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Cogan's Syndrome—Clinical Guidelines and Novel Therapeutic Approaches

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Abstract

Cogan's syndrome (CS) is a rare chronic inflammatory disorder, classically characterized by interstitial keratitis and sensorineural hearing loss. Recurrent episodes of inner ear disease might result in deafness. In some patients, it may also be accompanied by systemic vasculitis. Diagnosis of CS is often missed or delayed due to its rarity, the nonspecific clinical signs at onset, and the lack of a confirmatory diagnostic test. The mechanisms responsible for CS are unknown; however, in the last decade, the pathogenesis has been somewhat elucidated, suggesting that the disease is a result of inner ear autoimmunity. The autoimmune hypothesis postulates the triggering of the disease by a viral infection via a number of mechanisms, which are mainly as follows: antigenic mimicry, self-perpetuating inflammation by cytokine release, and unveiling hidden epitopes. Aside from its clinical resemblance to other autoimmune disorders, some autoantigen has apparently been identified, namely, CD148 and connexine 26. Treatment should begin as early as possible. While treatment is based primarily on glucocorticoids, there is no standard alternative for patients who respond poorly. Failure of conventional treatment could lead to profound sensorineural hearing loss. From the limited data we have, infliximab seems to be the most promising biological remedy, enabling steroid tapering and leading to improvement in auditory/ocular disease, with better results when administered in early stages. Proposed guidelines for the use of infliximab in CS are found in the last table of the review, in an attempt to define the proper timing for initiating infliximab treatment in order to avoid permanent disability.

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References

  1. Cogan DS (1945) Syndrome of nonsyphilitic interstitial keratitis and vestibuloauditory symptoms. Arch Ophthalmol 33:144–149

    Article  Google Scholar 

  2. Haynes BF, Kaiser-Kupfer MI, Mason P, Fauci AS (1980) Cogan syndrome: studies in thirteen patients, long-term follow-up, and a review of the literature. Medicine (Baltimore) 59:426–441

    Article  CAS  Google Scholar 

  3. Vollertsen RS, McDonald TJ, Younge BR, Banks PM, Stanson AW, Ilstrup DM (1986) Cogan’s syndrome: 18 cases and a review of the literature. Mayo Clin Proc 61:344–361

    Article  CAS  PubMed  Google Scholar 

  4. St Clair EW, McCallum RM (1999) Cogan’s syndrome. Curr Opin Rheumatol 11:47–52

    Article  CAS  PubMed  Google Scholar 

  5. Lunardi C, Bason C, Leandri M et al (2002) Autoantibodies to inner ear and endothelial antigens in Cogan’s syndrome. Lancet 360(9337):915–921

    Article  CAS  PubMed  Google Scholar 

  6. Fisher ER, Hellstrom HR (1961) Cogan’s syndrome and systemic vascular disease. Analysis of pathologic features with reference to its relationship to thromboangiitis obliterans (Buerger). Arch Pathol 72:572–592

    CAS  PubMed  Google Scholar 

  7. Gluth MB, Baratz KH, Matteson EL, Driscoll CL (2006) Cogan syndrome: a retrospective review of 60 patients throughout a half century. Mayo Clin Proc 81:483–488

    Article  PubMed  Google Scholar 

  8. Grasland A, Pouchot J, Hachulla E, Blétry O, Papo T, Vinceneux P (2004) Typical and atypical Cogan’s syndrome: 32 cases and review of the literature. Rheumatology 43:1007–1015

    Article  CAS  PubMed  Google Scholar 

  9. Vollertsen RS (1990) Vasculitis and Cogan’s syndrome. Rheum Dis Clin North Am 16:433–439

    CAS  PubMed  Google Scholar 

  10. Jacob A, Ledingham JG, Kerr AI, Ford MJ (1990) Ulcerative colitis and giant cell arteritis associated with sensorineural deafness. J Laryngol Otol 104:889–890

    Article  CAS  PubMed  Google Scholar 

  11. Thomas HG (1992) Case report: clinical and radiological features of Cogan’s syndrome—non-syphilitic interstitial keratitis, audiovestibular symptoms and systemic manifestations. Clin Radiol 45:418–421

