Blackwell Science, LtdOxford, UKCHACephalalgia0333-1024Blackwell Science, 2005264451456Original ArticlePrevalence of FMS in migraine patients G Ifergane et al. doi:10.1111/j.1468-2982.2005.01060.x Prevalence of fibromyalgia syndrome in migraine patients G Ifergane1, D Buskila2, N Simiseshvely2, K Zeev3 & H Cohen3 1 Headache Clinic, Department of Neurology, 2Department of Medicine H and Rheumatic Disease Unit, Soroka Medical Centre, Ben-Gurion University of the Negev, and 3Anxiety and Stress Research Unit, Ministry of Health Mental Health Centre, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel Ifergane G, Buskila D, Simiseshvely N, Zeev K & Cohen H. Prevalence of fibromyalgia syndrome in migraine patients. Cephalalgia 2006; 26:451–456. London. ISSN 0333-1024 Fibromyalgia syndrome (FMS) is a chronic pain syndrome of unknown aetiology characterized by diffuse pain over more than 3 months and tenderness in specific sites named tender points. The aim of this study was to assess the prevalence and severity of FMS among patients suffering from episodic migraine. Ninety-two consecutive patients (20 male, 72 female) fulfilling the International Headache Society criteria for migraine with and without aura from a tertiary headache clinic were evaluated. A headache and generalized pain history was recorded, tender points were evaluated by thumb palpation. The diagnosis of FMS was made based on the 1990 American College of Rheumatology classification criteria for FMS. Sixteen (22.2%) of the female patients and none of the male patients were diagnosed as suffering from FMS. Migraine severity and characteristics were similar to other female migraine patients. Patients suffering from migraine–FMS had lower quality of life scores and higher levels of mental distress. A high incidence of FMS was found among female migraine patients but not in males. The coexistence of FMS should be considered when choosing a prophylactic migraine therapy. 䊐 Central sensitization, fibromyalgia, mental distress, migraine, quality of life Gal Ifergane MD, Department of Neurology, Soroka Medical Centre, PO Box 151, BeerSheva, Israel. Tel. + 97 2 8640 0660, fax + 97 2 8640 3660, e-mail galif@clalit.org.il Received 6 June 2005, accepted 13 July 2005 Introduction Fibromyalgia syndrome (FMS) is a chronic pain syndrome of unknown aetiology characterized by diffuse pain over more than 3 months and tenderness in at least 11 tender points out of 18. Most FMS patients (90%) are female and complain of pain, insomnia, fatigue, and psychological distress (1). Sleep disorders, chronic fatigue syndrome, irritable bowl syndrome and mood disorders are common comorbidities (2). FMS patients show increased sensitivity to mechanical, thermal and electrical stimuli, which seems to suggest that abnormal central pain mechanisms may be important for the augmented pain experience of FMS patients (3–5). Important central nervous system mechanisms relevant to FMS pain include temporal summation of pain (wind-up) and central sensitization (6, 7). © Blackwell Publishing Ltd Cephalalgia, 2005, 26, 451–456 It has been suggested that central sensitization at the level of the spinal dorsal horn/trigeminal nucleus may also be involved in the progression of migraine attacks, and due to prolonged nociceptive inputs may result in supraspinal sensitization and central neuroplastic changes that may be maintained, leading to conversion of episodic to chronic headaches (8–10). Cutaneous allodynia, pain or discomfort resulting from a non-noxious stimulus to normal skin is a common manifestation of this kind of sensitization in migraine (11, 12). Usually it occurs in cephalic areas, but in nearly half of the patients who experience allodynia, extracephalic allodynia exists as well, suggesting the involvement of other nociceptive structures besides the trigeminal nucleus. An increased incidence of FMS has been found among patients with transformed migraine (13) and it has been hypothesized (14) that episodic migraine, 451 452 G Ifergane et al. chronic daily headache and FMS may actually be a continuum of the same disorder. The aim of this study was to assess the prevalence and severity of FMS among patients suffering from episodic migraine. In addition, we examined the characteristics of patients with migraine and concomitant FMS. Methods Patients We enrolled 92 consecutive patients fulfilling the International Headache Society (IHS) (15) criteria for migraine with and without aura treated in the Headache Clinic of the Soroka University Medical Centre in Beer-Sheva. The Headache Clinic is a tertiary referral centre, and the patients were referred by primary physicians as well as neurological and other specialty clinics. All participants gave written informed consent after