Longitudinal studies indicate that 17% to 64% of patients improve with treatment; however, less than 10% meet criteria for full recovery, and up to 20% of patients may worsen over time.[278]Vercoulen JH, Swanink CM, Fennis JF, et al. Prognosis in chronic fatigue syndrome: a prospective study of the natural course. J Neurol Neurosurg Psychiatry. 1996 May;60(5):489-94.
https://jnnp.bmj.com/content/jnnp/60/5/489.full.pdf
http://www.ncbi.nlm.nih.gov/pubmed/8778251?tool=bestpractice.com
[279]Ray C, Jefferies S, Weir WR. Coping and other predictors of outcome in chronic fatigue syndrome: A 1-year follow-up. J Psychosom Res. 1997 Oct;43(4):405-15.
http://www.ncbi.nlm.nih.gov/pubmed/9330240?tool=bestpractice.com
[280]Bonner D, Ron M, Chalder T, et al. Chronic fatigue syndrome: a follow-up study. J Neurol Neurosurg Psychiatry. 1994 May;57(5):617-21.
https://jnnp.bmj.com/content/jnnp/57/5/617.full.pdf
http://www.ncbi.nlm.nih.gov/pubmed/8201336?tool=bestpractice.com
It is important to review the severity of fatigue and criteria used for ME/CFS diagnoses in these studies. Longitudinal studies also suggest that recovery rates for patients who develop ME/CFS after infectious mononucleosis are better in younger patients than in older patients, with over 50% returning to work after average disease duration of 11.4 years.[281]Nyland M, Naess H, Birkeland JS, et al. Longitudinal follow-up of employment status in patients with chronic fatigue syndrome after mononucleosis. BMJ Open. 2014 Nov 26;4(11):e005798.
https://bmjopen.bmj.com/content/4/11/e005798.long
http://www.ncbi.nlm.nih.gov/pubmed/25428629?tool=bestpractice.com
Findings from one small observational study also suggest that adolescents with ME/CFS after infectious mononucleosis have a higher remission rate than adults and that they also tend to return to full functional capacity.[36]Katz BZ, Shiraishi Y, Mears CJ, et al. Chronic fatigue syndrome after infectious mononucleosis in adolescents. Pediatrics. 2009 Jul;124(1):189-93.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2756827
http://www.ncbi.nlm.nih.gov/pubmed/19564299?tool=bestpractice.com
In contrast, less than 10% of patients with ME/CFS without mononucleosis returned to premorbid levels of functioning despite standard therapies.[36]Katz BZ, Shiraishi Y, Mears CJ, et al. Chronic fatigue syndrome after infectious mononucleosis in adolescents. Pediatrics. 2009 Jul;124(1):189-93.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2756827
http://www.ncbi.nlm.nih.gov/pubmed/19564299?tool=bestpractice.com
One study carried out in a single tertiary-referral center found improvements within 5 years in a subset of patients with postinfectious ME/CFS who presented with a history of sudden-onset fatigue, fever, tender lymph nodes, and myalgia.[282]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 Mar-Apr;24(2):185-8.
http://iv.iiarjournals.org/content/24/2/185.long
http://www.ncbi.nlm.nih.gov/pubmed/20363992?tool=bestpractice.com
Poor prognostic factors include arthralgia, older age, longer illness duration, greater fatigue severity, and presence of comorbid psychiatric illness (self-reported depression).[283]Joyce J, Hotopf M, Wessely S. The prognosis of chronic fatigue and chronic fatigue syndrome: a systematic review. QJM. 1997 Mar;90(3):223-33.
https://academic.oup.com/qjmed/article/90/3/223/1633580
http://www.ncbi.nlm.nih.gov/pubmed/9093600?tool=bestpractice.com
Evidence regarding excess mortality rates in ME/CFS is limited, and mixed. One small study (n = 56) found that patients with ME/CFS had a younger average age of cardiovascular death (median = 58.8 years) compared with the overall US population (median = 77.7 years).[175]McManimen SL, Devendorf AR, Brown AA, et al. Mortality in patients with myalgic encephalomyelitis and chronic fatigue syndrome. Fatigue. 2016;4(4):195-207.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5218818
http://www.ncbi.nlm.nih.gov/pubmed/28070451?tool=bestpractice.com
A larger retrospective cohort study (n = 2147) did not note an increased risk of all-cause mortality, but did show a substantially increased risk of death from suicide.[213]Roberts E, Wessely S, Chalder T, et al. Mortality of people with chronic fatigue syndrome: a retrospective cohort study in England and Wales from the South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLaM BRC) Clinical Record Interactive Search (CRIS) Register. Lancet. 2016 Apr 16;387(10028):1638-43.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2815%2901223-4/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/26873808?tool=bestpractice.com