Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis (CFS / ME) is an illness characterized by disabling fatigue combined with multiple physiological impairments with so far unexplained pathophysiological cause. CFS patients often demonstrate a dysregulated cytokine and mediator profile. The spectrum of symptoms of CFS / ME patients is widespread and can involve chronic fatique, dizziness, muscle aches, nausea, gastrointestinal dysfunctions, widespread immune system disturbances, allergic disorders, endocrine dysfunctions, anxieties and depression, and cognitive problems. Many CFS patients demonstrate abnormal hypothalamic-pituitary-adrenal axis activity.

Chronic Fatigue Syndrome (CFS) / Myalgic Encephalomyelitis (ME) is quite common in patients with systemic mast cell activation. CRH and other related peptides secreted by inflammatory, immunologic stimulation, physical or emotional acute stress activate diencephalic MCs (located perivascularly in close proximity to neurons), either directly or through neuropeptides such as neurotensin, leading to the release of pro-inflammatory cytokines, such as IL-1, IL-4, IL-6, IL-17, histamine, TNF or IFN-γ that have shown in studies to contribute to CFS / ME pathogenesis and have been reported to be elevated in CFS / ME patients.

Further, mast cells could stimulate the hypothalamic-pituitary-adrenal axis through histamine and IL-1 or IL-6. Fifty percent of histamine in the brain derives from mast cells, whereas the rest is of neuronal origin. In a recent study, for the first time increased activated mast cells have been discovered in CFS / ME patients. Further, another study has determined an altered mast cell function in the tissues of CFS / ME patients.

In summary, mast cell–derived vasoactive, pro-inflammatory, and neuros-sensitizing mediators could significantly contribute to the pathogenesis of CFS / ME. In consequence, the controlled inhibition of mast cell activation could lead to an important breakthrough in the treatment of CFS / ME for a significant portion of patients.

Although the actual number is likely higher, about 0,5% to 1% of the global population is estimated to be diagnosed with CFS / ME resulting in about 50 million patients.