receiving a detailed explanation of the purpose and design of the study. After signing an informed consent, the patients were evaluated by one observer (N.S.). A headache and generalized pain history was recorded. Manual assessment of tenderness has been described in great detail elsewhere (1). In all subjects, a count of 18 tender points at nine symmetrical sites was performed by thumb palpation. Definite tenderness at any point was considered present if some involuntary verbal or facial expression of pain occurred or withdrawal was observed. The diagnosis of FMS was made based on the 1990 American College of Rheumatology classification criteria for the diagnosis of FMS, namely: widespread pain for more than 3 months, on both sides of the body, above and below the waist, and axial skeleton (cervical spine, anterior chest, thoracic pain or low back) as well as tenderness to palpation in 11 of 18 bilateral sites (1). The subjects were between the ages of 20 and 72 years, with a mean age of 42.5 ± 12.4 years. Seventy-one (77.2%) of the sample population were female. Two-thirds of them had suffered from migraine for more than 10 years. Most of the patients were married (76.1%), employed (72.8%) and their mean level of education was 14.6 ± 3.4 years (range 3–26). Patients suffering from current or recent substance abuse disorders, psychotic symptoms or significant cognitive impairment likely to interfere with study procedures or with informed consent were excluded from the study. Study instruments The questionnaires were filled out in the presence of an interviewer and subjects were assisted in answering the questions, if needed. Each interviewer ensured that all subjects clearly understood the content of each item and the different aspects of the various component questions. All subjects completed the following questionnaires. Demographics and background Participants were asked to answer questions regarding their personal background (e.g. family status, country of origin, level of education). Headache Impact Test (HIT-6) The HIT-6, a six-question survey, was used to measure the impact of headache on respondents’ lives. The questions cover six aspects of functioning most commonly impacted by headache: pain, role functioning (the ability to carry out usual activities), social functioning, energy or fatigue, cognition, and emotional distress (16). Scores are computed by assigning a value of 6 to a response of ‘never’, 8 to ‘rarely’, 10 to ‘sometimes’, 11 to ‘very often’, and 13 to ‘always’; these values were used to recalibrate scores from this static short form to scores from the total HIT item pool and have them both in the same norm-based metric (with a mean of 50 and a standard deviation of 10 in the general population of recent headache sufferers). HIT-6 scores, derived by adding the patient’s responses to all items, can range from 36 (lowest possible score) to 78 (highest possible score). Scores of ≤ 49 reflect little or no impact; scores between 50 and 55 reflect some headache impact; scores between 56 and 59 reflect substantial impact; and scores of ≥60 reflect severe headache impact on the patient’s ability to function in everyday life (17). Migraine Disability Assessment Scale The Migraine Disability Assessment (MIDAS) scale is used to quantify headache-related disability (18). MIDAS is a brief and reliable headache-specific tool which captures headache-related disability. Five questions investigate the influence of headache on everyday activities over the preceding 3 months. Items 1 and 2 investigate paid work, enquiring as to the number of days off work due to headache and the number of days where productivity was reduced by half or more. Items 3 and 4 ask the same questions about household work. Item 5 enquires about missed days of recreational, social and family © Blackwell Publishing Ltd Cephalalgia, 2005, 26, 451–456 Prevalence of FMS in migraine patients activities. The total score is obtained by summing the individual scores of the individual MIDAS items. From the score, one of four disability grades is assigned: grade I, minimal or infrequent disability corresponds to a MIDAS score of 0–5; grade II, mild or infrequent disability corresponds to a MIDAS score of 6–10; grade III, moderate disability corresponds to a MIDAS score of 11–20; and grade IV, severe disability correspondes to a MIDAS score of ≥ 21. Quality of life assessment Quality of life (QoL) was assessed by SF-36 (19). This is a health-related profile of QoL that contains 36 items and measures health status across three domains: functional status, well-being and overall evaluation of health. The Hebrew translation of the SF-36 was validated in an adult general population (20), and our group have used it on patients with widespread