Increased risks of cancer and autoimmune disease among the first-degree relatives of patients with myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS)

Background: Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is a disabling multi-system complex disorder with prevalence of 875 per 100,000 (up to 3.4 million people) in the United States. There are no known etiologic or risk factors and no approved treatments for ME/CFS. We conducted a molecular epidemiologic study to test the hypothesis that ME/CFS may be an autoimmune disease (AID) and explore the link between ME/CFS and cancer, specifically hematologic malignancies.Methods: Our clinic-based study involved carefully selected cases with confirmed diagnosis of ME/CFS (n=59) and healthy controls (n=54) frequency matched to cases on age, gender and ethnicity. During structured interviews, detailed multi-generation pedigrees, epidemiologic and medical questionnaires, and biospecimen were obtained on all subjects. Statistical analysis of pedigree data involved comparison of cases and controls with respect to the prevalence and cumulative incidence of AID and cancer among their first-degree relatives. For unadjusted analysis, risk ratios, 95% confidence intervals (CI), and p-values were calculated. For age-adjusted analyses, cumulative incidence estimates were compared using the log-rank test.

Results: The prevalence of AID was significantly higher among the first-degree relatives of cases compared to those of controls (OR=5.30; 95%CI: 1.83-15.38; p=0.001). The prevalence of AID among mothers was 14% for cases and 1.9% for controls (p=0.03). 11.2% of the first-degree relatives of cases had an AID compared to 3.1% of the relatives of controls (prevalence ratio=3.71; 95% CI: 1.74-7.88; p=0.0007). The cumulative incidence of AID among the first-degree relatives of ME/CFS cases was 9.4% compared to 2.7% for those of the controls (p=0.0025). First-degree relatives of ME/CFS cases had a significantly higher prevalence of any cancer compared to the relatives of unrelated controls (OR=4.06, 95%CI: 1.84-8.96, p=0.0005). Age-adjusted analysis revealed significantly higher (p=0.03) cumulative incidence of any cancer among the first-degree relatives of cases (20%) compared to the relatives of controls (15.4%). The cumulative incidence of hematologic cancers was also significantly higher among the relatives of cases (p<0.05).

Conclusions: We found statistically significant increased risks of AID and cancer among the first-degree relatives of ME/CFS cases. Our findings implicate immune dysregulation as an underlying mechanism, providing etiologic clues and leads for prevention. Given symptomatic similarities between ‘long COVID’ and ME/CFS, it is predicted that there will be a significant increase in incidence of ME/CFS as the result of COVID-19 pandemic. Our findings may enable defining a subset of COVID-19 patients who could be at risk of developing ME/CFS, and who may benefit from treatments used for certain AIDs.

Source: Roxana Moslehi, Anil Kumar, Amiran Dzutsev. Increased risks of cancer and autoimmune disease among the first-degree relatives of patients with myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 34. https://aacrjournals.org/cancerres/article/82/12_Supplement/34/700144

 

Adolescents and mothers value referral to a specialist service for chronic fatigue syndrome or myalgic encephalopathy (CFS/ME)

Abstract:

BACKGROUND: Paediatric chronic fatigue syndrome or myalgic encephalopathy (CFS/ME) is relatively common and disabling. Current guidance recommends referral to specialist services, although some general practitioners believe the label of CFS/ME is harmful and many are not confident about diagnosing CFS/ME. Aim Explore whether or not adolescents and their mothers value referral to a specialist service for young people with CFS/ME.

METHODS: A qualitative study nested within a feasibility study of interventions for CFS/ME [Specialist Medical Intervention and Lightning Evaluation (SMILE)]. In-depth interviews were undertaken with 13 mothers and 12 adolescents participating in the SMILE study. Transcripts were systematically assigned codes using the qualitative data organisation package NVivo and analysed thematically using techniques of constant comparison.

RESULTS: Gaining access to the specialist service was difficult and took a long time. Mothers felt that they needed to be proactive and persistent, partly because of a lack of knowledge in primary and secondary care. Having gained access, mothers felt the CFS/ME service was useful because it recognised and acknowledged their child’s condition and opened channels of dialogue between health-care professionals and education providers. Adolescents reported that specialist medical care resulted in better symptom management, although some adolescents did not like the fact that the treatment approach limited activity.

CONCLUSIONS: Adolescents and their mothers value receiving a diagnosis from a specialist service and making progress in managing CFS/ME. General practitioners should support adolescents with CFS/ME in accessing CFS/ME specialist services, consistent with current guidance.

