Correspondence

Treatment of the Nephrotic Syndrome with Etanercept in Patients with the Tumor Necrosis Factor Receptor–Associated Periodic Syndrome

N Engl J Med 2000; 343:1044-1045October 5, 2000

Article

To the Editor:

The tumor necrosis factor (TNF) receptor–associated periodic syndrome is a dominantly inherited, chronic inflammatory condition characterized by lifelong febrile attacks of abdominal and musculoskeletal pain associated with skin lesions. The attacks vary in severity and in frequency, usually last from 3 to 21 days, and respond to high-dose corticosteroids. Soluble TNF receptors can inhibit TNF activity by binding and preventing the interaction of TNF-α (TNFSF2) with its cell-surface receptor. Recombinant human TNF receptor (TNFRSF1B) (p75):Fc fusion protein (etanercept) inhibits the activity of TNF in vitro and reduces inflammation in animal models.1

We evaluated a woman with the TNF receptor–associated periodic syndrome due to a C33Y mutation in TNF receptor 1 (TNFRSF1A), who had the nephrotic syndrome in association with amyloidosis.2 The nephrotic syndrome improved rapidly during treatment with etanercept.

The woman was 25 years old and of Irish–Scottish descent. She had had recurrent attacks of fever, abdominal pain, and vomiting since 18 months of age, which had required intermittent courses of prednisolone (10 to 30 mg daily). In May 1999, she presented with peripheral edema of 10 days' duration and reported an increased frequency of inflammatory attacks during the previous 6 months.

The patient had positive results of radionuclide scanning with serum amyloid P, with abnormal uptake in the liver, spleen, and kidneys. A scan obtained in 1996 had shown no abnormalities. Serum amyloid P binds specifically to amyloid fibrils; a radionuclide scan with serum amyloid P is sensitive and specific for the detection of amyloid.3 The patient's father had had both positive findings on scanning with serum amyloid P and reactive amyloid on renal biopsy and had subsequently required renal transplantation. We did not perform a renal biopsy in our patient, in view of the increased risk of bleeding in patients with amyloidosis related to amyloid deposition in the walls of blood vessels.

In October 1999, treatment was started with twice-weekly subcutaneous injections of 25 mg of etanercept. The results are shown in Table 1Table 1Effect of Etanercept Treatment in a Woman with the Nephrotic Syndrome and the Tumor Necrosis Factor Receptor–Associated Periodic Syndrome.. The initial reduction in urinary protein reflects the reduction in the serum albumin concentration before treatment began. The rapid improvement in the nephrotic syndrome was unexpected. At seven months, the patient was still receiving twice-weekly treatment with etanercept and did not require diuretic therapy. A recent scan with serum amyloid P showed substantial regression of her amyloidosis. In addition, inflammatory attacks have become less frequent.

TNF-α stimulates the production of serum amyloid A by hepatocytes. In addition, TNF-α has been implicated in the pathogenesis of the nephrotic syndrome. The effects of TNF-α in the type of situation we describe may include glomerular inflammation4 and impairment of the glomerular barrier.5

Elizabeth Drewe, M.B., B.S.
Elizabeth M. McDermott, M.B., B.S., D.M.
Richard J. Powell, M.B., B.S., D.M.
Queens Medical Centre, Nottingham NG7 2UH, United Kingdom

5 References

1. 1

   Wooley PH, Dutcher J, Widmer MB, Gillis S. Influence of a recombinant human soluble tumor necrosis factor receptor FC fusion protein on type II collagen-induced arthritis in mice. J Immunol 1993;151:6602-6607
   Web of Science | Medline

2. 2

   McDermott MF, Aksentijevich I, Galon J, et al. Germline mutations in the extracellular domains of the 55kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes. Cell 1999;97:133-144
   CrossRef | Web of Science | Medline

3. 3

   Hawkins P, Lavender JP, Pepys MB. Evaluation of systemic amyloidosis by scintigraphy with ¹²³I-labeled serum amyloid P component. N Engl J Med 1990;323:508-513
   Full Text | Web of Science | Medline

