Delineating psychological and biomedical profiles in a heterogeneous fibromyalgia population using cluster analysis

The heterogeneity of patients meeting American College of Rheumatology (ACR) criteria for a diagnosis of fibromyalgia (FM) challenges our ability to understand the underlying pathogenesis and to optimize treatment of this enigmatic disorder. Our goal was to discern clinically relevant subgroups across multiple psychological and biomedical domains to better characterize the phenomenology of FM. Women meeting 1990 ACR criteria for FM (N = 107) underwent psychological (childhood trauma, mood, anxiety, and stress) and biomedical (neuroendocrine, immune, and metabolic) testing. Cluster analysis identified four distinct subgroups. Subgroups I, II, and III exhibited profiles that included high psychological distress. Subgroup I was further distinguished by a history of childhood maltreatment and hypocortisolism, and these women reported the most pain and disability. Subgroup II evinced more physiological dysregulation and also reported high levels of pain, fatigue, and disability. Subgroup III was characterized by normal biomarkers and reported intermediate pain severity with higher global functioning. Subgroup IV was distinguished by their psychological well-being, reporting less disability and pain. Our findings underscore the heterogeneity of both psychological and physiological features among FM patients presenting with nearly identical tender point counts. This subgroup categorization is compatible with hypothesized pathogenetic mechanisms of early trauma, stress system dysregulation, and pro-inflammatory bias, each prominent in some but not all FM patients. Appreciation of distinct FM subgroup features is invaluable for selecting the most appropriate treatment modalities.     

Risk factors for fibromyalgia: the role of violence against women

The objectives of the study were to analyse the association between fibromyalgia (FM) and violence against women and to explore the association between FM and sociodemographic factors, social support and psychological distress. A case-control study was conducted in a Spanish hospital. Cases were women diagnosed with FM, with no signs of any other type of inflammatory rheumatic disorder, who were seen at the Rheumatology Department of the hospital. Controls were women not diagnosed with FM who were seen at the Ear, Nose and Throat Department of the same hospital. A self-administered anonymous questionnaire was used to gather data on sociodemographic characteristics, violence, social support and psychological distress. Uni-, bi- and multivariate logistic regression analyses were conducted; 287 cases and 287 controls were recruited. The multivariate analysis showed that the probability of presenting FM increased with age (odds ratios (OR) = 1.06; CI95% = 1.03–1.09); that employed women and housewives were more likely to have the syndrome than unemployed women or students (OR = 4.97; CI95% = 1.45–17.02, and OR = 3.47; CI95% = 0.98–12.22, respectively); that the lower the educational level, the higher the probability of having FM; and that psychological distress was positively associated with the syndrome (OR = 4.62; CI95% = 2.68–7.97). Although abuse was more prevalent in cases than in controls, the differences were not statistically significant. However, frequency of abuse was positively and significantly correlated with FM. Although the aetiology of FM is still uncertain, it seems that certain psychosocial factors may be associated with the syndrome. Therefore, an interdisciplinary approach to the treatment of patients affected with this syndrome should be considered.     

Image analysis quantification of substance P immunoreactivity in the trapezius muscle of patients with fibromyalgia and myofascial pain syndrome

OBJECTIVE: Substance P (SP), a neurotransmitter stored within the afferent nociceptive fibers, is likely to be involved in the pathogenesis of musculoskeletal pain. We investigated SP immunoreactive (SP-ir) nerve fibers in the upper trapezius of patients with fibromyalgia (FM) and myofascial pain syndrome (MPS) by immunochemistry. METHODS: Trapezius muscle obtained from tender points of 9 women with primary FM, from trigger points of 9 women with regional myofascial pain, and from 9 control women were immunostained with anti-SP sera. Quantitative evaluation was performed by computerized image analysis. RESULTS: No significant differences in the number of SP-ir areas were detected between groups (one way ANOVA: p = 0.2); in contrast, mean optical density (OD) of SP-ir showed a significant difference comparing the groups (one way ANOVA: p < 0.0001). Mean OD of the immunostaining for SP was statistically greater in trapezius muscle of patients with MPS (0.594 +/- 0.096) compared to specimens from patients with FM (0.436 +/- 0.140) (p < 0.05) and controls (0.314 +/- 0.105) (p < 0.05); mean OD of immunostaining for SP was greater in FM specimens than in controls (p < 0.05). CONCLUSION: Our results point to a peripheral hyperactivity of the peptidergic nervous system in FM as well as in MPS. These findings support the notion of pathogenetic involvement of the afferent nervous system in the development and perception of myofascial pain.     

