Clinical Characteristics of Korean Patients with Fibromyalgia

Fibromyalgia (FM) is a common condition afflicting 2% of the population [1]. It is characterized by chronic widespread pain with increased sensitivity to pressure elicited pain. The American College of Rheumatology (ACR) classification criteria in 1990 stipulated the presence of chronic widespread pain for at least 3 months and the presence of at least 11 out of 18 tender points [2]. Aside from pain, common problems of FM are morning stiffness, fatigue, nonrestorative sleep, pain, concentration, and memory [3].

Epidemiological studies report a FM prevalence of between 2 and 7% in most nations, with a female to male ratio of approximately 9:1 [3]. The prevalence of FM was 2.2% in Korean and was significantly higher in female and aged individuals [4]. It is increasingly evident that FM represents a significant challenge in view of its high prevalence, frequent comorbidities, and frustration with current treatment modalities.

Although fibromyalgia (FM) has been known to present a variety of clinical symptoms, a detailed investigation on this topic has not been performed in Korean patients. We tried to identify various FM-related symptoms and compare the clinical features of patients with primary FM and those of patients with secondary FM.

Study population

Total 336 patients with FM were consecutively recruited from out patient rheumatic clinics of 10 medical centers participated in national survey on clinical characteristics of Korean patients with FM from June 2008 to March 2009 in Korea. All of them at the time of initial diagnosis met classification criteria for FM proposed by ACR in 1990 [2]. The protocol of this study was approved by Institutional Review Board at each medical center. Total participants gave informed consent for this research.

Data collection

Demographics of enrolled patients including age, gender, height, weight, symptom duration, disease duration after diagnosis, education, employment status, marital status, annual income and insurance were preliminary assessed. In addition, alcohol intake was identified such as current alcoholic and non-alcoholic at the time of enrollment in this study. Smoking status was also classified into current smoker and nonsmoker. At the assessment of medical history, we surveyed accompanying diseases in the participants such as diabetes mellitus, hypertension, hepatitis, thyroid disease, affective disorder and other rheumatic disease.

At the assessment of symptoms and signs, we surveyed past and current symptoms and signs in the participants such as generalized weakness, unrefreshing sleep, fatigue, stiffness, paresthesia, swelling, febrile sense, tension headache, subjective cognitive dysfunction, dry eye, dry mouth, swollen glands, vasomotor rhinitis, dizziness and vestibular complaints, syncope and neutrally mediated hypotension, temporomandibular joint syndrome, non-cardiac chest pain, costochondritis, dyspnea, esophageal dysmotility, dyspepsia, irritable bowel syndrome, irritable bladder and female urethral syndrome, vulvodynia and vagismus, skin redness, restless leg syndrome and reflex sympathetic dystrophy. The glossary of symptom and sign is defined in Table 1.

Table 1: Glossary of signs and symptoms.

We also surveyed stressors capable of triggering FM in the participants such as peripheral pain syndrome, infection, physical trauma, psychological stress/distress, hormonal alteration, drugs, vaccines and catastrophic events. In addition, we surveyed current medications in the participants such as selective serotonin reuptake inhibitor (SSRI), serotonin norepinephrine reuptake inhibitor (SNRI), pregabalin, gabapentin, tricyclic antidepressant (TCA), muscle relaxant, nonsteroidal anti-inflammatory drugs (NSAID), tramadol, acetaminophen, sedative-hypnotics and benzodiazepine etc.

Identification of tender points was assessed through direct palpation at 18 specific sites with a force amount of 4.0 kg according to the standardized manual tender point survey [5]. First, the presence of a tender point at specific sites was identified. Second, the intensity of each tender point was graded as follows: 0, no tenderness; 1, light tenderness (confirming answer when asked); 2, moderate tenderness (spontaneous verbal response); and 3, severe tenderness (moving away). The summation of these points was regarded as the score of total tender points. The Korean version of the fibromyalgia impact questionnaire (FIQ) was used to assess the functional abilities in patients with FMS on a scale of 0 to 100 for each subject [6]. Brief fatigue inventory (BFI) was used for the measure of fatigue severity in FMS patients [7]. The severity of depression was measured by brief depression inventory (BDI) [8,9]. The 36-item Medical Outcomes Study Short-Form Health Survey (SF-36) was evaluated for quality of life in FMS and consisted of eight items including physical health (physical functioning, role-physical, bodily pain, general health) and mental health (vitality, social functioning, role-emotional, mental health) [10]. The state-trait anxiety inventory (STAI)-1 and STAI-2 were developed as methods for evaluation of the degree of anxiety [11]. The state anxiety and trait anxiety were identified using these two methods. Self efficacy scale was assessed in our study [12]. Social family support and social friend support were also assessed in this study [13].

