Successful treatment of postural orthostatic tachycardia and mast cell activation syndromes using naltrexone, immunoglobulin and antibiotic treatment.

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). A dramatic and sustained response was documented. 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. 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. IVIg is emerging as a promising therapy for POTS. Diagnosis and treatment of SIBO in POTS is a new concept and appears to play an important role.

Low-dose Naltrexone for the treatment of sarcoidosis.

Systemic therapy is administered to 50% of patients and the need for long-term use of therapy is quite variable (1,2). Prednisone is often administered for many months with risk for multiple side effects, immunomodulators as steroid sparing agents have a delayed onset of action and have risks for infection and malignancies, and infliximab increases the risk for infection (1). In light of these issues, alternative options for therapy are desirable. We made a comparison between sarcoidosis and Crohn's disease in that in each disease there is unregulated lymphocyte activity, a common unique pathological finding of non-caseating granulomas, and a similar approach to medical therapy (3,4). Low dose naltrexone (LDN) has been utilized for many conditions (5). Efficacy has been documented in Crohn's disease with randomized controlled studies showing mucosal healing and histologic improvement (6-7). LDN is compounded in 1/10th to 1/20th the dose used for the FDA-approved indications of narcotic and alcohol dependence (8). Neuropeptides (e.g., enkephalins and endorphins) are present in the gastrointestinal tract and endocrine cells and modulate immune responses (9). Up-regulation of met-enkephelin and opioid receptors can be induced by a rebound effect by short-acting LDN (10). Higher levels of endogenous opioids and receptors inhibit cell proliferation which suppress T and B lymphocyte responses (11,12) and decrease production of pro-inflammatory interleukins-6 and -12 (13). In light of the Crohn's disease LDN literature and similar experiences with other inflammatory conditions in our clinic (14,15), LDN was administered to a sarcoidosis patient with severe fatigue, sarcoid rash, and marked radiographic evidence of gastrointestinal involvement. (Sarcoidosis Vasc Diffuse Lung Dis 2017; 34: 184-187).

Identification and Treatment of New Inflammatory Triggers for Complex Regional Pain Syndrome: Small Intestinal Bacterial Overgrowth and Obstructive Sleep Apnea.

Complex regional pain syndrome (CRPS) is evoked by conditions that may be associated with local and/or systemic inflammation. We present a case of long-standing CRPS in a patient with Ehlers-Danlos syndrome in which prolonged remission was attained by directing therapy toward concomitant small intestinal bacterial overgrowth, obstructive sleep apnea, and potential increased microglia activity. We theorize that cytokine production produced by small intestinal bacterial overgrowth and obstructive sleep apnea may act as stimuli for ongoing CRPS symptoms. CRPS may also benefit from the properties of low-dose naltrexone that blocks microglia Toll-like receptors and induces production of endorphins that regulate and reduce inflammation.