4. 4

   Pai R, Bassa B, Kirschenbaum MA, Kamanna VS. TNFα stimulates monocyte adhesion to glomerular mesangial cells: the role of intercellular adhesion molecule-1 gene expression and protein kinases. J Immunol 1996;156:2571-2579
   Web of Science | Medline

5. 5

   McCarthy ET, Sharma R, Sharma M, et al. TNFα increases albumin permeability of isolated rat glomeruli through the generation of superoxide. J Am Soc Nephrol 1998;9:433-438
   Web of Science | Medline

Citing Articles (40)

Citing Articles

1. 1

   Shabina Habibi, Athimalaipet V Ramanan. (2012) Review of biologics in children with rheumatic diseases. International Journal of Clinical Rheumatology 7:1, 81-93
   CrossRef

2. 2

   Lorenzo Cavagna, Vincenzo Sepe, Francesca Bobbio-Pallavicini, Filippo Mangione, Roberto Caporali, Carlomaurizio Montecucco. (2011) Rheumatoid arthritis and renal light-chain deposition disease: long-term effectiveness of TNF-α blockade with etanercept. International Urology and Nephrology 43:3, 909-912
   CrossRef

3. 3

   J. Schedel, B. Bach, J.B. Kümmerle-Deschner, I. Kötter. (2011) Autoinflammatorische Syndrome/Fiebersyndrome. Der Hautarzt 62:5, 389-402
   CrossRef

4. 4

   Gilles Grateau, Mehmet Tuncay Duruöz. (2010) Autoinflammatory conditions: when to suspect? How to treat?. Best Practice & Research Clinical Rheumatology 24:3, 401-411
   CrossRef

5. 5

   Petra Lehmann, Bernd Salzberger, Peter Haerle, Ivona Aksentijevich, Daniel Kastner, Juergen Schoelmerich, Stephanie Rosenfeld, Ulf Mueller-Ladner. (2010) Variable intrafamilial expressivity of the rare tumor necrosis factor-receptor associated periodic syndrome-associated mutation I170N that affects the TNFR1A cleavage site. Modern Rheumatology 20:3, 311-315
   CrossRef

6. 6

   Tom Pettersson, Yrjö T. Konttinen. (2010) Amyloidosis—Recent Developments. Seminars in Arthritis and Rheumatism 39:5, 356-368
   CrossRef

7. 7

   Zsuzsanna H. McMahan, Joseph L. Sailors, Robert Toto, Nancy J. Olsen. (2010) Systemic Amyloidosis Presenting as Chronic Diarrhea in a Patient With Ankylosing Spondylitis. JCR: Journal of Clinical Rheumatology 16:1, 22-25
   CrossRef

8. 8

   S. Lionaki, K. Siamopoulos, I. Theodorou, E. Papadimitraki, G. Bertsias, D. Boumpas, J. Boletis. (2009) Inhibition of tumour necrosis factor alpha in idiopathic membranous nephropathy: a pilot study. Nephrology Dialysis Transplantation 24:7, 2144-2150
   CrossRef

9. 9

   P. Lamprecht, W.L. Gross. (2009) Autoinflammatorische Syndrome. Der Internist 50:6, 676-684
   CrossRef

10. 10

    S. Leroy, V. Guigonis, D. Bruckner, V. Emal-Aglae, G. Deschênes, A. Bensman, T. Ulinski. (2009) Successful Anti-TNFα Treatment in a Child with Posttransplant Recurrent Focal Segmental Glomerulosclerosis. American Journal of Transplantation 9:4, 858-861
    CrossRef

11. 11

    I. Kötter, J. Schedel, J.B. Kümmerle-Deschner. (2009) Periodische Fiebersyndrome/autoinflammatorische Syndrome. Zeitschrift für Rheumatologie 68:2, 137-149
    CrossRef

12. 12

    Evelien J. Bodar, Joost P. H. Drenth, Jos W. M. van der Meer, Anna Simon. (2009) Dysregulation of innate immunity: hereditary periodic fever syndromes. British Journal of Haematology 144:3, 279-302
    CrossRef

