Rheumatology International

, Volume 31, Issue 1, pp 1–8 | Cite as

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

  • Antonella FioravantiEmail author
  • Luca Cantarini
  • Giacomo Maria Guidelli
  • Mauro Galeazzi
Review Article


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.


Spa therapy Balneotherapy Mud-packs Rheumatic diseases Mechanisms of action 


  1. 1.
    Sukenik S, Flusser D, Abu-Shakra M (1999) The role of SPA therapy in various rheumatic diseases. Rheum Dis North Am 25:883–897CrossRefGoogle Scholar
  2. 2.
    Bender T, Karagülle Z, Bàlint GP, Gutenbrunner C, Bàlint PV, Sukenik S (2005) Hydrotherapy, balneotherapy, and spa treatment in pain management. Rheumatol Int 25:220–224CrossRefPubMedGoogle Scholar
  3. 3.
    Nicholas JJ (1994) Physical modalities in rheumatological rehabilitation. Arch Phys Med Rehabil 75:994–1001CrossRefPubMedGoogle Scholar
  4. 4.
    Ofman JJ, Maclean CH, Straus WL, Morton SC, Berger ML, Roth EA et al (2002) A meta-analysis of severe upper gastrointestinal complications of nonsteroidal anti-inflammatory drugs. J Rheumatol 29:804–812PubMedGoogle Scholar
  5. 5.
    Bresalier RS, Sandler RS, Quan H, Bolognese JA, Oxenius B, Horgan K et al (2005) Trial investigations: cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med 352:1092–1102CrossRefPubMedGoogle Scholar
  6. 6.
    Kearney PM, Baigent C, Godwin J, Halls H, Emberson JR, Patrono C (2006) Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. BMJ 332:1302–1308CrossRefPubMedGoogle Scholar
  7. 7.
    Zhang W, Jones A, Doherty M (2004) Does paracetamol (acetaminophen) reduce the pain of osteoarthritis?: a meta-analysis of randomised controlled trials. Ann Rheum Dis 63:901–907CrossRefPubMedGoogle Scholar
  8. 8.
    Pincus T, Wang X, Chung C, Sokka T, Koch GG (2005) Patient preference in a crossover clinical trial of patients with osteoarthritis of the knee or hip: face validity of self-report questionnaire ratings. J Rheumatol 32:533–539PubMedGoogle Scholar
  9. 9.
    Verhagen AP, Bierma-Zeinstra SMA, Boers M et al (2007) Balneotherapy for osteoarthritis. Cochrane database of systemic reviews Issue 4. Art. No: CD006864. doi: 10.1002/14651858
  10. 10.
    O’Hare JP, Heywood A, Summerhayes C et al (1985) Observation on the effects of the immersion in bath spa water. Br Med J 291:1747–1751CrossRefGoogle Scholar
  11. 11.
    Weston CFM, O’Hare JP, Evans JM, Corral RJM (1987) Haemodynamic changes in man during immersion in water at different temperatures. Clin Sci 73:613–616PubMedGoogle Scholar
  12. 12.
    Epstein M (1992) Renal effects of head-out water immersion in humans: a 15 year update. Physiol Rev 72:563–621PubMedGoogle Scholar
  13. 13.
    Melzack R, Wall PD (1965) Pain mechanism: a new theory. Science 150:971–979CrossRefPubMedGoogle Scholar
  14. 14.
    Kuczera M, Kokot F (1996) The influence of SPA therapy on endocrine system. Stress reaction hormones. Pol Arch Med Wewn 95:11–20PubMedGoogle Scholar
  15. 15.
    Gur A, Cevik R, Sarac AJ, Colpan L, Em S (2004) Hypothalamic-pituitary-gonadal axis and cortisol in young women with primary fibromyalgia: the potential roles of depression, fatigue, and sleep disturbance in the occurrence of hypocortisolism. Ann Rheum Dis 63:1504–1506CrossRefPubMedGoogle Scholar
  16. 16.
    Laatikainen T, Salminen K, Kohvakka A, Pettersson J (1988) Response of plasma endorphins, prolactin and catecholamines in women to intense heat in a sauna. Eur J Appl Physiol Occup Physiol 57:98–102CrossRefPubMedGoogle Scholar
  17. 17.