 

Source: Beasant L, Mills N, Crawley E. Adolescents and mothers value referral to a specialist service for chronic fatigue syndrome or myalgic encephalopathy (CFS/ME). Prim Health Care Res Dev. 2014 Apr;15(2):134-42. doi: 10.1017/S1463423613000121. Epub 2013 Apr 25. https://www.ncbi.nlm.nih.gov/pubmed/23731646

 

The financial and psychological impacts on mothers of children with chronic fatigue syndrome (CFS/ME)

Abstract:

BACKGROUND: Paediatric chronic fatigue syndrome or myalgic encephalopathy (CFS/ME) is relatively common and children can be severely affected attending little or no school for extended periods. There are no studies quantifying the financial impact of having a child with CFS/ME and there is little information of the impact on parental mood.

METHODS: Forty mothers of children with CFS/ME from a regional specialist CFS/ME service completed inventories to assess their psychological well-being (Hospital Anxiety and Depression Scale, General Health Questionnaire-12) loss of earnings and increased expenditure. In addition, eight mothers took part in a semi-structured qualitative interview.

RESULTS: Most parents of children with CFS/ME experience loss of monthly income (mean = £247) and increase in monthly expenditure (mean = £206). Twenty-eight (72%) mothers were above the cut-off for the General Health Questionnaire-12 compared with 20% in the healthy population (95% CI 55, 85, P < 0.001) suggesting they probably have a mental health problem. This may be explained by the qualitative interviews where mothers described five areas contributing to poor parental health: lack of understanding from others; marital tension; concern about their child’s distress; concern about the impact on siblings and emotional distress causing physical symptoms.

CONCLUSIONS: The majority of families of children with CFS/ME experience decreased income and increased expenditure with a marked impact on maternal psychological health. Clinicians need to be aware of this to provide appropriate support to families who care for children with CFS/ME.

© 2011 Blackwell Publishing Ltd.

 

Source: Missen A, Hollingworth W, Eaton N, Crawley E. The financial and psychological impacts on mothers of children with chronic fatigue syndrome (CFS/ME). Child Care Health Dev. 2012 Jul;38(4):505-12. doi: 10.1111/j.1365-2214.2011.01298.x. Epub 2011 Sep 1. https://www.ncbi.nlm.nih.gov/pubmed/21880054

 

Adolescent offspring of mothers with chronic fatigue syndrome

Abstract:

PURPOSE: The goal of this study was to determine whether adolescent offspring of mothers with chronic fatigue syndrome(CFS) have higher prevalence of CFS and report more fatigue, greater pain sensitivity, more sleep problems, and poorer cardiopulmonary fitness in comparison with offspring with no exposure to maternal CFS.

METHODS: A total of 26 adolescent offspring of 20 mothers diagnosed with CFS were compared with 45 adolescent offspring of 30 age-matched healthy control mothers. Study measures included structured interviews and medical and laboratory examinations for CFS; tender point examination; maximum oxygen uptake and perceived exertion; dolorimetry pain ratings; and questionnaires on fatigue severity and sleepiness.

RESULTS: In comparison with offspring of healthy mothers, those exposed to mothers with CFS reported higher prevalence of fatigue of at least 1-month duration (23% vs. 4%), fatigue of 6 months or longer (15% vs. 2%), and met criteria for CFS (12% vs. 2%), although these differences only approached statistical significance. CFS and healthy mothers differed on almost all study outcomes, but offspring groups did not differ on measures of current fatigue severity, pain sensitivity, sleep, mean number of tender points, and cardiopulmonary fitness.

CONCLUSIONS: The higher prevalence of fatiguing states in offspring of CFS mothers, despite the lack of statistical significance, suggests that familial factors may potentially play a role in developing chronically fatiguing states. Alternately, perturbations in pain sensitivity and cardiopulmonary fitness may be consequences of CFS. Future studies should focus on examining the impact of maternal CFS and associated disability on psychosocial functioning of offspring.