13. 13

    T Pettersson, YT Konttinen, CPJ Maury. (2008) Treatment strategies for amyloid A amyloidosis. Expert Opinion on Pharmacotherapy 9:12, 2117-2128
    CrossRef

14. 14

    C. Masson, B. Bouvard, M. Audran. (2008) Sndromes autoinflamatorios. EMC - Aparato Locomotor 41:2, 1-11
    CrossRef

15. 15

    Senol Kobak, Fahrettin Oksel, Yasemin Kabasakal, Eker Doganavsargil. (2007) Ankylosing spondylitis-related secondary amyloidosis responded well to etanercept: a report of three patients. Clinical Rheumatology 26:12, 2191-2194
    CrossRef

16. 16

    Nobuo KANAZAWA, Fukumi FURUKAWA. (2007) Autoinflammatory syndromes with a dermatological perspective. The Journal of Dermatology 34:9, 601-618
    CrossRef

17. 17

    Juan I. Aróstegui, Jordi Yagüe. (2007) Enfermedades autoinflamatorias sistémicas hereditarias. Síndromes hereditarios de fiebre periódica. Medicina Clínica 129:7, 267-277
    CrossRef

18. 18

    Leigh D. Church, Sarah M. Churchman, Philip N. Hawkins, Michael F. McDermott. (2006) Hereditary auto-inflammatory disorders and biologics. Springer Seminars in Immunopathology 27:4, 494-508
    CrossRef

19. 19

    Silvia Stojanov, Daniel L Kastner. (2005) Familial autoinflammatory diseases: genetics, pathogenesis and treatment. Current Opinion in Rheumatology 17:5, 586-599
    CrossRef

20. 20

    David Raveh, Ovadia Shemesh, Yaakov Jack Ashkenazi, Robert Winkler, Vivian Barak. (2004) Tumor necrosis factor-? blocking agent as a treatment for nephrotic syndrome. Pediatric Nephrology 19:11, 1281-1284
    CrossRef

21. 21

    Charles Masson, Virginie Simon, Emmanuel Hoppé, Paolo Insalaco, Idrissa Cissé, Maurice Audran. (2004) Tumor necrosis factor receptor-associated periodic syndrome (TRAPS): definition, semiology, prognosis, pathogenesis, treatment, and place relative to other periodic joint diseases. Joint Bone Spine 71:4, 284-290
    CrossRef

22. 22

    Samy Metyas, Daniel G. Arkfeld, Deborah M. Forrester, Glenn R. Ehresmann. (2004) Infliximab Treatment of Familial Mediterranean Fever and Its Effect on Secondary AA Amyloidosis. JCR: Journal of Clinical Rheumatology 10:3, 134-137
    CrossRef

23. 23

    Anna Aldea, Josep M. Campistol, Juan I. Arostegui, Josefa Rius, Montserrat Maso, Jordi Vives, Jordi Yage. (2004) A severe autosomal-dominant periodic inflammatory disorder with renal AA amyloidosis and colchicine resistance associated to theMEFV H478Y variant in a Spanish kindred: An unusual familial Mediterranean fever phenotype or anotherMEFV-associated periodic inflammatory disorder?. American Journal of Medical Genetics 124A:1, 67-73
    CrossRef

24. 24

    Gilles Grateau. (2003) Musculoskeletal disorders in secondary amyloidosis and hereditary fevers. Best Practice & Research Clinical Rheumatology 17:6, 929-944
    CrossRef

25. 25

    V Hentgen, B Granel, C Dodé, L Cuisset, M Delpech, G Grateau. (2003) Le syndrome de fièvre héréditaire lié à un dysfonctionnement du récepteur du TNF ou Traps. La Revue de Médecine Interne 24:12, 781-785
    CrossRef

26. 26

    C. P. J. Maury, M. Liljestrm, K. Laiho, S. Tiitinen, K. Kaarela, M. Hurme. (2003) Tumor necrosis factor ?, its soluble receptor I, and -308 gene promoter polymorphism in patients with rheumatoid arthritis with or without amyloidosis: Implications for the pathogenesis of nephropathy and anemia of chronic disease in reactive amyloidosis. Arthritis & Rheumatism 48:11, 3068-3076
    CrossRef