    Article  CAS  PubMed  Google Scholar 

  12. St Clair EW, McCallum RM (2011) Cogan’s syndrome. In: Hochberg MC, Silman AJ, Smolen JS, Weinblatt ME, Weisman MH (eds) Rheumatology, 5th edn. Mosby, Philadelphia, pp 1625–1634

    Chapter  Google Scholar 

  13. Balink H, Bruyn JA (2007) The role of PET/CT in Cogan’s syndrome. Clin Rheumatol 26:2177–2179

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Mazlumzadeh M, Lowe VJ, Mullan BP, Fabry DA, McDonald TJ, Matteson EL (2003) The utility of positron emission tomography in the evaluation of autoimmune hearing loss. Otol Neurotol 24:201–204

    Article  PubMed  Google Scholar 

  15. Murphy G, Sullivan MO, Shanahan F, Harney S, Molloy M (2009) Cogan’s syndrome: present and future directions. Rheumatol Int 29:1117–1121

    Article  PubMed  Google Scholar 

  16. De Kleyn A (1944) Sudden complete or partial loss of function of the octavus-system in apparently normal persons. Acta Otolaryngol 32:407–429

    Article  Google Scholar 

  17. Oh JH, Park K, Lee SJ, Shin YR, Choung YH (2007) Bilateral versus unilateral sudden sensorineural hearing loss. Otolaryngol Head Neck Surg 136(1):87–91

    Article  PubMed  Google Scholar 

  18. Greco A, Fusconi M, Gallo A, Marinelli C, Macri GF, De Vincentiis M (2011) Sudden sensorineural hearing loss: an autoimmune disease? Autoimmun Rev 10(12):756–761

    Article  CAS  PubMed  Google Scholar 

  19. Pitkäranta A, Julkunen I (1998) Sudden deafness: lack of evidence for systemic viral infection. Otolaryngol Head Neck Surg 118:397–399

    Article  PubMed  Google Scholar 

  20. Greco A, Gallo A, Fusconi M et al (2012) Cogan’s syndrome: an autoimmune inner ear disease. Autoimmun Rev 12:396–400

    Article  PubMed  Google Scholar 

  21. Greco A, Gallo A, Fusconi M, Marinelli C, Macri GF, de Vincentiis M (2012) Meniere’s disease might be an autoimmune condition? Autoimmun Rev 11(10):731–738

    Article  CAS  PubMed  Google Scholar 

  22. Yoo TJ, Tomoda K, Hernandez AD (1984) Type II collagen-induced autoimmune inner ear lesions in guinea pigs. Ann Otol Rhinol Laryngol Suppl 113:3–5

    CAS  PubMed  Google Scholar 

  23. Boulassel MR, Tomasi JP, Deggouj N, Gersdorff M (2000) Identification of beta-actin as a candidate autoantigen in autoimmune inner ear disease. Clin Otolaryngol Allied Sci 25(6):535–541

    Article  CAS  PubMed  Google Scholar 

  24. Solares CA, Edling AE, Johnson JM et al (2004) Murine autoimmune hearing loss mediated by CD4+ T cells specific for inner ear peptides. J Clin Invest 113(8):1210–1217

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Nair TS, Kozma KE, Hoefling NL et al (2004) Identification and characterization of choline transporter-like protein 2, an inner ear glycoprotein of 68 and 72 kDa that is the target of antibody-induced hearing loss. J Neurosci 24(7):1772–1779

    Article  CAS  PubMed  Google Scholar 

  26. Belizna C, Tervaert JW (1997) Specificity, pathogenecity, and clinical value of antiendothelial cell antibodies. Semin Arthritis Rheum 27(2):98–109

    Article  CAS  PubMed  Google Scholar 

  27. Lefebvre PP, Van De Water TR (2000) Connexins, hearing and deafness: clinical aspects of mutations in the connexin 26 gene. Brain Res Brain Res Rev 32(1):159–162

    Article  CAS  PubMed  Google Scholar 

  28. Dong Y, Roos M, Gruijters T et al (1994) Differential expression of two gap junction proteins in corneal epithelium. Eur J Cell Biol 64(1):95–100

