Is there an association between rheumatoid arthritis (RA) and celiac disease?

Association Between Rheumatoid Arthritis and Celiac Disease

Yes, there is a documented connection between rheumatoid arthritis (RA) and celiac disease (CD), with shared genetic susceptibility and overlapping autoimmune mechanisms, though the clinical co-occurrence is relatively uncommon. 1

Genetic and Immunologic Overlap

The relationship between RA and celiac disease is rooted in shared genetic architecture:

• Both diseases share HLA-DQ2/DQ8 susceptibility genes along with 14 additional non-HLA genetic loci that create overlapping autoimmune risk. 1, 2
• Meta-analysis of genome-wide association studies identified specific shared risk variants including SNPs near DDX6, CD247, UBE2L3, UBASH3A, SH2B3, STAT4, and TRAF1-C5 genes. 2
• These shared genetic factors implicate antigen presentation and T-cell activation as common pathogenic mechanisms between the two diseases. 2
• Both conditions involve immune responses against post-translationally modified protein antigens—citrullinated proteins in RA and deamidated gluten peptides in celiac disease. 3

Clinical Co-occurrence

While genetically linked, the actual clinical overlap is modest:

• Approximately 2-4% of patients with autoimmune hepatitis develop RA, and celiac disease can rarely co-occur with autoimmune conditions. 4
• The shared genetic susceptibility explains why autoimmune diseases cluster in families and individuals, but does not mean most patients will develop both conditions. 1

When to Screen for Celiac Disease in RA Patients

Do not perform routine screening of all RA patients for celiac disease. 1 Instead, test selectively when specific clinical triggers are present:

• Unexplained iron-deficiency anemia that is resistant to oral iron supplementation. 1, 5
• Chronic diarrhea, weight loss, or malabsorption symptoms that cannot be attributed to RA medications. 1, 5
• Persistent elevation of liver transaminases without another identifiable cause. 1
• Premature or disproportionate osteoporosis relative to RA disease activity and corticosteroid exposure. 1
• Fatigue that is disproportionate to RA activity and lacks another explanation. 1, 5

When to Assess for RA in Celiac Disease Patients

Evaluate celiac disease patients for RA when:

• Morning stiffness lasting more than 30 minutes develops. 1
• Clinical synovitis is detected on physical examination. 1
• New joint symptoms emerge that are not explained by nutritional deficiencies from celiac disease. 1

Diagnostic Confirmation for Celiac Disease

If screening is indicated based on the above criteria:

• Ensure the patient has consumed at least 10 grams of gluten daily for 6-8 weeks before testing to avoid false-negative results. 1
• Perform serologic testing with tissue transglutaminase IgA as the initial test. 5
• Duodenal biopsy is mandatory before initiating a lifelong gluten-free diet: obtain at least 4 biopsies from the second part of the duodenum and 1-2 from the duodenal bulb. 1

Clinical Pitfalls to Avoid

• Do not assume gastrointestinal symptoms in RA patients are solely medication-related without considering celiac disease when the clinical triggers listed above are present. 1, 5
• Remember that many celiac disease patients present with extraintestinal symptoms rather than classic diarrhea, and only about 24% of those with celiac disease are diagnosed. 5
• Do not test for celiac disease in patients already on a gluten-free diet, as this will yield false-negative results. 1, 5
• The presence of one autoimmune disease should lower your threshold for considering others, but does not mandate universal screening. 1