27. 27

    Merlini, Giampaolo, Bellotti, Vittorio, . (2003) Molecular Mechanisms of Amyloidosis. New England Journal of Medicine 349:6, 583-596
    Full Text

28. 28

    Jacques-Eric Gottenberg, Florence Merle-Vincent, Fabrice Bentaberry, Yannick Allanore, Francis Berenbaum, Bruno Fautrel, Bernard Combe, Antoine Durbach, Jean Sibilia, Maxime Dougados, Xavier Mariette, . (2003) Anti-tumor necrosis factor ? therapy in fifteen patients with AA amyloidosis secondary to inflammatory arthritides: A followup report of tolerability and efficacy. Arthritis & Rheumatism 48:7, 2019-2024
    CrossRef

29. 29

    D. C. Knockaert, S. Vanderschueren, D. Blockmans. (2003) Fever of unknown origin in adults: 40 years on. Journal of Internal Medicine 253:3, 263-275
    CrossRef

30. 30

    Keith M. Hull, Nitza Shoham, Jae Jin Chae, Ivona Aksentijevich, Daniel L. Kastner. (2003) The expanding spectrum of systemic autoinflammatory disorders and their rheumatic manifestations. Current Opinion in Rheumatology 15:1, 61-69
    CrossRef

31. 31

    P. D. ARKWRIGHT, M. F. MCDERMOTT, S. M. HOUTEN, J. FRENKEL, H. R. WATERHAM, E. AGANNA, L. J. HAMMOND, R. M. MIRAKIAN, P. I. TOMLIN, P. I. VIJAYDURAI, A. J. CANT. (2002) Hyper IgD syndrome (HIDS) associated with in vitro evidence of defective monocyte TNFRSF1A shedding and partial response to TNF receptor blockade with etanercept. Clinical and Experimental Immunology 130:3, 484-488
    CrossRef

32. 32

    Michael F McDermott. (2002) Genetic clues to understanding periodic fevers, and possible therapies. Trends in Molecular Medicine 8:12, 550-554
    CrossRef

33. 33

    Ori Elkayam, Philip N. Hawkins, Helen Lachmann, Michael Yaron, Dan Caspi. (2002) Rapid and complete resolution of proteinuria due to renal amyloidosis in a patient with rheumatoid arthritis treated with infliximab. Arthritis & Rheumatism 46:10, 2571-2573
    CrossRef

34. 34

    KEITH M. HULL, ELIZABETH DREWE, IVONA AKSENTIJEVICH, HARJOT K. SINGH, KONDI WONG, ELIZABETH M. MCDERMOTT, JANE DEAN, RICHARD J. POWELL, DANIEL L. KASTNER. (2002) The TNF Receptor-Associated Periodic Syndrome (TRAPS). Medicine 81:5, 349-368
    CrossRef

35. 35

    Joost Frenkel, Wietse Kuis. (2002) Overt and occult rheumatic diseases: the child with chronic fever. Best Practice & Research Clinical Rheumatology 16:3, 443-469
    CrossRef

36. 36

    Apostolia-Maria Tsimberidou, Francis J Giles. (2002) TNF-α targeted therapeutic approaches in patients with hematologic malignancies. Expert Review of Anticancer Therapy 2:3, 277-286
    CrossRef

37. 37

    Enyu Imai, Yoshitaka Isaka. (2002) Targeting growth factors to the kidney: myth or reality?. Current Opinion in Nephrology and Hypertension 11:1, 49-57
    CrossRef

38. 38

    Drenth, Joost P.H., van der Meer, Jos W.M., . (2001) Hereditary Periodic Fever. New England Journal of Medicine 345:24, 1748-1757
    Full Text

39. 39

    (2001) Cytokine signalling and disease. Expert Opinion on Therapeutic Targets 5:6, 641-653
    CrossRef

40. 40

    Elizabeth Drewe, Richard J Powell. (2001) Etanercept AL amyloidosis. The Lancet 358:9283, 761
    CrossRef