Headache Associated with Coeliac Disease: A Systematic Review and Meta-Analysis

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Gluten-related disorders (GRDs) represent a diverse spectrum of clinical entities for which the ingestion of gluten is a common trigger. Although the gastrointestinal manifestations of GRDs are the most prevalent, a range of debilitating neurological manifestations are increasingly being recognised in clinical practice, often preceding or in the absence of gastro intestinal (GI) symptoms.

The most well-known neurological GRDs are cerebellar ataxia and peripheral neuropathy, however clear links between gluten sensitivity (GS)/ coeliac disease (CD) and epilepsy, various movement disorders, and headaches have also been described.
 
The aim of this paper was to systematically review the current literature in order to establish the relationship between headache and CD. A systematic search of the PubMed database was performed to identify studies in which subjects were diagnosed with idiopathic headache and gluten sensitivity or coeliac disease. In total 40 articles published between 1987 and 2017 qualified for inclusion in this review, studying a total of 42,388 individuals with either headache or GRD (mean number of patients per citation 1059.7 ± 4626.5). Eighteen studies were conducted in paediatric populations whilst a further 18 were conducted amongst adults, four studies involved mixed populations.

Prevalence of headache amongst patients with CD

Information about the prevalence of headache in adults with CD was available through five cohort and
four case-controlled studies. The pooled mean prevalence of headache in adults with CD was 26% (95% CI 19.5–33.9%). A meta-analysis of the four case-controlled studies revealed the odds of having a headache were significantly higher amongst those with CD versus controls (OR 2.7, 95% CI 1.7–4.3, p < 0.0001). Information about the prevalence of headache in children and adolescents was available through five cohort, one case-controlled, and one population-based study. The pooled mean prevalence of headache in children and adolescents with CD was 18.3% (95% CI 10.4–30.2%). A cross-sectional, population-based study investigating the association between CD and various comorbidities, demonstrated that the odds of suffering from headache were significantly higher in children and adolescents with CD when compared to controls (OR 2.3, 95% CI 2.1–2.5, p < 0.0001).
 

Prevalence of CD amongst patients with idiopathic headache

Conversely, several studies have compared the prevalence of CD amongst patients with idiopathic headache. Headache, usually migraine, has been reported as the first manifestation of CD in several case
Reports. In a case-controlled study investigating the prevalence of CD amongst 90 adults with idiopathic migraine, compared to blood donor controls, found that 4.4% of subjects had CD, compared with 0.4% of controls (p < 0.05). Information about prevalence of CD in children with headache was available through two case-control and two cohort studies. The pooled mean prevalence of CD in children with idiopathic headache was 2.4% (95% CI 1.5–3.7%), significantly higher when compared to the prevalence of CD in the general population in the same age group. Although in one of these studies the authors conclude that that the prevalence of CD was not higher in patients with migraine relative to the control group, the other three studies concluded that the odds of a child with headache having CD is significantly higher than in children without headaches, with OR ranging from, 1.7 – 8.3.

Further headline findings from this meta-analysis:

  • There is an increased prevalence of headache amongst patients with CD and an increased prevalence of CD amongst those with idiopathic headache. Such an increased prevalence is evident in both child and adult populations; however, the figures are higher in the latter.
  • Headaches that are associated with CD are predominantly migraines. However, many studies that were used in this report tended to report headaches without specifying the exact type (i.e., tension, cluster, migraine, etc.) making the interpretation of the findings more difficult.
  • Computed Tomography (CT) calcifications and white matter abnormalities (WMA) are frequent in patients with headaches that are related to CD, therefore patients with such imaging findings in in the context of idiopathic headache require further testing for CD.
  • A gluten-free diet (GFD) is a very effective treatment for headaches associated with CD and should therefore be offered as soon as possible. Specialist dietary advise should always be offered, as often patients consume gluten, whilst believe that they are on a strict GFD.
  • Further studies of the prevalence of GS in patients with idiopathic headache are needed. Although there is some evidence that brain hypoperfusion and perivascular inflammation might play a role in the pathogenesis of GS-related headaches more studies on the likely pathogenetic mechanisms are needed.

Serum positivity for TG6 antibodies have been identified as a sensitive measure of neurological involvement in GS. Therefore, a study of the prevalence of TG6 antibodies in patients with headaches that are related to CD and GS should be conducted.

 

Panagiotis Zis, Thomas Julian and Marios Hadjivassiliou
Nutrients 2018, 10, 1445; doi:10.3390/nu10101445

 

Link to full study