Health services costs and their determinants in women with fibromyalgia

OBJECTIVE: Patients with fibromyalgia (FM) use health services extensively. Knowledge about costs of FM is limited because of non-inclusiveness in assessing direct costs, because attempts to assess indirect costs are largely absent, and because determinants of costs have yet to be identified. We investigated the 6-month costs (direct and indirect) in women with primary FM, and we identified determinants of direct costs. METHODS: Subjects (n = 180 women) completed a health resource questionnaire as well as measures of pain, psychological distress, comorbidity, and disability. Unit costs for resources were obtained from government, hospital, laboratory, and professional association sources. Regression modeling for 6-month direct cost included age, disability, comorbidity, pain intensity, psychological distress, education, and work status. RESULTS: The average 6-month direct cost was $CDN 2298 (SD 2303). The largest components were medications ($CDN 758; SD 654), complementary and alternative medicine (CAM; $CDN 398; SD 776), and diagnostic tests ($CDN 356; SD 580). Our most conservative estimate of average 6-month indirect cost was $CDN 5035 (SD 7439). Comorbidity and FM disability were statistically significant contributors to direct costs in the multivariate analysis. Costs increased by approximately 20% with each additional comorbid condition. CONCLUSION: Women with FM are high consumers of both conventional and CAM services. Our estimates of costs exceed those from most other studies; this may be due to our inclusion of a broader set of health services, medications, and indirect costs. Although in univariate analyses the number of comorbidities and indices of the effect of FM, psychological distress, and pain intensity were associated with higher direct cost, in a multiple regression analysis, only the measure of FM disability and the number of comorbidities were significant direct-cost determinants. FM also imposes important indirect costs, which were nearly 70% of the economic burden.     

One year outcome of preadolescents with fibromyalgia

OBJECTIVE: Twenty-two children with fibromyalgia (FM), found in a population based study of 1756 Finnish preadolescents, were prospectively and blindly followed for one year to investigate their physical and psychological background factors and to determine the one year persistence of FM. METHODS: The American College of Rheumatology 1990 criteria for FM were used. Widespread pain was determined with a structured, pretested pain questionnaire, including items on disability both at baseline and at followup. At baseline, hypermobility was tested with Beighton's method and aerobic capacity with a 20 m shuttle run test, and psychological data were collected using the Children's Depression Inventory (CDI), a sleep questionnaire, and the Child Behavior Checklist and Teacher's Report Form. At followup, evaluations with the CDI and sleep questionnaire were repeated. RESULTS: At baseline, the prevalence of FM was 1.3% (95% CI 0.8 to 1.9). At followup, 16/22 (73%) children were available for evaluation; 4 (25%) had persistent FM. Children with FM had low pain thresholds. Only one of 19 children had hypermobility. Those with persistent FM had persistent subjective disability. Depressive symptoms diminished, but there was still comorbidity of pain and depressive symptoms at followup. CONCLUSION: This study supports a previous one, in which FM in children had a good outcome. However, fluctuation of pain symptoms in children might partly explain the outcome. Children with persistent FM showed persistent disability with a number of distress symptoms.     

<Emphasis Type="Italic">Helicobacter pylori</Emphasis> seropositivity in fibromyalgia syndrome

Although there are some studies suggesting relation between different types of infection and fibromyalgia syndrome (FM), there is presently no proof that FM is caused by an infection. Helicobacter pylori (HP) infection may cause extragastric manifestations. Inflammation is an important mediator of increased sympathetic nervous system activity and may lead to pain in fibromyalgia patients. In this study, we aimed to investigate the HP seropositivity in fibromyalgia patients compared with controls for possible role of HP infection in FM. Sixty-seven patients with fibromyalgia were evaluated. Two of them were excluded from the study because of high level of acute phase reactants. Sixty-five female patients with fibromyalgia and 41 randomly selected age-matched female healthy controls were enrolled to study. Serum HP IgA and IgG antibodies were measured by enzyme-linked immunosorbent assay technique. Fibromyalgia Impact Questionnaire was assessed in patients and controls. Seropositivity of HP IgG antibody in the fibromyalgia patients was significantly higher than in the control group. No statistically significant differences were found regarding the clinical features between fibromyalgia patients with HP IgG antibody and patients without IgG antibody. Our study suggests that former HP infection may have a role in the etiopathogenesis of fibromyalgia syndrome or may act as a triggering factor. However, high seroprevalence of HP in general population and prevalent asymptomatic infection make it difficult to interpret these results for the definite role of HP in FM. Highlighting the pathophysiologic mechanisms of FM will result in more effective treatment regimens.     

