Skip to main content

Advertisement

Log in

Interferon-alpha-associated presumed ocular sarcoidosis

  • Inflammatory Disorders
  • Published:
Graefe's Archive for Clinical and Experimental Ophthalmology Aims and scope Submit manuscript

Abstract

Background

Interferon alpha, used in the treatment of different viral, autoimmune and malignant diseases, is known to induce a variety of side effects. Recently, induction of sarcoidosis during interferon therapy has been reported. We analyzed patients for uveitis, possibly induced by interferon alpha.

Methods

We report on three patients who had developed typical signs of ocular sarcoidosis under treatment with interferon alpha for chronic hepatitis C virus infection. In two patients, conventional interferon alpha was used and in another one, pegylated interferon alpha-2b. All patients additionally received ribavirin.

Results

In all three cases, panuveitis was diagnosed. The mean duration of interferon treatment before development of uveitis was 10 months. Clinically, all patients demonstrated granulomatous panuveitis with choroidal granulomas of various sizes. In one case, the uveitis developed together with renal failure, fever and malaise. In this patient, an elevated ACE level was detected. In another patient, the diagnosis of sarcoid induced uveitis was confirmed by positive chest CT scan. The intraocular inflammation was managed with a reduction of the interferon dosage. The therapy with ribavirin was not changed. All patients received topical steroids. Systemic steroids were applied only in the case with systemic disease manifestations.

Conclusions

Uveitis can be a sign of sarcoidosis induced by interferon alpha. Further studies are required to support the observation that with early diagnosis the prognosis of uveitis seems to be good.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Abdi EA, Nguyen GK, Ludwig RN, Dickout WJ (1987) Pulmonary sarcoidosis following interferon therapy for advanced renal cell carcinoma. Cancer 59:896–900. doi:10.1002/1097-0142(19870301)59:5<896::AID-CNCR2820590507>3.0.CO;2-4

    Article  PubMed  CAS  Google Scholar 

  2. Alazemi S, Campos MA (2006) Interferon-induced sarcoidosis. Int J Clin Pract 60:201–211, doi:10.1111/j.1742–1241.2005.00651.x

    Article  PubMed  CAS  Google Scholar 

  3. Arimura K, Arima N, Ohtsubo H, Matsushita K, Kukita T, Ayukawa T, Kuroki T, Tei C (2004) Severe autoimmune thrombocytopenic purpura during interferon-alpha therapy for chronic myelogenous leukemia. Acta Haematol 112:217–218, doi:10.1159/000081276

    Article  PubMed  CAS  Google Scholar 

  4. Barnes B, Lubyova B, Pitha PM (2002) On the role of IFN in host defense. J Interferon Cytokine Res 22:59–71, doi:10.1089/107999002753452665

    Article  PubMed  CAS  Google Scholar 

  5. Baron S, Tyring SK, Fleischmann WR Jr, Coppenhaver DH, Niesel DW, Klimpel GR, Stanton GJ, Hughes TK (1991) The interferons. Mechanisms of action and clinical applications. JAMA 266:1375–1383, doi:10.1001/jama.266.10.1375

    Article  PubMed  CAS  Google Scholar 

  6. Billiau A, Dijkmans R (1990) Interferon-gamma: mechanism of action and therapeutic potential. Biochem Pharmacol 40:1433–1439, doi:10.1016/0006-2952(90)90437-P

    Article  PubMed  CAS  Google Scholar 

  7. Bodaghi B, Gendron G, Wechsler B, Terrada C, Cassoux N, du Huong LT, Lemaitre C, Fradeau C, LeHoang P, Piette JC (2007) Efficacy of interferon alpha in the treatment of refractory and sight-threatening uveitis: a retrospective monocentric study of 45 patients. Br J Ophthalmol 91:335–339, doi:10.1136/bjo.2006.101550

    Article  PubMed  Google Scholar 

  8. Butnor KJ (2005) Pulmonary sarcoidosis induced by interferon-alpha therapy. Am J Surg Pathol 29:976–979, doi:10.1097/01.pas.0000160442.23523.0a

