From: Current Opinion in Rheumatology
Curr Opin Rheumatol 15(2):145-150, 2003.
Haiko Sprott, M.D.
Symptoms of primary fibromyalgia (FM) persist for years, independent of applied therapy. That is the sad reality we have to deal with. But is that really true? The following review is a scan of literature from September 1, 2001 to August 31, 2002, concerning rehabilitation interventions for patients with FM, to find progress in this field and to ascertain state-of-the-art treatment strategies for the disease. The main problem when treating patients with FM successfully is the heterogeneity of the patients’ group. Several investigators determined subgroups within FM patients diagnosed by the 1990 American College of Rheumatology classification criteria of FM.
Therefore, uniform recommendations for treatment cannot be given. Current treatment recommendations for FM include reassurance and explanation of the nature of the illness, evaluation and eradication of mechanical stressors as far as possible, symptomatic analgesic drug treatment, moderate individually adapted physical exercises, and adjuvant psychotherapeutic support in an interdisciplinary setting. Individually adapted measures are highly emphasized to differentially treat FM subgroups, as far as identified.
This review will focus on these points on the one hand, and provide an overview about the current symptomatically-oriented therapy on the other hand. This all occurs against the background of an unknown etiology of the disease so far. Experimental approaches will be noted as well. The demonstration of a long-term effective intervention for managing the symptoms associated with FM is needed.
Diagnosis and Clinical Manifestations
The clinical pain of patients with primary fibromyalgia (FM) is chronic, widespread, and its pathogenesis is poorly understood. Symptoms of FM persist for years, independent of applied therapy. Some aspects of quality of life improve over time because of coping strategies patients with FM develop, with or without professional support. FM has significant impact on a patient’s quality of life and physical functioning. The development and exacerbation of FM are both associated with the occurrence of major life stressors.[2, 3] The etiology of FM is unknown. Therefore, prevention, causal therapy, and rehabilitation are not possible. Currently, therapy is polypragmatic and is aimed at reducing the pain and other symptoms associated with this condition.
Therapy consists of drug treatment, physical exercises, psychological interventions, and other symptomatically oriented therapies, such as acupuncture. Effective interventions that last for more than a year have not yet been shown. Research is increasing exponentially in this field, to help us better understand the reasons why this disease develops.
American College of Rheumatology (ACR) Classification criteria from 1990 are more or less used for the diagnosis of FM. These criteria suggest that if 40 to 60% of the tender point sites are positive and the patient has at least three of the following symptoms: fatigue, sleep disturbance, anxiety, irritable bowel syndrome, headache, or paresthesia, then the clinical diagnosis of FM can be made. Vegetative and functional symptoms that are constantly associated with FM are not part of the 1990 ACR classification criteria.
The ACR classification criteria are undergoing enormous critique at this time,[6, 7] given the fact that the group of patients diagnosed with FM is very heterogeneous and therefore cannot be treated with universally accepted strategies. There are no validated predictors for treatment success, mostly for this reason.[8*] Clinicians and investigators report that distinguishable subgroups and subsets within FM patients require different treatment strategies.[9, 10]
In a study by Sorensen et al. intravenous morphine (0.3 mg/kg), lidocaine (5 mg/kg), and ketamine (0.3 mg/kg) given over a 30-minute period were compared. In this study three patients did not respond and 13 responded to one or several drugs, but not to placebo. Pain reduction lasted from 1 to 5 days. It was concluded that there may be differences in pain processing in individual subsets of patients with FM and that a pharmacologic pain analysis should be considered before instituting therapeutic interventions.
Fibromyalgia is not always associated with psychopathology. Ahles et al. demonstrated that 49% of FM patients could be classified within normal limits. Significant depressive symptomatology (emotional distress, life interference, and anxiety) is limited to a subgroup of FM patients (28.6%;). Cianfrini et al. reported high pain levels in FM patients when exposed to relatively low levels of pressure stimulation, but these responses differ from those of patients with major depression and healthy controls, suggesting depression does not mediate pain sensitivity in FM. No single physician has the resources to care comprehensively for the complex psychological, social, legal, medical, and physical problems involved in FM patients with chronic pain.
