Chronic fatigue syndrome after infectious mononucleosis in adolescents

Abstract:

OBJECTIVE: The goal was to characterize prospectively the course and outcome of chronic fatigue syndrome in adolescents during a 2-year period after infectious mononucleosis.

METHODS: A total of 301 adolescents (12-18 years of age) with infectious mononucleosis were identified and screened for nonrecovery 6 months after infectious mononucleosis by using a telephone screening interview. Nonrecovered adolescents underwent a medical evaluation, with follow-up screening 12 and 24 months after infectious mononucleosis. After blind review, final diagnoses of chronic fatigue syndrome at 6, 12, and 24 months were made by using established pediatric criteria.

RESULTS: Six, 12, and 24 months after infectious mononucleosis, 13%, 7%, and 4% of adolescents, respectively, met the criteria for chronic fatigue syndrome. Most individuals recovered with time; only 2 adolescents with chronic fatigue syndrome at 24 months seemed to have recovered or had an explanation for chronic fatigue at 12 months but then were reclassified as having chronic fatigue syndrome at 24 months. All 13 adolescents with chronic fatigue syndrome 24 months after infectious mononucleosis were female and, on average, they reported greater fatigue severity at 12 months. Reported use of steroid therapy during the acute phase of infectious mononucleosis did not increase the risk of developing chronic fatigue syndrome.

CONCLUSIONS: Infectious mononucleosis may be a risk factor for chronic fatigue syndrome in adolescents. Female gender and greater fatigue severity, but not reported steroid use during the acute illness, were associated with the development of chronic fatigue syndrome in adolescents. Additional research is needed to determine other predictors of persistent fatigue after infectious mononucleosis.

 

Source: Katz BZ, Shiraishi Y, Mears CJ, Binns HJ, Taylor R. Chronic fatigue syndrome after infectious mononucleosis in adolescents. Pediatrics. 2009 Jul;124(1):189-93. doi: 10.1542/peds.2008-1879. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2756827/ (Full article)

 

Chronic fatigue syndrome and complement activation

Abstract:

This report describes a case of chronic fatigue syndrome (CFS) that followed a well-documented episode of acute Epstein-Barr virus (EBV) mononucleosis. All aetiological tests for chronic fatigue were found to be negative or normal, as were immunological tests. After 2 years of chronic fatigue following the acute illness, measurements of complement split products were performed to test for complement activation. These were positive and remained positive for 14 months, after which the patient then recovered from CFS.

 

Source: Geller RD, Giclas PC. Chronic fatigue syndrome and complement activation. BMJ Case Rep. 2009;2009. pii: bcr08.2008.0819. doi: 10.1136/bcr.08.2008.0819. Epub 2009 Mar 17. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3028106/ (Full article)

 

Gene expression correlates of postinfective fatigue syndrome after infectious mononucleosis

Abstract:

BACKGROUND: Infectious mononucleosis (IM) commonly triggers a protracted postinfective fatigue syndrome (PIFS) of unknown pathogenesis.

METHODS: Seven subjects with PIFS with 6 or more months of disabling symptoms and 8 matched control subjects who had recovered promptly from documented IM were studied. The expression of 30,000 genes was examined in the peripheral blood by microarray analysis in 65 longitudinally collected samples. Gene expression patterns associated with PIFS were sought by correlation with symptom factor scores.

RESULTS: Differential expression of 733 genes was identified when samples collected early during the illness and at the late (recovered) time point were compared. Of these genes, 234 were found to be significantly correlated with the reported severity of the fatigue symptom factor, and 180 were found to be correlated with the musculoskeletal pain symptom factor. Validation by analysis of the longitudinal expression pattern revealed 35 genes for which changes in expression were consistent with the illness course. These genes included several that are involved in signal transduction pathways, metal ion binding, and ion channel activity.

CONCLUSIONS: Gene expression correlates of the cardinal symptoms of PIFS after IM have been identified. Further studies of these gene products may help to elucidate the pathogenesis of PIFS.

