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    • "The association between coeliac disease (CD) and a wide spectrum of autoimmune diseases (AID) such as type 1 diabetes mellitus [1] [2], autoimmune thyroid disease [3], juvenile idiopathic arthritis [4] or autoimmune liver disease [5] has been well documented in the medical literature before. The appearance of CD -specific antibodies has also been described in patients with other AID, like systemic lupus erythematosus (SLE), with much lower prevalence and controversial clinical relevance, since not all of them were diagnosed as coeliac following intestinal biopsy [6] [7] "
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    ABSTRACT: The prevalence of coeliac disease (CD) in systemic lupus erythematosus (SLE) is unclear since evidence of this co -association is scarce. Furthermore, CD -specific antibodies have been described in patients with SLE without biopsy -confirmed CD. Here we describe the diagnostic challenges of CD in a patient suffering from SLE and secondary antiphospholipid syndrome, with transient positive serum levels of CD -specific antibodies, with an increased genetic risk for CD, demonstrated by HLA-DQ2 positivity. Guidance is still needed for the CD diagnosis in some atypical conditions
    Full-text · Article · Mar 2015
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    • "Finally, our earlier research has shown that CD is associated with a number of other immune-mediated diseases [33-35] and such comorbidity, if linked to prior head trauma, may also have influenced our risk estimates. "
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    ABSTRACT: TG6, a brain expressed transglutaminase, is implicated in the neurological manifestations of celiac disease (CD). We hypothesized that earlier brain injury due to head trauma may be more common in patients with CD, potentially through trauma-induced TG6 leading to interaction with TG2. Through biopsy reports from all 28 pathology departments in Sweden we identified 29,096 individuals with CD (in this study defined as villous atrophy). We then examined the risk of earlier head trauma in CD compared to the risk in 144,522 controls matched for age, sex, county and calendar year. Odds ratios (ORs) were calculated using conditional logistic regression. 981 (3.4%) individuals with CD and 4,449 (3.1%) controls had a record of earlier head trauma. Individuals with head trauma were hence at a 1.10-fold increased risk of future CD (95%CI = 1.02-1.17). ORs were independent of sex or age at CD. The highest risk of future CD was seen during the first year after trauma. There was no association between severity of trauma and risk of developing CD. This study found a very small excess risk for future CD in individuals with an earlier head trauma.
    Full-text · Article · Aug 2013 · BMC Neurology
    • "In a recent study, the aim was to investigate the risk of this disease in a nationwide cohort of patients with biopsy-verified CD compared to controls matched from the general population. The conclusion was that celiac patients were at 3-fold increased risk of developing SLE, but absolute risk was low [169]. This is striking because both disorders share the human leukocyte HLA-B8 and HLA-DR3 histocompatibility antigens, and a variety of antibodies including the detection of tTG IgA, antinuclear, and antidouble-stranded DNA antibodies. "
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    ABSTRACT: Celiac disease (CD) is frequently accompanied by a variety of extradigestive manifestations, thus making it a systemic disease rather than a disease limited to the gastrointestinal tract. This is primarily explained by the fact that CD belongs to the group of autoimmune diseases. The only one with a known etiology is related to a permanent intolerance to gluten. Remarkable breakthroughs have been achieved in the last decades, due to a greater interest in the diagnosis of atypical and asymptomatic patients, which are more frequent in adults. The known presence of several associated diseases provides guidance in the search of oligosymptomatic cases as well as studies performed in relatives of patients with CD. The causes for the onset and manifestation of associated diseases are diverse; some share a similar genetic base, like type 1 diabetes mellitus (T1D); others share pathogenic mechanisms, and yet, others are of unknown nature. General practitioners and other specialists must remember that CD may debut with extraintestinal manifestations, and associated illnesses may appear both at the time of diagnosis and throughout the evolution of the disease. The implementation of a gluten-free diet (GFD) improves the overall clinical course and influences the evolution of the associated diseases. In some cases, such as iron deficiency anemia, the GFD contributes to its disappearance. In other disorders, like T1D, this allows a better control of the disease. In several other complications and/or associated diseases, an adequate adherence to a GFD may slow down their evolution, especially if implemented during an early stage.
    No preview · Article · Jul 2013
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