Health care professionals should be familiar with the variety of symptoms associated with FM, so that they may refer their patients to their physicians when the condition is suspected.
Patients with FM may have difficulty remaining active because of exercise-induced pain. This may lead to extreme deconditioning, inability to remain employed, and eventually, even impaired ability to complete activities of daily living. Exercise that combats deconditioning without triggering pain is, therefore, a key component in treating FM. Clinicians who understand FM pain and the associated symptoms can minimize the negative impact of deconditioning by prescribing disease-specific exercises for people with FM.[16*]
Fibromyalgia is not simply an inexplicable generalized pain condition; rather it is a distinct clinical entity. The wide range of descriptions in different studies shows that the existing criteria for the classification/diagnosis of FM are not strict enough for diagnostic purposes. There is an essential need for clear criteria to diagnose and classify FM from other chronic pain diseases.
Fibromyalgia is a disease that usually occurs during early and middle age. A prevalence between 2 and 7% was described.[17-19] FM affects nearly 6 million people in the United States. The peak of disease frequency lies in people between 45 and 60 years of age. The disease is more prevalent in women than in men; it was found to exist in 3.4% of all women and 0.5% of all men, but may also occur in children and juveniles.
The aim of this review (scanning period from September 1, 2001 to August 31, 2002) is to highlight available, evidence-based treatment approaches for patients with FM, with the primary goals of alleviating the pain and enhancing the patients’ quality of life and functional capabilities. Part of the comprehensive pain management for patients with FM should include a thoughtful evaluation and search for peripheral pain generators that either are associated with FM or are coincidentally present. The identification and treatment of these pain generators lessen the total pain burden, facilitate rehabilitation, and decrease the stimuli for ongoing central sensitization.[22**, 23]
Interdisciplinary management (physician, physical therapist, occupational therapist, nurse, psychologist) and multiple treatment foci (eg, education, physical reconditioning, work conditioning, counseling, ergonomic assessment) are most effective and state-of-the-art.[24, 25] Positive attitudes, supportiveness, and optimism that interact to maximize the placebo, opioid, and analgesic effects and minimize all possible side effects are most welcome concomitant phenomena. In this manner, most patients with FM can be managed at the primary care level with intermittent consultations with rheumatologists and other specialists.
Passive treatment modalities are not recommended as a first line single treatment modality. These methods have to be integrated in the therapeutic concept in a “healthy” relation, (eg, 1:4, passive:active). The goals of interdisciplinary programs include improved functional activities of daily living, return to gainful employment, claim closure, discontinued use of the health care system, and pain control. Absolute absence of subjective complaints is uncommon, despite improvement in function. Early referral to an interdisciplinary pain management program may be indicated. Successful programs emphasize independence and behavioral modification.[28, 29]
The program should be goal-orientated, and the goalposts should be shifted as goals are achieved.[30, 31] The most effective rehabilitation regimen integrates an exercise program into a strategy of patient education and self-management techniques. This helps patients to better understand their condition, how it affects them, and how they can help themselves.
First and foremost, before any therapy is recommended for FM, patients should be educated about the disease itself. Therefore, better-educated health care professionals are needed. Education about rest and sleep hygiene is imperative because of the high rate of sleep disturbances in this population. This awareness results in more comprehensive management and an improved opportunity for optimal patient management, as well as improved sleep and diminished pain levels. Exercise was shown to reduce objective measures of pain in these patients.[36**]
Cognitive behavioral therapy and stress-reduction techniques may be beneficial for helping FM patients reduce stress. In a preliminary study by Robinson and Burns involving cognitive behavioral therapy and stress-reduction techniques, women showed greater improvement than men, and women younger than age 40 showed the most improvement. One of the most important aspects of the management of this disease is ensuring that patients understand the illness as much as possible. Practitioners should help patients to understand that this condition is not life threatening or crippling. Patients should understand that this disease is not one that progresses to the point of immobility, deformity, or early death.
