The prevalence of fibromyalgia and its relation with headache characteristics in episodic migraine
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- Küçükşen, S., Genç, E., Yılmaz, H. et al. Clin Rheumatol (2013) 32: 983. doi:10.1007/s10067-013-2218-2
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The objective of this study was to assess the prevalence of fibromyalgia (FM) in patients with episodic migraine and to evaluate the relationship between migraine characteristics and FM. One hundred and eighteen consecutive patients (mean age = 38 years, 75 % women) fulfilling the International Classification of Headache Disorders-II criteria for migraine with (n = 22) and without (n = 96) aura from an outpatient headache clinic of a university hospital were evaluated. The diagnosis of FM was made based on the 1990 American College of Rheumatology classification criteria. Participants completed some self-administered questionnaires ascertaining sociodemographics, headache severity, frequency and duration, headache-related disability (Headache Impact Test [HIT-6]) and Migraine Disability Assessment Scale, widespread musculoskeletal pain (visual analog scale), depression (Beck depression inventory), anxiety (Beck anxiety inventory), sleep quality (Pittsburgh Sleep Quality Index), fatigue (Multidimensional Assessment of Fatigue), and quality of life (Short Form-36 Health Survey [SF-36]). In patients with FM, the tender point count and the Fibromyalgia Impact Questionnaire were employed. FM was diagnosed in 37 (31.4 %) of the patients. FM comorbidity was equally distributed across patients with and without aura. Severity of migraine headache, HIT-6, and anxiety were especially associated with FM comorbidity. Patients suffering from migraine plus FM reported lower scores on all items of the SF-36. This study indicates that the assessment and management of coexisting FM should be taken into account in the assessment and management of migraine, particularly when headache is severe or patients suffer from widespread musculoskeletal pain.
Fibromyalgia (FM) is a chronic illness that presents with widespread musculoskeletal pain as well as a constellation of symptoms including fatigue, cognitive dysfunction, sleep disturbances, stiffness, anxiety, and depressed mood .
Migraine is a complex, recurrent headache disorder that may occur with symptoms such as nausea, vomiting, and increased sensitivity to light and sound. Migraine is divided into two broad groups based on the number of headache days. If attacks occur less than 15 days per month, the term “episodic migraine” (or simply migraine) is applied; when headaches occur on 15 or more days per month, the terms “chronic” or “transformed migraine” are used . Most migraine patients are episodic rather than chronic. The prevalence of migraine is about 12 %, while the prevalence of chronic migraine is approximately 2 % in the community .
Migraine has been noted to be comorbid with a variety of illnesses including FM, irritable bowel syndrome, interstitial cystitis, pelvic pain, and chronic fatigue syndrome [4–6]. These disorders are known as “central sensitivity syndromes” and are mutually associated [7–10]. The reason for the association of these various conditions with migraine is not certain, although, there is a growing body of evidence that central sensitization phenomena have a role in the pathogenesis of both FM [11, 12] and migraine [13–15].
The association between migraine and FM has been demonstrated in previous studies. While the prevalence of migraine in FM is increased compared with controls [16, 17], the same is also true for FM in a migraine population [18, 19]. In a study by Ifergane et al. , FM comorbidity was assessed with a prevalence of 22 % in episodic migraine patients and Peres et al. found the prevalence of FM to be 35.6 % in patients with transformed migraine . These studies suggest that both FM, as well as some types of chronic headache, may be associated with increased excitation within the nervous system, and it has been hypothesized that episodic migraine, chronic daily headache, and FM may actually be a continuum of the same disorder .
It is worthy to investigate the mutual comorbidity between migraine and FM since the comorbidity studies may provide epidemiological or biological clues to the pathophysiological mechanisms of diseases as well as clues regarding treatment strategies. Thus, an increased understanding of the comorbidities may result in improved treatment and functioning in many patients.
In this study, we investigated the prevalence of FM among episodic migraine patients. We also evaluated migraine characteristics (intensity, duration, frequency, disability), psychological features, fatigue, quality of life, and sleep in patients with migraine plus FM compared to patients with migraine alone.
