Authors: Juan Jiao, MD Ann Vincent, MD Stephen S. Cha, MS Connie A. Luedtke, RN Chul H. Kim, MD Terry H. Oh, MD
Fibromyalgia
ORIGINAL RESEARCH ARTICLE
Affiliations: From the Department of Physical Medicine and Rehabilitation (JJ, CHK, THO), Division of General Internal Medicine (AV), Fibromyalgia and Chronic Fatigue Clinic (AV, CAL, THO), and Division of Biomedical Statistics and Informatics (SSC), Mayo Clinic, Rochester, Minnesota; and Department of Rehabilitation Medicine, Kyungpook National University Hospital, Daegu, Korea (CHK). Dr Jiao is now with the Department of Rheumatology, Guang_anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
Correspondence: All correspondence and requests for reprints should be addressed to: Terry H. Oh, MD, Department of Physical Medicine and Rehabilitation, Mayo Clinic, 200 First St SW, Rochester, MN 55905.
Disclosures: Presented as a poster at the 2014 Association of Academic Physiatrists Annual Meeting, Nashville, TN, February 2014. Supported by grant number UL1TR000135 from the National Center for Advancing Translational Sciences. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article.
0894-9115/15/9412-1075 American Journal of Physical Medicine & Rehabilitation Copyright * 2015 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/PHM.0000000000000300
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Physical Trauma and Infection as Precipitating Factors in Patients with Fibromyalgia ABSTRACT Jiao J, Vincent A, Cha SS, Luedtke CA, Kim CH, Oh TH: Physical trauma and infection as precipitating factors in patients with fibromyalgia. Am J Phys Med Rehabil 2015;94:1075Y1082.
Objective: The objective of this study was to evaluate both precipitating factors in patients with fibromyalgia and any differences in clinical presentation, symptom severity, and quality-of-life between those with and without precipitating physical trauma or infection.
Design:
In a retrospective cross-sectional study, the authors compared patient characteristics and fibromyalgia symptom severity and quality-of-life with the Fibromyalgia Impact Questionnaire and the Short Form-36 Health Survey in patients seen in a fibromyalgia treatment program.
Results: Of 939 patients, 27% reported precipitating factors (trauma, n = 203; infection, n = 53), with the rest having idiopathic fibromyalgia (n = 683). Patients with precipitating trauma were more likely to have worse Fibromyalgia Impact Questionnaire physical function than patients with idiopathic onset (P = 0.03). Compared with patients with idiopathic onset and precipitating trauma, patients with precipitating infection were more likely to have worse Short Form-36 Health Survey physical component summary (P = 0.01 and P = 0.003) but better role emotional (P = 0.04 and P = 0.005), mental health index (P = 0.02 and P = 0.007), and mental component summary (P = 0.03 and P = 0.004), respectively.
Conclusions: One-fourth of this study_s patients with fibromyalgia had precipitating physical trauma or infection. Patients with precipitating infection had different sociodemographic characteristics, clinical presentation, and quality-of-life from the idiopathic and trauma groups. Further studies are needed to look into the relationships between precipitating events and fibromyalgia. Key Words: Clinical Presentation, Fibromyalgia, Idiopathic, Infection, Physical Trauma, Precipitating Factors, Quality-of-Life, Symptom Severity
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ibromyalgia is a common chronic syndrome characterized by widespread musculoskeletal pain, fatigue, and nonrefreshing sleep that occurs more commonly in women than in men.1,2 Patients often report that a precipitating event, such as physical or emotional trauma, an infection, or a peripheral pain syndrome, occurred before the onset of fibromyalgia.3,4 Those trigger events may have a role in pathogenesis of fibromyalgia, although the etiology of fibromyalgia is unclear.3 Genetic and environmental factors may also contribute to this syndrome_s development.4 Most studies on precipitating factors in patients with fibromyalgia primarily have examined physical trauma.5,6 Precipitating physical trauma, including motor vehicle accidents (MVAs), nonMVA injury, surgery, sexual and physical abuse, medical illness, and childbirth, have been reported in 21%Y47% of fibromyalgia patients.5Y8 Infectiontriggered fibromyalgia has been suggested by many studies.9Y12 In one previous study, viral illness preceded fibromyalgia symptoms in 4% of patients with fibromyalgia.7 Previous fibromyalgia studies compared patients with precipitating physical trauma and idiopathic presentation of clinical features and disability, and findings varied from no significant difference to negative effects in patients with traumatic onset compared with those with idiopathic onset. Symptoms of trauma precipitating fibromyalgia were quite similar to those occurring without precipitating trauma,13 whereas another study showed reduced physical activity, higher employment loss,5 and more physician consults7 in patients with precipitating trauma than those with idiopathic onset. Some infectious agents, for example, human immunodeficiency virus, hepatitis C virus, hepatitis B virus, Lyme disease, parvovirus B19, coxsackievirus B, Epstein-Barr virus, and mycoplasmas, have been proposed as triggers of fibromyalgia.9Y12,14,15 Although the association of infection and fibromyalgia has been increasingly reported and studied, understanding of infection-triggered fibromyalgia is limited. The evidence of an association between fibromyalgia due to infection remains tentative, and there is no correlation with persistent infection or infection therapies and pain improvement.12 The aims of this study were to evaluate the prevalence of precipitating factors in patients seen in the authors_ Fibromyalgia Treatment Program (FTP) and whether patients with precipitating factors of physical trauma or infection have different clinical presentation, fibromyalgia symptom
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severity, or quality-of-life (QOL) compared with those without precipitating factors.
MATERIALS AND METHODS Participants and Data Collection The authors_ institutional review board approved this study, and all participants had given previous research authorization and provided written informed consent. The study population consisted of 978 patients who were seen in the authors_ institution_s FTP from May 1, 2001, to April 30, 2004, and were confirmed to have fibromyalgia, according to the 1990 American College of Rheumatology criteria for the classification of fibromyalgia.1 All patients were referred to the FTP internally by their health care providers in the authors_ institution. Subjects were the same cohort described in previously published studies.16,17 The FTP is a 1.5-day brief interdisciplinary program that includes both evaluation and treatment. The FTP focused on cognitive-behavioral techniques and provided comprehensive information on fibromyalgia and self-management strategies, which emphasized stress management, sleep hygiene, and planning to improve self-efficacy and sense of control. Patients returned to their primary care provider for follow-up care after the FTP. The Fibromyalgia Impact Questionnaire (FIQ) and the Short Form-36 Health Survey (SF-36) were completed by all participants at the time of their evaluation in the FTP. Demographic and social variables; the number of tender points; body mass index; use of tobacco, alcohol, opioids, and nonsteroidal antiinflammatory drugs (NSAIDs); fibromyalgia symptom duration at the time of evaluation; presence or absence of precipitating physical trauma or infection events; gradual vs. sudden onset of symptoms; and the period from initial fibromyalgia-related symptoms to diagnosis of fibromyalgia (time to diagnosis) were abstracted from each patient_s electronic medical record.
Determination and Categorization of Precipitating Factors All participants underwent a standardized evaluation at the FTP, where a registered nurse obtained information identifying the gradual or sudden onset of symptoms and presence of any precipitating events. Patients were asked about specific types of precipitating events when a precipitating event was reported. A standardized pick list was used when asking patients about precipitating events related to the onset of fibromyalgia symptoms. This list was developed by the nursing and physician staff as a combination of potential precipitating events or contributing factors that
Am. J. Phys. Med. Rehabil. & Vol. 94, No. 12, December 2015 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
were identified in the literature,3Y12,14,15 as well as common Bstories[ from patients noted in the authors_ clinical practice. When the pick list was developed, it included phrases of questioning that began with how long the patient was experiencing the current symptoms and whether the patient was aware of any specific precipitating event at the time. Prompts were used if the patient could not readily identify a precipitating event. In addition, the nurse would ask if the patient could recall having a history of Bthis type[ of pain or any pain problems from childhood on. The list comprised the following: nothing specific that could be identified, MVA, non-MVA injury, surgery, medical illness other than infection, infection, prolonged work stress, prolonged personal stress, and other. The authors categorized physical trauma and infection separately, as suggested previously.4,18
Fibromyalgia-Related Symptoms and QOL Assessment The FIQ assesses the health status of patients with fibromyalgia.19 It contains 20 questions to measure the following 10 domains: physical functioning, feel good, days of work missed, pain, fatigue, morning tiredness, stiffness, job ability, depression, and anxiety. A total score was tallied from all 10 domains, ranging from 0 to 100. Higher scores indicate greater impact of fibromyalgia symptoms on daily life.19 The SF-36 is composed of 36 items to assess eight concepts of health-related QOL.20 The eight dimensions are physical functioning, role physical, pain index, general health, vitality, social functioning, role emotional, and mental health index. Two summary measures are included for physical and mental components. The total SF-36 score ranges from 0 to 100, with higher scores indicating better health.20
All statistical analyses were performed using JMP version 10.0 software (SAS Institute Inc, Cary, NC).
