Skip to main content
SpringerLink
Log in

How to Manage Familial Mediterranean Fever (FMF) Patients in Daily Practice

  • Chapter
Familial Mediterranean Fever

Part of the book series: Rare Diseases of the Immune System ((RDIS,volume 3))

  • 1099 Accesses

Abstract

Since the reports of Goldfinger and Ozkan in 1972, colchicine remains the treatment of choice for FMF [1, 2]. Colchicine is an alkaloid extracted from the bulbs of a plant called Colchicum autumnale (meadow saffron). It was first recommended for the treatment of gout by the Greek physician Alexander of Tralles in the sixth century A.D. [3]. Subsequently, it has been employed for an increasing number of suggested and approved indications including primary biliary cirrhosis (PBC), alcohol-induced hepatitis, psoriasis, Behcet’s disease, Sweet’s syndrome, scleroderma, sarcoidosis, and amyloidosis. Perhaps the most effective results have been obtained in the prophylaxis of familial Mediterranean fever (FMF).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 119.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Golfinger SE. Colchicine for familial Mediterranean fever. N Engl J Med. 1972;287:1302.

    Google Scholar 

  2. Ozkan E, Okur O, Eekmekci A, et al. A new approach to the treatment of periodic fever. Med Bull Istanbul Med Fac. 1972;5:44–9.

    Google Scholar 

  3. Ben-Chetrit E, Levy N. Colchicine: 1998 update. Semin Arthritis Rheum. 1998;28:48–59.

    Article  CAS  PubMed  Google Scholar 

  4. Besis M, Breton-Gorius J. Rapports entre noyau et centrioles dans les granulocytes étalalés. Rúle des microtubules. Nouv Rev Fr Hematol. 1967;7:601–20.

    Google Scholar 

  5. Sackett DL, Varma JK. Molecular mechanism of colchicine action: induced local unfolding of b-tubulin. Biochemistry. 1993;32:13560–5.

    Article  CAS  PubMed  Google Scholar 

  6. Vandcandelaere A, Martin SR, Engelborghs Y. Response of microtubules to the addition of colchicine and tubulin-colchicine: evaluation of models for the interaction of drugs with microtubules. Biochem J. 1997;323:189–96.

    Google Scholar 

  7. Li Z, Davis GS, Mohr C. Inhibition of LPS induced tumor necrosis factor-a production by colchicine and other microtubules disrupting drugs. Immunobiology. 1996;195:624–9.

    Article  CAS  PubMed  Google Scholar 

  8. Ding AH, Porteu F, Sanchez E, Nathan CF. Down-regulation of tumor necrosis factor receptors on macrophages and endothelial cells by microtubule depolarizing agents. J Exp Med. 1990;171:715–7.

    Article  CAS  PubMed  Google Scholar 

  9. Cronstein BN, Molad Y, Reiban J. Colchicine alters the quantitative and qualitative display of selectins on endothelial cells and neutrophils. J Clin Invest. 1995;96:994–1002.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Paya M, Terencio MC, Ferrandiz ML, Alcaraz MJ. Involvement of secretory phospholipase A2 activity in the zymosan air pouch model of inflammation. Br J Pharmacol. 1996;117:1773–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Zurier RB, Hoffstein S, Weissmann G. Mechanisms of lysosomal enzyme release from human leukocytes: I, effect of cyclic nucleotides and colchicine. J Cell Biol. 1973;58:27–41.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Wright DG, Malawista SE. Mobilization and extracellular release of granular enzymes from human leukocytes during phagocytosis: inhibition by colchicine and cortisol but not by salicylates. Arthritis Rheum. 1973;16:749–58.

    Article  CAS  PubMed  Google Scholar 

  13. Ben-Chetrit E, Fischel R, Hinz B, Levy M. The effects of colchicine and hydroxychloroquine on the cyclo-oxygenases COX-1 and COX-2. Rheumatol Int. 2005;25:332–5.