    Vescovi PP, Gerra G, Pioli G, Pedrazzoni M, Maninetti L, Passeri M (1990) Circulating opioid peptides during thermal stress. Horm Metab Res 22:44–46CrossRefPubMedGoogle Scholar
  18. 18.
    Kubota K, Kukabayashi H, Tamura K, Kawada E, Tamura J, Shirakura T (1992) A transient rise in plasma b-endorphin after a traditional 47°C hot-spring bath in Kusatsu-spa, Japan. Life Sci 51:1877–1901CrossRefPubMedGoogle Scholar
  19. 19.
    Cozzi F, Lazzarin I, Todesco S, Cima L (1995) Hypotalamic pituary-adrenal axis dysregulation in healthy subjects undergoing mud-bath-applications. Arthritis Rheum 38:724–725CrossRefPubMedGoogle Scholar
  20. 20.
    Ghersetich I, Freedman D, Lotti T (2000) Balneology today. JEADV 14:346–348PubMedGoogle Scholar
  21. 21.
    Berczi I, Chalmers IM, Nagy E, Warrington RJ (1996) The immune effects of neuropeptides. Baillieres Clin Rheumatol 10:227–257CrossRefPubMedGoogle Scholar
  22. 22.
    Guillemin F, Constant F, Collin JF, Boulange M (1994) Short and long-term effect of Spa therapy in chronic low back pain. Br J Rheumatol 33:148–151CrossRefPubMedGoogle Scholar
  23. 23.
    Nguyen M, Revel M, Dougados M (1997) Prolonged effects of 3 weeks therapy in a Spa resort on lumbar spine, knee and hip osteoarthritis: follow up after 6 months. A randomized controlled trial. Br J Rheumatol 36:77–81CrossRefPubMedGoogle Scholar
  24. 24.
    Elkayam O, Ophir J, Brener S, Paran D, Wigler I, Efron D et al (2000) Immediate and delayed effects of treatment at the Dead Sea in patients with psoriasis arthritis. Rheumatol Int 19:77–82CrossRefPubMedGoogle Scholar
  25. 25.
    van Tubergen A, Landewé R, van der Hetijede D, Hidding A, Walter N, Asscher M et al (2001) Combined Spa-Exercise therapy is effective in patients with ankylosing spondylitis: a randomized controlled trial. Arthritis Care Res 45:430–438CrossRefGoogle Scholar
  26. 26.
    Cantarini L, Leo G, Giannitti C, Cevenini G, Barberini P, Fioravanti A (2007) Therapeutic effect of spa therapy and short wave therapy in knee osteoarthritis: a randomized, single blind, controlled trial. Rheumatol Int 27:523–529CrossRefPubMedGoogle Scholar
  27. 27.
    Fioravanti A, Perpignano G, Tirri G, Cardinale G, Giannitti C, Lanza CE et al (2007) Effects of mud-bath treatment on fibromyalgia patients: a randomized clinical trial. Rheumatol Int 27:1157–1161CrossRefPubMedGoogle Scholar
  28. 28.
    Karagülle M, Karagülle MZ, Karagülle O, Dönmez A, Turan M (2007) A 10- day course of spa therapy is beneficial for people with severe knee osteoarthritis. Clin Rheumatol 26:2063–2071CrossRefPubMedGoogle Scholar
  29. 29.
    Harzy T, Ghani N, Akasbi N, Bono W, Nejjari C (2009) Short- and long-term therapeutic effects of thermal mineral waters in knee osteoarthritis: a systematic review of randomized controlled trials. Clin Rheumatol 28:501–507CrossRefPubMedGoogle Scholar
  30. 30.
    Forestier R, Desfour H, Tessier J-M, Françon A, Foote AM, Genty C et al (2009) Spa therapy in the treatment of knee osteoarthritis, a large randomised multicentre trial. Ann Rheum Dis 69:660–665CrossRefPubMedGoogle Scholar
  31. 31.
    Fioravanti A, Iacoponi F, Bellisai B, Cantarini L, Galeazzi M (2010) Short and long-term effect of spa therapy in knee osteoarthritis. Am J Phys Med Rehabil 89:125–132CrossRefPubMedGoogle Scholar
  32. 32.
