Two recently published longitudinal studies have shown that there is a unique two-way association between migraine and rheumatoid arthritis (RA), which suggests that the two diseases may be similar or even share different pathophysiological manifestations.1
Studies in the past ten years have examined the overlap in the occurrence of RA and migraine, although no strong correlation has been established. The 2008 response to the NHANES survey found that respondents with migraine were more likely to report at least two coexisting pain conditions, defined as low back pain and osteoporosis, and RA.2 Similarly, the results of a prospective survey and analysis published as the 2020 American Migraine Symptoms and Treatment (MAST) Study focused on the impact of comorbidities on the intensity of migraine reports, and other painful diseases such as osteoarthritis and RA.3 Another longitudinal study by Wang and colleagues found that patients with migraine have a significantly increased risk of RA.4 The results of all these studies are one-way, and until recently, no studies have evaluated the potential impact of two-way correlation.
It is estimated that 40 million people in the United States are affected by migraines, and migraines are reported to occur more frequently in women than men.5,6 The prevalence in the United States is about 12% and the global rate is 15%, making migraine the second most common disability affecting adults.5 Rheumatoid arthritis is the most common systemic arthritis, with a global prevalence of 1%.6
Korean matchmaking queue
The paired study evaluated two independent cohorts of migraine and RA patients from South Korea who were matched with control patients in a 1:4 ratio. All patients with active disease have been diagnosed with migraine or RA at least twice. The results of the first study showed that 31,589 patients previously diagnosed with migraine had a higher incidence of RA compared to 126,356 control patients (2% and 1.4%, respectively). The second cohort showed that 9287 patients with a previous diagnosis of RA had a higher incidence of migraine compared with 37,148 control patients (6.4% and 4.6%, respectively).1
The overall prevalence of migraine in the Korean population is 7.5%. Approximately 7.6% of these patients have migraine with aura, which is lower than the frequency generally recognized by external studies. The subgroup analysis supports the cross-correlation between migraine and RA, with the exception of men over 60 years of age in the RA cohort, whose migraine risk does not appear to increase. The study authors believe that this trend may be related to the higher natural prevalence of migraine in women, which peaks between 25 and 55 years of age, and the incidence declines thereafter.1
Potential sharing mechanism
The investigation in South Korea is based on the hypothesis of observing the mechanism of inflammation and endothelial cell activation. The immune system may establish a two-way channel between migraine and RA. At present, the underlying causes of migraine and RA are unclear, although both involve multiple mechanisms. Until recently, the understanding of migraine has gone beyond primitive vascular mechanisms, including a wide range of potential influencing factors such as neuroinflammation, CGRP activation, pituitary adenylate cyclase activating peptide and pro-inflammatory substances, and hormonal changes. The endothelial and systemic inflammatory mechanisms are also related to migraine and RA and metabolic dysfunction.1
Vincent Martin, MD, said that it is not surprising that RA is associated with migraine, because there are many other diseases with inflammatory mechanisms that are related to migraine, including allergic rhinitis, asthma, lupus, headache after COVID, etc. Director of the Headache and Facial Pain Center at the Gartner Institute of Neuroscience, University of Cincinnati School of Medicine, and Chairman of the National Headache Foundation.
The literature suggests that inflammation and immune mechanisms may be common, leading to a direct relationship between RA and migraine.1,3 “I suspect that inflammation is the most important mechanism,” Dr. Martin said. “Inflammation tends to exacerbate the sensitive trigeminal nerve, which may make migraine development easier. Another factor that may play a role is that some drugs used to treat RA may cause headaches.”
Co-morbidities of RA and migraine include obesity, sleep disorders, and especially depression.1 These comorbidities are reported almost twice as frequently in patients with chronic migraine (non-episodic migraine), and about 50% of them also report pain-related comorbidities, including osteoarthritis and RA. Burch et al. 2019 review5 It also shows that lingering comorbidities increase the risk of transitioning from an episodic migraine pattern to a chronic migraine pattern. Dr. Dawn Buse is a clinical psychologist at Montefiore Medical Center in New York City and a co-author of the MAST and CAMEO studies on migraine comorbidities. He found that the new data in South Korea is interesting because he noticed the combination of RA and migraine in these studies. disease. “But these are cross-sections and directionality cannot be determined,” she said, adding that the two-way aspect represents a new model that may be useful.
The idea that migraine and RA may have a two-way effect on each other suggests multiple effects, especially on treatment. Combination therapy may be beneficial in both cases. “These effects mainly apply to the role of inflammation in the development of migraine,” Dr. Martin said, noting that this suggests that the treatment of inflammatory diseases can reduce the likelihood of migraine. Another possible implication of these findings is that the diagnosis of one of these diseases may indicate susceptibility to another. Further research is needed to prove these theories.
- Kim YH, Lee JW, Kim Y, etc. The two-way association between migraine and rheumatoid arthritis: two longitudinal follow-up studies of a national sample cohort. BMJ Open. 2021;11(6):e046283. doi:10.1136/bmjopen-2020-046283
- Kalaydjian A, Merikangas K. Headache comorbidities in a nationally representative sample of American adults. Psychosom medicine. 2008;70(7):773-80. doi:10.1097/PSY.0b013e31817f9e80
- Bus DC, Reed ML, Fanning KM, etc. Comorbidities and comorbidities of migraine and the associated risks of increased headache intensity and frequency: results of the American Migraine Symptoms and Treatment (MAST) study. J has a headache. 2020;21(1):23. doi:10.1186/s10194-020-1084-y
- Wang YC, Huang YP, Wang MT, Wang HI, Pan SL. Patients with migraine are at increased risk of rheumatoid arthritis: a cohort study based on population and propensity score matching. Rheumatism International 2017;37(2):273-279. doi:10.1007/s00296-016-3604-2 Abstract
- Birch RC, Bus DC, Lipton RB. Migraine: Epidemiology, burden and comorbidities. Neurological Clinic. November 2019; 37(4): 631-649. doi:10.1016/j.ncl.2019.06.001
- Wasserman A. Rheumatoid arthritis: Frequently asked questions about diagnosis and management. family doctor. 2018;97(7):455-462. PMID: 29671563.