MCAS therapy is directed at MC stabilisation, which is complicated by the fact that MC can release 200 mediators many of which have a wide array of triggers. 5 7 POTS therapy has historically focused on treating orthostatic intolerance which does not address other systems (eg, GI tract, urinary bladder sphincter, ocular and central nervous system). POTS is generally divided into two categories: neuropathic and hyperadrenergic the latter is difficult to treat and is thought in part to be associated with MC as a driving force in some patients. 2 Physicians may erroneously attribute these frequent GI symptoms in undiagnosed MCAS and POTS patients to irritable bowel syndrome (IBS) and psychological disturbances as was the case in our patient.
![massive activation syndrome massive activation syndrome](https://www.lymedisease.org/wp-content/uploads/2019/02/mast-cell-activation-syndrome.jpg)
1–4 6 GI symptoms in MCAS can be explained by inappropriate release of mediators from mast cells (MCs) with KIT mutations whereas GI motility disorders in POTS may be due to active autoimmune muscarinic antibodies causing autonomic imbalance in some patients (S Vernino, personal communication, 2017). 5 Gastrointestinal (GI) symptoms are common in both syndromes. 4 To further complicate matters, 17 of 48 MCAS symptoms overlap with 33 POTS symptoms which is explained by comorbidity of the syndromes, where 30% of patients with POTS also have MCAS.
![massive activation syndrome massive activation syndrome](https://media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs41232-020-00131-w/MediaObjects/41232_2020_131_Fig1_HTML.png)
2 Postural lightheadedness especially in the morning, palpitations, presyncope, headache, blurry vision, memory problems are experienced by ≥50% of patients with POTS. 1–4 Fatigue, muscle pain, presyncope/syncope, headache, itching, urticaria, paraesthesia, nausea, chills, oedema, eye irritation, dyspnoea and heartburn are experienced by ≥50% of patients with MCAS. 1 2 The confusing magnitude of symptoms led to delay in diagnosis and disability in our patient as is the case for the majority of patients with these syndromes. The prevalence of postural orthostatic tachycardia syndrome (POTS) is at least 170/100 000, and the prevalence of mast cell activation syndrome (MCAS) is estimated between 1% and 17%. These syndromes are generally regarded as rare or are never diagnosed owing to lack of awareness by physicians. Diagnosis and treatment of SIBO in POTS is a new concept and appears to play an important role. IVIg is emerging as a promising therapy for POTS.
![massive activation syndrome massive activation syndrome](https://amjmed.org/wp-content/uploads/2014/06/pyrexia.jpg)
As a short-acting mu-opioid antagonist, LDN paradoxically increases endorphins which then bind to regulatory T cells which regulate T-lymphocyte and B-lymphocyte production and this reduces cytokine and antibody production. The utility of IVIg in autoimmune neuromuscular diseases has been published, but clinical experience with POTS is relatively unknown and has not been reported in MCAS. A dramatic and sustained response was documented. A patient with severe postural orthostatic tachycardia syndrome (POTS) and mast cell activation syndrome (MCAS) received immunotherapy with low-dose naltrexone (LDN) and intravenous immunoglobulin (IVIg) and antibiotic therapy for small intestinal bacterial overgrowth (SIBO).