 

Source: Smith MS, Buchwald DS, Bogart A, Goldberg J, Smith WR, Afari N. Adolescent offspring of mothers with chronic fatigue syndrome. J Adolesc Health. 2010 Mar;46(3):284-91. doi: 10.1016/j.jadohealth.2009.08.001. Epub 2009 Oct 13. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2824612/ (Full article)

 

Efficacy of cognitive behavioral therapy for adolescents with chronic fatigue syndrome: long-term follow-up of a randomized, controlled trial

Abstract:

OBJECTIVES: The purpose of this work was to assess the long-term outcome of adolescents with chronic fatigue syndrome who received cognitive behavioral therapy and to determine the predictive value of fatigue severity and physical impairments of the adolescent and the fatigue severity of the mother at baseline for the outcome of the treatment at follow-up.

PATIENTS AND METHODS: Sixty-six adolescent patients with chronic fatigue syndrome who previously participated in a randomized, controlled trial that showed that cognitive behavioral therapy was more effective than a waiting-list condition in reducing fatigue and improving physical functioning were contacted for a follow-up assessment. Fifty participants of the follow-up study had received cognitive behavioral therapy for chronic fatigue syndrome (32 formed the cognitive behavioral therapy group in the original trial, and 18 patients received cognitive behavioral therapy after the waiting period). The remaining 16 patients had refused cognitive behavioral therapy after the waiting period. The main outcome measures were fatigue severity (Checklist Individual Strength), physical functioning (Short-Form General Health Survey), and school attendance.

RESULTS: Data were complete for 61 patients at follow-up (cognitive behavioral therapy group: 47 patients; no-treatment group: 14 patients). The mean follow-up time was 2.1 years. There was no significant change in fatigue severity between posttreatment and follow-up in the cognitive behavioral therapy group. There was a significant further increase in physical functioning and school attendance (10% increase). The adolescents in the cognitive behavioral therapy group were significantly less fatigued and significantly less functionally impaired and had higher school attendance at follow-up than those in the no-treatment group. Fatigue severity of the mother was a significant predictor of treatment outcome.

CONCLUSIONS: The positive effects of cognitive behavioral therapy in adolescents with chronic fatigue syndrome are sustained after cognitive behavioral therapy. Higher fatigue severity of the mother predicts lower treatment outcome in adolescent patients.

 

Source: Knoop H, Stulemeijer M, de Jong LW, Fiselier TJ, Bleijenberg G. Efficacy of cognitive behavioral therapy for adolescents with chronic fatigue syndrome: long-term follow-up of a randomized, controlled trial. Pediatrics. 2008 Mar;121(3):e619-25. doi: 10.1542/peds.2007-1488. https://www.ncbi.nlm.nih.gov/pubmed/18310181

 

Mirrored symptoms in mother and child with chronic fatigue syndrome

Abstract:

OBJECTIVE: Our aim with this study was to assess the relation between chronic fatigue syndrome in adolescents and fatigue and associated symptoms in their fathers and mothers, more specifically the presence of chronic fatigue syndrome-like symptoms and psychologic distress.

METHOD: In this cross-sectional study, 40 adolescents with chronic fatigue syndrome according to the Centers for Disease Control and Prevention criteria were compared with 36 healthy control subjects and their respective parents. Questionnaires regarding fatigue (Checklist Individual Strength), fatigue-associated symptoms, and psychopathology (Symptom Checklist-90) were applied to the children and their parents.

RESULTS: Psychologic distress in the mother corresponds with an adjusted odds ratio of 5.6 for the presence of CFS in the child. The presence of fatigue in the mother and dimensional assessment of fatigue with the Checklist Individual Strength revealed odds ratios of, respectively, 5.29 and 2.86 for the presence of chronic fatigue syndrome in the child. An increase of 1 SD of the hours spent by the working mother outside the home reduced the risk for chronic fatigue syndrome in their child with 61%. The fathers did not show any risk indicator for chronic fatigue syndrome in their child.

CONCLUSIONS: Mothers of adolescents with chronic fatigue syndrome exhibit fatigue and psychologic symptoms similar to their child in contrast with the fathers. The striking difference between the absent association in fathers and the evident association in mothers suggests that the shared symptom complex of mother and child is the result of an interplay between genetic vulnerability and environmental factors.

Comment in: Potential polygenic influences on chronic fatigue syndrome. [Pediatrics. 2006]

 

Source: van de Putte EM, van Doornen LJ, Engelbert RH, Kuis W, Kimpen JL, Uiterwaal CS. Mirrored symptoms in mother and child with chronic fatigue syndrome. Pediatrics. 2006 Jun;117(6):2074-9. https://www.ncbi.nlm.nih.gov/pubmed/16740850