Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Comorbidities: Linked by Vascular Pathomechanisms and Vasoactive Mediators?

Abstract

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is often associated with various other syndromes or conditions including mast cell activation (MCA),  dysmenorrhea and endometriosis, postural tachycardia (POTS) and small fiber  neuropathy (SFN). The causes of these syndromes and the reason for their frequent  association are not yet fully understood. We previously published a comprehensive  hypothesis of the ME/CFS pathophysiology that explains the majority of symptoms,  findings and chronicity of the disease. We wondered whether some of the  identified key pathomechanisms in ME/CFS are also operative in MCA, endometriosis  and dysmenorrhea, POTS, decreased cerebral blood flow and SFN, and possibly may  provide clues on their causes and frequent co-occurrence. Our analysis indeed  provides strong arguments in favor of this assumption, and we conclude that the  main pathomechanisms responsible for this association are excessive generation  and spillover into the systemic circulation of inflammatory and vasoactive tissue  mediators, dysfunctional β2AdR, and the mutual triggering of symptomatology and  disease initiation. Overall, vascular dysfunction appears to be a strong common  denominator in these linkages.