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Patients with celiac disease may be at increased risk of neuropathy, Swedish researchers found.

In a large population-based, case-control study, patients who had biopsy-confirmed celiac disease were 2.5 times more likely to be diagnosed with neuropathy, , of the Karolinska Institute, in Stockholm, and colleagues .

"Given the autoimmune nature of celiac disease, our data reinforce the potential role of immunologic mechanisms for the development of neuropathy," they wrote.

Celiac disease is an immune-mediated enteropathy that occurs in genetically susceptible patients as a result of sensitivity to gluten. Its estimated prevalence is 1% in the general population.

Extra-intestinal neurology manifestations of celiac have been described in the literature, but there are few prevalence estimates of celiac-associated neuropathy, the researchers said.

To determine that prevalence, as well as the relative and absolute risks of developing neuropathy in celiac disease patients, Ludvigsson and colleagues looked at data from 28,232 patients who had their celiac disease confirmed by a biopsy and compared them with 139,473 matched controls.

They found that the absolute risk of neuropathy was 64 per 100,000 person-years in celiac patients within 1 year of celiac disease diagnosis, compared with 15 per 100,000 person-years for the general population.

That corresponded with hazard ratio of 2.5 for later neuropathy diagnosis (95% CI 2.1-3.0, P<0.001).

Risk remained similar when the analysis was controlled for a multitude of factors, including educational level, socioeconomic status, country of birth, type 1 and type 2 diabetes, autoimmune thyroid disease, rheumatologic diseases, pernicious anemia, vitamin deficiencies, and alcoholic disorders, the researchers wrote.

Risk estimates for neuropathy were highest in the first year after celiac diagnosis (HR 4.4, 95% CI 2.67-7.4, P<0.001), but there was still a significantly increased risk of neuropathy after the first year of follow-up, they reported.

There were no gender differences in neuropathy risk in celiac patients, they added.

Ludgivsson and colleagues also examined subtypes of neuropathy and found an increased risk of the following types:

• Chronic inflammatory demyelinating neuropathy (HR 2.8, 95% CI 1.6-5.1, P=0.001)
• Autonomic neuropathy (HR 4.2, 95% CI 1.4-12.3, P=0.009)
• Mononeuritis multiplex (HR 7.6, 95% CI 1.8-32.4, P=0.006)

However, there was no association between celiac disease and acute inflammatory demyelinating polyneuropathy, they reported.

Interestingly, in a separate analysis, the researchers found that patients with neuropathy were also at increased risk of future celiac disease (OR 1.8, 95% CI 1.4-2.2, P<0.001).

"There was also a bidirectional association between celiac disease and neuropathy, since patients with neuropathy were also at increased risk of future celiac disease," they wrote.

Ludvigsson and colleagues acknowledged that part of the increased risk of neuropathy may be due to surveillance bias, as physicians may be more likely to investigate patients with celiac for neuropathy. But they noted that the consistent excess risk of neuropathy, which lasted beyond 5 years after a diagnosis of celiac, makes that less likely.

They concluded that the data "may also suggest that the two diseases may share risk factors or a common underlying etiology for the development of neuropathy, such as a potential role of immunologic mechanisms. The association between celiac and different types of neuropathy suggests that there may be specific underlying mechanisms that may lead to the predominance of one type of neuropathy compared with others."

Based on their findings, they recommend that patients with neuropathy be screened for celiac disease.

"Although absolute risks for neuropathy are low, celiac is a potentially treatable condition with a young age of onset," they wrote. "Our findings suggest that screening could be beneficial in patients with neuropathy."

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