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

Abstract

The pathophysiological mechanisms involved in chronic disorders such as complex regional pain syndrome, fibromyalgia, chronic fatigue syndrome, silicone breast implant–related symptoms, and post-COVID syndrome have not been clearly defined. The course of the pain in some of the syndromes, the absence of evident tissue damage, and the predominance of alterations in the autonomic nervous system are shared similarities between them. The production of autoantibodies following a trigger in the syndromes was previously described, for instance, trauma in complex regional pain syndrome, infectious agents in fibromyalgia, chronic fatigue syndrome, and post-COVID syndrome, and the immune stimulation by silicone in women with breast implants. In fact, the autoantibodies produced were shown to be directed against the autonomic nervous system receptors, leading to the amplification of the perception of pain alongside various clinical symptoms seen during the clinical course of the syndromes. Therefore, we viewed autoantibodies targeting the autonomic nervous system resulting in autonomic dysfunction as likely the most comprehensive explanation of the pathophysiology of the disorders mentioned. Based on this, we aimed to introduce a new concept uniting complex regional pain syndrome, fibromyalgia, chronic fatigue syndrome, silicone breast implant–related symptoms, and post-COVID syndrome, namely “autoimmune autonomic dysfunction syndromes”. Due to its etiological, pathophysiological, and clinical implications, the suggested term would be more precise in classifying the syndromes under one title. The new title would doubtlessly facilitate both laboratory and clinical studies aimed to improve diagnosis and make treatment options more directed and precise.

Consistency of inconsistency in long‐COVID‐19 pain symptoms persistency: A systematic review and meta‐analysis

“…Persistent pain symptoms of long‐COVID, on the other hand, demonstrate resemblance with various features of other chronic pain conditions and syndromes, 81,82,95–97 with some proposals arguing even for their shared clustering under the same group of syndromes 96 . Of these, intriguing similarities could be noticed with fibromyalgia (FM), and especially with its defining symptoms concerning the existence of persistent and multiple widespread painful foci throughout the body 98 .…”

“…Pathological innate immune system activation at viral uptake and replication areas, which leads to “site‐specific” inflammation and vascular damage‐induced hypoxia with subsequent tissue necrosis and organ‐system damage, 18,115,120 probably account for long‐COVID symptom development 81 . However, “systemic‐sequalae” such as immune dysregulation with loss of self‐tolerance and hyperinflammation, viral latency and reservoir persistency, 118 endotheliopathy and thrombo‐embolic/coagulative processes hyperactivation, 46,117,121–123 and multiorgan and autonomic nervous system dysfunction 96 could further fuel previously mentioned pathological processes, leading to their overall chronification and amplification 119 …”

“…Moreover, in line with previous reports of shared similarities, 94 a relatively recently published systematic review noticed that most long-COVID individuals report experiencing the major criteria symptoms of Myalgic Encephalomyelitis/Chronic Fatigue syndrome (ME/CFS), which also tends to follow various infectious agents. 93 Resemblance with fibromyalgia Persistent pain symptoms of long-COVID, on the other hand, demonstrate resemblance with various features of other chronic pain conditions and syndromes, 81,82,[95][96][97] with some proposals arguing even for their shared clustering under the same group of syndromes. 96 Of these, intriguing similarities could with fibromyalgia (FM), and especially with its defining symptoms concerning the existence of persistent and multiple widespread painful foci throughout the body.…”

“…93 Resemblance with fibromyalgia Persistent pain symptoms of long-COVID, on the other hand, demonstrate resemblance with various features of other chronic pain conditions and syndromes, 81,82,[95][96][97] with some proposals arguing even for their shared clustering under the same group of syndromes. 96 Of these, intriguing similarities could with fibromyalgia (FM), and especially with its defining symptoms concerning the existence of persistent and multiple widespread painful foci throughout the body. 98 These, together with other characteristic symptoms such as fatigue, intestinal disorders, insomnia, and mood alterations, express a small part of the diverse range of possible FM manifestations able to overlap with those of long-COVID.…”

The persistent viral infections in the development and severity of myalgic encephalomyelitis/chronic fatigue syndrome

“…Viral infections have been considered as one of the potential etiological factors for ME/CFS, which accompanied by immune disturbances can facilitate the maintenance of disease symptoms [6][7][8][9]. Many patients confirm an onset of ME/CFS with flu-like symptoms.…”