    Article  CAS  PubMed  Google Scholar 

  14. Chappey ON, Niel E, Wautier JL, et al. Colchicine disposition in human leukocytes after single and multiple oral administration. Clin Pharmacol Ther. 1993;54:360–7.

    Article  CAS  PubMed  Google Scholar 

  15. Ertel NH, Wallace SL. Measurement of colchicine in urine and peripheral leukocytes. Clin Res. 1971;19:3480.

    Google Scholar 

  16. Ben-Chetrit E, Levy M. Does the lack of the P-glycoprotein efflux pump in neutrophils explain the efficacy of colchicine in familial Mediterranean fever and other inflammatory diseases? Med Hypotheses. 1998;51(5):377–80.

    Article  CAS  PubMed  Google Scholar 

  17. Klimecki WT, Futscher BW, Grogan TM, Dalton WS. P-glycoprotein expression and function in circulating blood cells from normal volunteers. Blood. 1994;83:2451–587.

    CAS  PubMed  Google Scholar 

  18. Abedat S, Urieli-Shoval S, Shapira E, Calko S, Ben-Chetrit E, Matzner Y. Effect of colchicine and cytokines on MEFV expression and C5a inhibitor activity in human primary fibroblast cultures. Isr Med Assoc J. 2002;4(1):7–12.

    CAS  PubMed  Google Scholar 

  19. Chae JJ, Wood G, Richard K, Jaffe H, Colburn NT, Masters SL, Gumucio DL, Shoham NG, Kastner DL. The familial Mediterranean fever protein, pyrin, is cleaved by caspase-1 and activates NF-kappaB through its N-terminal fragment. Blood. 2008;112:1794–803.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Taskiran EZ, Cetinkaya A, Balci-Peynircioglu B, Akkaya YZ, Yilmaz E. The effect of colchicine on pyrin and pyrin interacting proteins. J Cell Biochem. 2012;113(11):3536–46.

    Article  CAS  PubMed  Google Scholar 

  21. Ben-Chetrit E, Bergmann S, Sood R. Mechanism of the anti-inflammatory effect of colchicine in rheumatic diseases: a possible new outlook through microarray analysis. Rheumatology (Oxford). 2006;45(3):274–82. Epub 2005.

    Article  CAS  Google Scholar 

  22. Misawa T, Takahama M, Kozaki T, Lee H, Zou J, Saitoh T, Akira S. Microtubule-driven spatial arrangement of mitochondria promotes activation of the NLRP3 inflammasome. Nat Immunol. 2013;14:454–60.

    Article  CAS  PubMed  Google Scholar 

  23. Zemer D, Pras M, Sohar E, Modan M, Cabili S, Gafni J. Colchicine in the prevention and treatment of the amyloidosis of familial Mediterranean fever. N Engl J Med. 1986;314(16):1001–5.

    Article  CAS  PubMed  Google Scholar 

  24. Livneh A, Zemer D, Siegal B, Laor A, Sohar E, Pras M. Colchicine prevents kidney transplant amyloidosis in familial Mediterranean fever. Nephron. 1992;60(4):418–22.

    Article  CAS  PubMed  Google Scholar 

  25. Migita K, Uehara R, Nakamura Y, Yasunami M, Tsuchiya-Suzuki A, Yazaki M, et al. Familial Mediterranean fever in Japan. Medicine (Baltimore). 2012;91:337–43.

    Article  Google Scholar 

  26. Hentgen V, Kone-Paut GGI, Livneh A, Padeh S, Rozenbaum M, Amselem S, Gershoni-Baruch R, Touitou I, Ben-Chetrit E. Evidence-based recommendations for the practical management of familial Mediterranean fever. Semin Arthritis Rheum. 2013;43:387–91.

    Article  PubMed  Google Scholar 

  27. Tunca M, Turkish FMF Study Group, et al. Familial Mediterranean fever (FMF) in Turkey: results of a nationwide multicenter study. Medicine (Baltimore). 2005;84:1–11.

