State of the Art Pediatrics: ME/CFS in Children and Adolescents: What Every Pediatric Clinician Should Know

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a commonly underrecognized cause of prolonged school absence and functional impairment among children and adolescents. Early recognition and supportive management can improve long‑term outcomes. In the first half of this two-part series, we review the epidemiology, risk factors, clinical evaluation and diagnosis of ME/CFS.

Overview and Definition

ME/CFS is a chronic, multi‑system illness characterized by profound fatigue, post‑exertional malaise, sleep disturbance and impaired functioning. Additional symptoms—such as muscle or joint pain, headaches, gastrointestinal complaints, temperature sensitivity, visual changes, or food intolerances—are common but not required for diagnosis.

Epidemiology and Risk Factors

In pediatrics, ME/CFS occurs in approximately 0.75% of community youth, with many cases remaining undiagnosed. In adults, prevalence in the United States is estimated at 1.3%. The condition is more common in females, with a 3-4:1 female-to-male ratio. It is uncommon before age 10 and shows peak incidence in mid-adulthood. ME/CFS often develops gradually and frequently follows an infectious illness or significant stressor, with symptom onset approximately six months later. Of note, history of infection or major stressor is not required for diagnosis. There is evidence of familial risk, with higher concordance in monozygotic twins. Joint hypermobility is associated with an approximately three‑fold increased risk. The underlying pathophysiology remains unclear but is hypothesized to involve dysregulation of the central and autonomic nervous system with metabolic and immunologic changes. Research is ongoing to identify underlying mechanisms of disease.

When evaluating a patient with substantial and persistent fatigue, consider the following key components:

• Detailed history (often supported by symptom questionnaires or semi-structured assessment)
• Physical examination with attention to neuromuscular findings
• Beighton score to assess joint hypermobility
• Orthostatic testing (e.g., 10‑minute standing test)

The initial laboratory evaluation should assess for conditions that mimic or exacerbate ME/CFS (e.g., anemia, thyroid dysfunction, electrolyte abnormalities, altered kidney and liver function, diabetes mellitus, rheumatologic conditions, celiac disease) and includes:

• CBC with differential
• Thyroid‑stimulating hormone
• Complete chemistry panel, with kidney and liver function tests
• Ferritin and other iron studies as indicated
• Additional studies as indicated (e.g., ESR, CRP, HbA1C, vitamin B12, celiac screening, urinalysis)

Red flags for further evaluation of other causes include weight loss, fevers, clubbing, erythematous and swollen joints, cataplexy, and abnormalities on neuromuscular exam.

Diagnosis:

In 2015, the Institute of Medicine (IOM) published diagnostic criteria emphasizing core symptoms rather than exclusionary testing. This shift reflects a historical awareness that exclusionary diagnostic criteria led to delays in management and treatment.

Diagnosis requires all three core symptoms plus at least one additional symptom, resulting in a substantial reduction in pre‑illness levels of activity for at least six months (Table 1). Importantly, the IOM recommends that ME/CFS diagnosis should be made once criteria are met following an appropriately thorough history, physical examination and medical evaluation.

Other diagnostic criteria exist for ME/CFS. The Canadian Consensus Criteria (CCC), revised in 2010, present more granular and complex criteria for diagnosis. Compared with the IOM criteria, the CCC criteria also require the presence of pain and include neurologic/cognitive dysfunction as well as autonomic/neuroendocrine/immunologic manifestations for diagnosis. The older Fukuda criteria (1994) are less specific. The IOM and CCC criteria identify post-exertional malaise as a cardinal feature of ME/CFS, while the Fukuda criteria center on fatigue. The IOM criteria (Table 1) present the most up-to-date and balanced approach to diagnosing ME/CFS.

Prognosis and Functional Outcomes

ME/CFS is not associated with increased mortality, but often follows a prolonged, fluctuating course. Approximately 20% of patients report significant functional limitations after 10 years.

Children and adolescents with ME/CFS report lower health‑related quality of life than peers with other chronic illnesses, such as asthma, diabetes, epilepsy and cystic fibrosis. Continued engagement in education is among the strongest predictors of better long‑term outcomes. Patients benefit from developing healthy coping skills for living with a chronic condition. Patients who feel believed, receive a clear diagnosis and maintain supportive relationships are more likely to develop healthy coping skills to support optimal function.

Key Takeaways for Pediatricians

• ME/CFS is a chronic, debilitating, multi‑system illness. Symptoms must have been present for more than six months.
• Diagnosis is clinical and should be made when criteria are met. IOM criteria represent the most up-to-date and balanced approach and include reduced function, post-exertional malaise, poor sleep, as well as cognitive impairment or orthostatic intolerance.

Key Resources for Further Reading:

• Institute of Medicine. Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness. The National Academies Press; 2015. doi:10.17226/19012
• Rowe PC, Underhill RA, Friedman KJ, et al. Myalgic encephalomyelitis/chronic fatigue syndrome diagnosis and management in young people: a primer. Front Pediatr. 2017;5:121. doi:10.3389/fped.2017.00121
• Rowe K. Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) in adolescents: practical guidance and management challenges. Adolesc Health Med Ther. 2023;14:13-26. doi:10.2147/AHMT.S317314