para>Detailed mental status examination (or referral to psychiatrist) to rule out other primary etiologies or comorbidities á
DIFFERENTIAL DIAGNOSIS
- Idiopathic chronic fatigue (i.e., fatigue of unknown cause for >6 months without meeting criteria for CFS)
- Psychiatric disorders
- Major depression
- Somatization disorder
- Physiologic fatigue (inadequate or disrupted sleep, menopause)
- Pregnancy until 3 months postpartum
- Insomnia: primary (no clear etiology) versus secondary (e.g., due to anxiety, depression, environmental factors, poor sleep hygiene)
- Other known or defined systemic disease
- Endocrine disorder (hypothyroidism, Addison disease, Cushing syndrome, diabetes mellitus)
- Localized infection (e.g., occult abscess)
- Chronic or subacute bacterial disease (e.g., endocarditis)
- Lyme disease
- Fungal disease (e.g., histoplasmosis, coccidioidomycosis)
- Parasitic disease (e.g., amebiasis, giardiasis, helminth infestation)
- HIV or related disease
- Iatrogenic (e.g., medication side effects)
- Toxic agent exposure
- Obesity
- Malignancy
- Autoimmune disease
- Chronic inflammatory disease (sarcoidosis, Wegener granulomatosis)
- Neuromuscular disease (multiple sclerosis, myasthenia gravis)
DIAGNOSTIC TESTS & INTERPRETATION
No single diagnostic test available and finding an abnormal result is not always the same as discovering the cause of fatigue. Be prepared to renew the search for the cause if the problem is treated and the patient remains fatigued. á
Initial Tests (lab, imaging)
- Standard laboratory tests are recommended to rule out other causes for symptoms:
- Chemistry panel
- CBC
- Urinalysis
- Thyroid-stimulating hormone (TSH)
- ESR or C-reactive protein
- Liver function
- Screen for drugs of abuse
- Age/gender-appropriate cancer screening
- Additional studies, if clinical findings are suggestive or patient at risk:
- Antinuclear antibodies and rheumatoid factor (if elevated ESR)
- Creatine kinase
- Tuberculin skin test
- Serum cortisol
- HIV
- Venereal Disease Research Laboratory or rapid plasma reagin
- Lyme serology
- IgA tissue transglutaminase
- No applicable imaging tests available; however, EEG and/or MRI may be useful if patient has CNS symptoms; polysomnography, if patient is sleepy (4).
Follow-Up Tests & Special Considerations
- Assess for comorbid psychiatric disorders.
- Assess for personality and psychosocial factors and maladaptive coping styles.
- In patients with sleep disturbance, polysomnography may reveal a treatable comorbid disease.
TREATMENT
Focus on changes in lifestyle and insight, with a goal to avoid complicating treatments (e.g., addicting medications, invasive testing) or interventions that support secondary gain. á
GENERAL MEASURES
ALERT
Treatment cornerstones include both cognitive-behavioral therapy (CBT) and graded exercise therapy. Medication is of little value. Two treatments have been shown effective, often used in combination (6)[A]:
Individual CBT: Challenge fatigue-related cognition; plan social and occupational rehabilitation.
Graded exercise therapy (GET): Track amount of exercise patient can do without exacerbating symptoms and gradually increase intensity and duration. Both involve a careful balance between activity and rest (7)[A]. Fear of movement and avoidance of physical activity are common in CFS.
Patients learn how to gradually increase activity in a way that will not exacerbate their illness. Vigorous exercise can trigger relapse, perhaps related to immune dysregulation.
Improves functional capacity and diminishes sense of fatigue
GET is more effective with educational interventions using telephone reminders.
Duration of illness does not predict treatment outcome; aggressive combined care is indicated for all.
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MEDICATION
- No established pharmacologic treatment recommendations
- Studies have been conducted with antivirals, antidepressants, immunoglobulins, hydrocortisone, and modafinil. None has shown clear benefit.
- Agomelatine, an antidepressant with agonist activity at melatonin receptors, is promising in early studies (8)[C].
- If insomnia is present, use of nonaddicting sleep aids (hydroxyzine, trazodone, doxepin, etc.) may improve outcomes.
ISSUES FOR REFERRAL
- Psychiatrist to assist in managing comorbid disorders if needed
- Rehabilitative medicine
COMPLEMENTARY & ALTERNATIVE MEDICINE
- Insufficient to recommend any complementary and alternative medicine option for all (9)
- Social support groups have not proven to be effective.
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
- Gradual increase in physical exercise with scheduled rest periods
- Avoid extended periods of rest.
Patient Monitoring
Although no consensus exists, periodic reevaluation is appropriate for support, relief of symptoms, and assessment for other possible causes of symptoms. á
DIET
- No diet has been shown to be effective for treatment of CFS.
- Whether weight loss improves symptoms in obese CFS patients has yet to be tested.
PATIENT EDUCATION
- Patient education is an important part of treatment of CFS, such as education on the benefits of cognitive therapies, lifestyle changes, and pharmacologic therapy directed at specific-associated symptoms.