    Article  Google Scholar 

  28. Ben-Chetrit E, Levy M. Familial Mediterranean fever. Lancet. 1998;351:659–64.

    Article  CAS  PubMed  Google Scholar 

  29. Lidar M, Kedem R, Langevitz P, Pras M, Livneh A. Intravenous colchicine for treatment of patients with familial Mediterranean fever unresponsive to oral colchicine. J Rheumatol. 2003;30:2620–3.

    CAS  PubMed  Google Scholar 

  30. Tankurt E, Tunca M, Akbaylar H, Gonen O. Resolving familial Mediterranean fever attacks with interferon alpha. Br J Rheumatol. 1996;35:1188–9.

    Article  CAS  PubMed  Google Scholar 

  31. Tunca M, Tankurt E, Akbaylar Akpinar H, Akar S, Hizli N, Gonen O. The efficacy of interferon alpha on colchicine-resistant familial Mediterranean fever attacks: a pilot study. Br J Rheumatol. 1997;36:1005–8.

    Article  CAS  PubMed  Google Scholar 

  32. Calguneri M, Apras S, Ozturk MA, Ertenli I, Kiraz S. The efficacy of the interferon alfa on colchicine resistant familial Mediterranean fever (FMF). Clin Exp Rheumatol. 2002;20:S106. Abstract.

    Google Scholar 

  33. Tunca M, Akar S, Soyturk M, et al. The effect of interferon alpha administration on acute attacks of familial Mediterranean fever, a double blind and placebo controlled trial. Clin Exp Rheumatol. 2004;22 Suppl 34:S37–40.

    CAS  PubMed  Google Scholar 

  34. Seyahi E, Ozdogan H, Masatlioglu S, Yazici H. Successful treatment of familial Mediterranean fever attacks with thalidomide in a colchicine resistant patient. Clin Exp Rheumatol. 2002;20(4 Suppl 26):S43–4.

    CAS  PubMed  Google Scholar 

  35. Drenth JP, Vonk AG, Simon A, et al. Limited efficacy of thalidomide in the treatment of febrile attacks of the hyper IgD and periodic fever syndromes: a double-blind, placebo-controlled trial. J Pharmacol Exp Ther. 2001;298:1221–6.

    CAS  PubMed  Google Scholar 

  36. Erken E, Ozer HT, Bozkurt B, Gunesacar R, Erken EG, Dinkci S. Early suppression of familial Mediterranean fever attacks by single medium dose methyl-prednisolone infusion. Joint Bone Spine. 2008;75:370–2.

    Article  PubMed  Google Scholar 

  37. Amital H, Ben-Chetrit E. Therapeutic approaches to familial Mediterranean fever. What do we know and where are we going to? Clin Exp Rheumatol. 2004;22 Suppl 34:S4–7.

    CAS  PubMed  Google Scholar 

  38. Korkmaz C. Immunosuppressive treatment of AA amyloidosis of familial Mediterranean fever. Clin Exp Rheumatol. 2005;23 Suppl 38:S107–8.

    CAS  PubMed  Google Scholar 

  39. Sayarlioglu H. Successful treatment of nephrotic syndrome due to FMF amyloidosis with azathioprine: report of three Turkish cases. Rheumatol Int. 2006;27(2):197–9.

    Article  PubMed  Google Scholar 

  40. Milledge J, Shaw PJ, Mansour A, Williamson S, Bennetts B, Roscioli T, Curtin J, Christodoulou J. Allogeneic bone marrow transplantation: cure for familial Mediterranean fever. Blood. 2002;100:774–7.

    Article  CAS  PubMed  Google Scholar 

  41. Touitou I, Ben-Chetrit E, Gershoni-Baruch R, et al. Allogenic bone marrow transplantation: not a treatment yet for familial Mediterranean fever. Blood. 2003;102:409.