Materials and methods
This study was conducted between May 2011 and June 2012 in the outpatient headache clinic, Neurology Department, Necmettin Erbakan University Medical Faculty, Konya, Turkey. The clinic was a tertiary referral center to which patients are referred by primary physicians as well as by neurological and other specialty clinics.
One hundred and thirty-four consecutive outpatients who had been examined for the first time and fulfilled the International Headache Society criteria  for migraine with and without aura were screened for admission into the study, and 118 were included.
All participants gave written informed consent after receiving a detailed explanation of the purpose and design of the study. The study was approved by the local ethics committee of Selcuk University Medical Faculty.
The inclusion criteria were age between 18–50 years and a diagnosis of episodic migraine headache (International Classification of Headache Disorders-II [ICHD] 1.1 and 1.2) made by a neurologist with special experience in headache, according to the ICHD-II criteria .
Patients were excluded from the study if they had other types of headaches; psychotic symptoms; complicated neurological problems, i.e., underlying brain or systemic illness related to their headaches; and recent-onset headaches, i.e., less than one month prior to the study.
Particular attention was taken in screening out patients suffering from various conditions with diffuse pain such as arthritis, diabetes, or other causes of widespread pain. Patients with systemic, rheumatic, neurological, or psychiatric disorders were excluded from the study. Systemic and rheumatic diseases that are frequently confused with FM such as hypothyroidism, hypovitaminosis D, rheumatoid arthritis, or another inflammatory disorder were ruled out by patient history, physical examination and, if necessary, laboratory investigations including hemogram, C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, antinuclear antibodies, glucose, thyroid stimulating hormone, aspartate aminotransferase, alanine aminotransferase, creatine kinase, vitamin D, calcium, phosphorus, magnesium, and vitamin B12.
History and clinical examination
All patients underwent a clinical assessment consisting of a detailed history and clinical examination. The diagnosis of migraine was made by a neurologist (E Genç) with special experience in headache, according to the ICHD-II criteria. Information on sociodemographic variables (age, gender, education, occupation, marital status, body mass index (BMI), headache characteristics (headache severity, duration, frequency, age of onset, number of years with migraine), and physician-diagnosed comorbid conditions) was obtained from each patient. Average monthly headache characteristics over the prior three months were recorded. Headache severity was assessed using a 4-point verbal rating scale as follows: 1 = mild headache, does not interfere with usual activities; 2 = moderate headache, inhibits but does not wholly prevent usual activities; 3 = severe headache, prevents all activities; and 4 = unbearable headache. Headache duration was recorded on a 1–4 scale, with 1 = 4–12 h, 2 = 13–24 h, 3 = 25–48 h, and 4 = > 48 h. Headache frequency was rated as <1/month, 1–3/month, 4–6/month, and >6/month. Associated migraine symptoms occurring during the migraine attack (nausea, vomiting, photophobia, phonophobia) were also recorded.
Participants completed the following questionnaires, ascertaining headache-related disability, fatigue, depression, anxiety, sleep disturbance, and quality of life.
Headache impact test
The Headache Impact Test (HIT-6) is a reliable and validated tool to assess headache-related disability (range: 36–78). A HIT-6 score ≤49 is interpreted as consistent with little or no impact; 50–55 shows some impact; 56–59 shows substantial impact; and >60 shows severe impact .
The migraine disability assessment scale
The Migraine Disability Assessment Scale (MIDAS) was used to quantify headache-related disability in patients with a diagnosis of migraine. Based on the score, disability from migraine was determined as “minimal or infrequent” (0–5), “mild or infrequent” (6–10), “moderate” (11–20), and “severe” (≥21), on the MIDAS questionnaire .
Multidimensional assessment of fatigue test
Fatigue was assessed by the Multidimensional Assessment of Fatigue (MAF) test. The MAF scale contains 16 items and measures four dimensions of fatigue namely severity, distress, impact on activities of daily living, and timing. Each 100 mm visual analog scale (VAS) was changed to a 10-point numerical rating scale. Scores ranged from 0 (no fatigue) to 50 (severe fatigue) .
