Fibromyalgia

Fibromyalgia is a chronic pain syndrome characterized by widespread body pain, chronic fatigue, mood disturbance, and cognitive disturbance. It also presents with other comorbid symptoms such as migraine headaches, depression, sleep disturbance, and irritable bowel syndrome. Diagnosis is clinical with laboratory exams and imaging reserved to rule out other causes for the spectrum of symptoms. Management is centered around education and lifestyle modification, with both pharmacotherapy (e.g., antidepressants, anticonvulsants) and non-pharmacotherapy (low-impact exercise, cognitive behavioral therapy) showing efficacy.

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Overview

Epidemiology

  • High prevalence: up to 2%–3% of the U.S. population
  • More common in women than in men: ratio of 6:1
  • Prevalence rises with age: most common in women 20–55 years of age
  • Individuals with 1st-degree relatives who have fibromyalgia are more likely to be diagnosed with the disorder themselves.

Etiology

The following environmental triggers have been associated with the onset of fibromyalgia.

  • Physical stress:
    • Heavy lifting
    • Repetitive motion
    • Working at extreme temperatures
    • Traumatic injury
    • Chronic inflammatory disease
  • Psychological stress:
    • Emotional abuse
    • Physical abuse
    • Sexual abuse

Pathophysiology

  • Exact pathophysiology is unknown. 
  • No evidence of inflammation in the muscles, ligaments, and tendons, despite pain in these structures
  • The prevailing current theory is that fibromyalgia represents a state of “centralized pain.” 
    • Pathologic alterations in central processing of sensory input
    • Aberrations in the endogenous inhibitory pain pathways:
      • Affected individuals may feel pain at a lower threshold than normal.
      • Affected individuals may feel pain from normally nonpainful stimuli.
      • Supported by history of other pain disorders such as headaches, dysmenorrhea, chronic pelvic pain, and other regional pain syndromes 
  • Genetic factors may play a pathogenic role:
    • Widespread pain symptoms seem to aggregate in families.
    • Affective symptoms seem to aggregate in families.
    • Abnormalities of the serotonin transporter gene is under investigation for both fibromyalgia and depressive disorders.
  • Abnormalities in the ANS and the neuroendocrine system may play a pathogenic role:
    • Onset/exacerbation of symptoms with stress, trauma, sleep disturbance, or illness 
    • Abnormal levels of serotonin and norepinephrine (key neurotransmitters in endogenous inhibitory pain pathways) have been demonstrated.
    • Abnormal hypothalamic-pituitary-adrenal (HPA) axis function has been demonstrated.

Clinical Presentation

  • Widespread musculoskeletal pain
  • Fatigue
  • Morning stiffness 
  • Disturbances in sleep
  • Restless legs
  • Cognitive disturbances (“fibro fog”)
  • Problems with attention 
  • Other common symptoms: 
    • Depression
    • Anxiety 
    • Paresthesias 
    • Headaches (especially migraines)
    • Dysphagia  
    • Temporomandibular joint disorders
    • Dysmenorrhea
    • Chronic pelvic pain
    • Irritable bowel syndrome
Fibromyalgia tender points

Fibromyalgia tender points:
Historically, the American College of Rheumatology diagnostic criteria for fibromyalgia were based on the presence of tender points.

Image: “Tender points fibromyalgia” by Jmarchn. License: CC0 1.0

Diagnosis

History and physical exam

  • Fibromyalgia is a chronic syndrome; therefore, it is recommended to determine the diagnosis over multiple visits after sequential observation and physical exams. 
  • Quality and characteristics of pain
  • History of pain in other areas (e.g., headaches, abdominal/pelvic discomfort)
  • Nonspecific tenderness upon palpation in multiple soft tissue sites 
  • Inquire about use of drugs (such as statins) that can cause myalgias.

Official diagnostic criteria

An individual satisfies diagnostic criteria for fibromyalgia if the following 3 conditions are met:

  • Widespread pain index (WPI) > 7 and symptom severity (SS) > 5
  • Symptoms have been present at a similar level for ≥ 3 months.
  • The individual does not have a disorder that would otherwise explain the pain.

Widespread pain index (each area is worth 1 point): score will be between 0 and 19.

  • Shoulder girdle, left
  • Shoulder girdle, right
  • Upper arm, left
  • Upper arm, right
  • Lower arm, left
  • Lower arm, right
  • Hip (buttock, trochanter), left
  • Hip (buttock, trochanter), right
  • Upper leg, left
  • Upper leg, right
  • Lower leg, left
  • Lower leg, right
  • Jaw, left
  • Jaw, right
  • Chest
  • Abdomen
  • Upper back
  • Lower back
  • Neck

Symptom severity scale score:

The SS scale score is the sum of the severity of the 3 symptoms (fatigue, waking unrefreshed, cognitive symptoms) plus the extent (severity) of somatic symptoms in general. The final score is between 0 and 12. For each of the 3 symptoms, indicate the level of severity over the past week using the following scale:

