Pauline Anderson

July 03, 2012

July 3, 2012 (Los Angeles, California) — Two new studies provide more evidence of a link between migraine headaches and rhinitis.

The research shows not only that rhinitis is common in those with migraine headache, but also that migraine patients with allergic and nonallergic rhinitis triggers have more frequent and disabling headaches.

The 2 studies were presented here during the American Headache Society's 54th Annual Meeting.

Earlier research has shown that immunotherapy, commonly called allergy shots, is associated with reduced frequency and disability of migraine headache in younger patients with allergic rhinitis. Together, these results suggest that people who suffer migraines and rhinitis may represent a particularly severe clinical phenotype.

Evidence indicates that the trigeminal nerve that carries pain impulses from the periphery to the central nervous system may involve more than just the dura mater of the brain, and could encompass mast cells that play a key role in allergies, researchers speculate.

"This research is completely new and has the ability to change the way we think about migraine headache," lead author Vincent Martin, MD, professor of clinical medicine, at the University of Cincinnati School of Medicine, told Medscape Medical News. "Right now, people just focus on the trigeminal afferents that innervate the dura."

"The nose and sinuses could play a much bigger role in triggering migraine than previously recognized, as trigeminal afferents richly innervate the nose and paranasal sinuses," said Dr. Martin. "We hypothesize that a hypersensitized trigeminal system in the nose as seen in migraine patients may be activated and sensitized by allergic and nonallergic rhinitis triggers."

Population Study

The first study was a longitudinal, population-based study of respondents to a 2008 survey mailed to a sample of US households. The survey included questions on headache frequency, headache-related disability, and allergic and nonallergic rhinitis triggers.

The analysis included 6008 survey respondents meeting criteria for migraine who were divided into rhinitis and nonrhinitis groups based on the presence or absence of 2 or more rhinitis symptoms. Those with rhinitis were classified into those who reported only allergic triggers (AR), such as cats, dogs, and mildew; those with only nonallergic rhinitis (NAR) triggers, for example, smoking, perfumes, and weather; and those with both allergic and nonallergic triggers, or mixed rhinitis (MR).

Primary outcome measures included headache frequency (0-4, 5-9, 10-14, and 15 or more days/month) and headache-related disability (Migraine Disability Assessment Score [MIDAS] total score corresponding to MIDAS grades 0-5, 6-10, 11-20, and 20 or greater). The authors adjusted for age, gender, body mass index (BMI), use of migraine prevention agents, and medication overuse.

The analysis showed that rhinitis occurred in 65% of subjects: AR (n = 737), NAR (n = 379), MR (n = 1869), and unclassified (UC) (n = 924). The odds ratio (OR) for increasing migraine frequency for rhinitis overall was 1.30 (95% confidence interval [CI], 1.11-1.54); among rhinitis subtypes, it was significant for MR and UC.

In terms of headache-related disability (MIDAS sum score), the OR was 1.32 (95% CI, 1.13-1.54) for rhinitis overall compared with controls and was increased for the MR subtype.

"It seemed to be that the subgroup of patients who reported allergic and nonallergic triggers had a particularly high frequency of headache and also more disabling headaches as evidenced by MIDAS scores," said Dr. Martin.

"This could mean that allergic or nonallergic rhinitis triggers may directly activate trigeminal afferents in the nose, which could increase the frequency and disability of headache, or that a very hypersensitized trigeminal system is more responsive to allergic and nonallergic triggers," Dr. Martin suggested. "Regardless, it tends to identify a very severe phenotype of migraine."

"The results indicate that rhinitis is very common in headache patients," stated Dr. Martin. "It's the most common comorbid illness in patients with migraine; it's far more common than depression or anxiety; you're talking about 65% of the population, while depression might be something like 25%."

Clinic Study

A second study expanded the association between headache and rhinitis. Again, the study pointed to a pathway beyond the dura that may be involved in triggering headaches.