RESULTS Patients A total of 295 patients reported precipitating events, most of whom (n = 256) reported physical trauma and infection. Other precipitating events were emotional trauma (n = 26) and included death of a close relative (n = 7), divorce (n = 8), work stress (n = 5), family stress (n = 5), and involvement in a legal trial (n = 1). Because of this small group size and to have more statistical power to detect group differences, the authors excluded these patients from further analysis, along with those who reported more than one precipitating factor (n = 13). The final study population consisted of 939 patients: the 256 patients (27.3%) with precipitating factors, and 683 patients (72.7%) who were categorized as idiopathic because they reported no specific precipitating event. Among the patients who reported precipitating factors, 203 (21.6%) reported physical trauma and 53 (5.6%) reported infection. Mean (SD) age was 48.6 (12.9) yrs, with 94.4% women. The physical trauma factors included MVA, nonMVA injury, surgery, childbirth or pregnancy, and medical illness other than infection (Table 1). The BOverexertion[ subcategory of non-MVA injury included carrying or lifting heavy goods in 7 patients and 1 patient each with bike riding and hiking. The BOthers[ subcategory of non-MVA injury included back and joint injury in 3 patients each; head injury in TABLE 1 Prevalence of precipitating physical trauma (n = 203)
Statistical Analysis
Category of Physical Trauma
Summary data were reported as mean (SD) for continuous variables and frequency (percentage) for categorical variables. Patients_ demographic and social characteristics and FIQ and SF-36 scores were compared across three groups (idiopathic vs. trauma vs. infection) by one-way analysis of variance or Pearson W2 test, as appropriate. Pairwise comparisons were also performed. When the threegroup comparisons of FIQ and SF-36 scores were significant, multivariate logistic regression was performed to distinguish patients with precipitating trauma and infection from idiopathic onset, and infection from trauma, after adjusting for age, marital status, and disease duration. P values less than 0.05 were considered statistically significant.
Non-MVA injury (n = 62) Fall Overexertion Neck injury Insect bite Fracture Others MVA injury Surgery (n = 43) Hysterectomy Joint surgery Spine surgery Other surgery Childbirth and pregnancy (n = 28) Childbirth Pregnancy Medical illness other than infection
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n (%) 18 (8.9) 9 (4.4) 7 (3.4) 5 (2.5) 4 (2.0) 19 (9.4) 59 (29.1) 10 (4.9) 9 (4.4) 7 (3.4) 17 (8.4) 24 (11.8) 4 (2.0) 11 (5.4)
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TABLE 2 Prevalence of precipitating infection (n = 53) Category of Infection Respiratory (n = 27) Flu Cold and upper respiratory Pneumonia Epstein-Barr virus Borrelia burgdorferi Varicella zoster virus Other virus
n (%) 19 6 2 10 3 2 11
(35.8) (11.3) (3.8) (18.9) (5.7) (3.8) (20.8)
2 patients; 1 patient each in arm injury, gunshot injury, endoscopy, physical abuse, and mammography; and unspecified injury in 6 patients. Although 11 patients had a history of physical abuse, only 1 patient reported physical abuse as a precipitating factor. The category BMedical illness other than infection[ included arthritis in 2 patients and 1 patient each
with myocardial infarction, systemic sepsis episode, vasculitis, gross hematuria, anaphylactic reaction, radioactive iodine therapy, drug infusion, serum sickness from antibiotics, and collagen injection. The infection factors included respiratory tract, EpsteinBarr virus, Borrelia burgdorferi, varicella zoster, and other viral infections (Table 2). Nonspecific viral infection was reported in 11 patients, and the authors included them as BOther virus.[ The demographic, social, and clinical presentation characteristics of the idiopathic, trauma, and infection groups are shown in Table 3. Age, marital status, symptom duration, gradual vs. sudden onset, and time to diagnosis were found to be significantly different among three groups (all P e 0.01). Patients with precipitating infection were more likely to be unmarried and to have shorter fibromyalgia symptom duration and time to diagnosis than those with idiopathic and traumatic onset and to be younger and to have had sudden onset compared with those with idiopathic onset. Patients
TABLE 3 Demographic, social, and clinical characteristics of 939 fibromyalgia patients by precipitating factor group Characteristic
Idiopathic (n = 683)
Female sex, n (%) Age, mean (SD), yrs White race, n (%) BMI,a mean (SD) Current tobacco use,b n (%) Current alcohol use,c n (%) Married, n (%) Employment, n (%) Employed outside the home Homemaker Retired Unemployed Education level, n (%) G12th grade High school Some college/technical College/graduate school Unknown Abuse history,d n (%) Disease duration, mean (SD), mos Disease onset, n (%) Gradual Sudden Opioid usee NSAID usee Tender points, mean (SD) Time to diagnosis, mean (SD), mos
Trauma (n = 203)
Infection (n = 53)
P
52 (98.1) 44.1 (14.8) 53 (100.0) 28.4 (6.7) 7 (13.2) 22 (41.5) 30 (56.6)
0.29 0.009 0.65 0.21 0.46 90.99 0.001 0.23
640 49.2 672 30.0 94 283 517
(93.7) (13.0) (98.4) (7.3) (13.8) (41.6) (75.7)
194 (95.6) 47.7 (11.8) 200 (98.5) 29.3 (7.2) 35 (17.2) 84 (41.6) 164 (80.8)
364 59 87 173
(53.3) (8.6) (12.7) (25.3)
116 15 18 54
(57.1) (7.4) (8.9) (26.6)
23 (43.4) 3 (5.7) 6 (11.3) 21 (39.6) 0.28
25 220 205 221 12 195 136.7
(3.7) (32.2) (30.0) (32.4) (1.8) (29.1) (140.4)
6 (3.0) 61 (30.0) 69 (34.0) 65 (32.0) 2 (1.0) 67 (33.0) 132.5 (123.6)
0 (0.0) 10 (18.9) 21 (39.6) 22 (41.5) 0 (0.0) 15 (28.8) 62.2 (59.8)
643 40 152 335 16.1 101.0
(94.1) (5.9) (22.5) (49.5) (2.2) (126.9)
26 (12.8) 177 (87.2) 60 (29.7) 90 (44.6) 16.3 (2.0) 98.5 (117.8)
6 (11.3) 47 (88.7) 15 (28.3) 28 (52.8) 16.3 (2.1) 43.3 (50.8)
0.57 G0.001 G0.001 0.09 0.38 0.64 0.004
a
Idiopathic group, n = 618; trauma group, n = 185; infection group, n = 49. Idiopathic group, n = 679; trauma group, n = 203; infection group, n = 53. c Idiopathic group, n = 680; trauma group, n = 202; infection group, n = 53. d Idiopathic group, n = 669; trauma group, n = 203; infection group, n = 52. e Idiopathic group, n = 677; trauma group, n = 202; infection group, n = 53. BMI, body mass index; NSAID, nonsteroidal anti-inflammatory drug. b
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with precipitating trauma were more likely to have had sudden onset compared with those with idiopathic onset. Among patients with precipitating trauma or infection, 87.5% reported sudden onset of symptoms compared with 5.9% of those with idiopathic onset. Time to diagnosis was shortest in the infection group, 43.3 T 50.8 mos, compared with 101.0 T 126.9 mos in the idiopathic group and 98.5 T 117.8 mos in the trauma group. There were no significant group differences in body mass index, employment, education level, tobacco use, alcohol use, opioid use, NSAID use, or tender points.
