Extraintestinal Manifestations of Celiac Disease
Celiac disease frequently presents with extraintestinal manifestations affecting multiple organ systems—including dermatological, musculoskeletal, neurological, hematological, hepatic, and reproductive systems—often without any gastrointestinal symptoms, making recognition of these manifestations critical for diagnosis. 1
Dermatological Manifestations
Dermatitis herpetiformis (DH) is the pathognomonic cutaneous manifestation of celiac disease, characterized by intensely itchy, herpetiform clusters of urticated papules and small blisters on the extensor surfaces of elbows and knees, buttocks, and scalp. 2, 3
- DH occurs most commonly between the third and fourth decades, with males affected twice as often as females. 2
- The diagnostic criterion is granular IgA deposits in dermal papillae of uninvolved perilesional skin on direct immunofluorescence—diagnosis should not be made without this confirmation. 2
- Approximately 70% of DH patients have total or subtotal villous atrophy, while 25% have normal villous architecture with increased intraepithelial lymphocytes. 2
- Less than 10% of DH patients have malabsorption symptoms at presentation, though most have underlying celiac disease that responds to a gluten-free diet. 2
- More than 70% of patients on strict gluten-free diet can wean off dapsone over 24 months. 2
Other cutaneous manifestations include alopecia, angular stomatitis, aphthous ulcerations, and chronic urticaria, all of which may improve with gluten-free diet. 4, 5, 6
Musculoskeletal Manifestations
Osteopenia and osteoporosis are among the most common extraintestinal manifestations, with worldwide prevalence ranging from 1.7% to 42% depending on sex, geography, age at diagnosis, and clinical phenotype. 1, 7
- Fracture risk shows 60-100% excess compared to the general population before diagnosis. 1, 7
- Fracture risk normalizes after the first year on gluten-free diet despite persistent low bone mineral density. 1
- Treatment with gluten-free diet results in improvements in bone mineral density, with greatest improvements in the first years of treatment. 2
Hematological Manifestations
Iron deficiency anemia is the most common hematological manifestation, affecting 48% of adults at presentation and frequently resistant to oral iron supplementation. 1, 7
- Anemia may occur even in the absence of gastrointestinal symptoms. 1, 3
- Other nutritional deficiencies include folic acid, vitamin B12, and vitamin D deficiencies. 5
Neurological and Psychiatric Manifestations
Cerebellar ataxia is a well-established neurological complication that can occur as both a complication and presenting manifestation. 1, 7
- Peripheral neuropathy occurs frequently in celiac disease patients. 1, 3
- Epilepsy and seizures are documented in both children and adults. 1, 7
- Depression and psychiatric disorders affect approximately 24% of adults with celiac disease. 1, 7
- Irritability and inability to concentrate are particularly noted in children. 7, 8
Reproductive and Endocrine Manifestations
Infertility and recurrent miscarriages are associated with untreated celiac disease, along with adverse pregnancy outcomes in undiagnosed disease. 1, 7, 5
- Short stature is the most common extraintestinal manifestation in children (33%), though 28% of those unresponsive to gluten-free diet have other comorbidities. 1, 7
- Growth failure and delayed tooth eruption are significant pediatric concerns. 8, 5
Hepatic Manifestations
Patients with autoimmune liver disease should be screened for celiac disease, as unexplained elevation of transaminases may be the presenting feature. 1, 5
Oral Manifestations
Dental enamel hypoplasia, delayed tooth eruption, and recurrent oral aphthae are recognized oral manifestations of celiac disease. 5
Associated Autoimmune Conditions
Type 1 diabetes has a 5-10% prevalence in celiac patients, requiring screening particularly in those with unexplained hypoglycemia or deteriorating glycemic control. 1, 7
- Autoimmune thyroid disease has a 3% prevalence of celiac disease. 1, 7
- Down syndrome has a confirmed celiac prevalence of 5.5%. 1, 7
- Turner syndrome has a celiac prevalence of 6.3%. 1, 7
Critical Clinical Pitfalls
Many patients present exclusively with extraintestinal symptoms without gastrointestinal complaints, leading to significant diagnostic delay. 1, 7, 8
- Only 24% of those with celiac disease are diagnosed, creating a "celiac iceberg" of undiagnosed cases. 1, 7, 8
- Extraintestinal manifestations can occur even in potential celiac disease patients with normal small intestinal biopsies, and these patients may benefit from gluten-free diet before end-stage intestinal disease develops. 9
- Left undiagnosed and untreated, even asymptomatic celiac disease leads to higher risk of complications including osteoporosis, infertility, and small bowel lymphoma. 1
- DH shares with celiac disease an increased risk of developing lymphomas, particularly in those with severe gut involvement, though this risk declines with time on strict gluten-free diet. 2