    Article  CAS  PubMed  Google Scholar 

  42. Taylor EW. Mechanism of colchicine inhibition of mitosis I. Kinetics of inhibition and the binding of H3-colchicine. J Cell Biol. 1965;25(1):145–60.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  43. Merlin HE. Azoospermia caused by colchicine – a case report. Fertil Steril. 1972;23:180–1.

    CAS  PubMed  Google Scholar 

  44. Barsou IS. The effect of colchicine on the spermatogenesis of rabbits. J Pharmacol Exp Ther. 1955;113:319–22.

    Google Scholar 

  45. Cohen MM, Levy M, Eliakim M. A cytogenetic evaluation of long-term colchicine therapy in the treatment of familial Mediterranean fever (FMF). Am J Med Sci. 1977;274:147–52.

    Article  CAS  PubMed  Google Scholar 

  46. Levy M, Yaffe C. Testicular function in patients with familial Mediterranean fever, on long-term colchicine treatment. Fertil Steril. 1978;29:662–8.

    Google Scholar 

  47. Ehrenfeld M, Levy M, Margalioth EJ, Eliakim M. The effects of long-term colchicine therapy on male fertility in patients with familial Mediterranean fever. Andrologia. 1986;13:420–6.

    Google Scholar 

  48. Ben-Chetrit A, Ben-Chetrit E, Nitzan R, Ron M. Colchicine inhibits spermatozoal motility in vitro. Int J Fertil. 1993;38:301–4.

    CAS  Google Scholar 

  49. Bremner WJ, Paulson CA. Colchicine and testicular function in man. N Engl J Med. 1976;294:1384–5.

    Article  CAS  PubMed  Google Scholar 

  50. Sarica K, Suzer O, Gurler A, Baltaci S, Ozdiler E, Dincel C. Urological evaluation of Behcet’s patients and the effect of colchicine on fertility. Eur J Mol. 1995;22:39–42.

    Google Scholar 

  51. Haimov-Kochman R, Prus D, Ben-Chetrit E. Azoospermia due to testicular amyloidosis in a patient with familial Mediterranean fever. Hum Reprod. 2001;16:1218–20.

    Article  CAS  PubMed  Google Scholar 

  52. Zemer TD, Pras M, Shemer Y. Daily prophylactic colchicine in familial Mediterranean fever amyloid and amyloidosis. Proceedings of the 3rd International Symposium on Amyloidosis, Exerpta Medica, Amsterdam-Oxford-Prinston; 1980. p. 580

    Google Scholar 

  53. Ben-Chetrit E, Berkun Y, Ben-Chetrit A. The outcome of pregnancy in the wives of men with familial Mediterranean fever treated with colchicine. Semin Arthritis Rheum. 2004;34:549–52.

    Article  CAS  PubMed  Google Scholar 

  54. Schwartz J. Periodic peritonitis, onset simultaneously with menstruation. Ann Intern Med. 1960;53:407–11.

    Article  CAS  PubMed  Google Scholar 

  55. Golden RL, Weigers EW, Meagher JG. Periodic fever and menses. Am J Obstet Gynecol. 1973;117:855–6.

    CAS  PubMed  Google Scholar 

  56. Milano AM. Familial Mediterranean fever associated with menstruation. Am J Gastroenterol. 1981;76:363–4.

    CAS  PubMed  Google Scholar 

  57. Ben-Chetrit E, Ben-Chetrit A. Familial Mediterranean fever and menstruation. Br J Obstet Gynecol. 2001;108:403–7.

    CAS  Google Scholar 

  58. Koh KK, Bui MN, Mincemoyer R, Cannon RO. Effects of hormone therapy on inflammatory cell adhesion molecules in postmenopausal healthy women. Am J Cardiol. 1997;80:1505–7.

    Article  CAS  PubMed  Google Scholar 

  59. Chaudoreille MM, Peyrot V, Braguer D, Codaccioni F, Crevat A. Qualitative study of the interaction mechanism of estrogenic drugs with tubulin. Biochem Pharmacol. 1991;41:685–93.