    Shani J, Barak S, Levi D, Ram M, Schachner ER, Schlesinger T et al (1985) Skin penetration of minerals in psoriatics and guinea pigs bathing in hypertonic salt solutions. Pharmacol Res 17:501–506Google Scholar
  33. 33.
    Beer AM, Junginger HE, Lukanov J, Sagorchev P (2003) Evaluation of the permeation of peat substances through human skin in vitro. Int J Pharm 253:169–175CrossRefPubMedGoogle Scholar
  34. 34.
    Odabasi E, Turan M, Erdem H, Tekbas F (2008) Does mud pack treatment have any clinical effect? A randomized controlled clinical study. J Altern Complement Med 14:559–565CrossRefPubMedGoogle Scholar
  35. 35.
    Sukenik S, Abu-Shakra M, Flusser D (1997) Balneotherapy in autoimmune diseases. Isr J Med Sci 33:258–261PubMedGoogle Scholar
  36. 36.
    Sobieska M, Stratz T, Samborski W, Hrycaj P, Mennet P, Müller W (1993) Interleukin-6 (IL-6) after whole body cryotherapy and local hot mud pack treatment. Eur J Phys Med Rehabil 3:205Google Scholar
  37. 37.
    Olszewski WL, Grzelak I, Ziolkowska A, Engeset A (1989) Effect of local hyperthermia on lymph immune cells and lymphokines of normal human skin. J Surg Oncol 41:109–116CrossRefPubMedGoogle Scholar
  38. 38.
    Schmidt KL, Simon E (2001) Thermotherapy of pain, trauma and inflammatory and degenerative rheumatic diseases. Thermotherapy for Neoplasia, Inflammation and Pain. Springer, Berlin, pp 527–539Google Scholar
  39. 39.
    Lange U, Müller-Ladner U, Schmidt KL (2006) Balneotherapy in rheumatic diseases-an overview of novel and known aspects. Rheumatol Int 26:497–499CrossRefPubMedGoogle Scholar
  40. 40.
    Valitutti S, Costellino F, Musiani P (1990) Effect of sulfurous (thermal) water on T lymphocyte proliferative response. Ann Allergy 65:463–468PubMedGoogle Scholar
  41. 41.
    Smith JB, Knowlton RP, Agarwal SS (1978) Human lymphocyte responses are enhanced by culture at 40°C. J Immunol 121:691–696PubMedGoogle Scholar
  42. 42.
    Ghersetic I, Lotti T (1996) Immunologic aspects: immunology of mineral waters. Clin Dermatol 14:563–566CrossRefGoogle Scholar
  43. 43.
    Tarner IH, Müller-Ladner U, Uhlemann C, Lange U (2009) The effect of mild whole-body hyperthermia on systemic levels of TNF-alpha, IL-1 beta, and IL-6 in patients with ankylosing spondylitis. Clin Rheumatol 28:397–402CrossRefPubMedGoogle Scholar
  44. 44.
    Bellometti S, Galzigna L (1998) Serum levels of a prostaglandin and a leukotriene after termal mud-pack therapy. J Invest Med 46:140–145Google Scholar
  45. 45.
    Ardiç F, Ozgen M, Aybek H, Rota S, Cubukçu G, Gökgöz A (2007) Effect of balneotherapy on serum IL-1, PGE2 and LTB4 levels in fibromyalgia patients. Rheumatol Int 27:441–446CrossRefPubMedGoogle Scholar
  46. 46.
    Cecchettin M, Bellometti S, Lalli A, Galzigna L (1995) Serum interleukin 1 changes in arthrosic patients after mud-pack treatment. Phys Rheab Kur Med 5:92–93CrossRefGoogle Scholar
  47. 47.
    Bellometti S, Cecchettin M, Galzigna L (1997) Mud-pack therapy in osteoarthrosis changes levels of chondrocytes markers. Clin Chim Acta 268:101–106CrossRefPubMedGoogle Scholar
  48. 48.
    Bellometti S, Galzigna L, Richelmi P, Gregotti C, Berté F (2002) Both serum receptors of tumor necrosis factor are influenced by mud pack treatment in osteoarthrotic patients. Int J Tissue React 24:57–64PubMedGoogle Scholar
  49. 49.