Statistical analysis

Data were described as the mean ± standard deviation or number with percent (%) of cases. For the comparison of clinical characteristics between primary and secondary FM, Chi-square test was used for the comparison of categorical variables and Mann-Whitney U test was applied in the assessment of the differences of sequential variables. A p value

General characteristics of enrolled subjects

Generalized demographic and clinical characteristics are identified in Table 2. The majority (89.6%) of participants were women (n=301), and the average age was 47.9 years. On average, participants were diagnosed with FM approximately two years prior to recruitment and participation in this study. Mean duration of education was approximately 11.0 years, which was comparable with a high school degree. The study population having an occupation of physical labor was 32.9% (n=107). Current alcohol consumers were estimated at 22.0% (n=74) of the study population. The prevalence of accompanying affective disorders such as depression or anxiety was estimated as approximately 26.5%. Approximately 26.2% of the patients had underlying rheumatic diseases including Behcet’s disease, osteoarthritis, rheumatoid arthritis, Sjögren syndrome, systemic lupus erythematosus, or other rheumatic disorders.

Table 2: Demographics, social and medical characteristics in enrolled patients (n=336).

Current and past accompanying symptoms and signs

The following symptoms were exhibited by more than two-thirds of FM patients, in order of frequency: fatigue, unrefreshing sleep, generalized weakness, stiffness, tension headache, swelling, febrile sense, and dizziness (Table 3).

Table 3: Current and past accompanying symptoms and signs in the 336 patients with fibromyalgia.

Stressors that triggered fibromyalgia symptoms

Stressors that triggered FM symptoms were found in 58.6% of the patients and can be listed in the following order: psychological distress, peripheral pain syndrome, catastrophic events, physical trauma, hormonal alteration, infections, and drugs (Table 4).

Table 4: Stressors that triggered fibromyalgia symptoms.

Comparison of clinical characteristics between primary and secondary fibromyalgia

Compared to patients with primary FM, patients with secondary FM were significantly older, less educated, more Medical Aid beneficiaries, had more dizziness, received more NSAIDs and analgesics, and had higher levels of trait anxiety (p<0.05, p<0.05, p=0.001, p<0.05, p<0.01, p<0.01, and p<0.05, respectively) (Table 5).

Table 5: Comparison of clinical characteristics between primary and secondary fibromyalgia.

Comparison of clinical characteristics among patients with fibromyalgia in Korea and other countries

The frequencies of the various subjective symptoms in the present study and other Caucasian and Asian published series of FM patients were shown in Tables 6 and 7. Korean patients with FM had fewer symptoms related to cognitive dysfunction and vulvodynia than Western (especially, German) patients (Table 6). Korean patients with FM had more symptoms related to restless leg syndrome, temporomadibular joint syndrome and skin redness than Western (especially, USA) patients (Table 6). Unrefreshing sleep, fatigue, stiffness, headache, and subjective swelling were more frequently found in Korean patients than in Caucasian and other Asian patients (Table 7).

Table 6: Comparison of FM symptoms in NFA and DFV cases with those in Korean cases.

Table 7: Comparison of FM symptoms in Caucasian and Asian cases with those in Korean cases.