Pharmacologic therapy aims to enhance the pain threshold and to support sleep. Antidepressive acting agents are in the first line of drug treatment because of their serotoninergic activity and the decreased serotonin levels in FM patients.
Nonpharmacologic therapies play an important role in this condition.
Cognitive Behavioral Therapy
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Fibromyalgia patients report significantly more frequent and more severe daily hassles than other rheumatic disease patients. Consequently, increased life stress may be associated with FM. The inclusion of cognitive behavioral therapy in a standard medical regimen for FM can favorably influence physical functioning in a subset of patients.
Reconditioning of FM patients is essential. For the first time, in a study by Jones et al., the effectiveness of a muscle-strengthening program was compared with a stretching program in women with FM in an isolated design without mixed exercises (aerobic, muscle strengthening, and flexibility).
Exercise intensity was adapted for possible central and peripheral mechanisms of FM (nociceptive input from muscles, abnormal sensory processing at the level of the spinal cord and the brain), which is different from the interventions geared to the general public.[36**] Outcome measures included muscle strength, flexibility, weight, body fat, tender point count, and disease and symptom severity scales.
The authors could not find statistically significant differences between the groups, but reported that the patient had a good experience, and completed the specially tailored program without experiencing a flare in pain (dropout rates in other studies were 40 to 87%![43, 44]). FM patients in the muscle-strengthening group experienced an improvement in overall disease activity. Flexibility training alone also results in overall improvements, albeit to a lesser degree. Exercise can improve the mood and physical function of individuals with FM.[45**]
Richards and Scott call the conventional medical treatment of FM “relatively ineffective” and therefore designed a 3-month parallel-group, randomized, controlled trial to address these issues.[46**] They compared prescribed graded aerobic exercises (active treatment) with relaxation and flexibility (control treatment). Compared with relaxation exercises this led to significantly more participants rating themselves as much or very much better at three months: 24/69 (35%) versus 12/67 (18%), P = 0.03. Benefits were maintained or improved at one-year follow up when fewer participants in the exercise group fulfilled the ACR criteria for FM (31/69 vs 44/67, P = 0.01).
People in the exercise group also had greater reductions in tender point counts (4.2 vs 2.0, P = 0.02) and in scores on the Fibromyalgia Impact Questionnaire (FIQ) (4.0 vs 0.6, P = 0.07). Therefore, they concluded that prescribed graded aerobic exercise is a simple, cheap, effective, and potentially widely available treatment for FM. That is the only randomized controlled study reporting 1-year follow-up improvements.
Balneotherapy (20-minute bathing, once a day, five times per week, for a 3-week period) was found effective in one study from Turkey measured by the number of tender points, the Visual Analogue Scale for pain, and the FIQ, all of which still showed improvement 6 months later, and the Beck’s Depression Index. The authors concluded that this might be an alternative method for treating FM patients. Treatment of FM at the Dead Sea (sulfur baths), is effective and safe and may become an additional therapeutic modality in FM.
Future studies should address the outcome and possible mechanisms of this treatment for FM patients. Karagülle and Dönmez reported the vasodilatative effects of sulfur baths with concentrations of 4 to 10 mg/l sulfide (H2S) levels. Pressure and cold pain thresholds were also found to increase for patients with FM treated with sulfur baths.
Other Nonpharmacologic Treatment Approaches
A study by Gamber et al. found osteopathic manipulative treatment combined with standard medical care was more efficacious for treating FM than standard care alone. This finding needs to be replicated to determine if cost savings are incurred when treatments for FM incorporate nonpharmacologic approaches such as osteopathic manipulative treatment. Acupuncture showed normalization of disturbed microcirculation in FM patients. Low power laser therapy may be an effective treatment for pain, muscle spasm, morning stiffness, and total tender point count in patients with FM, but there is effectiveness also in the placebo laser group.
These methods can be used additionally within the framework of an interdisciplinary treatment strategy to reduce patients’ most prominent symptoms. However, these measures are within the scope of a polypragmatically therapeutic regimen.
