Autoimmune Autonomic Dysfunction Syndromes: Potential Involvement and Pathophysiology Related to Complex Regional Pain Syndrome, Fibromyalgia, Chronic Fatigue Syndrome, Silicone Breast Implant-Related Symptoms and Post-COVID Syndrome.
Mahroum, Naim, Shoenfeld, Yehuda · Pathophysiology : the official journal of the International Society for Pathophysiology · 2022 · DOI
Quick Summary
This article suggests that several chronic conditions—including ME/CFS, fibromyalgia, long COVID, and complex regional pain syndrome—may share a common cause: the immune system mistakenly producing antibodies that attack the autonomic nervous system (the part of your body that controls automatic functions like heart rate and blood pressure). The authors propose calling these conditions "autoimmune autonomic dysfunction syndromes" to highlight this shared mechanism and potentially help doctors diagnose and treat them more effectively.
Why It Matters
For ME/CFS patients, this framework offers a potentially unifying explanation for why the disease involves both pain and dysautonomia (abnormal autonomic function), and suggests that autoimmune mechanisms may be central to pathophysiology. Recognition of ME/CFS within a broader autoimmune autonomic dysfunction category could accelerate development of targeted immunological treatments and improve diagnostic approaches across related conditions.
Observed Findings
Chronic pain, autonomic nervous system alterations, and absence of evident tissue damage are shared features across CRPS, fibromyalgia, ME/CFS, SBIS, and post-COVID syndrome.
Autoantibodies have been previously documented in these syndromes following identifiable triggers (trauma, infection, immune stimulation).
Studies show autoantibodies in these conditions are directed against autonomic nervous system receptors.
Autoantibodies targeting autonomic receptors correlate with pain amplification and various clinical symptoms across these conditions.
Inferred Conclusions
Autoimmune mechanisms targeting the autonomic nervous system may represent a common pathophysiological pathway across five distinct clinical syndromes.
A unified classification term—"autoimmune autonomic dysfunction syndromes"—would have etiological, pathophysiological, and clinical utility.
Adopting this framework could improve diagnostic precision and enable more targeted laboratory and clinical research.
Recognition of shared pathophysiology may facilitate development of more directed and effective treatment options.
Remaining Questions
What are the specific autoantigen targets across ME/CFS and related syndromes, and do they differ by condition or trigger type?
What This Study Does Not Prove
This review does not provide new experimental evidence that autoantibodies against autonomic receptors are present in ME/CFS patients or that they directly cause symptoms. It does not establish causation—only proposes a unifying hypothesis. The paper does not validate diagnostic criteria for this proposed new category or demonstrate that treatment approaches effective for one syndrome would work for others.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →