A 22-year-old man comes to the office due to worsening burning sensations in his hands and feet for the past several months. He also reports soreness in his mouth and has had intermittent episodes of a postprandial bloating sensation and diarrhea. The patient drinks alcohol occasionally but does not use tobacco or illicit drugs. He is sexually active and does not use condoms consistently. Vital signs are within normal limits. BMI is 20 kg/m2. On physical examination, the tongue appears red and smooth. The neck is supple and has no lymphadenopathy. Heart and lung sounds are normal. The abdomen is soft and nontender. Neurologic examination shows decreased pinprick and vibration sensation in the bilateral fingers and toes. Muscle strength and deep tendon reflexes are normal. Laboratory testing reveals microcytic anemia. Which of the following is the most likely underlying cause of this patient's symptoms?
Clinical manifestations of celiac disease | |
Gastrointestinal |
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Mucocutaneous |
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Endocrine |
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Bone disorders |
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Hematologic |
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Neuropsychiatric |
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This young patient has developed progressive paresthesia and sensory loss in a distal, symmetric, stocking-glove distribution. This is characteristic of a length-dependent axonal polyneuropathy, which raises concern for an underlying systemic disease. The findings of atrophic glossitis (ie, smooth, red tongue with burning pain), microcytic anemia, and gastrointestinal symptoms (eg, bloating, diarrhea) are suspicious for celiac disease.
Celiac disease is an autoimmune disorder triggered by gluten ingestion. Classically, an immune response to gliadin causes inflammation in the small intestine, resulting in atrophy of the villi, leading to malabsorption. In addition to gastrointestinal symptoms, malabsorption can result in other clinical manifestations, including iron deficiency anemia and bone mineral disorders related to vitamin D deficiency (eg, osteomalacia, osteoporosis, rickets).
Other extraintestinal manifestations of celiac disease may be related to an overlapping autoimmune response. Peripheral neuropathy, seen in up to 50% of patients, and other neuropsychiatric manifestations may be due to autoantibody production, rather than nutritional deficiency, because they often precede symptoms of malabsorption. Although atrophic glossitis may be caused by vitamin deficiencies, it might be due to autoantibodies, given that it manifests early in the disease course.
(Choice A) Chronic alcohol use can cause polyneuropathy. However, the severity typically correlates with lifetime alcohol consumption and therefore would be unlikely in a young patient who drinks occasionally. Postprandial diarrhea is uncommon with alcohol use.
(Choice C) Prolonged hyperglycemia in uncontrolled diabetes can cause distal symmetric polyneuropathy. However, this patient's atrophic glossitis, microcytic anemia, bloating, and diarrhea in the absence symptoms of diabetes mellitus type 1 (eg, polyuria, polydipsia) or risk factors for diabetes mellitus type 2 (eg, obesity) make celiac disease more likely.
(Choice D) Peripheral neuropathy can occur in patients with HIV either due to the neurotoxic effects of antiretroviral medications or to mitochondrial dysfunction related to virus activity. Sore throat and painful mucocutaneous ulceration, rather than atrophic glossitis, can be seen. Normocytic, rather than microcytic, anemia is common with HIV. In addition, most patients with HIV have constitutional symptoms and lymphadenopathy.
(Choice E) Hypothyroidism can cause polyneuropathy. However, in addition to sensory loss, decreased deep tendon reflexes are typically present. Constipation, rather than diarrhea, and normocytic anemia (due to decreased proliferation of erythrocyte precursors), rather than microcytic anemia, would also be expected.
Educational objective:
Celiac disease can present with a diverse array of symptoms related to malabsorption (eg, diarrhea, microcytic anemia, vitamin D deficiency) or autoimmune inflammation (eg, peripheral neuropathy, atrophic glossitis).