Is there a predisposition for the development of autoimmune diseases in patients with fibromyalgia? Retrospective analysis with long term follow-up

The objectives of the study were to evaluate the prevalence of antinuclear antibodies (ANA) in patients with fibromyalgia (FM) and the probability of the development of clinically overt connective tissue diseases. Four hundred and fifty FM patients were compared to 129 healthy matched blood donors. ANA testing was performed by immunofluorescence on rat tissue sections; in case of highly positive results, ANA were specified further by ELISA and immunodiffusion. All ANA positive FM patients were invited for a control examination. The ANA negative patients received a questionnaire, which was designed to identify those patients with possible connective tissue diseases (CTD). There was no significant difference in the frequency of ANA or thyroid antibodies between patients and controls (11.6% vs. 7%). Two patients had developed SLE: one was already ANA/anti-dsDNA positive at time of first diagnosis of FM; in the other, specific antibodies and SLE-related symptoms developed after 4.5 years. The probability for FM patients to develop CTD (SLE) within one year is 0.0027%, which is comparable to the incidence of SLE in the general population (0.005%). The risk of CTD is not increased in FM. The detection of ANA does not predict the development of CTD. However, in individual cases, FM may be an early sign of an autoimmune disease.     

The assessment of functional impairment in fibromyalgia (FM): Rasch analyses of 5 functional scales and the development of the FM Health Assessment Questionnaire

OBJECTIVE: Functional assessment by self-report questionnaire plays an important role in most rheumatic conditions, but psychometric properties of questionnaires have not been studied in fibromyalgia (FM), particularly by Rasch analysis, which allows for examining adequacy of the questionnaire scale. To assess currently used instruments, we examined the Fibromyalgia Impact Scale (FIQ), 4 versions of the Health Assessment Questionnaire (HAQ), and the Medical Outcome Survey Short Form (SF-36). METHODS: More than 2,500 patients from 4 sites (3 US, 1 Israel) completed the FIQ. The HAQ questionnaires were completed by 1438 patients participating in the US National Data Bank for Rheumatic Diseases. Seven hundred sixty patients from Wichita, Kansas, completed the SF-36. Rasch analysis was applied separately to each of these data sets. RESULTS: The FIQ systematically underestimated functional impairment by its handling of activities not usually performed. All questionnaires had problems with non-unidimensionality and ambiguous items when applied to patients with FM. In addition, scales were found to be non-linear. Because of these findings we used the 20 item HAQ questionnaire as an item bank to develop a new questionnaire more suitable for use in FM, the fibromyalgia HAQ (FHAQ). This questionnaire fits the Rasch model well, is relevant, is linear, and has a long, well spaced scale. CONCLUSION: No available functional assessment questionnaire works well in FM. A new questionnaire, the FHAQ, was developed. It has appropriate metric properties and should function well in this condition. Since the FHAQ is a subset of the larger HAQ questionnaire, a new questionnaire is not required; only a different method of scoring is needed. Additional studies regarding sensitivity to change are required to fully validate the FHAQ.     

Looking at fibromyalgia differently – An observational study of the meaning and consequences of fibromyalgia as a dimensional disorder

