22 May, 15 | by EBM
By: Dr. Geoffrey Modest
Peripheral neuropathy has been associated with celiac disease in past studies, typically based in referral centers. The current population-based study in Sweden looked more systematically at the association (see doi:10.1001/jamaneurol.2015.0475). As background, celiac disease is pretty common, with prevalence of about 1%, and peripheral neuropathy is present in 2-7% of the population. Details of the study:
–Data collected on small intestine biopsies performed at Sweden’s 28 pathology departments from 1969-2008
–They compared the risk of neuropathy in 28,232 patients with celiac disease vs 139,473 age- and sex-matched controls (median age at diagnosis of 29: 42% were 0-19 yo, 18% 20-39, 22% 40-59, 18% >60; 62% female; comorbidity of type 1 diabetes in 3.2 vs 0.4% in controls, alcohol use in 2.7 vs 2.6%). Patients had confirmed celiac disease (CD), with villous atrophy, Marsh 3
–CD was associated with a 2.5-fold (2.1-3.0, p<0.001) increased risk of later neuropathy (0.7% vs 0.3% in controls, absolute risk of 64/100K vs 15/100K)
–CD also associated with increased risk of
–chronic inflammatory demyelinating neuropathy: 2.8-fold (1.6-5.1, p<0.001)
–autonomic neuropathy: 4.2-fold (1.4-12.3, p=0.009)
–mononeuritis multiplex: 7.6-fold (1.8-32.4, p=0.006)
–but not with acute inflammatory demyelinating polyneuropathy: 0.8-fold (0.3-2.1, p=0.68)
–No difference in neuropathy by sex, or age. Overall risk decreased minimally from 2.5 fold to 2.3-fold (1.9-2.7) after controlling for educational level, SES, type 1 or 2 diabetes, autoimmune thyroid disease, rheumatologic diseases, pernicious anemia, vitamin deficiencies, and alcoholic disorders.
–Association with neuropathy was pretty consistent in group with <1 yr of followup vs 1-5 yr, vs >5 yr
–There was a positive association between any neuropathy and CD, even when the diagnosis of neuropathy preceded the diagnosis of CD with an odds ratio of 1.8; 1.4-2.2, p<0.001
So, seems like we really should add an evaluation for CD as part of our neuropathy workup. In small studies, it seems that the association of CD with neuropathy is not necessarily associated with CD-related vitamin deficiencies (one study of 18 patients with confirmed CD and neuropathy found that they all had normal vitamin B12 levels). My sense, given the pretty low absolute association as noted above in Sweden, is that screening questions about GI symptoms seem appropriate. It might also be reasonable to perform serologic studies for CD, since there are some data suggesting that a gluten-free diet may either prevent or ameliorate the neuropathy (this is not very robust data), and on the other hand there are data suggesting that there are many people with “asymptomatic” CD who actually do feel better on a gluten-free diet, they might have significant malabsorption issues that should be detected/addressed, and (data not so robust) asymptomatic patients may still be at higher risk of lymphoma or autoimmune diseases which decreases with a gluten-free diet.