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“Doctor, I’m So Tired!” Refining Your Work-up for Chronic Fatigue

Clinician Reviews. 2015 February;25(2):84-91

References

1. Nijrolder I, van der Windt DA, van der Horst HE. Prognosis of fatigue and functioning in primary care: a 1-year follow-up study. Ann Fam Med. 2008;6:519-527.

2. Griffith JP, Zarrouf FA. A systematic review of chronic fatigue syndrome: don’t assume it’s depression. Primary Care Companion J Clin Psychiatry. 2008;10:120-128.

3. Holmes GP, Kaplan JE, Gantz NM, et al. Chronic fatigue syndrome: a working case definition. Ann Intern Med. 1988;108:387-389.

4. Morris G, Maes M. Case definitions and diagnostic criteria for myalgic encephalomyelitis and chronic fatigue syndrome: from clinical consensus to evidence-based case definitions. Neuro Endocrinol Lett. 2013;34:185-199.

5. Fukuda K, Straus SE, Hickie I, et al. The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. Ann Intern Med. 1994;121:953-959.

6. Centers for Disease Control and Prevention. Chronic fatigue syndrome. Centers for Disease Control and Prevention Web site. Available at: http://www.cdc.gov/cfs/diagnosis/index.html. Accessed January 6, 2015.

7. Carruthers BM, van de Sande MI, De Meirleir KL, et al. Myalgic encephalomyelitis: International Consensus Criteria. J Intern Med. 2011;270:327-338.

8. Johnston SC, Brenu EW, Hardcastle S, et al. A comparison of health status in patients meeting alternative definitions for chronic fatigue syndrome/myalgic encephalomyelitis. Health Qual Life Outcomes. 2014;12:64.

9. Anderson VR, Jason LA, Hlavaty LE, et al. A review and meta-synthesis of qualitative studies on myalgic encephalomyelitis/chronic fatigue syndrome. Patient Educ Couns. 2012;86:147-155.

10. Christley Y, Duffy T, Everall IP, et al. The neuropsychiatric and neuropsychological features of chronic fatigue syndrome: revisiting the enigma. Curr Psychiatry Rep. 2013;15;353.

11. Henningsen P, Zimmermann T, Sattel HH. Medically unexplained physical symptoms, anxiety, and depression: a meta-analytic review. Psychosom Med. 2003;65:528-533.

12. Nater UM, Jones JF, Lin JM, et al. Personality features and personality disorders in chronic fatigue syndrome: a population-based study. Psychother Psychosom. 2010;79:312-318.

13. Taylor RR, Jason LA, Jahn SC. Chronic fatigue and sociodemographic characteristics as predictors of psychiatric disorders in a community-based sample. Psychosom Med. 2003;65:896-901.

14. Leonard B, Maes M. Mechanistic explanations of how cell-mediated immune activation, inflammation and oxidative and nitrosative stress pathways and their sequels and concomitants play a role in the pathophysiology of unipolar depression. Neurosci Biobehav Rev. 2012;36:764-785.

15. DeLuca J, Christodoulou C, Diamond BJ, et al. Working memory deficits in chronic fatigue syndrome: differentiating between speed and accuracy of information processing. J Int Neuropsychol Soc. 2004;10:101-109.

16. Cockshell SJ, Mathias JL. Cognitive functioning in chronic fatigue syndrome: a meta-analysis. Psychol Med. 2010;40:1253-1267.

17. Komaroff AL, Cho TA. Role of infection and neurologic dysfunction in chronic fatigue syndrome. Semin Neurol. 2011;31:325-337.

18. Naess H, Sundal E, Myhr KM, et al. Postinfectious and chronic fatigue syndromes: clinical experience from a tertiary-referral centre in Norway. In Vivo. 2010;24:185-188.

19. Hickie I, Davenport T, Wakefield D, et al; Dubbo Infection Outcomes Study Group. Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study. BMJ. 2006;333:575.

20. Plioplys AV, Plioplys S. Electron-microscopic investigation of muscle mitochondria in chronic fatigue syndrome. Neuropsychobiology. 1995;32:175-181.

21. Vernon SD, Whistler T, Cameron B, et al. Preliminary evidence of mitochondrial dysfunction associated with post-infective fatigue after acute infection with Epstein Barr virus. BMC Infect Dis. 2006;6:15.

22. Miwa K, Fujita M. Fluctuation of serum vitamin E (alpha-tocopherol) concentrations during exacerbation and remission phases in patients with chronic fatigue syndrome. Heart Vessels. 2010;25:319-323.

23. Rosenblum H, Shoenfeld Y, Amital H. The common immunogenic etiology of chronic fatigue syndrome: from infections to vaccines via adjuvants to the ASIA syndrome. Infect Dis Clin North Am. 2011;25:851-863.

24. Vincent A, Brimmer DJ, Whipple MO, et al. Prevalence, incidence, and classification of chronic fatigue syndrome in Olmsted County, Minnesota as estimated using the Rochester Epidemiology Project. Mayo Clin Proc. 2012;87:1145-1152.

25. Goroll AH, Mulley AG. Primary Care Medicine: Office Evaluation and Management of the Adult Patient. 7th ed. Morrisville, PA: Wolters Kluwer; 2014.

