Celiac disease is an immune-mediated disorder of the small intestine, which is triggered by dietary gluten in persons with genetic predisposition to the disease. Adults with celiac disease mostly do not present with the typical gastrointestinal signs and symptoms such as diarrhea, bloating. Extraintestinal presentations are more common; hence, diagnosis of celiac disease in the adult population is not easy. The patient moves through a gamut of specialities before celiac disease is thought of as the cause for the symptoms. Undiagnosed and therefore untreated disease can lead to severe complications, both intestinal and extraintestinal. Timely recognition of the atypical presentations is of paramount importance for better patient outcomes. 

The cutaneous manifestations include dermatitis herpetiformis, atopic dermatitis, psoriasis, urticaria, alopecia areata and chronic ulcerative stomatitis. Dermatitis herpetiformis is the most common extra-intestinal manifestation of celiac disease. Lesions in the oral cavity include recurrent aphthous stomatitis, delayed dental eruption and enamel defects. Some of the other cutaneous manifestations include cutaneous vasculitis, pemphigus, hereditary angioneurotic edema, erythema nodosum, vitiligo, oral lichen planus, dermatomyositis, porphyria, pyoderma gangrenosum, ichthyosiform dermatoses, pellagra and skin malignancies.

Neurological disorders are not infrequent in patients with celiac disease and include ataxia (most common), gluten neuropathy, headache, epilepsy and cognitive impairment. Sometimes, the only presenting feature of celiac disease may be cerebellar ataxia, also called “gluten ataxia”. The most common neuropsychiatric manifestations include depression, anxiety, attention deficit/hyperactivity disorder (ADHD) and autism.

Liver involvement in celiac disease patients may present as isolated hypertransaminasemia and has been termed as “gluten-induced hepatitis”. Therefore, patients who present with raised aminotransferase levels without any identified liver disease or no other explanation for the high transaminase levels should be evaluated for celiac disease. And, celiac disease should be a part of differential diagnosis of hepatitis.

Infertility may be another manifestation of celiac disease. Women presenting with infertility must be tested for celiac disease. Late menarche, secondary amenorrhea, early menopause, recurrent miscarriages and preterm pregnancy are few other reproductive manifestations of celiac disease.

Endocrinological disorders include type 1 diabetes mellitus (T1DM), autoimmune thyroiditis, autoimmune polyendocrine syndrome. These do not resolve with gluten-free diet, whereas cutaneous, neuropsychiatric, hepatic, and reproductive manifestations may even completely disappear following strict adherence to gluten-free diet. Hence, endocrinological disorders are characteristically called as “associated diseases” of celiac disease.

This article gives an overview of the major extraintestinal manifestations of celiac disease, which relate to cutaneous disorders, neurological and neuropsychiatric disorders and abnormalities of the liver and the reproductive system. The authors conclude by stating that awareness about these extra-intestinal signs and symptoms will expedite appropriate investigation of the patient and early institution of gluten-free diet.

Durazzo M, et al. J Clin Med. 2022 Jan 4;11(1):258.