Symptom Severity and QOL The FIQ comparison across idiopathic, trauma, and infection groups is shown in Table 4. The authors found significant group differences in the FIQ physical functioning subscales (P = 0.04). Further logistic regression analysis (Table 5) showed that patients with precipitating trauma were more likely to have worse FIQ physical functioning than patients with idiopathic onset (odds ratio, 1.08; P = 0.03). The infection group also reported worse FIQ physical functioning than the idiopathic group. However, logistic regression adjusted for age, marital status, and disease duration showed that marital status and disease duration had more dominant roles; hence, FIQ physical functioning in patients with precipitating infection was not significantly different from patients with idiopathic onset (odds ratio, 1.08; P = 0.22). The SF-36 comparison across idiopathic, trauma, and infection groups is shown in Table 6. The authors found significant group differences in the SF-36 physical component summary and mental component summary, as well as SF-36 role emotional and mental health index (all P e 0.03). By multivariate logistic regression (Table 5), patients
with precipitating infection were more likely to have worse SF-36 physical component summary (P = 0.01 and P = 0.003) but better role emotional (P = 0.04 and P = 0.005), mental health index (P = 0.02 and P = 0.007), and mental component summary (P = 0.03 and P = 0.004), respectively, than patients with idiopathic onset and precipitating trauma. The authors did not find significant differences between patients with precipitating trauma and idiopathic onset.
DISCUSSION In this study_s clinical sample of patients with fibromyalgia, precipitating physical trauma or infection was reported in 27%. Precipitating infection was frequently reported in approximately one-fifth of those with precipitating factors. When the trauma, infection, and idiopathic groups were compared, group differences were found primarily in the infection group. In patients with precipitating infection, their QOL was worse in terms of physical health whereas mental health was better compared with the idiopathic and trauma groups. The authors did not observe significant differences in QOL between the trauma and idiopathic groups. Previous studies on precipitating factors in patients with fibromyalgia primarily reported findings related to traumatic onset compared with idiopathic onset.5Y7,13 In this study, differences between those in the trauma and idiopathic groups were limited to more sudden onset and worse FIQ physical functioning in the trauma group. Those findings contradict previous findings of no difference in FIQ physical functioning between patients with and without traumatic onset7 but agree with more reduced physical activity in patients with traumatic onset.5
TABLE 4 FIQ comparison of 939 fibromyalgia patients by precipitating factor group FIQ Characteristicsa
Idiopathic (n = 683)
Trauma (n = 203)
Infection (n = 53)
One-Way ANOVA P
Total score Physical functioning Feel good Work missed Job ability Pain Fatigue Morning tiredness Stiffness Depression Anxiety
62.9 (17.0) 4.5 (2.3) 7.8 (2.3) 4.0 (3.6) 6.8 (2.4) 7.2 (2.1) 8.1 (2.0) 7.8 (2.3) 7.3 (2.3) 4.2 (3.3) 5.0 (3.1)
63.0 (16.8) 4.9 (2.2) 7.6 (2.3) 4.1 (3.7) 6.7 (2.5) 7.1 (2.1) 8.1 (2.2) 7.8 (2.4) 7.4 (2.2) 4.1 (3.0) 5.0 (3.0)
63.1 (16.7) 5.0 (2.1) 8.0 (2.2) 5.0 (3.6) 6.9 (2.4) 7.0 (2.2) 8.4 (1.8) 7.8 (2.0) 7.0 (2.5) 3.1 (3.0) 4.8 (3.1)
90.99 0.04 0.32 0.14 0.77 0.82 0.53 0.97 0.59 0.07 0.91
Values are mean (SD). a The FIQ total score ranges from 0 to 100, and subscales range from 0 to 10. ANOVA, analysis of variance.
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TABLE 5 Logistic regression to distinguish among patients with precipitating trauma, precipitating infection, and idiopathic onset Trauma vs. Idiopathic
P
Infection vs. Trauma
OR (95% CI)
P
0.99 (0.98Y1.00) 1.46 (0.99Y2.20) 1.00 (1.00Y1.00) 1.08 (1.01Y1.16)
0.13 0.06 0.95 0.03
0.99 0.46 0.99 1.08
(0.97Y1.01) 0.47 0.99 (0.97Y1.02) (0.25Y0.86) 0.01 0.34 (0.17Y0.67) (0.99Y1.00) G0.001 0.99 (0.99Y1.00) (0.95Y1.24) 0.22 0.99 (0.84Y1.16)
0.62 0.002 0.001 0.87
0.99 (0.98Y1.00) 1.47 (0.99Y2.22) 1.00 (1.00Y1.00) 1.00 (0.99Y1.00)
0.09 0.06 0.92 0.21
0.99 0.46 0.99 1.01
(0.97Y1.01) 0.47 0.99 (0.97Y1.02) (0.25Y0.85) 0.01 0.29 (0.14Y0.59) (0.99Y1.00) G0.001 0.99 (0.99Y1.00) (1.00Y1.01) 0.04 1.01 (1.00Y1.02)
0.70 0.001 0.001 0.005
0.99 (0.98Y1.00) 1.47 (0.99Y2.22) 1.00 (1.00Y1.00) 1.00 (0.99Y1.00)
0.10 0.06 0.95 0.34
0.99 0.45 0.99 1.02
(0.97Y1.01) 0.30 0.99 (0.96Y1.02) (0.25Y0.84) 0.01 0.31 (0.15Y0.62) (0.99Y1.00) G0.001 0.99 (0.99Y1.00) (1.00Y1.03) 0.02 1.02 (1.01Y1.04)
0.44 0.001 0.001 0.007
0.99 (0.98Y1.00) 1.47 (0.99Y2.22) 1.00 (1.00Y1.00) 1.01 (0.99Y1.03)
0.10 0.07 0.90 0.26
0.99 0.47 0.99 0.95
(0.97Y1.01) 0.43 1.00 (0.97Y1.03) 0.89 (0.26Y0.88) 0.02 0.35 (0.18Y0.71) 0.003 (0.99Y1.00) G0.001 0.99 (0.99Y1.00) G0.001 (0.91Y0.99) 0.01 0.93 (0.88Y0.97) 0.003
0.99 (0.98Y1.00) 1.47 (0.99Y2.22) 1.00 (1.00Y1.00) 0.99 (0.98Y1.00)
0.15 0.06 0.95 0.18
0.99 0.46 0.99 1.03
(0.97Y1.01) 0.29 0.99 (0.96Y1.01) (0.25Y0.86) 0.01 0.31 (0.15Y0.62) (0.99Y1.00) G0.001 0.99 (0.99Y1.00) (1.00Y1.05) 0.03 1.04 (1.01Y1.08)
Measure FIQ part Age Marital status Duration of symptoms FIQ physical function SF-36 part Role emotional Age Marital status Duration of symptoms Role emotional Mental health Age Marital status Duration of symptoms Mental health index Physical component Age Marital status Duration of symptoms Physical component summary Mental component Age Marital status Duration of symptoms Mental component summary
Infection vs. Idiopathic OR (95% CI)
OR (95% CI)
P
0.36 0.001 0.001 0.004
CI, confidence interval; OR, odds ratio.
In this study, precipitating infection was reported in approximately 1 in 5 of those with precipitating events. Although reports of precipitating infection are limited, similar frequency (18%) of precipitating illness or infection has been reported previously in patients with fibromyalgia.9 Road traffic accidents, but not other traumatic events, were associated with an increase in the risk of chronic
widespread pain onset in a prospective populationbased study with a 4-yr follow-up.21 In this study, MVA was the most common trauma (29% of the group), but other traumatic events made up the majority of the group. Patients with precipitating trauma or infection were more likely than those with idiopathic conditions to have sudden onset of fibromyalgia. The
TABLE 6 SF-36 comparison of 939 fibromyalgia patients by precipitating factor group SF-36 Characteristicsa Physical functioning Role physical Pain index General health Vitality Social functioning Role emotional Mental health index Physical component summary Mental component summary
Idiopathic (n = 683) Trauma (n = 203) Infection (n = 53) One-Way ANOVA P 39.2 (22.9) 8.7 (20.6) 24.9 (14.8) 38.5 (21.0) 18.1 (16.5) 40.3 (25.4) 46.5 (43.0) 57.0 (21.1) 26.8 (7.8) 40.1 (11.9)
40.2 (21.7) 8.3 (18.0) 25.9 (15.1) 38.3 (20.2) 17.7 (16.3) 38.1 (25.2) 41.9 (41.8) 55.0 (22.0) 27.6 (7.6) 38.3 (12.2)
37.6 (20.3) 4.7 (12.1) 24.2 (15.4) 35.3 (19.6) 15.1 (15.8) 38.0 (22.6) 59.7 (42.5) 63.5 (20.2) 24.0 (6.3) 43.4 (10.5)
0.74 0.36 0.64 0.56 0.44 0.49 0.03 0.03 0.01 0.02
Values are mean (SD). a The score ranges of SF-36 subscales were 0 to 100 each. ANOVA, analysis of variance.