Comment in: What causes prolonged fatigue after infectious mononucleosis: and does it tell us anything about chronic fatigue syndrome? [J Infect Dis. 2007]

 

Source: Cameron B, Galbraith S, Zhang Y, Davenport T, Vollmer-Conna U, Wakefield D, Hickie I, Dunsmuir W, Whistler T, Vernon S, Reeves WC, Lloyd AR; Dubbo Infection Outcomes Study. Gene expression correlates of postinfective fatigue syndrome after infectious mononucleosis. J Infect Dis. 2007 Jul 1;196(1):56-66. Epub 2007 May 24. http://jid.oxfordjournals.org/content/196/1/56.long (Full article)

 

The nosology of sub-acute and chronic fatigue syndromes that follow infectious mononucleosis

Abstract:

BACKGROUND: A previous principal components analysis of symptoms occurring after infectious mononucleosis suggested that a discrete fatigue syndrome occurs, which is independent of psychiatric disorder. This work has not been replicated and no latent class analysis of subjects has been published.

METHOD: We prospectively examined a cohort of 150 American primary care patients 2 and 6 months after the onset of corroborated infectious mononucleosis. A subset of 50 subjects was studied 4 years after onset. We performed principal components analyses of both psychological and somatic symptoms and latent class analyses of subjects.

RESULTS: Principal components analyses consistently delineated two fatigue factors at 2 and 6 months and one fatigue factor at 4 years. These factors were separate from a mixed anxiety and depressive factor. A four-class solution for the latent class analyses consisted of most subjects with few symptoms, a few with many symptoms, a group with predominantly mood symptoms and some subjects with fatigue symptoms.

CONCLUSIONS: The symptoms of the principal factors with fatigue were similar to those previously described. Both the factors and classes were independent of an equally delineated mood factor and class. These results support the existence of two discrete chronic fatigue syndromes after infectious mononucleosis, one of which is still demonstrable 4 years after onset.

 

Source: White PD, Thomas JM, Sullivan PF, Buchwald D. The nosology of sub-acute and chronic fatigue syndromes that follow infectious mononucleosis. Psychol Med. 2004 Apr;34(3):499-507. http://www.ncbi.nlm.nih.gov/pubmed/15259835

 

Recovery from infectious mononucleosis: a case for more than symptomatic therapy? A systematic review

Abstract:

Infectious mononucleosis is usually an acute, transiently incapacitating condition, but for some sufferers it precipitates chronic illness. It is unclear which patients are at risk of a prolonged state of illness following onset of infectious mononucleosis and if there are any useful preventive measures that would facilitate recovery. The aim of this study was to review all cohort studies and intervention trials that provide information on: (a) the longitudinal course of ill health subsequent to the onset of infectious mononucleosis; (b) the relationship between psychosocial and clinical factors and recovery rate; and (c) the effect of interventions on recovery.

A systematic review was conducted, based on a search of the PSYCHINFO, MEDLINE, EMBASE and CINHAL databases up to October 2001, and ISI Science and Social Sciences Citation Indices up to 22 November 2001. Eight papers were identified that gave data on illness following onset of infectious mononucleosis. The best evidence concluded that there is a distinct fatigue syndrome after infectious mononucleosis. Eight papers explored risk factors for prolonged illness following acute infectious mononucleosis.

Results varied on the association of acute illness characteristics and psychological features with prolonged ill health. Poor physical functioning, namely lengthy convalescence and being less fit or active, consistently predicted chronic ill health. Three trials reported on interventions that aimed to shorten the time taken to resolve symptoms after uncomplicated infectious mononucleosis. None of the drug trials found any evidence that drug therapy shortens recovery time. The trial that compared the effect of activity with imposed bed rest, found that those patients allowed out of bed as soon as they felt able reported a quicker recovery. More information is needed on the course of ill health subsequent to the onset of infectious mononucleosis. Certain risk factors associated with delay may be amenable to a simple intervention in primary care.

 

Source: Candy B, Chalder T, Cleare AJ, Wessely S, White PD, Hotopf M. Recovery from infectious mononucleosis: a case for more than symptomatic therapy? A systematic review. Br J Gen Pract. 2002 Oct;52(483):844-51. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1316091/ (Full article)

 

Predictions and associations of fatigue syndromes and mood disorders that occur after infectious mononucleosis

Abstract:

BACKGROUND: Certain infections can trigger chronic fatigue syndromes (CFS) in a minority of people infected, but the reason is unknown. We describe some factors that predict or are associated with prolonged fatigue after infectious mononucleosis and contrast these factors with those that predicted mood disorders after the same infection.

METHODS: We prospectively studied a cohort of 250 primary-care patients with infectious mononucleosis or ordinary upper-respiratory-tract infections until 6 months after clinical onset. We sought predictors of both acute and chronic fatigue syndromes and mood disorders from clinical, laboratory, and psychosocial measures.