ObjectiveDespite data showing that fibromyalgia can be represented as a dimensional disorder, almost all assessments treat fibromyalgia as a dichotomous categorial disorder; and research shows that agreement between community diagnosis of fibromyalgia and fibromyalgia criteria is poor. We investigated the validity of FM as a discrete disorder by exploring the relationships of categorical fibromyalgia, the polysymptomatic distress (PSD) scale, and clinical variables.MethodsIn a databank of 33,972 rheumatic disease patients, we studied the categorical diagnosis of fibromyalgia, the PSD scale separately and divided into severity groups, measures of widespread pain, as well as somatic syndrome questionnaires like the Patient Health Questionnaire-15 (PHQ-15), and clinical pain, global, HAQ disability and quality of life scales (EQ-5D).ResultsClinical and demographic variables became more abnormal with increasing PSD score groups, indicating substantial increase in symptoms and pain. The changes across PSD categories were linear and large. When we compared FM- (PSD 8-11) with FM+ (PSD 12-18) patients we found considerable overlap in scores for pain, HAQ disability, patient global, PHQ-15, psychological status, and other variables. Somatic symptom scores were highly correlated with PSD (r=0.718). There was no evidence of a differential pain effect that was present in FM+ but not FM- subjects.ConclusionFibromyalgia is more accurately considered a dimensional than a dichotomous disorder. There is vast variability among fibromyalgia positive and negative cases that is governed by the strong and linear relationships between the dimensional PSD scale and clinical variables. The PSD scale provides measurements of the fibromyalgia dimension that support and enlighten categorical fibromyalgia and are an effective tool to measure clinical status and changes. Whatever the mechanism of the pain and symptom increase in fibromyalgia, it appears to operate over the entire fibromyalgia symptom dimension, not just in those with categorical fibromyalgia.     

The frequency of thyroid antibodies in fibromyalgia patients and their relationship with symptoms

We determined the frequency of thyroid autoantibodies in fibromyalgia (FM) patients and the relationship between FM symptoms and these antibodies. Euthyroid 128 FM patients, 64 rheumatoid arthritis (RA) patients, and 64 healthy control subjects were included in the study. The sociodemographic features and the clinical features of FM patients were determined. By using a visual analog scale, patients were questioned about the severity of FM-related symptoms. All patients were administered with Duke-Anxiety Depression (Duke-AD) scale, the physical function items of the fibromyalgia impact questionnaire scale. Thyroid autoimmunity was defined as the presence of detectable antithyroglobulin (TgAb) and/or antithyroid peroxidase (TPOAb) antibodies by the immunometric methods. Patients with a connective tissue disorder, hypo- or hyperthyroidism, and patients who had psychiatric treatment within the last 6 months were not included into the study. The frequencies of thyroid autoimmunity in FM (34.4%) and RA (29.7%) patients were significantly higher than controls (18.8%) (p<0.05). Twenty-six (20.3%) FM patients had positive TgAb and 31 (24.2%) had positive TPOAb. When patients with thyroid autoimmunity were compared to others, it was seen that the mean age, the percentage of postmenopausal patients, the frequency of dryness of the mouth, and the percentage of patients with a previous psychiatric treatment were higher in this group (p<0.05). FM patients had thyroid autoimmunity similar to the frequency in RA and higher than controls. Age and postmenopausal status seemed to be associated with thyroid autoimmunity in FM patients. The presence of thyroid autoimmunity had no relationship with the depression scores of FM patients.     

Fibromyalgia in inflammatory bowel disease.

OBJECTIVE: Studies of the rheumatological complications of inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis) have focused on peripheral arthritis and spondylitis, and less is known about soft tissue rheumatism, specifically the fibromyalgia syndrome (FM). Our aim was to estimate the prevalence of FM and assess pain thresholds in patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: Seventy-two patients with UC and 41 with CD attending consecutively at the Gastroenterology Outpatient Clinic were assessed for the presence of FM and tenderness thresholds. FM was diagnosed according to the American College of Rheumatology 1990 criteria. Tenderness was measured by manual palpation and with a dolorimeter. One hundred twenty healthy subjects served as controls. RESULTS: FM was documented in 30 of 113 patients with IBD (30%), specifically in 49% of patients with CD and 19% with UC (p = 0.001); in controls the rate was 0%. Subjects with CD exhibited more tenderness and reported more frequent and more severe FM associated symptoms than subjects with UC. Patients with CD had a higher tender point count, 11.3 (+/- 6.5), than those with UC, 6.4 (+/- 5.7) (p = 0.001); in healthy controls, the count was 0.1 (+/- 0.5). Tenderness thresholds (kg) were lower in CD 2.9 (+/- 1.7) than UC 3.9 (+/- 2.0) (p = 0.005) and controls 5.8 (+/- 0.9). CONCLUSION: FM is common in IBD, particularly Crohn's disease. The lower pain threshold in Crohn's disease may suggest a disease-specific effect. Recognizing FM in patients with IBD will prevent misdiagnosis and ensure correct treatment.     

