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The recent opinion by Charlton
et al. published in
Trends in Endocrinology & Metabolism [
1] provides a thought-provoking discussion of the overlap between long coronavirus disease (long-COVID) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), emphasizing the centrality of post-exertional malaise (PEM) as a shared mechanism. Here, we suggest that fibromyalgia should be included in the discussion, given the established role of PEM in this condition [
2]. In addition, fibromyalgia not only shares symptomatic and mechanistic overlaps with ME/CFS, but also offers a complementary perspective on the pathophysiology of PEM. Considering that PEM is a key symptom in both fibromyalgia and long COVID, exploring skeletal muscle function in fibromyalgia could provide complementary insights into the muscle-specific alterations that contribute to this debilitating phenomenon.
PEM is a hallmark symptom of ME/CFS and is increasingly recognized in long COVID. Substantial evidence demonstrates that PEM is equally pertinent in fibromyalgia, manifesting as a disproportionate exacerbation of symptoms following minimal physical or cognitive exertion [
2]. This overlap is underscored by research showing that both fibromyalgia and ME/CFS exhibit heightened central sensitization, driven by shared neuroimmune and neuroendocrine dysregulation [
3]. For example, significant differences were identified in gene expression related to sensory, adrenergic, and immune pathways in patients with fibromyalgia and ME/CFS following moderate exercise [
4]. These findings highlight the relevance of PEM across multiple chronic conditions.
Including fibromyalgia in the discussions on PEM also brings practical implications for patient care. Patients with fibromyalgia frequently report PEM, yet this symptom remains underappreciated in clinical settings. Recognizing the role of fibromyalgia could enhance diagnostic accuracy and inform personalized management strategies for syndromic conditions characterized by PEM. For instance, research demonstrates that, compared with those with CFS, patients with fibromyalgia exhibit distinct baseline increases in sensory receptor and cytokine gene expression, such as
P2X4,
TRPV1, and
IL10, which may predispose them to heightened PEM responses [
4,
5]. These biomarkers could guide targeted interventions, particularly in differentiating fibromyalgia from ME/CFS and long COVID.
The shared biological mechanisms of PEM across fibromyalgia, ME/CFS, and long COVID suggest a continuum of syndromic conditions rather than discrete entities. Dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, as well as altered adrenergic receptor activity, is evident in fibromyalgia and ME/CFS, contributing to impaired stress responses and heightened pain sensitivity [
6]. Including fibromyalgia in the broader narrative of PEM research would provide a more comprehensive understanding of these mechanisms and facilitate the development of cross-condition therapeutic strategies.
Furthermore, fibromyalgia represents a substantial burden to healthcare systems and society. It affects an estimated 2–4% of the global population, with a substantial overlap with ME/CFS [
7]. Studies indicate that up to 70% of patients with ME/CFS meet criteria for fibromyalgia, underscoring the intertwined nature of these conditions [
8]. Therefore, incorporating fibromyalgia into PEM-focused research would not only enhance scientific accuracy, but also address a critical gap in addressing the needs of a large, and often underserved, patient population. Similarly, the importance of recognizing overlapping symptoms and mechanisms across these syndromes, particularly PEM, to improve diagnostic precision and therapeutic outcomes has been recently emphasized [
9].
We propose that future reviews and research on PEM consider fibromyalgia as a critical component of the spectrum of conditions linked by this symptom. Such inclusion would bridge gaps in research and clinical practice, fostering a more integrated approach to understanding and managing PEM. By leveraging insights from fibromyalgia research, we can advance our understanding of the role of PEM in ME/CFS and long COVID, ultimately improving outcomes for patients across these conditions.
Seems like an advertisement for the society of fibromyalgologists.