"It's pretty unique to have 2 observational studies from 2 separate populations that are implicating rhinitis as having more frequent and disabling headaches," commented Dr. Martin.

This second study was much better characterized as to the diagnosis of rhinitis subtypes, according to Dr. Martin.

This cross-sectional observational study used data from the Migraine, Allergy, and Rhinitis Study (MARS), which included adult rhinitis patients from an allergy clinic and control subjects from a primary care internal medicine practice.

A subgroup of these patients with a diagnosis of migraine headache participated in the study (n = 366). Patients from the allergy practice were phenotyped as AR (n = 99), MR (n = 143), and NAR (n = 59) based on allergy testing and irritant questionnaires. Controls (n = 65) reported rhinitis symptoms "rarely" or "never" to allergic and nonallergic triggers.

Researchers determined the headache characteristics and frequency (days/month) and duration of headaches among all participants, who were then assigned a headache diagnosis by a headache specialist blinded to the rhinitis diagnosis. The MIDAS score served as an indicator of their headache-related disability. Researchers then compared the frequency of migraine and the headache-related disability between these groups at the 25th, 50th, and 75th percentiles of these outcome measures.

They found that migraine frequency and disability were significantly higher at the 25th, 50th, and 75th percentiles in each of the rhinitis groups compared with nonrhinitis controls (all P values < .02).

Effect sizes were greater in the nonallergic rhinitis phenotypes (MR, NAR) compared with AR. AR patients experienced 0.37, 0.62, and 1.5 additional days per month of migraine at the 25th, 50th, and 75th percentiles compared with controls, while MR/NAR patients experienced 0.67/0.58, 1.00/1.64, and 3.43/4.58 additional days, respectively, at these percentiles.

"Not only does the relationship become much greater as people have more frequent headaches, you also notice that the effects seem to be the greatest in those that had the mixed and nonallergic triggers," said Dr. Martin.

Allergy Shots as Migraine Treatment?

"These results could have important implications for treatment approaches," said Dr. Martin. Today, almost all headache patients are treated the same way. "We don't have any separate treatment for one group over another, but it could be that certain subgroups of patients might have different clinical phenotypes much like you see with rhinitis, and that those patients might deserve different treatments."

Dr. Martin has already reported that allergy shots might be a successful treatment route for some patients. His earlier study compared patients in an allergy clinic who received immunotherapy with those who did not. The study showed that those receiving allergy shots had 50% fewer self-reported migraine days per month and 50% less disability—but only patients who were younger than 45 years.

"This makes some sense," said Dr. Martin, "as allergies peak in younger age groups."

Allergic triggers could be mediated by mast cells that release histamine and other chemicals and are in close proximity to the trigeminal nerve in the nose and the dura. "I think that both areas are involved in migraine," stated Dr. Martin. "The mast cell and its relationship to allergies is probably where I'd put my money. If you could identify patients that had a real hypersensitized mast cell, then you would target therapies toward that."

In his own practice, Dr. Martin treats patients he thinks have allergic rhinitis with nasal steroids, nasal antihistamines, and montelukast.

"The studies presented here add to the 'evolving evidence' that there might be multiple ways to activate this trigeminal system and initiate a migraine," explained Dr. Martin. He cautioned, however, that firm conclusions about cause and effect cannot be made from this research.

Asked to comment on these findings, Randolph W. Evans, MD, clinical professor of neurology, at Baylor College of Medicine, Houston, Texas, said he found these new studies 'intriguing."

"They provide further evidence for the link between chronic rhinitis and migraine," he told Medscape Medical News.

Replication of the study by Dr. Martin and his colleagues, which showed a reduction in migraine frequency with immunotherapy, "will be of great interest," noted Dr. Evans.

Dr. Martin has received grant support from GlaxoSmithKline, and is a consultant for Allergan, MAPP, Nautilus, and Zogenix, and a speaker for Zogenix and Allergan.

American Headache Society 54th Annual Scientific Meeting: Posters P44 and P48. Presented June 2012.

Headache. 2011;51:8-20.


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