Dietary aspects in fibromyalgia patients: results of a survey on food awareness, allergies, and nutritional supplementation

Fibromyalgia (FM) is a common disease that results in poor quality of life, causing widespread musculoskeletal pain and stiffness, fatigue, sleep disorders, and cognitive impairment among other symptoms. The lack of an effective treatment makes necessary a multidimensional management. FM patients usually seek, from different sources, information about possible benefits from foods, nutrients, or diets. Our objective was to investigate the dietary awareness, food allergies and/or intolerances (FAIs), and nutritional supplement (NS) consumption of FM patients. A questionnaire was prepared with six questions regarding dietary habits, FAIs, and NS use. The questionnaire was filled out by patients recruited in local fibromyalgia associations. One hundred and one women were suffering from FM, diagnosed for more than 6 months, mean age of 53.88 ± 7.78 years; 30% of them changed their diet because of their disease, trying to improve it, and most of them were also using some NS; 7% of women in this group had FAIs, a figure slightly higher than the FAI prevalence in the general population (2-5%) and positively associated with consumption of supplements. Among NS users, some differences were observed; past NS users currently consume a wider range of products, more than new NS users. Magnesium was one of the supplements most recommended specifically for FM. Seventy-four percentage of these patients used NS following advice from health professionals. Once patients are diagnosed, they change their dietary habits and nutritional supplement intake, seeking nutritional strategies to improve their symptoms. Health professionals' advice plays a relevant role.     

Patients treated by tegaserod for irritable bowel syndrome with constipation showed significant improvement in fibromyalgia symptoms. A pilot study

The symptoms of irritable bowel syndrome (IBS) are commonly seen in fibromyalgia (FM) patients. This study aimed to evaluate the effect of 5-hydroxytryptamin-4 receptor partial agonist (tegaserod) on the symptoms of FM among the patients who receive the medicine because of IBS. Forty-one female patients with IBS and constipation, which were subjects to tegaserod treatment, were examined by rheumatologist and 14 were found to suffer from FM. The fibromyalgia impact questionnaire (FIQ) and clinical examination were done before tegaserod treatment and 1 month after. The IBS status, the total FIQ score, the number of tender points and pain in tender points were lowered significantly after the treatment (p < 0.001 for all variables). The results of this pilot study provide the preliminary evidence that FM patients can benefit from treatment by 5-hydroxytryptamin-4 receptor partial agonist. Additional studies are needed to support this conclusion.     

Serum antioxidants and nitric oxide levels in fibromyalgia: a controlled study

We proposed to assess antioxidant status and nitric oxide in fibromyalgia (FM) patients in comparison to healthy controls. Additionally, the association between the serum antioxidant levels and clinical findings in FM patients was also investigated. Thirty-seven FM patients and 37 healthy controls were enrolled in this study. Severity of fatigue and pain were determined by Visual Analogue Scale. Functional capacity in daily living activities was evaluated by fibromyalgia impact questionnaire. Serum NO, catalase and glutathione were measured. Serum glutathione and catalase levels were significantly lower in FM patients than controls. However, no significant difference was seen in serum NO levels between the two groups. A significant correlation was evident between serum NO level and pain. Additionally, the correlation between glutathione level and morning stiffness was found to be significant. These findings support other studies, we assume that these two antioxidants might have impact on the pathogenesis of FM disease.     

Vitamin D levels in women with systemic lupus erythematosus and fibromyalgia.