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high prevalence of sudden onset of fibromyalgia in patients with precipitating viral infection was also noted in a previous study.22 Furthermore, those with precipitating infection in this study were more likely to have a shorter time to diagnosis (P = 0.004). The sudden onset of symptoms with a better-defined condition may lead to earlier diagnosis of fibromyalgia in these patients than in patients with idiopathic and traumatic onset. Patients with precipitating infection had worse QOL in physical health but better mental health compared with patients in the idiopathic and trauma groups. The reasons for lower SF-36 physical component summary score in those with precipitating infection compared with the trauma and idiopathic groups are not clear. A parallel example occurs in chronic fatigue syndrome. In patients with chronic fatigue syndrome after Giardia enteritis, the SF-36 scores for role physical and vitality were markedly reduced compared with scores in the general population, whereas the decrease in the SF-36 role emotional score and mental health functioning was not as prominent.23 The authors did not find significant group differences in the FIQ fatigue score or the SF-36 role physical or vitality scores in this study, although the means of the measures were lowest in the infection group. Patients with precipitating infection may have concerns about possible recurrent, inadequately treated, or ongoing infection, which may lead to a maladaptive behavior pattern of avoidance, inactivity, and deconditioning.9 Educating and reassuring patients that fibromyalgia, not recurrent infection, is causing their symptoms may help them move forward with active rehabilitation. To the authors_ knowledge, mechanisms underlying the long-term association of fibromyalgia and precipitating physical trauma and infection have not been fully studied. As possible triggers, trauma and infection have been suggested to precipitate the onset of fibromyalgia by altering normal sleep patterns, turning local injury sites to distant regional pain and causing neural plasticity,24 immunologic activation,25 and neuroendocrine dysregulation.26 In addition, patients who are genetically predisposed to develop fibromyalgia may have a response that is different from that in patients without a genetic predisposition who are exposed to the same trauma or infection. However, more work still remains to be done. Further prospective studies are needed to better understand which types of infection or trauma are more likely to lead to fibromyalgia and which patient characteristics are most likely associated with development of fibromyalgia after precipitating events. www.ajpmr.com
This study has several limitations. First, the precipitating history was obtained retrospectively from each patient_s self-report and may have been influenced by recall bias. Patients with more severe fibromyalgia symptoms and worse physical functioning might be more likely to recall having a precipitating event. Therefore, the authors did additional analysis to examine the possible association between the worse and better symptom severity and physical functioning groups. It was reassuring that the authors found no significant differences in the distribution of precipitating events between the groups. Second, patients in the trauma and infection groups had been experiencing fibromyalgia symptoms for an average of 11 and 5 yrs, respectively, and disease duration was a confounder for symptom severity measured by the FIQ. Therefore, the authors performed multivariate logistic regression to distinguish patients with precipitating trauma and infection from idiopathic onset, and infection from trauma on the FIQ, after adjusting for factors including disease duration. However, it is still possible that there was a recall bias. This limitation is not unique to this study. Previous studies on precipitating factors also reported a many-year duration of fibromyalgia.8,13 Third, the authors did not confirm the precipitating events and did not have documentation of trauma and infection or its severity and duration. Among the 10 patients reported to have Epstein-Barr virus in this study, 3 of the 5 with results of virus antibody titers had positive titers. Among the 3 patients who reported Lyme disease, 2 had Lyme screening with negative results. Identification of the characteristics of infection or trauma that have a greater association awaits future study. Fourth, the data in this study were from patients seen in 2001 to 2004 at a tertiary referral center, and the clinical sample may not be representative of typical fibromyalgia patients. The new American College of Rheumatology criteria for fibromyalgia were published in 2010 after the study period. The authors used the 1990 American College of Rheumatology criteria for the classification of fibromyalgia, and that may also be a study limitation. Fifth, no clear guidelines exist for categories of precipitating factors, specifically what factors should be included in the trauma category. The authors categorized medical illness, pregnancy, and childbirth as physical trauma, as in previous studies.5,7,8 The authors found similar results when they analyzed the data with and without medical illness and childbirth or pregnancy in the trauma group. Sixth, this cross-sectional study does not allow the authors to address causality. Physical Trauma, Infection, and Fibromyalgia
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In conclusion, precipitating trauma or infection was noted in approximately 27% of fibromyalgia patients, with infection being reported in approximately one-fifth of those with precipitating factors. Patients with precipitating infection showed differences in sociodemographic characteristics, clinical presentation, and QOL compared with those with idiopathic or traumatic onset. The findings of this study may help clinicians recognize fibromyalgia symptoms in those who continue to have persistent symptoms after treatment of infections or after experiencing a physical trauma. The findings may also allow clinicians to help patients by not only avoiding repeated diagnostic testing or antibiotic treatment but also providing education, reassurance, and rehabilitation. Further prospective studies of infection or trauma triggers would be helpful to understand a causal relationship, which types of infection or trauma are more likely to lead to fibromyalgia, and what patient characteristics are likely associated with developing fibromyalgia after precipitating events. REFERENCES 1. Wolfe F, Smythe HA, Yunus MB, et al: The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia: Report of the Multicenter Criteria Committee. Arthritis Rheum 1990;33:160Y72 2. Lawrence RC, Felson DT, Helmick CG, et al: National Arthritis Data Workgroup: Estimates of the prevalence of arthritis and other rheumatic conditions in the United States: Part II. Arthritis Rheum 2008;58:26Y35 3. Clauw DJ, Crofford LJ: Chronic widespread pain and fibromyalgia: What we know, and what we need to know. Best Pract Res Clin Rheumatol 2003;17:685Y701 4. Buskila D: Developments in the scientific and clinical understanding of fibromyalgia. Arthritis Res Ther 2009;11:242 5. Greenfield S, Fitzcharles MA, Esdaile JM: Reactive fibromyalgia syndrome. Arthritis Rheum 1992;35: 678Y81 6. Turk DC, Okifuji A, Starz TW, et al: Effects of type of symptom onset on psychological distress and disability in fibromyalgia syndrome patients. Pain 1996; 68:423Y30 7. Aaron LA, Bradley LA, Alarcon GS, et al: Perceived physical and emotional trauma as precipitating events in fibromyalgia: Associations with health care seeking and disability status but not pain severity. Arthritis Rheum 1997;40:453Y60 8. Al-Allaf AW, Dunbar KL, Hallum NS, et al: A casecontrol study examining the role of physical trauma in the onset of fibromyalgia syndrome. Rheumatology (Oxford) 2002;41:450Y3 9. Goldenberg DL: Do infections trigger fibromyalgia? Arthritis Rheum 1993;36:1489Y92
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10. Ablin JN, Shoenfeld Y, Buskila D: Fibromyalgia, infection and vaccination: Two more parts in the etiological puzzle. J Autoimmun 2006;27:145Y52 11. Buskila D, Atzeni F, Sarzi-Puttini P: Etiology of fibromyalgia: The possible role of infection and vaccination. Autoimmun Rev 2008;8:41Y3 12. Cassisi G, Sarzi-Puttini P, Cazzola M: Chronic widespread pain and fibromyalgia: Could there be some relationships with infections and vaccinations? Clin Exp Rheumatol 2011;29:S118Y26 13. Waylonis GW, Perkins RH: Post-traumatic fibromyalgia: A long-term follow-up. Am J Phys Med Rehabil 1994;73:403Y12 14. Adak B, Tekeoglu I, Ediz L, et al: Fibromyalgia frequency in hepatitis B carriers. J Clin Rheumatol 2005;11:157Y9 15. Mohammad A, Carey JJ, Storan E, et al: Prevalence of fibromyalgia among patients with chronic hepatitis C infection: Relationship to viral characteristics and quality of life. J Clin Gastroenterol 2012;46:407Y12 16. Luedtke CA, Thompson JM, Postier JA, et al: A description of a brief multidisciplinary treatment program for fibromyalgia. Pain Manag Nurs 2005;6:76Y80 17. Oh TH, Stueve MH, Hoskin TL, et al: Brief interdisciplinary treatment program for fibromyalgia: Six to twelve months outcome. Am J Phys Med Rehabil 2010;89:115Y24 18. Martinez-Lavin M: Biology and therapy of fibromyalgia: Stress, the stress response system, and fibromyalgia. Arthritis Res Ther 2007;9:216 19. Burckhardt CS, Clark SR, Bennett RM: The fibromyalgia impact questionnaire: Development and validation. J Rheumatol 1991;18:728Y33 20. Ware JE Jr, Sherbourne CD: The MOS 36-item shortform health survey (SF-36): I. Conceptual framework and item selection. Med Care 1992;30:473Y83 21. Jones GT, Nicholl BI, McBeth J, et al: Role of road traffic accidents and other traumatic events in the onset of chronic widespread pain: Results from a population-based prospective study. Arthritis Care Res (Hoboken) 2011;63:696Y701 22. Wittrup IH, Jensen B, Bliddal H, et al: Comparison of viral antibodies in 2 groups of patients with fibromyalgia. J Rheumatol 2001;28:601Y3 23. Naess H, Nyland M, Hausken T, et al: Chronic fatigue syndrome after Giardia enteritis: Clinical characteristics, disability and long-term sickness absence. BMC Gastroenterol 2012;12:13 24. White KP, Carette S, Harth M, et al: Trauma and fibromyalgia: Is there an association and what does it mean? Semin Arthritis Rheum 2000;29:200Y16 25. Thompson ME, Barkhuizen A: Fibromyalgia, hepatitis C infection, and the cytokine connection. Curr Pain Headache Rep 2003;7:342Y7 26. Di Franco M, Iannuccelli C, Valesini G: Neuroendocrine immunology of fibromyalgia. Ann N Y Acad Sci 2010;1193:84Y90
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Fibromyalgia
ORIGINAL RESEARCH ARTICLE
Affiliations: From the Department of Physical Medicine and Rehabilitation (JJ, CHK, THO), Division of General Internal Medicine (AV), Fibromyalgia and Chronic Fatigue Clinic (AV, CAL, THO), and Division of Biomedical Statistics and Informatics (SSC), Mayo Clinic, Rochester, Minnesota; and Department of Rehabilitation Medicine, Kyungpook National University Hospital, Daegu, Korea (CHK). Dr Jiao is now with the Department of Rheumatology, Guang_anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
Correspondence: All correspondence and requests for reprints should be addressed to: Terry H. Oh, MD, Department of Physical Medicine and Rehabilitation, Mayo Clinic, 200 First St SW, Rochester, MN 55905.
Disclosures: Presented as a poster at the 2014 Association of Academic Physiatrists Annual Meeting, Nashville, TN, February 2014. Supported by grant number UL1TR000135 from the National Center for Advancing Translational Sciences. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article.
0894-9115/15/9412-1075 American Journal of Physical Medicine & Rehabilitation Copyright * 2015 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/PHM.0000000000000300
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Physical Trauma and Infection as Precipitating Factors in Patients with Fibromyalgia ABSTRACT Jiao J, Vincent A, Cha SS, Luedtke CA, Kim CH, Oh TH: Physical trauma and infection as precipitating factors in patients with fibromyalgia. Am J Phys Med Rehabil 2015;94:1075Y1082.
Objective: The objective of this study was to evaluate both precipitating factors in patients with fibromyalgia and any differences in clinical presentation, symptom severity, and quality-of-life between those with and without precipitating physical trauma or infection.
Design:
In a retrospective cross-sectional study, the authors compared patient characteristics and fibromyalgia symptom severity and quality-of-life with the Fibromyalgia Impact Questionnaire and the Short Form-36 Health Survey in patients seen in a fibromyalgia treatment program.
Results: Of 939 patients, 27% reported precipitating factors (trauma, n = 203; infection, n = 53), with the rest having idiopathic fibromyalgia (n = 683). Patients with precipitating trauma were more likely to have worse Fibromyalgia Impact Questionnaire physical function than patients with idiopathic onset (P = 0.03). Compared with patients with idiopathic onset and precipitating trauma, patients with precipitating infection were more likely to have worse Short Form-36 Health Survey physical component summary (P = 0.01 and P = 0.003) but better role emotional (P = 0.04 and P = 0.005), mental health index (P = 0.02 and P = 0.007), and mental component summary (P = 0.03 and P = 0.004), respectively.
Conclusions: One-fourth of this study_s patients with fibromyalgia had precipitating physical trauma or infection. Patients with precipitating infection had different sociodemographic characteristics, clinical presentation, and quality-of-life from the idiopathic and trauma groups. Further studies are needed to look into the relationships between precipitating events and fibromyalgia. Key Words: Clinical Presentation, Fibromyalgia, Idiopathic, Infection, Physical Trauma, Precipitating Factors, Quality-of-Life, Symptom Severity
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ibromyalgia is a common chronic syndrome characterized by widespread musculoskeletal pain, fatigue, and nonrefreshing sleep that occurs more commonly in women than in men.1,2 Patients often report that a precipitating event, such as physical or emotional trauma, an infection, or a peripheral pain syndrome, occurred before the onset of fibromyalgia.3,4 Those trigger events may have a role in pathogenesis of fibromyalgia, although the etiology of fibromyalgia is unclear.3 Genetic and environmental factors may also contribute to this syndrome_s development.4 Most studies on precipitating factors in patients with fibromyalgia primarily have examined physical trauma.5,6 Precipitating physical trauma, including motor vehicle accidents (MVAs), nonMVA injury, surgery, sexual and physical abuse, medical illness, and childbirth, have been reported in 21%Y47% of fibromyalgia patients.5Y8 Infectiontriggered fibromyalgia has been suggested by many studies.9Y12 In one previous study, viral illness preceded fibromyalgia symptoms in 4% of patients with fibromyalgia.7 Previous fibromyalgia studies compared patients with precipitating physical trauma and idiopathic presentation of clinical features and disability, and findings varied from no significant difference to negative effects in patients with traumatic onset compared with those with idiopathic onset. Symptoms of trauma precipitating fibromyalgia were quite similar to those occurring without precipitating trauma,13 whereas another study showed reduced physical activity, higher employment loss,5 and more physician consults7 in patients with precipitating trauma than those with idiopathic onset. Some infectious agents, for example, human immunodeficiency virus, hepatitis C virus, hepatitis B virus, Lyme disease, parvovirus B19, coxsackievirus B, Epstein-Barr virus, and mycoplasmas, have been proposed as triggers of fibromyalgia.9Y12,14,15 Although the association of infection and fibromyalgia has been increasingly reported and studied, understanding of infection-triggered fibromyalgia is limited. The evidence of an association between fibromyalgia due to infection remains tentative, and there is no correlation with persistent infection or infection therapies and pain improvement.12 The aims of this study were to evaluate the prevalence of precipitating factors in patients seen in the authors_ Fibromyalgia Treatment Program (FTP) and whether patients with precipitating factors of physical trauma or infection have different clinical presentation, fibromyalgia symptom
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severity, or quality-of-life (QOL) compared with those without precipitating factors.
MATERIALS AND METHODS Participants and Data Collection The authors_ institutional review board approved this study, and all participants had given previous research authorization and provided written informed consent. The study population consisted of 978 patients who were seen in the authors_ institution_s FTP from May 1, 2001, to April 30, 2004, and were confirmed to have fibromyalgia, according to the 1990 American College of Rheumatology criteria for the classification of fibromyalgia.1 All patients were referred to the FTP internally by their health care providers in the authors_ institution. Subjects were the same cohort described in previously published studies.16,17 The FTP is a 1.5-day brief interdisciplinary program that includes both evaluation and treatment. The FTP focused on cognitive-behavioral techniques and provided comprehensive information on fibromyalgia and self-management strategies, which emphasized stress management, sleep hygiene, and planning to improve self-efficacy and sense of control. Patients returned to their primary care provider for follow-up care after the FTP. The Fibromyalgia Impact Questionnaire (FIQ) and the Short Form-36 Health Survey (SF-36) were completed by all participants at the time of their evaluation in the FTP. Demographic and social variables; the number of tender points; body mass index; use of tobacco, alcohol, opioids, and nonsteroidal antiinflammatory drugs (NSAIDs); fibromyalgia symptom duration at the time of evaluation; presence or absence of precipitating physical trauma or infection events; gradual vs. sudden onset of symptoms; and the period from initial fibromyalgia-related symptoms to diagnosis of fibromyalgia (time to diagnosis) were abstracted from each patient_s electronic medical record.
