Mechanisms of action of spa therapies in rheumatic diseases: what scientific evidence is there?

Spa therapy represents a popular treatment for many rheumatic diseases. The mechanisms by which immersion in mineral or thermal water or the application of mud alleviates suffering in rheumatic diseases are not fully understood. The net benefit is probably the result of a combination of factors, with mechanical, thermal and chemical effects among the most prominent ones. Buoyancy, immersion, resistance and temperature all play important roles. According to the gate theory, pain relief may be due to the pressure and temperature of the water on skin; hot stimuli may influence muscle tone and pain intensity, helping to reduce muscle spasm and to increase the pain threshold. Mud-bath therapy increases plasma β-endorphin levels and secretion of corticotrophin, cortisol, growth hormone and prolactin. It has recently been demonstrated that thermal mud-pack therapy induces a reduction in the circulating levels of prostaglandin E2 (PGE2), leukotriene B4 (LTB4), interleukin-1β (IL-1β) and tumour necrosis factor-α (TNF-α), important mediators of inflammation and pain. Spa therapy has been found to cause an increase in insulin-like growth factor-1 (IGF1), which stimulates cartilage metabolism, and transforming growth factor-β (TGF-β). There is also evidence of the positive action of mud-packs and thermal baths on the oxidant/antioxidant system, with a reduction in the release of reactive oxygen (ROS) and nitrogen (RNS) species. Overall, thermal stress has an immunosuppressive effect. Many other non-specific factors may also contribute to the beneficial effects observed after spa therapy in some rheumatic diseases, including effects on cardiovascular risk factors, and changes in the environment, pleasant surroundings and the absence of work duties

Long-term treatment of antiphospholipid syndrome with intravenous immunoglobulin in addition to conventional therapy.

OBJECTIVES: This work aims to prospectively assess the long-term effects of intravenous immunoglobulin (IVIG Flebogamma®) in a small cohort of patients affected by primary or secondary antiphospholipid syndrome (APS), in addition to conventional therapy. METHODS: Three primary and four secondary APS patients (6 women and 1 man), aged between 40 and 62 years, were treated with IVIG in addition to conventional therapy with anticoagulants or antiplatelets, while six primary and one secondary APS patients (6 women and 1 man), aged between 31 and 61 years, continued their regular conventional therapy. One infusion of IVIG was administered at a dose of 0.4 g/kg/day every month to the first group of patients for two years. Patients were assessed at baseline, after 1 year and 2 years from the beginning of the study and were evaluated for the occurrence of any thromboembolic events and by laboratory measurement of antiphospholipides antibodies (aPL). RESULTS: No venous or arterial thromboses occurred in patients treated with IVIG, whereas in the control group two patients presented cerebral ischaemic attacks and one patient reported a deep vein thrombosis during the follow-up. At the end of the study, in the group treated with IVIG, we observed a statistically significant decrease of anticardiolipin antibodies (IgG and IgM) and of IgM anti-β2-glycoprotein I antibodies. CONCLUSIONS: Our results show the efficacy of IVIG in addition to conventional therapy, in primary and secondary APS patients, preventing the occurrence of thromboembolic events. However, further clinical studies on a larger group of patients are necessary to fully understand the mechanisms of action and the optimal doses of IVIG in APS