FINDINGS: An empirically defined fatigue syndrome 6 months after onset, which excluded comorbid psychiatric disorders, was most reliably predicted by a positive Monospot test at onset (odds ratio 2.1 [95% CI 1.4-3.3]) and lower physical fitness (0.35 [0.15-0.8]). Cervical lymphadenopathy and initial bed rest were associated with, or predicted, a fatigue syndrome up to 2 months after onset. By contrast, mood disorders were predicted by a premorbid psychiatric history (2.3 [1.4-3.9]), an emotional personality score (1.21 [1.11-1.35]), and social adversity (1.7 [1.0-2.9]). Definitions of CFS that included comorbid mood disorders were predicted by a mixture of those factors that predicted either the empirically defined fatigue syndrome or mood disorders.

INTERPRETATION: The predictors of a prolonged fatigue syndrome after an infection differ with both definition and time, depending particularly on the presence or absence of comorbid mood disorders. The particular infection and its consequent immune reaction may have an early role, but physical deconditioning may also be important. By contrast, mood disorders are predicted by factors that predict mood disorders in general.

 

Source: White PD, Thomas JM, Kangro HO, Bruce-Jones WD, Amess J, Crawford DH, Grover SA, Clare AW. Predictions and associations of fatigue syndromes and mood disorders that occur after infectious mononucleosis. Lancet. 2001 Dec 8;358(9297):1946-54. http://www.ncbi.nlm.nih.gov/pubmed/11747919

 

Incidence, risk and prognosis of acute and chronic fatigue syndromes and psychiatric disorders after glandular fever

Abstract:

BACKGROUND: The role of viruses in the aetiology of both chronic fatigue syndrome (CFS) and depressive illness is uncertain.

METHOD: A prospective cohort study of 250 primary care patients, presenting with glandular fever or an ordinary upper respiratory tract infection (URTI).

RESULTS: The incidence of an acute fatigue syndrome was 47% at onset, after glandular fever, compared with 20% with an ordinary URTI (relative risk 2.3, 95% CI 1.3-4.1). The acute fatigue syndrome lasted a median (interquartile range) of eight weeks (4-16) after glandular fever, but only three weeks (2-4) after an URTI. The prevalence of CFS was 9-22% six months after glandular fever, compared with 0-6% following an ordinary URTI, with relative risks of 2.7-5.1. The most conservative measure of the incidence of CFS was 9% after glandular fever, compared with no cases after an URTI. A conservative estimate is that glandular fever accounts for 3113 (95% CI 1698-4528) new cases of CFS per annum in England and Wales. New episodes of major depressive disorder were triggered by infection, especially the Epstein-Barr virus, but lasted a median of only three weeks. No psychiatric disorder was significantly more prevalent six months after onset than before.

CONCLUSIONS: Glandular fever is a significant risk factor for both acute and chronic fatigue syndromes. Transient new major depressive disorders occur close to onset, but are not related to any particular infection if they last more than a month.

 

Source: White PD, Thomas JM, Amess J, Crawford DH, Grover SA, Kangro HO, Clare AW. Incidence, risk and prognosis of acute and chronic fatigue syndromes and psychiatric disorders after glandular fever. Br J Psychiatry. 1998 Dec;173:475-81. http://www.ncbi.nlm.nih.gov/pubmed/9926075

 

Chronic fatigue syndrome in psychiatric patients: lifetime and premorbid personal history of physical health

Abstract:

OBJECTIVE: This preliminary report compares a group of chronic fatigue syndrome (CFS) patients and controls on several variables of potential significance in the etiology of CFS.

METHOD: The lifetime prevalence of reported physical disorders was compared among 46 CFS psychiatric patients, 92 relatively physically healthy psychiatric patients (C-I), and 46 psychiatric patients selected without regard to physical health (C-II). All patients were matched on age, sex, and psychiatric diagnosis and were drawn from the same psychiatric practice. The same groups were compared on a 7-point scale of lifetime physical health by three raters independently evaluating physical health narratives of the CFS patients up to the time of onset of CFS and that of the controls up to the corresponding age.

RESULTS: The CFS patients had a significantly higher reported lifetime prevalence of irritable bowel syndrome (IBS), infectious mononucleosis-like syndromes (IM), infectious mononucleosis-like syndromes two or more times (IM x 2), and herpes (other than genital or perioral herpes) than one or both control groups. The CFS group also had a higher incidence of allergic rhinitis or asthma, IBS, IM, and IM x 2 than the combined controls. On the independent ratings, the CFS patients had significantly more impaired physical health up to the time of onset of the CFS than C-I at a comparable age.

