Male patients with rosacea have increased risk for migraine: a population‐based study
Authors: S‐P. Sinikumpu, H. Vähänikkilä, J. Jokelainen, K. Tasanen, L. Huilaja
Journal: British Journal of Dermatology (2021)

Dear Editor, Previous reports have demonstrated an association between rosacea and migraine.1 This relationship has been found in postmenopausal women, particularly in large registry studies, but also in some smaller clinical studies.1 A nationwide study (n = 49 475) from Denmark reported that female patients with rosacea who were aged > 50 years had a 1·3-fold increased risk for migraine.2 We studied the association between rosacea and migraine in the general population of the Northern Finland Birth Cohort 1966 Study (NFBC66), which is a longitudinal research programme based in the two northernmost provinces in Finland. The whole NFBC66 cohort has been evaluated regularly since birth by means of health questionnaires and clinical examinations. In connection with a 46-year follow-up survey, a total of 3181 persons living in a given geographical area (in the city of Oulu and within 100 km of the city, including rural areas) were asked to attend a clinical examination, which included a whole-body examination performed by dermatologists; 1932 of them responded (60·7%). Overall, 53·7% (n = 1036) of these participants were women and 46·3% (n = 896) were men.3 Diagnosis and classification of rosacea was based on the evaluation by a dermatologist at the study visit3 and on the internationally accepted criteria.4 Rosacea was classified using the following four subtypes according to its clinical presentation: erythematotelangiectatic rosacea (ETR), papulopustular rosacea, phymatous rosacea and ocular rosacea.4 Patients self-reported information regarding doctor-diagnosed migraine. The symptoms relating to migraine were gathered using specific questions [the symptoms of migraine without aura according to The International Classification of Headache Disorders, 3rd edition (beta version)] (see Table 1 for questions).5 The prevalence of rosacea was 15·1% (n = 292); 10·5% for men (n = 94) and 19·1% for women (n = 198). Subtypes of rosacea were divided as follows: ETR 83·2% (n = 242), papulopustular rosacea 15·4% (n = 45), ocular rosacea 0·3% (n = 1) and phymatous rosacea 0·1% (n = 3). The prevalence of self-reported migraine in the whole cohort was 21·5% (n = 61) among those with rosacea and was 18·5% (n = 290) among those without (P = 0·2). The patients with rosacea had more one-sided [25·3% (n = 74)] and throbbing headache [33·9% (n = 99)] when compared with those without rosacea [18·4% (n = 301) and 24·6% (n = 402), respectively] (P < 0·01). Those with rosacea more often had several simultaneous symptoms relating to migraine than those without rosacea (P < 0·01, data not shown). Using logistic regression analyses we found that male patients with rosacea had a twofold higher risk for self-reported migraine, for 'one-sided and throbbing headache', 'headache that prevents doing daily activities' and for 'headache that is irritated by bright lights and loud voices'. A corresponding association was not seen in female patients (Table 1). Those with papulopustular rosacea experienced migraine symptoms more often than patients with the ETR subtype, but the difference was not statistically significant (P < 0·8) (data not shown). The exact pathophysiology of rosacea remains unknown.6 In addition to genetic predisposition, impairment in epidermal barrier and dysregulation of the immune system, rosacea is characterized by neurovascular dysregulation and neurogenic inflammation, thus sharing similar pathomechanisms with migraine.6, 7 Furthermore, in both rosacea and migraine, symptoms (such as episodes of flushing, erythema, telangiectasia, headache, photophobia and phonophobia) are presented mainly in the area innervated by the trigeminal nerve.6, 7 Thus, changes in facial blood flow and neuroinflammation have been considered to suggest a possible relationship between these two diseases.6 Previously, contrary to our results, the association between rosacea and migraine has been shown primarily in female patients.1, 2 Previous studies have mostly based their findings on registry data, which may have caused selection bias and prevented the discovery of migraine risk in men. The main strength of registry studies is the use of large datasets. However, individuals with mild symptoms who do not seek help from a physician can be missed. Thus, men who are less eager to seek help for their disease may have been omitted. Furthermore, in database studies, it is usually not possible to differentiate between rosacea subtypes or take confounding factors into consideration. The major strength of our study is a pure general population. Study cases were not selected for the study and both sexes were represented almost equally. Furthermore, the diagnosis of rosacea was evaluated by dermatologists and subtypes of rosacea were reported. The migraine or headache symptoms were surveyed using multidisciplinary questions. The setting of the cohort study made it possible to take several confounding factors into consideration. One limitation of this study is that not all study cases who were invited chose to participate. In addition, diagnosing ETR is especially difficult as the diagnosis is solely clinical.8 Based on our findings, we recommend that physicians who encounter patients with rosacea, especially male patients, ask them about migraine symptoms while simultaneously ensuring the exact diagnosis of rosacea subtype.8 We would like to thank the whole NFBC66 study personnel and Paula Rantakallio, who launched the NFBC66. Suvi-Päivikki Sinikumpu: Conceptualization (lead); Data curation (equal); Formal analysis (equal); Investigation (equal); Methodology (equal); Project administration (lead); Writing-original draft (lead). Hannu Vähänikkilä: Data curation (equal); Formal analysis (equal); Methodology (equal). Jari Jokelainen: Data curation (equal); Formal analysis (lead); Methodology (supporting). Kaisa Tasanen: Conceptualization (supporting); Writing-review & editing (equal). Laura Huilaja: Conceptualization (supporting); Data curation (supporting); Formal analysis (supporting); Methodology (supporting); Supervision (lead); Writing-review & editing (equal).