26. Brown RF, Schutte NS. Direct and indirect relationships between emotional intelligence and subjective fatigue in university students. J Psychosom Res. 2006;60:585-593.

27. Pigeon WR, Sateia MJ, Ferguson RJ. Distinguishing between excessive daytime sleepiness and fatigue: toward improved detection and treatment. J Psychosom Res. 2003;54:61-69.

28. Bailes S, Libman E, Baltzan M, et al. Brief and distinct empirical sleepiness and fatigue scales. J Psychosom Res. 2006;60:605-613.

29. National Collaborating Centre for Primary Care (UK). Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (or Encephalopathy): Diagnosis and Management of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (or Encephalopathy) in Adults and Children. London, UK: Royal College of General Practitioners; 2007.

30. Lane TJ, Matthews DA, Manu P. The low yield of physical examinations and laboratory investigations of patients with chronic fatigue. Am J Med Sci. 1990;299:313-318.

31. Vaucher P, Druisw PL, Waldvogel S, et al. Effect of iron supplementation on fatigue in nonanemic menstruating women with low ferritin: a randomized controlled trial. CMAJ. 2012;184:1247-1254.

32. US Preventive Services Task Force. Hepatitis C: Screening. US Preventive Services Task Force Web site. Available at: http://www.uspreventiveservicestaskforce.org/uspstf/uspshepc.htm. Accessed January 7, 2015.

33. Rolfe A, Burton C. Reassurance after diagnostic testing with a low pretest probability of serious disease: a systematic review and meta-analysis. JAMA Intern Med. 2013;173:407-416.

34. Smith RC, Lyles JS, Gardiner JC, et al. Primary care clinicians treat patients with medically unexplained symptoms: a randomized controlled trial. J Gen Intern Med. 2006;21:671-677.

35. White PD, Goldsmith KA, Johnson AL, et al; PACE trial management group. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue (PACE): a randomised trial. Lancet. 2011;377:823-836.

36. van Weert E, Hoekstra-Weebers J, Otter R, et al. Cancer-related fatigue: predictors and effects of rehabilitation. Oncologist. 2006;11:184-196.

CHRONIC FATIGUE & NEUROPSYCHIATRIC CONDITIONS: COMMON THREADS
Recent research has made it clear that depression, somatization, and CFS share some biological underpinnings. These include biomarkers for inflammation, cell-mediated immune activation—which may be related to the symptoms of fatigue—autonomic dysfunction, and hyperalgesia.⁹ Evidence suggests that up to two-thirds of patients with CFS also meet the criteria for a psychiatric disorder.¹⁰ The most common psychiatric conditions are major depressive disorder (MDD), affecting an estimated 22% to 32% of those with CFS; anxiety disorder, affecting about 20%; and somatization disorder, affecting about 10%—at least double the incidence of the general population.¹⁰

Others point out, however, that up to half of those with CFS do not have a psychiatric disorder.¹¹ A diagnosis of somatization disorder, in particular, depends largely on a subjective interpretation of whether or not the presenting symptoms have a physical cause.¹⁰

CFS and MDD comorbidity. The most widely studied association between CFS and psychiatric disorders involves MDD. Observational studies have found patients with CFS have a lifetime prevalence of MDD of 65%,^12,13 which is higher than that of patients with other chronic diseases. Overlapping symptoms include fatigue, sleep disturbance, poor concentration, and memory problems. However, those with CFS have fewer symptoms related to anhedonia, poor self-esteem, guilt, and suicidal ideation compared with individuals with MDD.^12,13

There are several possible explanations for CFS and MDD comorbidity, which are not necessarily mutually exclusive.¹⁰ One theory is that CFS is an atypical form of depression; another holds that the disability associated with CFS leads to depression, as is the case with many other chronic illnesses; and a third points to overlapping pathophysiology.¹⁰

An emerging body of evidence suggests that CFS and MDD have some common oxidative and nitrosative biochemical pathways. Activated by infection, psychological stress, and immune disorders, they are believed to have damaging free radical and nitric oxide effects at the cellular level.¹⁴ The cellular effects can result in fatigue, muscle pain, and flu-like malaise.

Cortisol response differs

The majority of patients with CFS report symptoms of cognitive decline, with the acquisition of new verbal learning and information-processing speed particularly likely to be impaired.CFS and MDD might be distinguishable by another pathway—the hypothalamic-pituitary-adrenal (HPA) axis. MDD is classically associated with activation and raised cortisol levels, while CFS is consistently associated with impaired HPA axis functioning and reduced cortisol levels.¹⁰ The majority of patients with CFS report symptoms of cognitive decline, with the acquisition of new verbal learning and information-processing speed particularly likely to be impaired.¹⁵

A meta-analysis of 50 studies of patients with CFS showed deficits in attention, memory, and reaction time, but not in fine motor speed, vocabulary, or reasoning.¹⁶ Autonomic dysfunction has also been observed, including disordered sympathetic activity. The most frequently observed abnormalities on autonomic testing are postural hypotension, tachycardia syndrome, neurally mediated hypotension, and heart rate variability during tilt table testing.¹⁶

Continue for the link between infection & CFS >>