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.