Abstract and Commentary
Commentary by Michael Rubin, MD, Professor of Clinical Neurology, New York Presbyterian Hospital-Cornell Campus, and Assistant Editor, Neurology Alert.
Synopsis: Celiac disease is present in 2.4% of patients referred for suspected dysautonomia, similar to the 2.5% incidence of celiac disease in idiopathic peripheral neuropathy.
Source: Gibbons CH, et al. Autonomic Neuropathy and Celiac Disease. J Neurol Neurosurg Psychiatry. 2005;76;579-581.
Celiac disease (gluten enteropathy) is associated with neurologic involvement at all levels of the neuraxis, including hemispheral white matter, peripheral sensory, and motor nerve fibers and muscle. Symptomatic autonomic nervous system involvement has previously not been documented. Retrospective review of all 164 patients referred to the Autonomic Function Laboratory at Beth Israel Deaconess Medical Center in Boston, during a 1-year period, revealed 4 patients, 1 man and 3 women, aged 38 to 78 years, with autonomic dysfunction and celiac disease, documented by small bowel biopsy and IgA anti-gliadin antibodies. Two additional patients were excluded from analysis, one each because of lack of confirmatory biopsy or concomitant diabetes. All 4 study subjects complained of postural-nausea on standing or sitting, but not when lying down, despite a gluten-free diet, lightheadedness, and syncope or presyncope. Other symptoms included palpitations, fatigue, weakness, and dizziness. Formal neurological examination was normal in all. Autonomic function studies included heart rate variation with respiration and Valsalva, heart rate and lowest blood pressure response to tilt, and blood pressure response to standing for 5 minutes. Valsalva heart rate response, a measure of cardiac parasympathetic activity, was abnormal in 3. Valsalva blood pressure response was abnormal in all, and orthostatic hypotension on tilt-table testing and postural tachycardia syndrome was present in 2. Celiac disease is present in 2.4% of patients referred for suspected dysautonomia, similar to the 2.5% incidence of celiac disease in idiopathic peripheral neuropathy. However, given a 40% incidence of anti-gliadin antibodies in the latter and a 6-12% incidence in the general population, a causal relationship has yet to be demonstrated.
Commentary
Celiac disease is common, with a prevalence approaching 1% in Europe and the United States. It may be asymptomatic or present with severe malnutrition, but often causes abdominal pain, weight loss, anemia, chronic diarrhea, and weakness. In its atypical form, extra-intestinal manifestations override the former, and include short stature, infertility, cardiomyopathy, hepatitis, and neurologic disease comprising ataxia, neuropathy, epilepsy, and migraine (Alaedini A, et al. Ann Intern Med. 2005:142;289-298).
Small bowel villous atrophy, crypt hyperplasia, and lymphocytic infiltration are the end result of an inflammatory response triggered by wheat gluten and related proteins, particularly in rye and barley. Human leukocyte antigens, DQ2 and DQ8, confer disease susceptibility by presenting intestinal T-cells with gluten peptides, but antibodies to transglutaminase 2 (tissue transglutaminase) are also strongly associated with the disease. Diagnosis is best approached by first obtaining serological confirmation. IgA anti-transglutaminase 2 (anti-endomysial) is more specific than the IgG isotype but IgA deficiency, seen in up to 2.6% of the celiac population, mandates that all patients undergo total IgA measurement. If low, IgG anti-transglutaminase 2 (anti-endomysial) or antigliadin antibody measurement is warranted. If all are negative, the probability of celiac disease is low, but biopsy may be pursued if suspicion remains high. If either IgA or IgG transglutaminase 2 (anti-endomysial) or antigliadin antibody is positive, intestinal biopsy is indicated to document the histologic features. If a gluten-free diet then results in improvement, the diagnosis is confirmed. Pitfalls in diagnosis include false negative or equivocal biopsy due to the patchiness of the intestinal damage, poor sensitivity or specificity of the anti-transglutaminase 2 antibody test, IgA deficiency, or previous immunosuppressive therapy, which may result in false negative antibody studies. Negative HLA-DQ2 and HLA-DQ8 markers have excellent predictive value in excluding the diagnosis, as nearly all celiac patients are positive for at least one. Treatment is straightforward: strict avoidance of gluten-containing foods, wheat, rye, or barley. Acceptable alternatives include rice, corn, quinoa, and buckwheat (Alaedini A, et al. Ann Intern Med. 2005:142;289-298). — Michael Rubin
Celiac disease is present in 2.4% of patients referred for suspected dysautonomia, similar to the 2.5% incidence of celiac disease in idiopathic peripheral neuropathy.
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