    Article  PubMed  Google Scholar 

  9. Cacoub P, Sbai A, Frances C, Genesti C, Hausfater P, Piette JC (2000) Systemic sarcoidosis during interferon-alpha therapy for chronic hepatitis C virus infection. Gastroenterol Clin Biol 24:364–366

    PubMed  CAS  Google Scholar 

  10. Chakrabarti D, Hultgren B, Stewart TA (1996) IFN-alpha induces autoimmune T cells through the induction of intracellular adhesion molecule-1 and B7.2. J Immunol 157:522–528

    PubMed  CAS  Google Scholar 

  11. Conlon KC, Urba WJ, Smith JW, Steis RG, Congo DL, Clark JW (1990) Exacerbation of symptoms of autoimmune disease in patients receiving alpha-interferon therapy. Cancer 65:2237–2242, doi:10.1002/1097-0142(19900515)65:10<2237::AID-CNCR2820651013>3.0.CO;2-5

    Article  PubMed  CAS  Google Scholar 

  12. Dean GE, Spears L, Ferrell BR, Quan WD, Groshon S, Mitchell MS (1995) Fatigue in patients with cancer receiving interferon alpha. Cancer Pract 3:164–172

    PubMed  CAS  Google Scholar 

  13. Deuter CM, Kötter I, Günaydin I, Zierhut M, Stübiger N (2003) Behcet’s disease: visual acuity after 5 years in patients with alpha-interferon treatment. Adv Exp Mol Biol 528:525–528, doi:10.1007/0-306-48382-3_105

    Article  CAS  Google Scholar 

  14. Fattovich G, Giustina G, Favarato S, Ruol A (1996) A survey of adverse events in 11,241 patints with chrinic viral hepatitis treated with alpha interferon. J Hepatol 24:38–47, doi:10.1016/S0168-8278(96)80184-X

    Article  PubMed  CAS  Google Scholar 

  15. Gidlund M, Orn A, Wigzell H, Senik A, Gresser I (1978) Enhanced NK cell activity in mice injected with interferon and interferon inducers. Nature 273:759–761, doi:10.1038/273759a0

    Article  PubMed  CAS  Google Scholar 

  16. Guyer DR, Tiedeman J, Yannuzzi LE, Slakter JS, Parke D, Kelly J, Tang RA, Marmor M, Abraham G, Miller JW (1993) Interferon associated retinopathy. Arch Ophthalmol 111:350–356

    PubMed  CAS  Google Scholar 

  17. Hayasaka S, Nagaki Y, Matsumoto M, Sato S (1998) Interferon associated retinopathy. Br J Ophthalmol 82:323–325

    Article  PubMed  CAS  Google Scholar 

  18. Hermann P, Rubio M, Nakajima T, Delespesse G, Sarfati M (1998) IFN-alpha priming of human monocytes dufferentially regulates gram-positive and gram-negative bacteria-induced IL-10 release and selectively enhances IL-12p70, CD80 and MHC class I expression. J Immunol 161:2011–2018

    PubMed  CAS  Google Scholar 

  19. Hirano A, kataoka M, Nakata Y, Takeda K, Kamao T, Hiramatsu J, Kimura G, Tanimoto Y, Kanehiro A, Tanimoto M (2005) Sarcoidosis occurring after interferon-alpha therapy for chronic hepatitis C: report of two cases. Respirology 10:529–534, doi:10.1111/j.1440-1843.2005.00745.x

    Article  PubMed  Google Scholar 

  20. Hunninghake GW, Costabel U, Ando M, Baughman R, Cordier JF, du Bois R, Eklund A, Kitaichi M, Lynch J, Rizzato G, Rose C, Selroos O, Semenzato G, Sharma OP (1999) Statement of sarcoidosis. Am J Respir Crit Care Med 160:736–755

    Google Scholar 

  21. Jonasch E, Haluska FG (2001) Interferon in oncological practice: review of interferon biology, clinical applications and toxicities. Oncologist 6:34–55, doi:10.1634/theoncologist.6-1-34