    Lohmander LS, Hoermer LA, Lark MV (1993) Metalloproteinases, tissue inhibitor, and proteoglycan fragments in kneesynovial fluid in human osteoarthritis. Arthritis Rheum 36:181–189PubMedGoogle Scholar
  50. 50.
    Malemud CJ, Islam N, Haqqi TM (2003) Pathophysiological mechanisms in osteoarthritis lead to novel therapeutic strategies. Cell Tissue Organs 174:34–348CrossRefGoogle Scholar
  51. 51.
    Bellometti S, Richelmi P, Tassoni T, Bertè F (2005) Production of matrix metalloproteinases and their inhibitors in osteoarthritic patients undergoing mud bath therapy. Int J Clin Pharm Res 25:77–94Google Scholar
  52. 52.
    Trippel SB (1995) Growth factor action on articular cartilage. J Rheumatol 43:129Google Scholar
  53. 53.
    Shehata M, Schwarzmeier JD, Hilgarth M, Demirtas D, Richter D, Hubmann R et al (2006) Effect of combined spa-exercise on circulating TGF-ß1 levels in patients with ankylosing spondylitis. Wien Klin Wochenschr 118:266–272CrossRefPubMedGoogle Scholar
  54. 54.
    Centrella M, Horowitz MC, Wozney JM, McCarthy TL (1994) Transforming growth factor-beta gene family members and bone. Endocr Rev 15:27–39PubMedGoogle Scholar
  55. 55.
    Shehata M, Schwarzmeier JD, Hilgarth M, Hubmann R, Duechler M, Gisslinger H (2004) TGF-beta 1 induces bone marrow reticulin fibrosis in hairy cell leukemia. J Clin Invest 113:676–685PubMedGoogle Scholar
  56. 56.
    Farrell AJ, Blake DR, Palmer RM, Moncada S (1992) Increased concentrations of nitrite in synovial fluid and serum samples suggest increased nitric oxide synthesis in rheumatic diseases. Ann Rheum Dis 51:1219–1222CrossRefPubMedGoogle Scholar
  57. 57.
    Mazzetti I, Grigolo B, Pulsatelli L, Dolzani P, Silvestri T, Roseti L et al (2001) Differential roles of nitric oxide and oxygen radicals in chondrocytes affected by osteoarthritis and rheumatoid arthritis. Clin Science 101:593–599CrossRefGoogle Scholar
  58. 58.
    Braga PC, Sambataro G, Dal Sasso M, Culici M, Alfieri M, Nappi G (2008) Antioxidant effect of sulphurous thermal water on human neutrophil bursts: chemiluminescence evaluation. Respiration 75:193–201CrossRefPubMedGoogle Scholar
  59. 59.
    Grabski M, Wozakowska-Kaplon B, Kedziora J (2004) Hydrogen sulphide water balneum effect on erythrocyte superoxide dismutase activity in patients with rheumatoid arthritis-in vitro study. Przegl Lek 61:1405–1409PubMedGoogle Scholar
  60. 60.
    Eckmekcioglu C, Strauss-Blasche G, Holzer F, Marktl W (2002) Effect of sulfur baths on antioxidative defense systems, peroxide concentrations and lipid levels in patients with degenerative osteoarthritis. Forsch Komplementarmed Klass Naturheilkd 9:216–220CrossRefGoogle Scholar
  61. 61.
    Bender T, Bariska J, Vàghy R, Gomez R, Kovàcs I (2007) Effect of balneotherapy on the antoxidant system—a controlled pilot study. Arch Med Res 38:86–89CrossRefPubMedGoogle Scholar
  62. 62.
    Bellometti S, Poletto M, Gregotti C, Richelmi P, Berte F (2000) Mud bath therapy influences nitric-oxide, myeloperoxidase and glutathione peroxidase serum levels in arthritic patients. Int J Clin Pharmacol Res 20:69–80PubMedGoogle Scholar
  63. 63.
    Fioravanti A, Cantarini L, Bacarelli MR, de Lalla A, Ceccatelli L, Blardi P (2010) Effects of spa therapy on serum leptin and adiponectin levels in patients with knee osteoarthritis. Rheumatol Int [Epub ahead of print]Google Scholar
  64. 64.
    Dumond H, Presle N, Terlain B, Mainard D, Loeuille D, Netter P et al (2003) Evidence for a key role of leptin in osteoarthritis. Arthritis Rheum 48:3118–3129CrossRefPubMedGoogle Scholar
  65. 65.