- Chronic Fatigue and Immune Dysfunction Syndrome Association of America: http://solvecfs.org/
- CDC, Chronic Fatigue Syndrome: http://www.cdc.gov/cfs/
PROGNOSIS
- Fluctuating course is common.
- Generally, improvement is slow, with a course of months to years.
- An estimated 5% fully recover.
- Patients with poor social adjustment, a strong belief in an organic etiology, financial secondary gain, or age >50 years are less likely to improve (10).
COMPLICATIONS
- CFS patients may reduce physical activity out of fear that it may worsen symptoms.
- Depression
- Unemployment: Although studies document improvement with treatment, <1/3 of patients in trials return to work.
- The U.S. Social Security Administration lists CFS as a bona fide form of disability.
- Receipt of government payments (secondary gain) has been associated with treatment nonresponse.
- Polypharmacy
- Chronic immune activation or an infection associated with CFS may play a role in an increased risk for non-Hodgkin lymphoma in elderly (>80 years) CFS patients.
REFERENCES
11 Baker áR, Shaw áEJ. Diagnosis and management of chronic fatigue syndrome or myalgic encephalomyelitis (or encephalopathy): summary of NICE guidance. BMJ. 2007;335(7617):446-448.22 Dinos áS, Khoshaba áB, Ashby áD, et al. A systematic review of chronic fatigue, its syndromes and ethnicity: prevalence, severity, co-morbidity and coping. Int J Epidemiol. 2009;38(6):1554-1570.33 Lievesley áK, Rimes áKA, Chalder áT. A review of the predisposing, precipitating and perpetuating factors in chronic fatigue syndrome in children and adolescents. Clin Psychol Rev. 2014;34(3):233-248.44 Duffy áFH, McAnulty áGB, McCreary áMC, et al. EEG spectral coherence data distinguish chronic fatigue syndrome patients from healthy controls and depressed patients-a case control study. BMC Neurol. 2011;11:82.55 Boneva áRS, Maloney áEM, Lin áJM, et al. Gynecological history in chronic fatigue syndrome: a population-based case-control study. J Womens Health (Larchmt). 2011;20(1):21-28.66 White áPD, Goldsmith áKA, Johnson áAL, et al. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet. 2011;377(9768):823-836.77 Nijs áJ, Paul áL, Wallman áK. Chronic fatigue syndrome: an approach combining self-management with graded exercise to avoid exacerbations. J Rehabil Med. 2008;40(4):241-247.88 Pardini áM, Cordano áC, Benassi áF, et al. Agomelatine but not melatonin improves fatigue perception: a longitudinal proof-of-concept study. Eur Neuropsychopharmacol. 2014;24(6):939-944.99 Adams áD, Wu áT, Yang áX, et al. Traditional Chinese medicinal herbs for the treatment of idiopathic chronic fatigue and chronic fatigue syndrome. Cochrane Database Syst Rev. 2009;(4):CD006348.1010 Cairns áR, Hotopf áM. A systematic review describing the prognosis of chronic fatigue syndrome. Occup Med (Lond). 2005;55(1):20-31.
ADDITIONAL READING
- Carruthers áBM, van de Sande áMI, De Meirleir áKL, et al. Myalgic encephalomyelitis: international consensus criteria. J Intern Med. 2011;270(4):327-328.
- Centers for Disease Control and Prevention. Diagnosis and management of chronic fatigue syndrome, CDC course for clinicians. http://www.cdc.gov/cfs/education/diagnosis/course.html.
- Freeman áR, Wieling áW, Axelrod áFB, et al. Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Clin Auton Res. 2011;21(2):69-72.
- Social Security Administration. Providing medical evidence to the social security administration for individuals with chronic fatigue syndrome fact sheet. https://www.socialsecurity.gov/disability/professionals/cfs-pub063.htm.
- The IOM convened an expert panel at the request of several US government agencies. In the report submitted to HHS, they suggest changing name from CFS to "Systemic Exertion Intolerance Disease,"Ł and redefining diagnostic criteria. http://www.ncbi.nlm.nih.gov/pubmed/25695122.
SEE ALSO
Algorithm: Fatigue á
CODES
ICD10
R53.82 Chronic fatigue, unspecified á
ICD9
780.71 Chronic fatigue syndrome á
SNOMED
52702003 Chronic fatigue syndrome (disorder) á
CLINICAL PEARLS
- CFS and depression can be comorbid. However, to differentiate between the two, sore throat, tender lymph nodes, and postexercise fatigue are much more characteristic of CFS.
- No universal pharmacologic agents (e.g., antidepressants, immune modulators) have been shown to be consistently effective.
- ~70% of patients show improvement with CBT, compared to 55% with GET; in many cases, these two treatments can be undertaken in combination.
- There are many more patients with idiopathic chronic fatigue than true CFS. To diagnose CFS, CDC criteria need to be met; standardized instruments (SF-36, symptom index and Multidimensional Fatigue Inventory [MFI]) have been shown to be of use in the empirical diagnosis of CFS and may be helpful for following patients' progress.