Beck depression inventory
Beck Depression Inventory (BDI) is a standard self-report questionnaire consisting of 21 multiple-choice items designed to assess the presence and severity of depressive symptomatology. On the BDI, higher scores indicate more severe depression .
Beck anxiety inventory
The Beck Anxiety Inventory (BAI) assesses the severity of patient anxiety. The questionnaire consists of both physiological and cognitive components of anxiety addressed in the 21 items describing subjective, somatic, or panic-related symptoms .
Pittsburgh sleep quality index
The Pittsburgh Sleep Quality Index (PSQI) is a self-rated questionnaire that assesses sleep quality and disturbances over a one-month time interval. Nineteen individual items generate seven “component” scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The sum of scores for these seven components yields one global score .
Medical outcomes survey short form quality of life questionnaire
The Short Form-36 Health Survey (SF-36), a 36-question self-report measure of quality of life, has been widely used in medical and chronic pain populations. Scores are calculated for eight domains: physical functioning (ability to perform physical tasks), role physical (ability to perform life role, e.g., work, based on physical functioning), pain, general health, vitality, social functioning (ability to perform social tasks), role emotional (ability to perform life role based on emotional functioning), and mental health (depression and anxiety). Possible scores in each domain range from 0 to 100. Normative data are available for a variety of populations .
Fibromyalgia diagnosis and tender point count
All patients were assessed for FM diagnosis by the same investigator (S Küçükşen). The diagnosis of FM was made based on the 1990 American College of Rheumatology classification criteria , which require a history of widespread pain present for > 3 months with pain in 11 of 18 tender point sites on digital palpation. The FM tender point examination was performed using digital palpation with the pulp of the thumb, at a pressure of approximately 4 kg/cm . Patients presenting with FM comorbidity answered the Fibromyalgia Impact Questionnaire (FIQ).
Fibromyalgia impact questionnaire
The FIQ is a FM-specific patient reported outcome instrument designed to assess health status, progress, and outcomes in patients with FM. It contains 10 subscales that are combined to yield a total score (range: 0–100) .
The headache characteristics, headache-related disability, fatigue, sleep disturbance, anxiety, depression, and quality of life were compared between migraine patients with and without FM. In addition, the correlation of headache variables (severity, duration, frequency, and disability) with the FIQ and tender point count was also evaluated.
Statistical analysis of data was performed by using SPSS 15.0 (SPSS Inc., Chicago, IL, USA) software. Normality of the sampling distribution of each dependent variable was tested with the Lilliefors test for normality (a modified Kolmogorov–Smirnov test). Normally distributed variables were expressed as mean±standard deviation (SD) and non-normally distributed variables were expressed as median (minimum–maximum).
Chi-square tests were performed to evaluate the difference in categorical variables between the groups. Differences in continuous data between the groups were analyzed by using Student t test for normally distributed variables, such as BMI, duration of migraine illness, FIQ, BDI, and BAI.
Mann–Whitney U test was used to compare differences between non-normally distributed variables, including age, age of onset of migraine (years), headache frequency, headache severity, duration of migraine attack, widespread pain intensity, HIT-6, MIDAS, fatigue, PSQI, and SF-36.
The correlation between the headache characteristics (headache severity, duration, frequency, age of onset of headaches, number of years with migraine, HIT-6, MIDAS) and the severity of FM symptoms, expressed by the FIQ and tender point count, was analyzed by using Spearman’s rank correlation coefficient. A two-tailed p value <0.05 was accepted as statistically significant.
Among a total of 142 consecutive patients who presented for the first time to our center and were diagnosed as episodic migraine (ICHD-II, 1.1 and 1.2), 118 patients were included in this study. The remaining 24 patients were excluded for various reasons: 4 were hypothyroid, 6 were diabetic, 3 were affected by systemic rheumatic diseases, 5 were affected by complicated neurological problems or psychiatric comorbidities, and 6 were taking central nervous system-acting drugs.