    Article  CAS  PubMed  Google Scholar 

  60. Tanchev S, Papov I, Tomov S. A rare combination of pregnancy and periodic disease treated with colchicine. Akush Gynecol Sofiia. 1993;32:41–2.

    CAS  Google Scholar 

  61. Cousin C, Palaric JC, Jacquemand F, Lucas S, Girard JR. Periodic disease and pregnancy. J Gynecol Obstet Biol Reprod Paris. 1991;20:554–61.

    CAS  PubMed  Google Scholar 

  62. Ehrenfeld M, Bzezinski A, Levy M, Eliakim M. Fertility and obstetric history in patients with familial Mediterranean fever on long-term colchicine therapy. Br J Obstet Gynecol. 1987;94:1186–91.

    Article  CAS  Google Scholar 

  63. Ben-Chetrit E, Levy M. Colchicine prophylaxis in familial Mediterranean fever: reappraisal after 15 years. Semin Arthritis Rheum. 1991;20:241–6.

    Article  CAS  PubMed  Google Scholar 

  64. Granat M, Tur Kaspa I, Zylber-Katz E, Schenker JG. Reduction of peritoneal adhesion formation by colchicine: a comparative study in the rat. Fertil Steril. 1983;40:369–72.

    CAS  PubMed  Google Scholar 

  65. Rabinovitch O, Zemer D, Kurkia E, Sohar E, Mashiach S. Colchicine treatment in conception and pregnancy: two hundred and thirty-one pregnancies in patients with familial Mediterranean fever. Am J Reprod Immunol. 1992;28:245–6.

    Article  CAS  PubMed  Google Scholar 

  66. Berkenstadt M, Weisz B, Cuckle H, Di-Castro M, Guetta E, Barkai G. Chromosomal abnormalities and birth defects among couples with colchicine treated familial Mediterranean fever. Am J Obstet Gynecol. 2005;193:1513–6.

    Article  CAS  PubMed  Google Scholar 

  67. Ben-Chetrit E, Ben-Chetrit A, Berkun Y. Pregnancy outcomes in women with familial Mediterranean fever receiving colchicine: is amniocentesis justified? Arthritis Care Res. 2010;62:143–8.

    Article  Google Scholar 

  68. Ofir D, Levy A, Wiznitzer A, Mazor M, Sheiner E. Familial Mediterranean fever during pregnancy: an independent risk factor for preterm delivery. Eur J Obstet Gynecol Reprod Biol. 2008;141:115–8.

    Article  PubMed  Google Scholar 

  69. Diav-Citrin O, Shechtman S, Schwartz V, Avgil-Tsadok M, Finkel-Pekarsky V, Wajnberg R, et al. Pregnancy outcome after in utero exposure to colchicine. Am J Obstet Gynecol. 2010;203:144.e1–6.

    Article  Google Scholar 

  70. Briggs GG, Freeman RK, Yaffe RS. Drugs in pregnancy and lactation. 4th ed. Baltimore: Williams & Wilkins; 1994.

    Google Scholar 

  71. Milunsky JM, Milunsky A. Breast feeding during colchicine therapy for familial Mediterranean fever. J Pediatr. 1991;119:163.

    Article  Google Scholar 

  72. Ben-Chetrit E, Scherrmann JM, Levy M. Colchicine in breast milk of patients with familial Mediterranean fever. Arthritis Rheum. 1996;39:1213–7.

    Article  CAS  PubMed  Google Scholar 

  73. Zemer D, Livneh A, Danon YL, Pras M, Sohar E. Long-term colchicine treatment in children with familial Mediterranean fever. Arthritis Rheum. 1991;34:973–7.

    Article  CAS  PubMed  Google Scholar 

  74. Maged HM, Carroll JE, Khuffash FA, Hijazi Z. Long-term colchicine prophylaxis in children with familial Mediterranean fever (recurrent hereditary polyserositis). J Pediatr. 1990;116:997–9.

