How Celiac Disease Causes Both Iron Deficiency Anemia and Joint Pain
Celiac disease causes iron deficiency anemia through duodenal villous atrophy that disrupts iron absorption at its primary site, while joint pain occurs as an extraintestinal immunological manifestation that can present even before gastrointestinal symptoms become apparent.
Mechanism of Iron Deficiency Anemia in Celiac Disease
Primary Malabsorption Pathway
Iron deficiency occurs in celiac disease as a result of epithelial cell injury and subsequent duodenal villous atrophy, which disrupts normal absorption at the duodenum—the primary site of iron uptake 1.
The severity of anemia correlates with the degree of mucosal damage: patients with celiac disease who are anemic at presentation tend to have higher anti-tissue transglutaminase levels and higher degrees of villous atrophy than non-anemic patients 1.
Malabsorption from celiac disease is the most common cause of iron deficiency anemia in the UK after gastrointestinal blood loss 1.
Secondary Inflammatory Mechanisms
Beyond direct malabsorption, the chronic inflammation in celiac disease triggers anemia of chronic disease (ACD), creating a dual mechanism where both true iron deficiency and inflammatory anemia coexist 1, 2.
The inflammatory process affects iron metabolism independently of absorption, with elevated inflammatory markers (CRP, ESR) altering ferritin levels and making diagnosis more complex 1.
Persistent Iron Deficiency Despite Treatment
Up to 20% of patients remain iron deficient even with strict gluten avoidance, suggesting ultrastructural and molecular alterations in enterocytes may persist despite histological healing 1, 3.
Some patients show persistent iron deficiency anemia despite normalization of villous atrophy on biopsy, indicating that the Marsh classification does not capture all functional absorptive defects 3.
Mechanism of Joint Pain in Celiac Disease
Immunological Extraintestinal Manifestation
Joint manifestations are common early features of celiac disease that are frequently overlooked and can present as unexplained inflammatory polyarthralgia 4.
The joint pain represents an extraintestinal immunological manifestation of the autoimmune process, occurring through immune-mediated mechanisms rather than direct gluten exposure to joints 4.
Clinical Presentation Pattern
Joint symptoms can occur even in the absence of classic gastrointestinal symptoms like diarrhea or weight loss, making celiac disease an important differential diagnosis for unexplained polyarthralgia 4.
The autoimmune nature of celiac disease means it frequently coexists with other autoimmune conditions (such as autoimmune thyroiditis), which may contribute to joint symptoms 4.
Clinical Implications and Diagnostic Approach
Screening Recommendations
All premenopausal women with iron deficiency anemia should be screened for celiac disease using tissue transglutaminase (tTG) antibody or endomysial antibody testing 1.
All patients with iron deficiency anemia should be screened for celiac disease regardless of the presence or absence of gastrointestinal symptoms 1.
Diagnostic Pitfalls
Celiac disease is present in 2% to 6% of asymptomatic patients with iron deficiency anemia, making it easy to miss without systematic screening 1.
The combination of unexplained polyarthralgia and iron deficiency anemia should prompt immediate celiac disease screening, as this presentation is characteristic 4.
In patients over 50 years or with marked anemia or significant family history of colorectal carcinoma, lower gastrointestinal investigation should still be considered even if celiac disease is found, as dual pathology can occur 1.
Treatment Considerations
Most patients without another explanation for iron deficiency will see anemia improve after initiation of a strict gluten-free diet even without iron supplementation, though response can be slow 1.
Oral iron supplementation is less likely to be effective in patients with more severe degrees of villous atrophy, and intravenous iron may be indicated in these patients or those with more severe symptoms 1.
Recovery from anemia usually occurs within 1 year after commencement of a strict gluten-free diet, but 6% of patients still have iron deficiency anemia after 1 year, especially women 1.