Characteristics of migraine patients with and without FM
Migraine patients without FM (n = 81)
Migraine patients with FM (n = 37)
Age (years), median (min–max)
Gender, n (%)
26.3 ± 5.1
26.6 ± 4.94
Marital status, n (%)
Educational level, n (%)
High school graduate
11 ( 29.7)
Comparison of headache characteristics and psychological variables between migraine patients with and without FM
Migraine patients without FM n = 81 n (%)
Migraine patients with FM n = 37 n (%)
International headache society diagnosis II, n (%)
Migraine without aura (1.1)
Migraine with aura (1.2)
Duration of migraine illness year, (mean±SD)
8.6 ± 6.8
6.8 ± 7.3
Age of onset of migraine years, median (min–max)
Average monthly headache frequency (days/month), n (%)
Duration of migraine attack, n (%)
Headache severity, n (%)
HIT-6, median (min–max)
MIDAS, median (min–max)
I. Little or no disability (0–5), n (%)
II. Mild disability (6–10), n (%)
III. Moderate disability (11–20), n (%)
IV. Severe disability (21+), n (%)
Accompanying symptoms, n (%)
FIQ, (mean ± SD)
53.2 ± 12.8
Tender points count, median (min–max)
15.3 ± 2.4
Widespread pain (VAS), median (min–max)
PSQI, median (min–max)
Fatique, median (min–max)
11.4 ± 7.4
13.6 ± 7.7
<9, n (%)
9–15, n (%)
16–20, n (%)
>21, n (%)
12.5 ± 10.1
20.6 ± 12.3
<8, n (%)
8–15, n (%)
16–25, n (%)
26–63, n (%)
The migraine patients with FM scored higher on the HIT-6 [64 (min–max: 48–78) vs. 62 (min–max: 42–71), p < 0.005]; however, the MIDAS score did not differ significantly between the groups.
Headaches were more often rated as unbearable in patients with FM (62.2 %) than in patients without FM (42 %) (p = 0.017). Among migraine patients with FM, two patients with mild to moderate headache severity were not analyzed. When the FIQ scores of patients with FM were compared in terms of headache severity, patients with unbearable headaches had significantly higher FIQ scores than those with severe headaches (57.2 ± 11.4 vs. 46.4 ± 13.1, p = 0.02). The headache severity was positively correlated with FIQ score (r = 0.381, p < 0.05), HIT-6 score (r = 0.342, p < 0.001), MIDAS score (r = 0.632, p < 0.001), and widespread pain intensity (r = 0.209, p < 0.05).
BDI scores were similar between the groups, although at least 60 % of the patients in each group had high BDI scores (>9). Higher anxiety scores were noted in patients with migraine and FM compared to patients with migraine alone (t = −3.7, df = 116, p < 0.001; t = −3.4, df = 58.9, p < 0.001, respectively). Widespread pain scores were significantly higher in migraine patients with FM (p < 0.001).
Health related quality of life (SF-36) among migraine patients with and without FM
Migraine patients without FM 81 (68.6 %)
Migraine patients with FM 37 (31.4 %)
42.7 ± 16.6
39.8 ± 19.9
In this study, we investigated the frequency of FM in episodic migraine patients and evaluated the relationship between FM and migraine characteristics. The prevalence of FM in our migraine patients (31.4 %) was higher than that reported in the general population (3.6 %) in our country . A clear association between FM and migraine was verified by our data, as also observed in prior studies [18–20].
The association between FM and migraine may be explained by shared pathophysiology. There is a growing body of evidence that central sensitization phenomena have a role in the pathogenesis of both FM [11, 12] and migraine [13, 15, 33]. If sensitization of cerebral pain pathways and persistent activation occur in patients with repeated headache episodes, this central sensitivity may predispose to the development of other conditions, like FM . On the other hand, reduced habituation to pain, common to migraine and FM , may facilitate central sensitization in the presence of other favoring conditions such as anxiety and sleep disturbances.