    Article  Google Scholar 

  75. Savgan-Gürol E, Kasapçopur Ö, Hatemi S, Ercan O, Çaliskan S, Sever L, Özdogan H, Arisoy N. Growth and IGF-1 levels of children with familial Mediterranean fever on colchicine treatment. Clin Exp Rheumatol. 2001;19 Suppl 24:S72–5.

    PubMed  Google Scholar 

  76. Slopa EG, O’Brien R, Katz M. Effect of colchicine on guinea pig intrinsic factor vitamin B12 receptor. Gastroenterology. 1979;26:309–14.

    Google Scholar 

  77. Fradkin A, Yahav J, Zemer D, Jonas A. Colchicine-induced lactose malabsorption in patients with familial Mediterranean fever. Isr J Med Sci. 1995;31:616–20.

    CAS  PubMed  Google Scholar 

  78. Hart J, Lewin KJ, Peters RS, Scher AD. Effect of long-term colchicine therapy on jejunal mucosa. Dig Dis Sci. 1993;38:2017–21.

    Article  CAS  PubMed  Google Scholar 

  79. Desmond PV, Patwardhan RV, Parker R, Schenker S, Speeg KV. Effect of cimetidine and other antihistaminics on the elimination of aminopyrine phenacetin and caffeine. Life Sci. 1989;26:1261–8.

    Article  Google Scholar 

  80. Terkeltaub RA, Furst DE, DiGiacinto JL, Kook KA, Matthew W. Novel evidence-based colchicine dose-reduction algorithm to predict and prevent colchicine toxicity in the presence of cytochrome P450 3A4/P-glycoprotein inhibitors. Arthritis Rheum. 2011;63:2226–37.

    Article  CAS  PubMed  Google Scholar 

  81. Putterman C, Ben-Chetrit E, Caraco Y, Levy M. Colchicine intoxication clinical pharmacology, risk factors, features and management. Semin Arthritis Rheum. 1991;21:143–55.

    Article  CAS  PubMed  Google Scholar 

  82. Macleod G, Phillips L. Hypersensitivity to colchicine. Ann Rheum Bis. 1947;6:224–9.

    Article  Google Scholar 

  83. Jarevic D, Park J, Steward MJ. Estimation of colchicine in a poisoned patient by using high performance liquid chromatography. Clin Toxicol. 1979;14:375–81.

    Article  Google Scholar 

  84. Nadius RB, Rodvien R, Mielke CH. Colchicine toxicity: a multisystem disease. Arch Intern Med. 1977;127:394–6.

    Google Scholar 

  85. Baud FJ, Sabourand A, Vicente E, Taboulet P, Lang J, Bismuth C. Treatment of severe colchicine overdose with colchicine specific fab fragments. N Engl J Med. 1995;332:642–5.

    Article  CAS  PubMed  Google Scholar 

  86. Blankestijn PJ, Vos FP. High flux dialysis membranes improve lipid profile in chronic hemodialysis patients. J Am Soc Nephrol. 1995;5:1703–7.

    CAS  PubMed  Google Scholar 

  87. Ben-Chetrit E, Backenroth R, Levy M. Colchicine clearance by high-flux polysulfone dialyzers. Arthritis Rheum. 1998;41:749–50.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Rheumatology Unit, Hadassah Hebrew University Medical Center, Ein Kerem, Jerusalem, 91120, Israel

    Eldad Ben-Chetrit MD

Authors
  1. Eldad Ben-Chetrit MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eldad Ben-Chetrit MD .

Editor information

Editors and Affiliations

  1. II Paediatric Unit-Rheumatology, G. Gaslini Institute, Genova, Genova, Italy

    Marco Gattorno

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Ben-Chetrit, E. (2015). How to Manage Familial Mediterranean Fever (FMF) Patients in Daily Practice. In: Gattorno, M. (eds) Familial Mediterranean Fever. Rare Diseases of the Immune System, vol 3. Springer, Cham. https://doi.org/10.1007/978-3-319-14615-7_8

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-14615-7_8

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-14614-0

  • Online ISBN: 978-3-319-14615-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation