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Celiac Disease and Myopathy
Abstract & Commentary
By Michael Rubin, MD, Professor of Clinical Neurology, NewYork-Presbyterian Hospital, Weill Cornell Medical Center. Dr. Rubin is on the speaker's bureau for Athena Diagnostics, and does research for Pfizer and Merck.
Synopsis: Celiac disease is a cause of treatable inflammatory myopathy, and is easily diagnosed with serum antibody studies.
Source: Hadjivassiliou M et al. Myopathy associated with gluten sensitivity. Muscle Nerve. 2007;35;443-450.
Clinical manifestations of gluten sensitivity encompass diverse organ systems. When restricted to the gastrointestinal tract and associated with villous atrophy, crypt hyperplasia, and small bowel intraepithelial lymphocytosis, the term celiac disease is appropriate. Skin involvement defines dermatitis herpetiformis, while neuropathy or ataxia remain its most common neurologic expression. Myopathy, hitherto not well characterized, may also occur. Among 300 patients referred over 12 years to the Gluten Sensitivity/Neurology Clinic at The Royal Hallamshire Hospital, Sheffield England, 13 presented with myopathy, 4 of which additionally demonstrated neuropathy alone (=2) or ataxia and neuropathy (n=2). Only 1 was previously known to have celiac disease at the time of presentation. Workup failed to reveal any cause for myopathy other than gluten seropositivity in 12 patients, including positive IgG or IgA antigliadin (n = 12) or antiendomysial (n = 2) antibodies. Electrodiagnostic studies, duodenal biopsy, and muscle biopsy was performed following serologic diagnosis.
Mean age of onset was 54 years, with females outnumbering males (8:5). Weakness was proximal in 8 (62%), both proximal and distal in 4 (31%), and predominantly distal in 1 (8%). Creatine kinase (CK) was elevated in 11 (range 221-4380 IU/L, normal < 190), 10 had the HLA-DQ2 genotype, and 6 each had duodenal biopsy-proven enteropathy or associated autoimmune diseases included high thyroid antibodies (n = 3), hypothyroidism (n = 2), or inflammatory arthropathy (n = 1). Electrodiagnostic studies yielded normal nerve conduction studies in 10, with 3 showing loss of evoked motor potential amplitude. Needle electromyography revealed myopathic features in 10, demonstrating short-duration, small amplitude motor unit potentials in at least 1 proximal muscle, with fibrillation potentials seen in 2 of these patients. Inflammatory myositis was seen on biopsy in 6, 1 patient also having features of inclusion body myositis with basophilic rimmed vacuoles. Nonspecific myopathy was evident in the remaining biopsies.
Of 6 patients on a gluten-free diet and immunosuppressive therapy, 5 improved and one normalized serum CK values while remaining clinically unchanged. Of 7 patients solely on dietary management, 4 improved clinically with reduction or normalization of serum CK. Refusal to adopt a gluten free diet was associated with progressive myopathy in a single patient. Myopathy is a manifestation of gluten sensitivity, appears to be immune mediated, and may be positively affected by dietary control.
Screening for celiac disease, an immune non-IgE-mediated enteropathy, requires a blood test for measurement of anti-gliadin and anti-endomysial antibodies. Measurement of IgA autoantibodies to tissue transglutaminase (tTG), or endomysial antibody, has 95-100% sensitivity and specificity (Allergy Asthma Proc 2007,28:20-24). Concomitant measurement of serum IgA levels excludes the possibility of IgA deficiency and increases the validity of a negative test. Small bowel biopsy is then recommended to exclude the marginal likelihood of an alternative diagnosis. Among patients with screening positive serology, 25-30% will have negative biopsies and it remains unclear whether these represent false positive results, mild celiac disease, or autoantibody production of undetermined significance. Genetic testing is not useful for confirming the diagnosis.