In our current study, FM prevalence did not differ significantly between migraine patients with and without aura. The published data regarding this issue are conflicting. Ifergan et al.  reported that almost all of the FM-migraine patients suffered from migraine without aura, and de Tommaso et al.  found that FM comorbidity was absent in patients presenting exclusively with aura attacks. However, Tietjen et al.  recently found that the presence of aura did not protect patients who presented with both types of migraine from FM comorbidity. It seems that our results, along with the report of Tietjen et al. , are more reasonable because acute central sensitization phenomena were firstly observed in migraine patients with aura. In our sample, migraine patients complaining of FM comorbidity had higher headache severity. Headaches were more often rated as unbearable in patients with FM (62.2 %) than in patients without FM (42 %), (p = 0.017). The results for the HIT-6 score also confirmed that patients with FM had the highest level of migraine severity. Although the findings reported by Ifergane et al.  and Marcus et al.  did not support headache severity as an aggravating factor for FM, our data suggests that migraine pain intensity is correlated with associated FM. Our results are consistent with the report of de Tommaso et al.  suggesting that headache severity is linked to an increase in the expression of FM symptoms. Moreover, in the study by Peres et al. , transformed migraine patients with FM were 1.3 times more likely to report headaches as incapacitating as those without coexisting FM. Our findings show a very convincing correlation of the intensity of the migraine pain to associated FM. Nevertheless, these data need to be confirmed in larger series and need to be supported by a pathophysiological explanation.
Although according to studies of de Tommaso [19, 35] headache frequency was among the best discriminating variables for FM comorbidity; in the present study, headache frequency was not a risk factor for FM comorbidity. Sauro et al.  compared the HIT-6 and MIDAS scores as clinical measures of headache-related disability, and they found that headache intensity appears to influence the HIT-6 score more than the MIDAS scale, whereas the MIDAS scale was influenced more by headache frequency. Indeed, in our study, while migraine patients with FM had increased headache severity and HIT-6 score, the headache frequency and MIDAS scale were similar between migraine patients with and without FM.
Migraine and FM are frequently associated with depression and anxiety [38, 39]. Although there was no difference between the two groups in our study, the majority of patients in both groups had high BDI score. Depression (BDI > 9) was identified in 75 % of migraine patients with FM and in 62 % of patients with migraine alone.
In our study, we found an association between anxiety and FM comorbidity. We identified anxiety (BAI > 8) in 63 % of patients with migraine alone and in 86 % of migraine patients with FM. de Tommaso et al.  also showed that anxiety is a risk factor for FM comorbidity. Mongini et al.  found that the presence of anxiety considerably increases the level of muscle tenderness in the head, and even more so, in the neck. Thus, anxiety may also facilitate muscle pain and FM comorbidity in headache patients presenting with higher pericranial muscle tenderness.
Migraine patients with FM reported a much poorer quality of life. As shown in many studies, [41, 42] FM has a significant negative impact on patients’ quality of life. Even though the negative effect of migraine on quality of life is well known [43, 44], there was a significant difference in quality of life between FM and migraine patients, demonstrating the strong impact of FM on the patient’s quality of life.
Our study has some strengths. Our sample is composed of consecutive patients newly diagnosed with migraine, minimizing a selection bias. The sample includes men and women with a wide age range. Migraine diagnoses were based on standardized diagnostic criteria by one physician specializing in headache medicine. The limitations to this study are that some of the patients were taking medication for migraine and, therefore, some variables might have been affected. Furthermore, this is a study of a single tertiary care clinic. Patients are often referred to tertiary clinics due to high pain complaints, disability, or medication overuse. As a result, the sample in this study may be different from patients treated in general practice. Population-based epidemiological studies are needed in order to evaluate the exact prevalence of this comorbidity.
In summary, FM is frequent in patients with migraine. The high frequency and significant impact of FM in migraine patients require that FM screening and treatment should be a part of the routine care of migraine patients. The mechanisms and pathways of these comorbidities and effective strategies for prevention, diagnosis, and treatment of both diseases remain to be elucidated in future studies.