Determination and Categorization of Precipitating Factors All participants underwent a standardized evaluation at the FTP, where a registered nurse obtained information identifying the gradual or sudden onset of symptoms and presence of any precipitating events. Patients were asked about specific types of precipitating events when a precipitating event was reported. A standardized pick list was used when asking patients about precipitating events related to the onset of fibromyalgia symptoms. This list was developed by the nursing and physician staff as a combination of potential precipitating events or contributing factors that
Am. J. Phys. Med. Rehabil. & Vol. 94, No. 12, December 2015 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
were identified in the literature,3Y12,14,15 as well as common Bstories[ from patients noted in the authors_ clinical practice. When the pick list was developed, it included phrases of questioning that began with how long the patient was experiencing the current symptoms and whether the patient was aware of any specific precipitating event at the time. Prompts were used if the patient could not readily identify a precipitating event. In addition, the nurse would ask if the patient could recall having a history of Bthis type[ of pain or any pain problems from childhood on. The list comprised the following: nothing specific that could be identified, MVA, non-MVA injury, surgery, medical illness other than infection, infection, prolonged work stress, prolonged personal stress, and other. The authors categorized physical trauma and infection separately, as suggested previously.4,18
Fibromyalgia-Related Symptoms and QOL Assessment The FIQ assesses the health status of patients with fibromyalgia.19 It contains 20 questions to measure the following 10 domains: physical functioning, feel good, days of work missed, pain, fatigue, morning tiredness, stiffness, job ability, depression, and anxiety. A total score was tallied from all 10 domains, ranging from 0 to 100. Higher scores indicate greater impact of fibromyalgia symptoms on daily life.19 The SF-36 is composed of 36 items to assess eight concepts of health-related QOL.20 The eight dimensions are physical functioning, role physical, pain index, general health, vitality, social functioning, role emotional, and mental health index. Two summary measures are included for physical and mental components. The total SF-36 score ranges from 0 to 100, with higher scores indicating better health.20
All statistical analyses were performed using JMP version 10.0 software (SAS Institute Inc, Cary, NC).
RESULTS Patients A total of 295 patients reported precipitating events, most of whom (n = 256) reported physical trauma and infection. Other precipitating events were emotional trauma (n = 26) and included death of a close relative (n = 7), divorce (n = 8), work stress (n = 5), family stress (n = 5), and involvement in a legal trial (n = 1). Because of this small group size and to have more statistical power to detect group differences, the authors excluded these patients from further analysis, along with those who reported more than one precipitating factor (n = 13). The final study population consisted of 939 patients: the 256 patients (27.3%) with precipitating factors, and 683 patients (72.7%) who were categorized as idiopathic because they reported no specific precipitating event. Among the patients who reported precipitating factors, 203 (21.6%) reported physical trauma and 53 (5.6%) reported infection. Mean (SD) age was 48.6 (12.9) yrs, with 94.4% women. The physical trauma factors included MVA, nonMVA injury, surgery, childbirth or pregnancy, and medical illness other than infection (Table 1). The BOverexertion[ subcategory of non-MVA injury included carrying or lifting heavy goods in 7 patients and 1 patient each with bike riding and hiking. The BOthers[ subcategory of non-MVA injury included back and joint injury in 3 patients each; head injury in TABLE 1 Prevalence of precipitating physical trauma (n = 203)
Statistical Analysis
Category of Physical Trauma
Summary data were reported as mean (SD) for continuous variables and frequency (percentage) for categorical variables. Patients_ demographic and social characteristics and FIQ and SF-36 scores were compared across three groups (idiopathic vs. trauma vs. infection) by one-way analysis of variance or Pearson W2 test, as appropriate. Pairwise comparisons were also performed. When the threegroup comparisons of FIQ and SF-36 scores were significant, multivariate logistic regression was performed to distinguish patients with precipitating trauma and infection from idiopathic onset, and infection from trauma, after adjusting for age, marital status, and disease duration. P values less than 0.05 were considered statistically significant.
Non-MVA injury (n = 62) Fall Overexertion Neck injury Insect bite Fracture Others MVA injury Surgery (n = 43) Hysterectomy Joint surgery Spine surgery Other surgery Childbirth and pregnancy (n = 28) Childbirth Pregnancy Medical illness other than infection
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n (%) 18 (8.9) 9 (4.4) 7 (3.4) 5 (2.5) 4 (2.0) 19 (9.4) 59 (29.1) 10 (4.9) 9 (4.4) 7 (3.4) 17 (8.4) 24 (11.8) 4 (2.0) 11 (5.4)
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TABLE 2 Prevalence of precipitating infection (n = 53) Category of Infection Respiratory (n = 27) Flu Cold and upper respiratory Pneumonia Epstein-Barr virus Borrelia burgdorferi Varicella zoster virus Other virus
n (%) 19 6 2 10 3 2 11
(35.8) (11.3) (3.8) (18.9) (5.7) (3.8) (20.8)
2 patients; 1 patient each in arm injury, gunshot injury, endoscopy, physical abuse, and mammography; and unspecified injury in 6 patients. Although 11 patients had a history of physical abuse, only 1 patient reported physical abuse as a precipitating factor. The category BMedical illness other than infection[ included arthritis in 2 patients and 1 patient each
with myocardial infarction, systemic sepsis episode, vasculitis, gross hematuria, anaphylactic reaction, radioactive iodine therapy, drug infusion, serum sickness from antibiotics, and collagen injection. The infection factors included respiratory tract, EpsteinBarr virus, Borrelia burgdorferi, varicella zoster, and other viral infections (Table 2). Nonspecific viral infection was reported in 11 patients, and the authors included them as BOther virus.[ The demographic, social, and clinical presentation characteristics of the idiopathic, trauma, and infection groups are shown in Table 3. Age, marital status, symptom duration, gradual vs. sudden onset, and time to diagnosis were found to be significantly different among three groups (all P e 0.01). Patients with precipitating infection were more likely to be unmarried and to have shorter fibromyalgia symptom duration and time to diagnosis than those with idiopathic and traumatic onset and to be younger and to have had sudden onset compared with those with idiopathic onset. Patients
TABLE 3 Demographic, social, and clinical characteristics of 939 fibromyalgia patients by precipitating factor group Characteristic
Idiopathic (n = 683)
Female sex, n (%) Age, mean (SD), yrs White race, n (%) BMI,a mean (SD) Current tobacco use,b n (%) Current alcohol use,c n (%) Married, n (%) Employment, n (%) Employed outside the home Homemaker Retired Unemployed Education level, n (%) G12th grade High school Some college/technical College/graduate school Unknown Abuse history,d n (%) Disease duration, mean (SD), mos Disease onset, n (%) Gradual Sudden Opioid usee NSAID usee Tender points, mean (SD) Time to diagnosis, mean (SD), mos
Trauma (n = 203)
Infection (n = 53)
P
52 (98.1) 44.1 (14.8) 53 (100.0) 28.4 (6.7) 7 (13.2) 22 (41.5) 30 (56.6)
0.29 0.009 0.65 0.21 0.46 90.99 0.001 0.23
640 49.2 672 30.0 94 283 517
(93.7) (13.0) (98.4) (7.3) (13.8) (41.6) (75.7)
194 (95.6) 47.7 (11.8) 200 (98.5) 29.3 (7.2) 35 (17.2) 84 (41.6) 164 (80.8)
364 59 87 173
(53.3) (8.6) (12.7) (25.3)
116 15 18 54
(57.1) (7.4) (8.9) (26.6)
23 (43.4) 3 (5.7) 6 (11.3) 21 (39.6) 0.28
25 220 205 221 12 195 136.7
(3.7) (32.2) (30.0) (32.4) (1.8) (29.1) (140.4)
6 (3.0) 61 (30.0) 69 (34.0) 65 (32.0) 2 (1.0) 67 (33.0) 132.5 (123.6)
0 (0.0) 10 (18.9) 21 (39.6) 22 (41.5) 0 (0.0) 15 (28.8) 62.2 (59.8)
643 40 152 335 16.1 101.0
(94.1) (5.9) (22.5) (49.5) (2.2) (126.9)
26 (12.8) 177 (87.2) 60 (29.7) 90 (44.6) 16.3 (2.0) 98.5 (117.8)
6 (11.3) 47 (88.7) 15 (28.3) 28 (52.8) 16.3 (2.1) 43.3 (50.8)
0.57 G0.001 G0.001 0.09 0.38 0.64 0.004
a
Idiopathic group, n = 618; trauma group, n = 185; infection group, n = 49. Idiopathic group, n = 679; trauma group, n = 203; infection group, n = 53. c Idiopathic group, n = 680; trauma group, n = 202; infection group, n = 53. d Idiopathic group, n = 669; trauma group, n = 203; infection group, n = 52. e Idiopathic group, n = 677; trauma group, n = 202; infection group, n = 53. BMI, body mass index; NSAID, nonsteroidal anti-inflammatory drug. b
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Am. J. Phys. Med. Rehabil. & Vol. 94, No. 12, December 2015 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
with precipitating trauma were more likely to have had sudden onset compared with those with idiopathic onset. Among patients with precipitating trauma or infection, 87.5% reported sudden onset of symptoms compared with 5.9% of those with idiopathic onset. Time to diagnosis was shortest in the infection group, 43.3 T 50.8 mos, compared with 101.0 T 126.9 mos in the idiopathic group and 98.5 T 117.8 mos in the trauma group. There were no significant group differences in body mass index, employment, education level, tobacco use, alcohol use, opioid use, NSAID use, or tender points.
Symptom Severity and QOL The FIQ comparison across idiopathic, trauma, and infection groups is shown in Table 4. The authors found significant group differences in the FIQ physical functioning subscales (P = 0.04). Further logistic regression analysis (Table 5) showed that patients with precipitating trauma were more likely to have worse FIQ physical functioning than patients with idiopathic onset (odds ratio, 1.08; P = 0.03). The infection group also reported worse FIQ physical functioning than the idiopathic group. However, logistic regression adjusted for age, marital status, and disease duration showed that marital status and disease duration had more dominant roles; hence, FIQ physical functioning in patients with precipitating infection was not significantly different from patients with idiopathic onset (odds ratio, 1.08; P = 0.22). The SF-36 comparison across idiopathic, trauma, and infection groups is shown in Table 6. The authors found significant group differences in the SF-36 physical component summary and mental component summary, as well as SF-36 role emotional and mental health index (all P e 0.03). By multivariate logistic regression (Table 5), patients
with precipitating infection were more likely to have worse SF-36 physical component summary (P = 0.01 and P = 0.003) but better role emotional (P = 0.04 and P = 0.005), mental health index (P = 0.02 and P = 0.007), and mental component summary (P = 0.03 and P = 0.004), respectively, than patients with idiopathic onset and precipitating trauma. The authors did not find significant differences between patients with precipitating trauma and idiopathic onset.
DISCUSSION In this study_s clinical sample of patients with fibromyalgia, precipitating physical trauma or infection was reported in 27%. Precipitating infection was frequently reported in approximately one-fifth of those with precipitating factors. When the trauma, infection, and idiopathic groups were compared, group differences were found primarily in the infection group. In patients with precipitating infection, their QOL was worse in terms of physical health whereas mental health was better compared with the idiopathic and trauma groups. The authors did not observe significant differences in QOL between the trauma and idiopathic groups. Previous studies on precipitating factors in patients with fibromyalgia primarily reported findings related to traumatic onset compared with idiopathic onset.5Y7,13 In this study, differences between those in the trauma and idiopathic groups were limited to more sudden onset and worse FIQ physical functioning in the trauma group. Those findings contradict previous findings of no difference in FIQ physical functioning between patients with and without traumatic onset7 but agree with more reduced physical activity in patients with traumatic onset.5
TABLE 4 FIQ comparison of 939 fibromyalgia patients by precipitating factor group FIQ Characteristicsa
Idiopathic (n = 683)
Trauma (n = 203)
Infection (n = 53)
One-Way ANOVA P
Total score Physical functioning Feel good Work missed Job ability Pain Fatigue Morning tiredness Stiffness Depression Anxiety
62.9 (17.0) 4.5 (2.3) 7.8 (2.3) 4.0 (3.6) 6.8 (2.4) 7.2 (2.1) 8.1 (2.0) 7.8 (2.3) 7.3 (2.3) 4.2 (3.3) 5.0 (3.1)
63.0 (16.8) 4.9 (2.2) 7.6 (2.3) 4.1 (3.7) 6.7 (2.5) 7.1 (2.1) 8.1 (2.2) 7.8 (2.4) 7.4 (2.2) 4.1 (3.0) 5.0 (3.0)
63.1 (16.7) 5.0 (2.1) 8.0 (2.2) 5.0 (3.6) 6.9 (2.4) 7.0 (2.2) 8.4 (1.8) 7.8 (2.0) 7.0 (2.5) 3.1 (3.0) 4.8 (3.1)
90.99 0.04 0.32 0.14 0.77 0.82 0.53 0.97 0.59 0.07 0.91
Values are mean (SD). a The FIQ total score ranges from 0 to 100, and subscales range from 0 to 10. ANOVA, analysis of variance.
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TABLE 5 Logistic regression to distinguish among patients with precipitating trauma, precipitating infection, and idiopathic onset Trauma vs. Idiopathic
P
Infection vs. Trauma
OR (95% CI)
P
0.99 (0.98Y1.00) 1.46 (0.99Y2.20) 1.00 (1.00Y1.00) 1.08 (1.01Y1.16)
0.13 0.06 0.95 0.03
0.99 0.46 0.99 1.08
(0.97Y1.01) 0.47 0.99 (0.97Y1.02) (0.25Y0.86) 0.01 0.34 (0.17Y0.67) (0.99Y1.00) G0.001 0.99 (0.99Y1.00) (0.95Y1.24) 0.22 0.99 (0.84Y1.16)
0.62 0.002 0.001 0.87
0.99 (0.98Y1.00) 1.47 (0.99Y2.22) 1.00 (1.00Y1.00) 1.00 (0.99Y1.00)
0.09 0.06 0.92 0.21
0.99 0.46 0.99 1.01
(0.97Y1.01) 0.47 0.99 (0.97Y1.02) (0.25Y0.85) 0.01 0.29 (0.14Y0.59) (0.99Y1.00) G0.001 0.99 (0.99Y1.00) (1.00Y1.01) 0.04 1.01 (1.00Y1.02)
0.70 0.001 0.001 0.005
0.99 (0.98Y1.00) 1.47 (0.99Y2.22) 1.00 (1.00Y1.00) 1.00 (0.99Y1.00)
0.10 0.06 0.95 0.34
0.99 0.45 0.99 1.02
(0.97Y1.01) 0.30 0.99 (0.96Y1.02) (0.25Y0.84) 0.01 0.31 (0.15Y0.62) (0.99Y1.00) G0.001 0.99 (0.99Y1.00) (1.00Y1.03) 0.02 1.02 (1.01Y1.04)
0.44 0.001 0.001 0.007
0.99 (0.98Y1.00) 1.47 (0.99Y2.22) 1.00 (1.00Y1.00) 1.01 (0.99Y1.03)
0.10 0.07 0.90 0.26
0.99 0.47 0.99 0.95
(0.97Y1.01) 0.43 1.00 (0.97Y1.03) 0.89 (0.26Y0.88) 0.02 0.35 (0.18Y0.71) 0.003 (0.99Y1.00) G0.001 0.99 (0.99Y1.00) G0.001 (0.91Y0.99) 0.01 0.93 (0.88Y0.97) 0.003
0.99 (0.98Y1.00) 1.47 (0.99Y2.22) 1.00 (1.00Y1.00) 0.99 (0.98Y1.00)
0.15 0.06 0.95 0.18
0.99 0.46 0.99 1.03
(0.97Y1.01) 0.29 0.99 (0.96Y1.01) (0.25Y0.86) 0.01 0.31 (0.15Y0.62) (0.99Y1.00) G0.001 0.99 (0.99Y1.00) (1.00Y1.05) 0.03 1.04 (1.01Y1.08)
Measure FIQ part Age Marital status Duration of symptoms FIQ physical function SF-36 part Role emotional Age Marital status Duration of symptoms Role emotional Mental health Age Marital status Duration of symptoms Mental health index Physical component Age Marital status Duration of symptoms Physical component summary Mental component Age Marital status Duration of symptoms Mental component summary
Infection vs. Idiopathic OR (95% CI)
OR (95% CI)
P
0.36 0.001 0.001 0.004
CI, confidence interval; OR, odds ratio.
In this study, precipitating infection was reported in approximately 1 in 5 of those with precipitating events. Although reports of precipitating infection are limited, similar frequency (18%) of precipitating illness or infection has been reported previously in patients with fibromyalgia.9 Road traffic accidents, but not other traumatic events, were associated with an increase in the risk of chronic
widespread pain onset in a prospective populationbased study with a 4-yr follow-up.21 In this study, MVA was the most common trauma (29% of the group), but other traumatic events made up the majority of the group. Patients with precipitating trauma or infection were more likely than those with idiopathic conditions to have sudden onset of fibromyalgia. The
TABLE 6 SF-36 comparison of 939 fibromyalgia patients by precipitating factor group SF-36 Characteristicsa Physical functioning Role physical Pain index General health Vitality Social functioning Role emotional Mental health index Physical component summary Mental component summary
Idiopathic (n = 683) Trauma (n = 203) Infection (n = 53) One-Way ANOVA P 39.2 (22.9) 8.7 (20.6) 24.9 (14.8) 38.5 (21.0) 18.1 (16.5) 40.3 (25.4) 46.5 (43.0) 57.0 (21.1) 26.8 (7.8) 40.1 (11.9)
40.2 (21.7) 8.3 (18.0) 25.9 (15.1) 38.3 (20.2) 17.7 (16.3) 38.1 (25.2) 41.9 (41.8) 55.0 (22.0) 27.6 (7.6) 38.3 (12.2)
37.6 (20.3) 4.7 (12.1) 24.2 (15.4) 35.3 (19.6) 15.1 (15.8) 38.0 (22.6) 59.7 (42.5) 63.5 (20.2) 24.0 (6.3) 43.4 (10.5)
0.74 0.36 0.64 0.56 0.44 0.49 0.03 0.03 0.01 0.02
Values are mean (SD). a The score ranges of SF-36 subscales were 0 to 100 each. ANOVA, analysis of variance.
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high prevalence of sudden onset of fibromyalgia in patients with precipitating viral infection was also noted in a previous study.22 Furthermore, those with precipitating infection in this study were more likely to have a shorter time to diagnosis (P = 0.004). The sudden onset of symptoms with a better-defined condition may lead to earlier diagnosis of fibromyalgia in these patients than in patients with idiopathic and traumatic onset. Patients with precipitating infection had worse QOL in physical health but better mental health compared with patients in the idiopathic and trauma groups. The reasons for lower SF-36 physical component summary score in those with precipitating infection compared with the trauma and idiopathic groups are not clear. A parallel example occurs in chronic fatigue syndrome. In patients with chronic fatigue syndrome after Giardia enteritis, the SF-36 scores for role physical and vitality were markedly reduced compared with scores in the general population, whereas the decrease in the SF-36 role emotional score and mental health functioning was not as prominent.23 The authors did not find significant group differences in the FIQ fatigue score or the SF-36 role physical or vitality scores in this study, although the means of the measures were lowest in the infection group. Patients with precipitating infection may have concerns about possible recurrent, inadequately treated, or ongoing infection, which may lead to a maladaptive behavior pattern of avoidance, inactivity, and deconditioning.9 Educating and reassuring patients that fibromyalgia, not recurrent infection, is causing their symptoms may help them move forward with active rehabilitation. To the authors_ knowledge, mechanisms underlying the long-term association of fibromyalgia and precipitating physical trauma and infection have not been fully studied. As possible triggers, trauma and infection have been suggested to precipitate the onset of fibromyalgia by altering normal sleep patterns, turning local injury sites to distant regional pain and causing neural plasticity,24 immunologic activation,25 and neuroendocrine dysregulation.26 In addition, patients who are genetically predisposed to develop fibromyalgia may have a response that is different from that in patients without a genetic predisposition who are exposed to the same trauma or infection. However, more work still remains to be done. Further prospective studies are needed to better understand which types of infection or trauma are more likely to lead to fibromyalgia and which patient characteristics are most likely associated with development of fibromyalgia after precipitating events. www.ajpmr.com
This study has several limitations. First, the precipitating history was obtained retrospectively from each patient_s self-report and may have been influenced by recall bias. Patients with more severe fibromyalgia symptoms and worse physical functioning might be more likely to recall having a precipitating event. Therefore, the authors did additional analysis to examine the possible association between the worse and better symptom severity and physical functioning groups. It was reassuring that the authors found no significant differences in the distribution of precipitating events between the groups. Second, patients in the trauma and infection groups had been experiencing fibromyalgia symptoms for an average of 11 and 5 yrs, respectively, and disease duration was a confounder for symptom severity measured by the FIQ. Therefore, the authors performed multivariate logistic regression to distinguish patients with precipitating trauma and infection from idiopathic onset, and infection from trauma on the FIQ, after adjusting for factors including disease duration. However, it is still possible that there was a recall bias. This limitation is not unique to this study. Previous studies on precipitating factors also reported a many-year duration of fibromyalgia.8,13 Third, the authors did not confirm the precipitating events and did not have documentation of trauma and infection or its severity and duration. Among the 10 patients reported to have Epstein-Barr virus in this study, 3 of the 5 with results of virus antibody titers had positive titers. Among the 3 patients who reported Lyme disease, 2 had Lyme screening with negative results. Identification of the characteristics of infection or trauma that have a greater association awaits future study. Fourth, the data in this study were from patients seen in 2001 to 2004 at a tertiary referral center, and the clinical sample may not be representative of typical fibromyalgia patients. The new American College of Rheumatology criteria for fibromyalgia were published in 2010 after the study period. The authors used the 1990 American College of Rheumatology criteria for the classification of fibromyalgia, and that may also be a study limitation. Fifth, no clear guidelines exist for categories of precipitating factors, specifically what factors should be included in the trauma category. The authors categorized medical illness, pregnancy, and childbirth as physical trauma, as in previous studies.5,7,8 The authors found similar results when they analyzed the data with and without medical illness and childbirth or pregnancy in the trauma group. Sixth, this cross-sectional study does not allow the authors to address causality. Physical Trauma, Infection, and Fibromyalgia
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In conclusion, precipitating trauma or infection was noted in approximately 27% of fibromyalgia patients, with infection being reported in approximately one-fifth of those with precipitating factors. Patients with precipitating infection showed differences in sociodemographic characteristics, clinical presentation, and QOL compared with those with idiopathic or traumatic onset. The findings of this study may help clinicians recognize fibromyalgia symptoms in those who continue to have persistent symptoms after treatment of infections or after experiencing a physical trauma. The findings may also allow clinicians to help patients by not only avoiding repeated diagnostic testing or antibiotic treatment but also providing education, reassurance, and rehabilitation. Further prospective studies of infection or trauma triggers would be helpful to understand a causal relationship, which types of infection or trauma are more likely to lead to fibromyalgia, and what patient characteristics are likely associated with developing fibromyalgia after precipitating events. REFERENCES 1. Wolfe F, Smythe HA, Yunus MB, et al: The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia: Report of the Multicenter Criteria Committee. Arthritis Rheum 1990;33:160Y72 2. Lawrence RC, Felson DT, Helmick CG, et al: National Arthritis Data Workgroup: Estimates of the prevalence of arthritis and other rheumatic conditions in the United States: Part II. Arthritis Rheum 2008;58:26Y35 3. Clauw DJ, Crofford LJ: Chronic widespread pain and fibromyalgia: What we know, and what we need to know. Best Pract Res Clin Rheumatol 2003;17:685Y701 4. Buskila D: Developments in the scientific and clinical understanding of fibromyalgia. Arthritis Res Ther 2009;11:242 5. Greenfield S, Fitzcharles MA, Esdaile JM: Reactive fibromyalgia syndrome. Arthritis Rheum 1992;35: 678Y81 6. Turk DC, Okifuji A, Starz TW, et al: Effects of type of symptom onset on psychological distress and disability in fibromyalgia syndrome patients. Pain 1996; 68:423Y30 7. Aaron LA, Bradley LA, Alarcon GS, et al: Perceived physical and emotional trauma as precipitating events in fibromyalgia: Associations with health care seeking and disability status but not pain severity. Arthritis Rheum 1997;40:453Y60 8. Al-Allaf AW, Dunbar KL, Hallum NS, et al: A casecontrol study examining the role of physical trauma in the onset of fibromyalgia syndrome. Rheumatology (Oxford) 2002;41:450Y3 9. Goldenberg DL: Do infections trigger fibromyalgia? Arthritis Rheum 1993;36:1489Y92
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