OBJECTIVE: Many patients with systemic lupus erythematosus (SLE) and fibromyalgia (FM) may spend less time exposed to the sun than healthy individuals and thus might have low vitamin D levels. It is known that hydroxychloroquine (HCQ) inhibits conversion of 25(OH)- to 1,25(OH)2-vitamin D both in vitro and in patients with sarcoidosis. We assessed winter serum 25(OH)- and 1,25(OH)2-vitamin D levels in patients with SLE and FM. METHODS: We recruited 25 consecutive female SLE and 25 female FM patients in London, Ontario, between January and March 2000. Subjects completed a brief questionnaire. Serum levels of 25(OH)-, 1,25(OH)2-vitamin D, and parathyroid hormone (PTH) were measured. RESULTS: In SLE patients mean 25(OH)-vitamin D was 46.5 nmol/l and mean 1,25(OH)2-vitamin D was 74.4 pmol/l. In FM patients these means were 51.5 nmol/l and 90.1 pmol/l, respectively. Serum 25(OH)-vitamin D levels did not significantly differ between SLE and FM patients, nor after adjusting for age and vitamin D, milk consumption, and sun block use. In 14 of the SLE patients and 12 of the FM patients 25(OH)-vitamin D levels < 50 nmol/l were found. SLE patients not using vitamin D supplements had lower 25(OH)-vitamin D levels than those who did. 1,25(OH)2-vitamin D tended to be lower in the SLE compared to the FM patients. This difference could be attributed to HCQ use: HCQ users (n = 17) had lower 1,25(OH)2-vitamin D levels than nonusers (n = 33); the mean adjusted difference was 24.4 pmol/l (95% CI 2.8-49.9). CONCLUSION: Half the SLE and FM patients had 25(OH)-vitamin D levels < 50 nmol/l, a level at which PTH stimulation occurs. Our data suggest that in SLE patients HCQ might inhibit conversion of 25(OH)-vitamin D to 1,25(OH)2-vitamin D.     

Clinical and psychological assessment of patients with rheumatoid arthritis and fibromyalgia: a real-world study

Clinical Rheumatology - To assess the clinical features and functional and psychological status of patients with rheumatoid arthritis (RA) and those with fibromyalgia (FM) in a real-world setting....     

Does psychological vulnerability determine health-care utilization in fibromyalgia?

OBJECTIVES: Patients with fibromyalgia (FM) undergo multiple testing and referral to specialists, and often use complementary/alternative medicine (CAM) services. The objectives of the study were: (i) to document health service utilization, and (ii) to examine whether psychological vulnerability was associated with visits to physicians and CAM providers. METHODS: Women (N = 178) with a diagnosis of primary FM completed a psychosocial test measuring pain, perceived stress, global psychological distress, sexual abuse history, co-morbidity and disability due to FM. Subjects also completed a health services questionnaire, documenting visits to physicians and CAM providers during the previous 6 months. Psychological vulnerability was operationalized as obtaining high scores on psychological distress, perceived stress and reporting at least one abusive event. RESULTS: The average number of visits was 7.2 to physicians and 11.3 to CAM providers. CONCLUSIONS: The number of physician visits was significantly associated with more co-morbidity. Psychologically vulnerable subjects were more likely to use CAM services than those not so classified.     

Clinical,psychological features and quality of life of fibromyalgia patients: a cross-sectional study of Chinese sample

Clinical Rheumatology - This study aimed to determine the clinical, psychological features, and quality of life in Chinese fibromyalgia (FM) patients who fulfilled the American College of...     

Pathophysiology and antioxidant status of patients with fibromyalgia

Fibromyalgia syndrome (FMS) is characterized by systemic pain of unknown etiology and is often accompanied by various psychological symptoms. Research on different parameters in fibromyalgia (FM) indicates that multifactors are involved in its pathophysiology; such as genetic factors, substance P, serotonin, hypothalamic pituitary adrenal axis (HPA), muscles metabolic dysfunction, reactive oxygen species (ROS) and reactive nitrogen species (RNS). Oxidative stress has also been implicated in the pathophysiology of FM; therefore, supplementation with antioxidants may be important in modulation of the effects of ROS in patients with FM.     

The relationship between tender point count and disease severity in patients with primary fibromyalgia

Objective of this study is to asses the relationship between tender point count (TPC) and the severity of disease in patients with primary fibromyalgia (FM). One hundred and seven female patients with FM diagnosis according to ACR criteria were included to the study. Main outcome measures were fibromyalgia impact questionnaire (FIQ), Beck depression inventory (BDI), visual analog scale (VAS) and tender point assessment. Mean TPC was 14.66 ± 2.50 and mean VAS was 6.6 ± 1.2 cm. Mean total FIQ score and BDI was 62.75 ± 15.57 and 16.17 ± 7.12, respectively. TPC was correlated positively with FIQ and VAS scores. There was no correlation between TPC and age and duration of symptoms. In conclusion, TPC is a simple and noninvasive examination finding that can supply information about the disease severity and the depression in FM.