Pharmacologic therapy (nonsteroidal anti-inflammatory drugs, narcotic medications, adjuvant analgesic drugs, tricyclic antidepressants and selective serotonin reuptake inhibitors) is aimed at pain relief.
The tricyclic antidepressants and muscle relaxants, used before bedtime, may help to restore a normal sleep pattern, helping the patient to feel less fatigued. Benzodiazepines should be avoided by patients with FM because of their negative effects on the sleep cycle.
Fluoxetine, a selective serotonin reuptake inhibitor, in dosages more than 20 mg/d (mean dose [± SD], 45 ± 25 mg/d) was recently found to be effective on outcome measures such as the FIQ total score, the FIQ pain score, the FIQ fatigue and depression score and the McGill Pain Questionnaire, when compared with subjects who received placebo (P = 0.005). The number of tender points and the total myalgic scores did not change significantly. The observation period of this study was 12 weeks. Unfortunately, follow-up tests were not performed.[55*]
Nonsteroidal anti-inflammatory drugs and other analgesics only partially improve the symptoms of some patients with FM. This could be because of different subgroups in FM with different pathogenetic backgrounds, eg, different expression of cytokines[56*, 57*] and/or different expression of opioid receptors.[58*] Therefore, selective opioid agonists might be helpful in a subgroup of FM patients, all the more because -endorphin concentrations are significantly lower in patients with FM than in normal subjects and depressed patients (P < 0.001 and P < 0.01, respectively).
Thus, evaluation of peripheral blood mononuclear cell -endorphin concentrations could represent a diagnostic tool for FM to distinguish the disease from chronic fatigue syndrome, major depression, or healthy subjects. The results obtained from Panerai et al. are also consistent with the hypothesis that the immune system is activated in FM.[59*]
Glucocorticoids are of little benefit, and should be avoided except by FM patients with carpal tunnel syndrome, who can receive this treatment via local injections.
Why do FM patients respond differently to different treatments?
It seems to depend on the different pathogenetic mechanisms in the (not yet well defined) subgroups of FM patients. Principally at least four different phenomena play a role within this: disturbances in the inhibitory system; neuro-endocrine disturbances;[62, 63] disturbances in neuropeptides; and a pathologic decreased secretion of the growth hormone.[65**] The authors suggest a growth hormone supplementation may be helpful in a subset of FM patients. Furthermore, recent findings suggest that cytokines,[56*, 57*] biogenic amines, nitric oxide, microcirculatory changes[68, 69] and prostaglandins may contribute to FM pain. Out of the pathophysiologic changes, an appropriate therapeutic approach within an interdisciplinary concept should be recruited to reach optimal treatment goals for each individual FM patient. Experimental approaches already follow this line.
In summary, treatment recommendations for FM include (1) reassurance and explanation of the nature of the illness; (2) evaluation and eradication of mechanical stressors as far as possible; (3) symptomatic analgesic drug treatment; (4) and moderate individually adapted physical exercises. Furthermore, adjuvant psychotherapeutic support in an interdisciplinary setting is necessary.[72**] Individually adapted measures are highly emphasized to differentially treat FM subgroups, as far as identified.
The demonstration of a long-term effective intervention for managing the symptoms associated with FM is needed. Subgroups of FM patients need to be clearly identified (new criteria) so that appropriate treatment packages might be developed. An interdisciplinary team approach is necessary in most cases. Rehabilitation plays a crucial role in the treatment of FM, particularly among patients more severely disabled by their chronic painful condition.
The authors thank Beatrice Giachino for her assistance with the literature search and Leanne Pobjoy from the Institute of Physical Medicine, University Hospital Zurich, for her aid in the preparation of the manuscript.
Correspondence to Haiko Sprott, MD, Department of Rheumatology and Institute of Physical Medicine, University Hospital Zurich, Gloriastrasse 25, CH-8091 Zurich, Switzerland; e-mail: email@example.com
FM, primary fibromyalgia; FIQ, Fibromyalgia Impact Questionnaire
Source: Medscape. © 2003 Lippincott Williams & Wilkins