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Etanercept plus colchicine treatment in a child with tumour necrosis factor receptor-associated periodic syndrome abolishes auto-inflammatory episodes without normalising the subclinical acute phase response

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We investigated the cause of hereditary periodic fever syndrome in a Spanish child with recurrent long episodes of fever, migratory skin rash, myalgia, arthralgia, conjunctivitis and abdominal pain. Infectious and autoimmune causes were ruled out. No familial history was reported. Analysis of the tumour necrosis factor receptor superfamily 1A ( TNFRSF1A) gene identified a missense mutation (G36E) on exon 3. The absence of this variant in the patient’s parents and in controls identified it as a de novo disease-associated mutation. Clinical symptoms disappeared with administration of etanercept; however, levels of acute-phase reactants remained increased and could not be stabilised by the addition of colchicine. We believe that this patient gained some symptomatic relief with etanercept therapy, although not enough to completely avoid the risk of amyloidosis. Thus it is debatable whether etanercept alone or combined with other drugs, is the treatment of choice for patients with tumour necrosis factor receptor-associated periodic syndrome. Conclusion:Since there is variability in treatment responses among different patients with tumour necrosis factor receptor-associated periodic syndrome, we suggest that a systematic evaluation of acute-phase reactants, especially SAA-1, could be useful in maintaining or modifying a given therapeutic approach in these patients.

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familial Mediterranean fever


hyper-IgD and periodic fever syndrome


hereditary periodic fever syndromes


Muckle-Wells syndrome

TNF α :

tumour necrosis factor α


tumour necrosis factor receptor 1


tumour necrosis factor receptor-associated periodic syndrome


  1. Aganna E, Hammond L, Hawkins PN, Aldea A, McKee SA, van Amstel HK, Mischung C, Kusuhara K, Saulsbury FT, Lachmann HJ, Bybee A, McDermott EM, La Regina M, Arostegui JI, Campistol JM, Worthington S, High KP, Molloy MG, Baker N, Bidwell JL, Castaner JL, Whiteford ML, Janssens-Korpola PL, Manna R, Powell RJ, Woo P, Solis P, Minden K, Frenkel J, Yague J, Mirakian RM, Hitman GA, McDermott MF (2003) Heterogeneity among patients with tumor necrosis factor receptor-associated periodic syndrome (TRAPS) phenotypes. Arthritis Rheum 48: 2632–2644

    Article  CAS  Google Scholar 

  2. Aksentijevich I, Galon J, Soares M, Mansfield E, Hull K, Oh HH, Goldbach-Mansky R, Dean J, Athreya B, Reginato AJ, Henrickson M, Pons-Estel B, O’Shea JJ, Kastner DL (2001) The tumour-necrosis-factor receptor-associated periodic syndrome: new mutations in TNFRSF1A, ancestrals origins, genotype-phenotype studies, and evidence for further genetic heterogeneity of periodic fevers. Am J Hum Genet 69: 301–314

    Article  CAS  Google Scholar 

  3. Dode C, Papo T, Fieschi C, Pecheux C, Dion E, Picard F, Godeau P, Bienvenu J, Piette JC, Delpech M, Grateau G (2000) A novel missensse mutation (C30S) in the gene encoding tumor necrosis factor receptor 1 linked to autosomal-dominant recurrent fever with localized myositis in a French family. Arthritis Rheum 43: 1535–1542

    Article  CAS  Google Scholar 

  4. Drewe E, McDermott EM, Powell PT, Isaacs JD, Powell RJ (2003) Prospective study of anti-tumour necrosis factor receptor superfamily 1B fusion protein, and case study of anti-tumour necrosis factor receptor superfamily 1A fusion protein, in tumour necrosis factor receptor associated periodic syndrome (TRAPS): clinical and laboratory findings in a series of seven patients. Rheumatology 42: 235–239

    Article  CAS  Google Scholar 

  5. Drewe E, Huggins ML, Morgan AG, Cassidy MJD, Powell RJ (2004) Treatment of renal amyloidosis with etanercept in tumor necrosis factor receptor-associated periodic syndrome. Rheumatology. Advance online publication August 17, 2004 (doi 10.1093/rheumatology/keh357)

  6. Gillmore JD, Lovat LB, Persey MR, Pepys MB, Hawkins PN (2001) Amyloid load and clinical outcome in AA amyloidosis in relation to circulating concentration of serum amyloid A protein. Lancet 358: 24–29

    Article  CAS  Google Scholar 

  7. Gomez-Reino JJ, Carmona L, Valverde VR, Mola EM, Montero MD, BIOBADASER Group (2003) Treatment of rheumatoid arthritis with tumor necrosis factor inhibitors may predispose to significant increase in tuberculosis risk: a multicenter active-surveillance report. Arthritis Rheum 48: 2122–2127

    Article  CAS  Google Scholar 

  8. Hull KM, Drewe E, Aksentijevich I, Singh HK, Wong K, McDermott EM, Dean J, Powell RJ, Kastner DL (2002) The TNF receptor-associated periodic syndrome (TRAPS). Emerging concepts of an autoinflammatory disorder. Medicine 81: 349–368

    Article  CAS  Google Scholar 

  9. Hull KM, Shoham N, Chae JJ, Aksentijevich I, Kastner DL (2003) The expanding spectrum of systemic autoinflammatory disorders and their rheumatic manifestations. Curr Opin Rheumatol 15: 61–69

    Article  CAS  Google Scholar 

  10. Kwon HJ, Coté TR, Cuffe MS, Kramer JM, Braun MM (2003) Case reports of heart failure after therapy with a tumor necrosis factor antagonist. Ann Intern Med 138: 807–811

    Article  Google Scholar 

  11. McDermott MF, Aksentijevich I, Galon J, McDermott EM, Ogunkolade BW, Centola M, Mansfield E, Gadina M, Karenko L, Pettersson T, McCarthy J, Frucht DM, Aringer M, Torosyan Y, Teppo AM, Wilson M, Karaarslan HM, Wan Y, Todd I, Wood G, Schlimgen R, Kumarajeewa TR, Cooper SM, Vella JP, Kastner DL (1999) Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes. Cell 97: 133–44

    Article  CAS  Google Scholar 

  12. Sarrauste de Menthiere C, Terriere S, Pugnere D, Ruiz M, Demaille J, Touitou I (2003) INFEVERS: the registry for FMF and hereditary inflammatory disorders mutations. Nucleic Acids Res 31: 282–285

    Article  Google Scholar 

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We wish to thank the patient and his family for their participation, Dr L. Alvarez and Dr. M. Elena for technical assistance in the SAA-1 protein quantification, and Mike Maudsley for assistance in manuscript preparation. This study was supported by grant 003110 from the “MARATO TV3” sponsor.

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Correspondence to Juan I. Aróstegui.

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Both J. I. Aróstegui and P. Solís contributed equally to this work.

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Aróstegui, J.I., Solís, P., Aldea, A. et al. Etanercept plus colchicine treatment in a child with tumour necrosis factor receptor-associated periodic syndrome abolishes auto-inflammatory episodes without normalising the subclinical acute phase response. Eur J Pediatr 164, 13–16 (2005).

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