CONCLUSIONS: The findings suggest that a general health factor may be involved in the pathogenesis of some cases of CFS.

 

Source: Endicott NA. Chronic fatigue syndrome in psychiatric patients: lifetime and premorbid personal history of physical health. Psychosom Med. 1998 Nov-Dec;60(6):744-51. http://www.ncbi.nlm.nih.gov/pubmed/9847035

 

Functional status in patients with chronic fatigue syndrome, other fatiguing illnesses, and healthy individuals

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a condition that may be associated with substantial disability. The Medical Outcomes Study Short-Form General Health Survey (SF-36) is an instrument that has been widely used in outpatient populations to determine functional status. Our objectives were to describe the usefulness of the SF-36 in CFS patients and to determine if subscale scores could distinguish patients with CFS from subjects with unexplained chronic fatigue (CF), major depression (MD), or acute infectious mononucleosis (AIM), and from healthy control subjects (HC). An additional goal was to ascertain if subscale scores correlated with the signs and symptoms of CFS or the presence of psychiatric disorders and fibromyalgia.

DESIGN: Prospectively collected case series.

SETTING: Patients with CFS and CF were seen in a university-based referral clinic and had undergone a complete medical and psychiatric evaluation. Other study subjects were recruited from the community to participate in research studies.

PARTICIPANTS: The study included 185 patients with CFS, 246 with CF, 111 with AIM, and 25 with MD. There were 99 HC subjects.

MEASURES: The SF-36 and a structured psychiatric interview were used. The SF-36 contains 8 subscales: physical, emotional, social, and role functioning, body pain, mental health, vitality, and general health- and a structured psychiatric interview.

RESULTS: Performance characteristics (internal reliability coefficients, convergent validity) of the SF-36 were excellent. A strikingly consistent pattern was found for the physical functioning, role functioning, social functioning, general health, and body pain subscales, with the lowest scores in CFS patients, intermediate scores in AIM patients, and the highest scores in the HC subjects. The CFS patients had significantly lower scores than patients with CF alone on the physical functioning (P < or = 0.01), role functioning (P < or = 0.01), and body pain (P < or = 0.001) subscales. The emotional functioning and mental health scores were worst among those with MD. The presence of fibromyalgia, being unemployed, and increasing fatigue severity all were associated with additional functional limitations across multiple functional domains, with increasing fatigue appearing to have the greatest effect.

CONCLUSIONS: The SF-36 is useful in assessing functional status in patients with fatiguing illnesses. Patients with CFS and CF have marked impairment of their functional status. The severity and pattern of impairment as documented by the SF-36 distinguishes patients with CFS and CF from those with MD and AIM, and from HC, but does not discriminate between CF and CFS.

 

Source: Buchwald D, Pearlman T, Umali J, Schmaling K, Katon W. Functional status in patients with chronic fatigue syndrome, other fatiguing illnesses, and healthy individuals. Am J Med. 1996 Oct;101(4):364-70. http://www.ncbi.nlm.nih.gov/pubmed/8873506

 

Behavioural effects of infectious mononucleosis

Abstract:

The aim of the present study was to provide preliminary information on the acute and chronic effects of infectious mononucleosis (IM) on memory, attention, psychomotor performance and mood. These issues were examined by comparing individuals with acute IM, those who had the initial illness some months before, and matched healthy controls.

Objective measures of memory, attention, motor skills and visual functions were obtained, as were subjective reports of mood. The results showed selective effects of acute IM on performance and mood, with the profile of impairments being very similar to those observed in previous studies of influenza.

Different impairments were observed in subjects who had the primary illness several months before, and the effects observed in this group were similar to those observed in recent studies of chronic fatigue syndrome patients.

Both acute and chronic IM subjects reported similar levels of symptoms and psychopathology, with both groups having greater scores than the controls. However, the performance impairments did not reflect symptoms or psychopathology. One may conclude that the study of IM will provide important data on both the acute and longer lasting effects of viral infections on the brain and behaviour.

 

Source: Hall SR, Smith AP. Behavioural effects of infectious mononucleosis. Neuropsychobiology. 1996;33(4):202-9. http://www.ncbi.nlm.nih.gov/pubmed/8840344