Celiac disease (CD), which is one of the most important malabsorptive diseases in adults, has been associated with several neurological disorders including peripheral neuropathy, cerebellar ataxia, myopathy, and attention deficit hyperactivity disorders. Recently, 2 independent studies 1,2 reported a high prevalence of restless legs syndrome (RLS) in CD patients (25%-31%). In the first study, 1 iron deficiency was present in 40% of CD patients with active RLS compared with 6% of patients without RLS, whereas in the second study, 2 no significant correlation was found between RLS and iron parameters. Other authors 3 reported 4 patients with RLS and serum ferritin below 25 ng/mL whose screening tests were positive for CD. Because these data suggest that CD is frequently associated with RLS and because CD could be an underlying correctable factor for some patients diagnosed with idiopathic RLS, we evaluated the absorptive status in 112 consecutive patients referred to our Sleep Disorders Center (68 women, 44 men; mean age, 59.6 years) with a diagnosis of idiopathic RLS. The diagnosis of RLS was made by face-to-face interview using International Restless Legs Syndrome Study Group (IRLSSG) criteria. 4 In our patients, mean RLS severity according to the IRLSSG rating scale 5 was 24.9 (range, 10-38). Using current criteria, 6 CD diagnosis was based on the presence of specific screening antibodies in serum (antitransglutaminase IgAtTG) and on the evidence of intestinal damage at duodenal biopsy.
For investigating malabsorption in our RLS patients, the following typical symptoms and signs of CD 7 were considered: abdominal pain, anorexia, diarrhea, flatulence, muscle wasting, vomiting, and weight loss. Moreover, all patients were tested for anti-tTG antibodies with the Eu-tTG Quick test (refence 9113, lot 3368, Eurospital). 8 Symptoms and signs of malabsorption in our RLS patients were uncommon (diarrhea in 14.3%, flatulence in 3.6%, abdominal pain in 1.8%).
In our sample, only 2 patients affected by CD (1.8%) were found: a woman (age 57 years; body mass index, 23.3; serum ferritin level, 9 ng/mL; IRLSSG rating scale score ΒΌ 18) positive for anti-tTG antibodies by the eu-tTG Quick Test (CD diagnosis confirmed by duodenal biopsy) and another woman (age 74; body mass index, 18.0; serum ferritin level, 15 ng/mL; IRLSSG rating scale score ΒΌ 38) whose Eu-tTG Quick test was negative because of a gluten-free diet, but with a previous diagnosis of CD confirmed by duodenal biopsy. No cause for the iron deficiency was found in these 2 cases other than CD. Both patients had a family history positive for RLS. The first patient had never received specific treatments for RLS, whereas the second patient had used only clonazepam (0.5 mg/day) for several months without significant effect on her RLS symptoms.
In the first patient, a gluten-free diet and supplemental iron (4 treatments of 200 mg of intravenous iron sucrose spread over 1 week) determined an increase in serum ferritin level to 46 ng/mL without any significant improvement in RLS symptoms (IRLSSG rating scale score ΒΌ 15). The second patient, already on a gluten-free diet, with the supplemental iron (5 treatments of 200 mg of intravenous iron sucrose spread over 1 week) had an increase in serum ferritin (39 ng/mL) with a concomitant marked improvement in RLS (IRLSSG rating scale score ΒΌ 13).
The currently estimated prevalence of CD is 1%, with a statistical range of probability of 0.5%-1.26% in the general population in Europe and the United States. 6 In our sample of consecutive patients with RLS, the prevalence of CD was 1.8%; thus, it is very difficult to state that CD is frequently associated with RLS. By observing our cases, we cannot conclude that gluten withdrawal determined an improvement in RLS symptoms. In both our patients we observed very low ferritin levels, and this seems to suggest that CD may be associated with RLS because of an association with iron deficiency. However, in a previous study in a CD population, 2 we found lower hemoglobin levels in CD patients with RLS than in those without RLS, but no significant correlation between the presence of RLS and iron metabolism. Finally, the marked improvement observed in our second patient suggests that before providing specific treatments with dopaminergic compounds for RLS, a gluten-free diet and supplemental iron should be considered in patients with RLS plus CD.