    Article  PubMed  CAS  Google Scholar 

  22. Kasahara A, Hiraide A, Tomita N, Iwahashi H, Imagawa A, Ohguro N, Yamamoto S, Mita E, Hayashi N (2004) Vogt-Koyanagi-Harada disease occurring during interferon alpha therapy for chronic hepatitis C. J Gastroenterol 39:1106–1109, doi:10.1007/s00535-004-1452-4

    Article  PubMed  Google Scholar 

  23. Krown SE, Burk MW, Kirkwood JM, Kerr D, Morton DL, Oettgen HF (1984) Human leukocyte (alpha) interferon in metastatic malignant melanoma: the American Cancer Society phase II trial. Cancer Treat Rep 68:723–726

    PubMed  CAS  Google Scholar 

  24. Levy DE, Garcia-Sastre A (2001) The virus battles: IFN induction of the antiviral state and mechanisms of viral evasion. Cytokine Growth Factor Rev 12:143–156, doi:10.1016/S1359-6101(00)00027-7

    Article  PubMed  CAS  Google Scholar 

  25. Massaguer S, Sanchez M, Castel T (2004) Mediastinal sarcoidosis induced by high-dose alpha-2-interferon therapy in a patient with malignant melanoma. Eur Radiol 14:1716–1717, doi:10.1007/s00330-003-2207-y

    Article  PubMed  Google Scholar 

  26. Marzouk K, Saleh S, Kannass M, Sharma OP (2004) Interferon-induced granulomatous lung disease. Curr Opin Pulm Med 10:435–440, doi:10.1097/01.mcp.0000134400.88832.9c

    Article  PubMed  Google Scholar 

  27. Nagaoka T, Sato E, Takabashi A, Yokobama S, Yoshida A (2007) Retinal circulatory changes associated with interferon-induced retinopathy in patients with hepatitis C. Invest Ophthalmol Vis Sci 48:368–375, doi:10.1167/iovs.06-0182

    Article  PubMed  Google Scholar 

  28. Ning Q, Brown D, Parodo J, Cattral M, Gerczynski R, Cole E, Fung L, Ding JW, Liu MF, Rotstein O, Phillips MJ, Levy G (1998) Ribavirin inhibits virus-induced macrophage production of TNF alpha, IL-1, the procoagulant fg12 prothrombinasa and preserves Th1 cytokine production but inhibits Th2 cytokine response. J Immunol 160:3487–3490

    PubMed  CAS  Google Scholar 

  29. Nishiwaki H, Ogura Y, Miyamoto K, Matsuda N, Honda Y (1996) Interferon alpha induces leukocyte capillary trapping in rat retinal microcirculation. Arch Ophthalmol 114:726–730

    PubMed  CAS  Google Scholar 

  30. Noguchi K, Enjoji M, Nakamuta M, Sugimoto R, Kotoh K, Nawata H (2002) Varous sarcoid lesions in a patient induced by interferon therapy for chronic hepatitis C. J Clin Gastroenterol 35:282–284, doi:10.1097/00004836-200209000-00018

    Article  PubMed  Google Scholar 

  31. Parronchi P, Mohapatra S, Sampognaro S, Giannarini L, Wahn U, Chong P, Maggi E, Renz H, Romagnani S (1996) Effects of interferon-alpha on cytokine profile, T cell receptor repertoire and peptide reactivity of human allergic-specific T cells. Eur J Immunol 26:697–703, doi:10.1002/eji.1830260328

    Article  PubMed  CAS  Google Scholar 

  32. Paty DW, Li DK (1993) Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. II. MRI analysis results of a multicenter, randomized, double-blind, placebo-controlled trial. UBC MS/MRI Study Group and the IGNB Multiple Sclerosis Study Group. Neurology 43:662–667