pain, with and without FMS (21). The SF-36 contains eight scales: physical functioning, social functioning, and role limitations attributable to physical and emotional problems, mental health, vitality, bodily pain and general health. Each scale generates a score from 0 to 100, with a high score indicating better health and less body pain. The Psychiatric Symptom Check List This comprises 90 items measuring nine psychiatric clinical subscales. The SCL-90 was developed as a measure of general psychiatric symptom severity, as a descriptive measure of psychopathology (22). The clinical subscales are: somatization (12 items), obsession-compulsion (10 items), interpersonal sensitivity (nine items), depression (13 items), anxiety (10 items), hostility (six items), phobic anxiety (seven items), paranoid ideation (six items) and psychoticism (10 items). The SCL-90 has been extensively 453 used and validated in Hebrew (23). Subjects are required to rate specific complaints on a 5-point Likert scale running from 0 = ‘never’ to 4 = ‘frequently’. Higher scores indicate greater distress. The Cronbach’s α values for the scales of somatization, depression, anxiety and hostility in this study were 0.89, 0.90, 0.92, and 0.91, respectively. Data analysis Means, standard deviations and frequencies were computed to summarize the distribution of values for each variable. Age, years of education, family status, number of years of marriage, immigrant/ veteran status in Israel (a country with high rates of immigrations) and number of years in Israel were analysed as continuous data and compared by oneway analysis of variance (ANOVA). The Sheffé post hoc test was used to examine pair-wise differences between the groups. χ2 tests were used for categorical data such as sex, place of birth and religion. Results Sixteen (17.4%) of the patients who met the IHS criteria for episodic migraine with and without aura also met the currently accepted criteria of the American College of Rheumatology for classification of FMS. All of the patients who suffered from both migraine and FMS were women (22.2% of the female patients). Since none of the male patients suffered from FMS, we compared migraine–FMS sufferers with female migraine sufferers without FMS. The demographic characteristics of the female migraine patients with and without FMS are summarized in Table 1. The two groups, migraine patients with and without FMS, did not differ significantly on any of the demographic measures, such as Table 1 Characteristics of female migraine patients with and without fibromyalgia syndrome (FMS) Variable Age (years) Mean ± SD, range Employed, N (%) Married, N (%) Education (years) Mean ± SD, range Migraine duration, N (%) ≤10 years >10 years Migraine patients with FMS N = 16 Migraine patients without FMS N = 56 43.4 ± 11.4 20–60 10 (62.5%) 14 (87.5%) 14.4 ± 4 10–26 43.6 ± 12.5 21–72 46 (82%) 44 (78.5) 14.8 ± 2.8 9–21 4 (25%) 12 (75%) 18 (32.1%) 38 (67.9%) © Blackwell Publishing Ltd Cephalalgia, 2005, 26, 451–456 ANOVA NS NS NS NS NS NS 454 G Ifergane et al. Table 2 Headache characteristics among female Migraine patients with and without fibromyalgia syndrome (FMS) Variable Aura Headache features Unilateral Throbbing Moderate to severe intensity Exacerbated by activity Accompanying features Vomiting/nausea Phonophobia/photophobia Exacerbating factors Menstruation Mental stress Sleep deprivation Nutritional Migraine severity indices HIT-6, mean ± SD (range) MIDAS, mean ± SD (range) Migraine patients with FMS N = 16 N (%) Migraine patients without FMS N = 56 N (%) ANOVA 1 (6.25%) 15 (26.7%) NS* 14 (87.5%) 15 (93.7%) 15 (93.7%) 10 (62.5%) 48 (85.7%) 44 (78.6) 56 (100%) 36 (64.3%) NS NS NS NS 13 (81.2%) 14 (87.5%) 47 (84%) 51 (91%) NS NS 6 (37.5%) 11 (68.7%) 12 (75%) 8 (50%) 34 (60.7%) 38 (67.9%) 33 (59%) 23 (41%) NS* NS NS NS 49.2 ± 9.9 (30–64) 17.8 ± 23.4 (0–90) 48.4 ± 9.5 (30–66) 15.6 ± 21.1 (0–95) NS NS *P = 0.08. Table 3 Quality of life among Migraine patients with and without fibromyalgia syndrome (FMS) according to SF-36 scores Variable Migraine patients with FMS N = 16 Migraine patients without FMS N = 56 ANOVA Physical function Physical role function General health perception Emotional role Social functioning Bodily pain Mental health Vitality Total 58.4 ± 17.1 39.1 ± 40.8 40.9 ± 22.4 68.75 ± 41.2 57.66 ± 13.1 38.37 ± 11.8 59.5 ± 18.7 35.3 ± 18.9 48.5 ± 11.5 85.4 ± 18.3 63.4 ± 40.16 70.1 ± 23.3 75.6 ± 39.4 50.4 ± 8.58 42.3 ± 11.36 67.8 ± 19.09 49.4 ± 18.76 63.04 ± 13.46 F(1,7) = 27.8, P < 0.00001 F(1,7) = 4.5, P < 0.04 F(1,7) = 19.9, P < 0.0003 NS NS NS NS F(1,7) = 6.9, P < 0.01 F(1,7) = 15.4, P < 0.0002 age, gender, marital status, level of education and disease duration. The features of the migraine attacks in patients with and without FMS are