  • 0 = no problem
  • 1 = slight or mild problems, generally mild or intermittent
  • 2 = moderate, considerable problems, often present and/or at a moderate level
  • 3 = severe: pervasive, continuous, life-disturbing problems

Considering somatic symptoms in general, indicate whether the individual has:

  • 0 = no symptoms
  • 1 = few symptoms
  • 2 = a moderate number of symptoms
  • 3 = a great number of symptoms

Laboratory testing

  • No biomarkers linked with fibromyalgia 
  • Used to rule out other causes:
    • Hypothyroidism
    • Polymyalgia rheumatica
    • Vitamin deficiency:
      • B12
      • Folate
      • Vitamin D

Imaging

  • No specific imaging indicated to diagnose fibromyalgia
  • Used to rule out other causes or identify comorbid conditions

Management

Education

  • Initial goal is to create therapeutic rapport with the individual. 
  • Education is geared to set treatment/prognosis expectations and create self-management skills. 
  • Comorbid disorders must be identified and managed. 
  • Shows evidence for sustaining improvement for several months

Pharmacotherapy

  • Goal is to treat pain as well as depression and sleep disturbances. 
  • Antidepressants are shown to improve sleep and depression, as well as to have analgesic properties: 
    • Tricyclic antidepressants: 
      • Amitriptyline
      • Nortriptyline 
    • Serotonin–norepinephrine reuptake inhibitor (SNRI): 
      • Duloxetine
      • Venlafaxine
  • Muscle relaxants (cyclobenzaprine) have strong evidence for efficacy.
  • Anticonvulsants such as gabapentin and pregabalin have also shown efficacy. 
  • Limited evidence for opioids or NSAIDs

Other therapeutic regimens

  • Aerobic exercises and low-impact strength conditioning improve physical function and sleep.
  • Psychosocial interventions, including CBT, is recommended in those with a poor initial response. 
  • Complementary and alternative medicine: 
    • Includes yoga and acupuncture, among other therapies
    • Allowing the individual to choose their own treatment program may increase compliance and self-efficacy.

Differential Diagnosis

  • Polymyositis: autoimmune inflammatory myopathy. Polymyositis is most commonly seen in middle-aged women. Presentation is with progressive, symmetric, proximal muscle weakness and constitutional symptoms. The diagnosis is based on the clinical presentation and laboratory studies and confirmed by muscle biopsy. Management includes systemic glucocorticoids, immunosuppressive medications, and physiotherapy.
  • Polymyalgia rheumatica: inflammatory condition that affects adults > 55 years of age. Presentation is with pain and stiffnesses of the proximal muscles. There is no muscle weakness or atrophy. Diagnosis is clinical and is supported by elevated inflammatory markers. Management includes corticosteroids, and individuals should be evaluated for temporal arteritis.
  • Myofascial pain syndrome (MPS): regional pain condition originating from myofascial structures. Affected individuals present with pain in a specific area, often with predictable pain referral patterns. Pain emanates from myofascial trigger points in the affected area. The diagnosis is clinical, with a history of regional pain and physical examination findings of myofascial trigger points. Management consists of physical therapy, massage, myofascial manipulation, and/or trigger point injections.  
  • Drug-induced myopathy: certain drugs (e.g., statins) can cause myopathy and myotoxicity, which can result in muscle weakness and myalgias. The CK will also be elevated. The clinical history and a review of medications can lead to the diagnosis. Management includes withdrawal of the offending medication, and steroids may be required in some cases.
  • Hypothyroidism: thyroid hormone deficiency that can result from a disease of the thyroid, hypothalamus, or pituitary. Proximal muscle weakness is a common presenting symptom. Individuals with hypothyroidism will usually also have multiple other systemic manifestations, such as cold intolerance, neuropsychiatric changes, dry skin, constipation, and bradycardia. Thyroid function tests can provide the diagnosis, and management involves thyroid hormone replacement.

References

  1. Clauw D. J. (2014). Fibromyalgia: a clinical review. JAMA 311:1547–1555. https://doi.org/10.1001/jama.2014.3266 
  2. Goldenberg, D. L., Burckhardt, C., Crofford, L. (2004). Management of fibromyalgia syndrome. JAMA 292:2388–2395. https://doi.org/10.1001/jama.292.19.2388
  3. Wolfe, F., et al. (2016). 2016 Revisions to the 2010/2011 fibromyalgia diagnostic criteria. Seminars in Arthritis and Rheumatism 46:319–329. https://doi.org/10.1016/j.semarthrit.2016.08.012
  4. Bennett, R. M. (2009). Clinical manifestations and diagnosis of fibromyalgia. Rheumatic Disease Clinics of North America 35:215–232. https://pubmed.ncbi.nlm.nih.gov/19647138/
  5. Bradley, L. A. (2009). Pathophysiology of fibromyalgia. American Journal of Medicine 122(12 Suppl):S22–S30. https://pubmed.ncbi.nlm.nih.gov/19962493/

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