The results of this study are from 336 patients and from 10 medical centers all over the country. This is the first report of clinical characteristics of Korean patients with FM. Although chronic widespread pain was the dominant symptom, patients with FM also experienced multiple symptoms in addition to pain. The most commonly reported symptoms were fatigue, unrefreshing sleep, generalized weakness, stiffness, tension headache, swelling, febrile sense, and dizziness. The range of FM symptoms in the Korean population are similar to the Western population [3,14,15]. The economic impact of FM on employment was also notable, with current employment 32.9% which was corroborated by others (22~67%, average 40%) [14]. It took an average of 2 years before receiving a diagnosis of FM. The diagnosis of FM is delayed. Patients wait a significant period of time before presenting to a physician, adding to the prolonged time to diagnosis. Helping clinicians to diagnose patients with FM should benefit both patients and funders of healthcare.

Commonly used medications for FM, as reported by the clinicians, were NSAID, TCA, tramadol, SSRI, and muscle relaxant in descending order of frequency. Pregabalin, SNRI, benzodiazepine, sedativehypnotics, and gabapentin etc were used above this. Pregabalin prescription rate was relatively low because in that time (early phase of patients enrollment) there was no approval to prescription of pregabalin for FM by Korea Food and Drug Administration.

The frequencies of the various subjective symptoms in the present study and other Caucasian and Asian published series of FM patients [16-25] seem fairly identical as shown in Tables 6 and 7. However, the frequencies of the various subjective symptoms in USA (National Fibromyalgia Association, NFA) study [3] were much less than ours (Table 6). The surveyed NFA population was self-selected as people with FM who had Internet access and was familiar with the NFA website. Approximately 70% of the respondents mentioned that they obtained information about FM from the website. It is possible that those familiar with NFA differ in important ways from people with FM in general. They were not personally interviewed or formally diagnosed. Thus an unknown proportion of those responding may not have met 1990 ACR classification criteria for a diagnosis of FM [2]. In addition, only some 60 percent of them took medications, which suggest they had less severe symptoms than our patients. Our all patients, on the other hand, met 1990 ACR classification criteria for a diagnosis of FM [2], which means their symptoms were severe and frequently appeared.

Furthermore, the frequencies of the various symptoms in German (German Fibromyalgia Association, GFA) study [25] were much more than ours (Table 6). The terminology of symptoms in GFA study is more of a ordinary person’s expression than a medical term. In addition, that terminology was not defined in that study. On the other hand, the symptoms and sign were defined by glossary before study enrollment and patients were personally interviewed in our study. It might be the reason why the frequencies of the symptoms in GFA study were different from ours.

The other Caucasian studies were tried in USA (16-19), Sweden (20), Denmark [21] and Israel [22] etc. Asian studies were tried in Japan [23] and Bangladesh [24]. Variation of the prevalence of the each symptom may depend on different classification criteria, different definitions of the symptoms and sign, actual patient differences or various biases in the studies. In particular, a large variation is seen for the percentage of patients complaining of unrefreshing sleep, fatigue, stiffness, headache, and subjective swelling, with the highest frequencies obtained in this study (Table 7). The frequencies of the various subjective symptoms in our study and German study were much more than USA (Table 6). That is the most likely explanation why pregabalin and SNRI (e.g., milnacipran) were not usual prescription for FM in 2 countries on that time (from 2007 till 2008).

Several limitations of this study should be considered. First, although the study was open to women and men, the majority of people enrolled in the study were women. Although the majority of people diagnosed with FM are women, future studies should include men in order to assess any variance in symptoms experienced by men or any differences in the way that FM impacts the lives of men. Second, patients were recruited by the investigators and were required to be able to participate in this study and therefore may not be representative of all Korean patients with FM. Finally, while the size of the groups allowed for an intensive survey and tender point examination, confirmatory information with a larger population of patients is needed. However, the strengths of this study may be summarized as follows. First, the symptoms and sign were defined by glossary before study enrollment. Similar studies of clinical feature used the terminology on symptoms and sign without definite glossary. Second is a comparison between Korea and other countries. Several differences were found between the Korean and the other countries patients with FM in the clinical features. Further study will be needed to clarify whether these differences arise from racial factor(s).

We found that the range of FM symptoms in the Korean population are similar to the Western population. A comprehensive assessment of the multiple symptoms domains associated with FM and the impact of FM on multidimensional aspects of function should be a routine part of the care of FM patients.