summarized in Table 2. Migraine with aura was less prevalent in female migraine patients with FMS (6.25%) than in patients without FMS (26.7%), but the difference was not significant (P = 0.08). Migraine severity scores were similar. Migraine patients with FMS reported an impaired quality of life in comparison with other female migraine patients in almost all the domains of the SF-36 (Table 3) and displayed higher levels of mental distress (SCL-90 scores are displayed in Table 4). Distress symptoms, including hostility, interpersonal sensitivity, somatization, depression, anxiety, phobia, obsession, paranoia and psychoticism, are presented in Table 4. The subscales of somatization, obsessive-compulsive, depression, phobic anxiety, anxiety, anger-hostility, and psychoticism displayed significant differences between the samples, with significantly higher mean scores for migraine patients with FMS compared with migraine patients without FMS, representing higher levels of mental distress. © Blackwell Publishing Ltd Cephalalgia, 2005, 26, 451–456 Prevalence of FMS in migraine patients 455 Table 4 Mental distress among migraine patients with and without fibromyalgia syndrome (FMS) according to Symptom Check List (SCL)-90 scores Variable Migraine patients with FMS N = 16 Migraine patients without FMS N = 56 ANOVA Somatization Obsessive-compulsive Interpersonal sensitivity Depression Hostility Phobic anxiety Anxiety Paranoid ideation Psychoticism Global Severity Index 1.65 ± 0.81 1.1 ± 0.96 0.69 ± 0.61 0.98 ± 0.7 0.85 ± 0.84 0.49 ± 0.51 0.84 ± 0.55 0.31 ± 0.59 1.1 ± 0.9 0.9 ± 0.63 0.92 ± 0.69 0.53 ± 0.58 0.4 ± 0.56 0.49 ± 0.52 0.38 ± 0.59 0.13 ± 0.32 0.44 ± 0.58 0.14 ± 0.3 0.47 ± 0.56 0.45 ± 0.46 F(1,7) = 12.5, P < 0.0007 F(1,7) = 8.6, P < 0.005 NS F(1,7) = 9.1, P < 0.004 F(1,7) = 6.3, P < 0.015 F(1,7) = 11.4, P < 0.0015 F(1,7) = 6.2, P < 0.015 NS F(1,7) = 11.5, P < 0.0015 F(1,7) = 9.8, P < 0.003 Discussion As many as 22.2% of the female migraine patients also met criteria for FMS. Our results represent the first comprehensive study using structured clinical assessment measures of FMS in a group of migraine patients. The prevalence of FMS among the migraine patients in this study was significantly higher than in the general population. The prevalence of FMS in the general population (24, 25) in the USA has been estimated to be between 2% and 3% (3.4% of women and 0.5% of men). This finding further strengthens previous observations of a high incidence of migraine among FMS patients (26). The findings appear to indicate a clear association between FMS and migraine among women, although whether this is one of causality or consequence is not clear. Since the study was conducted in a tertiary headache clinic, this very high prevalence of FMS among migraine patients does not necessarily reflect the general population of migraine sufferers. The study population suffered from more severe migraines than reported in other groups of patients, as reflected by high MIDAS scores. It thus seems likely that a large proportion of female (but not male) patients with severe migraine, who attend headache clinics, suffer from FMS as well. Previous reports (12) suggest that an even larger proportion (35.6%) of patients with transformed migraine suffer from the same condition. Community studies are needed in order to establish comorbidity of these conditions in the general population. Migraine severity was similar in female migraine patients with and without FMS. This does not necessarily apply to the general population of migraine patients. © Blackwell Publishing Ltd Cephalalgia, 2005, 26, 451–456 Although not significant, almost all of the FMS– migraine patients suffered from migraine without aura. No other differences in headache features were noted between the two groups. FMS–migraine patients differed from other female migraine patients in two major aspects. They reported a much poorer quality of life and suffered from higher levels of mental distress. It is not clear whether the mental distress is caused by the FMS or by the headache disorder, or is an independent exacerbating factor for either or both of them. The causative relationship between FMS and severe migraine is not yet clear. On the one hand, FMS may be an aggravating factor for migraine, and on the other hand, the migrainous sensitization of pain pathways may be an aggravating or even a causative factor for the FMS. It is also possible that the co-existence of both conditions is caused by a third, pain-sensitizing factor. Whether FMS–migraine is a distinct syndrome or not, the co-existence of both clearly affect the patient’s well-being and should be taken into consideration when choosing therapeutic strategies. 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