    Lago R, Gomez R, Otero M, Lago F, Gallego R, Dieguez C et al (2008) A new player in cartilage homeostasis: adiponectin induces nitric oxide synthase type II and pro-inflammatory cytokines in chondrocytes. Osteoarthritis Cartilage 16:1101–1109CrossRefPubMedGoogle Scholar
  66. 66.
    Gomez R, Lago F, Gomez-Reino J, Dieguez C, Gualillo O (2009) Adipokines in the skeleton: influence on cartilage function and joint degenerative diseases. J Mol Endocrinol 43:11–18CrossRefPubMedGoogle Scholar
  67. 67.
    Cozzi F, Carrara M, Sfriso P, Todesco S, Cima L (2004) Anti-inflammatory effect of mud-bath applications on adjuvant arthritis in rats. Clin Exp Rheumatol 22:763–766PubMedGoogle Scholar
  68. 68.
    Britschka ZMN, Teodoro WR, Velosa APP, de Mello SBV (2007) The effect of Brazilian black mud treatment in chronic experimental arthritis. Rheumatol Int 28:39–45CrossRefPubMedGoogle Scholar
  69. 69.
    Mizoguchi T (1970) Effects of thermal spring bath on lipids in serum. Med Balneol Climat 33:115–120Google Scholar
  70. 70.
    Strauss-Blasche G, Eckmekcioglu C, Leibetseder V, Marktl W (2003) Seasonal variation of lipid-lowering effects of complex spa therapy. Forsch Komplementarmed Klass Naturheilkd 10:78–84CrossRefPubMedGoogle Scholar
  71. 71.
    Bostom AG, Selhub J (1999) Homocysteine and arteriosclerosis: subclinical and clinical disease associations. Circulation 99:2361–2363PubMedGoogle Scholar
  72. 72.
    Vasan RS, Beiser A, D’Agostino RB, Levy D, Selhub J, Jacques PF et al (2003) Plasma homocysteine and risk for congestive heart failure in adult without prior myocardial infarction. JAMA 289:1251–1257CrossRefPubMedGoogle Scholar
  73. 73.
    Agullo-Ortuno MT, Albaladejo MD, Parra S, Rodrìguez-Manotas M, Fenollar M, Ruìz-Espejo F et al (2002) Plasmatic homocysteine concentration and its relationship with complications associated to diabetes mellitus. Clin Chim Acta; 326:105–112CrossRefPubMedGoogle Scholar
  74. 74.
    Sun C-F, Haven TR, Wu T-L, Tsao K-C, Wu JT (2002) Serum total homocysteine increases with the rapid proliferation rate of tumor cells and decline upon cell death: a potential new tumor marker. Clin Chim Acta 321:55–62CrossRefPubMedGoogle Scholar
  75. 75.
    Cavalca V, Cighetti G, Bamonti F, Loaldi A, Bortone L, Novembrino C et al (2001) Oxidative stress and homocysteine in coronary artery disease. Clin Chem 471:887–892Google Scholar
  76. 76.
    Leibetseder V, Strauss-Blasche G, Holzer F, Marktl W, Ekmercioglu C (2004) Improving homocysteine levels through balneotherapy: effects of sulphur baths. Clin Chim Acta 343:105–111CrossRefPubMedGoogle Scholar
  77. 77.
    Oláh M, Koncz A, Fehér J, Kálmánczhey J, Oláh C, Balogh S et al (2010) The effect of balneotherapy on C-reactive protein, serum cholesterol, triglyceride, total antioxidant status and HSP-60 levels. Int J Biometeorol 54:249–254CrossRefPubMedGoogle Scholar
  78. 78.
    Turesson C, Jacobsson LTH, Matteson EL (2008) Cardiovascular co-morbidity in rheumatic diseases. Vasc Health Risk Manag 43:605–614Google Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Antonella Fioravanti
    • 1
    Email author
  • Luca Cantarini
    • 1
  • Giacomo Maria Guidelli
    • 1
  • Mauro Galeazzi
    • 1
  1. 1.Rheumatology Unit, Department of Clinical Medicine and ImmunologyUniversity of SienaSienaItaly

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