    PubMed  CAS  Google Scholar 

  33. Pichler WJ (2006) Adverse side-effects to biological agents. Allergy 61:912–920 doi:10.1111/j.1398-9995.2006.01058.x

    Article  PubMed  CAS  Google Scholar 

  34. Raanani P, Ben-Bassat I (2002) Immune-mediated complications during interferon therapy in hematological patients. Acta Haematol 107:133–144, doi:10.1159/000057631

    Article  PubMed  CAS  Google Scholar 

  35. Ramos-Casals M, Mana J, Nardi N, Brito-Zeron P, Xauber A, Sanchez-Tapias JM, Cervera R, Font J (2005) Sarcoidosis in patients with chronic hepatitis C virus infection. Analysis of 68 Cases. Medicine 84:69–80, doi:10.1097/01.md.0000157577.69729.e6

    CAS  Google Scholar 

  36. Randall RE, Goodbourn S (2008) Interferons and viruses: an interplay between induction, signaling, antiviral responses and virus counter measures. J Gen Virol 89:1–47, doi:10.1099/vir.0.83391-0

    Article  PubMed  CAS  Google Scholar 

  37. Rogge L, D’Ambrosio D, Biffi M, Penna G, Minetti LJ, Presky DA, Adorini L, Sinigaglia F (1998) The role of Stat4 in species-specific regulation of Th cell development by type I IFNs. J Immunol 161:6567–6574

    PubMed  CAS  Google Scholar 

  38. Schilling PJ, Kurzrock R, Kantarjian H, Gutterman JU, Talpaz M (1991) Development of systemic lupus erythematosus after interferon therapy for chronic myelogenous leukemia. Cancer 68:1536–1537, doi:10.1002/1097-0142(19911001)68:7<1536::AID-CNCR2820680713>3.0.CO;2-B

    Article  PubMed  CAS  Google Scholar 

  39. Stuebiger N, Kotter I, Deuter C, Zierhut M (2001) Behçet’s disease: uveitis-therapy with interferon alpha2b – prospective clinical study in 33 patients. Klin Monatsbl Augenheilkd 218:768–773, doi:10.1055/s-2001-19687

    Article  Google Scholar 

  40. Takase B, Uehata A, Fujioka T, Kondo T, Nishioka T, Isojima K, Satomura K, Ohsuzu F, Kurita A (2001) Endothelial dysfunction and decreased exercise tolerance in interferon-alpha therapy in chronic hepatitis C: relation between exercise hyperemia and endothelial function. Clin Cardiol 24:286–290

    Article  PubMed  CAS  Google Scholar 

  41. Tam RC, Pai B, Bard J, Lim C, Averett DR, Phan UT, Milovanovic T (1999) Ribavirin polarizes human T cell responses towards a type 1 cytokine profile. J Hepatol 30:376–382, doi:10.1016/S0168-8278(99)80093-2

    Article  PubMed  CAS  Google Scholar 

  42. Tu KL, Bowyer J, Schofield K, Harding S (2003) Severe interferon associated retinopathy. Br J Ophthalmol 87:247–248, doi:10.1136/bjo.87.2.247

    Article  PubMed  CAS  Google Scholar 

  43. Tugal-Tutkun I, Güney-Tafekli E, Urgancioglu M (2006) Results of interferon alpha-therapy in patients with Behçet uveitis. Graefes Arch Clin Exp Ophthalmol 244:1692–1695, doi:10.1007/s00417-006-0346-y

    Article  PubMed  CAS  Google Scholar 

  44. Yan KK, Dininhan I, Freiman J, Zekry A (2008) Sarcoidosis presenting with granulomatous uveitis induced by pegilated interferon and ribavirin therapy for hepatitis C. Intern Med J 38:207–210, doi:10.1111/j.1445-5994.2007.01625.x

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Deshka Doycheva.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Doycheva, D., Deuter, C., Stuebiger, N. et al. Interferon-alpha-associated presumed ocular sarcoidosis. Graefes Arch Clin Exp Ophthalmol 247, 675–680 (2009). https://doi.org/10.1007/s00417-008-1002-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00417-008-1002-5

Keywords

Navigation