    CAS  PubMed  Google Scholar 

  29. Allan NB, Cox CC, Cobo M et al (1990) Use of immunosuppressive agents in the treatment of severe ocular and vascular manifestations of Cogan’s syndrome. Am J Med 88:296–301

    Article  Google Scholar 

  30. Walsh LJ, Trinchieri G, Waldorf HA, Whitaker D, Murphy GF (1991) Human dermal mast cells contain and release tumor necrosis factor alpha, which induces endothelial leukocyte adhesion molecule 1. Proc Natl Acad Sci U S A 88(10):4220–4224

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Locksley RM, Killeen N, Lenardo MJ (2001) The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell 104(4):487–501

    Article  CAS  PubMed  Google Scholar 

  32. Said EA, Dupuy FP, Trautmann L et al (2010) Programmed death-1-induced interleukin-10 production by monocytes impairs CD4+ T cell activation during HIV infection. Nat Med 16(4):452–459

    Article  CAS  PubMed  Google Scholar 

  33. Grewal IS, Grewal KD, Wong FS, Picarella DE, Janeway CA Jr, Flavell RA (1996) Local expression of transgene encoded TNF alpha in islets prevents autoimmune diabetes in nonobese diabetic (NOD) mice by preventing the development of auto-reactive islet-specific T cells. J Exp Med 184(5):1963–1974

    Article  CAS  PubMed  Google Scholar 

  34. Comarmond C, Plaisier E, Dahan K et al (2012) Anti TNF-α in refractory Takayasu’s arteritis: cases series and review of the literature. Autoimmun Rev 11(9):678–684

    Article  CAS  PubMed  Google Scholar 

  35. Fricker M, Baumann A, Wermelinger F, Villiger PM, Helbling A (2007) A novel therapeutic option in Cogan’s disease? TNF-a blockers. Rheumatol Int 27:493–495

    Article  CAS  PubMed  Google Scholar 

  36. Aeberli D, Oertle S, Mauron H, Reichenbach S, Jordi B, Villiger PM (2002) Inhibition of the TNF pathway: use of infliximab and etanercept as remission inducing agents in cases of therapy-resistant chronic inflammatory disorders. Swiss Med Wkly 132:414–422

    CAS  PubMed  Google Scholar 

  37. Touma Z, Nawwar R, Hadi U, Hourani M, Arayssi T (2007) The use of TNF-a blockers in Cogan’s syndrome. Rheumatol Int 27:995–996

    Article  CAS  PubMed  Google Scholar 

  38. Ghadban R, Couret M, Zenone T (2008) Efficacy of infliximab in Cogan’s syndrome. J Rheumatol 35:2456–2458

    Article  PubMed  Google Scholar 

  39. Beccastrini E, Emmi G, Squatrito D, Vannucchi P, Emmi L (2010) Infliximab and Cogan’s syndrome. Clin Otolaryngol 35:441–442

    Article  CAS  PubMed  Google Scholar 

  40. Weinblatt ME, Kremer JM, Bankhurst AD et al (1999) A trial of etanercept, a recombinant tumor necrosis factor receptor: Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. N Engl J Med 340(4):253–259

    Article  CAS  PubMed  Google Scholar 

  41. Matteson EL, Choi HK, Poe DS et al (2005) Etanercept therapy for immune-mediated cochleovestibular disorders: a multi-center open-label, pilot study. Arthritis Rheum 53:337–342

    Article  CAS  PubMed  Google Scholar 

  42. Edwards JC, Szczepanski L, Szechinski J et al (2004) Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med 350(25):2572–2581

    Article  CAS  PubMed  Google Scholar 

  43. Tak PP, Kalden JR (2011) Advances in rheumatology: new targeted therapeutics. Arthritis Res Ther 13(1):S5

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  44. Ramos-Casals M, Sanz I, Bosch X, Stone JH, Khamashta MA (2012) B-cell-depleting therapy in systemic lupus erythematosus. Am J Med 125(4):327–336

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  45. Cartin-Ceba R, Fervenza FC, Specks U (2012) Treatment of antineutrophil cytoplasmic antibody-associated vasculitis with rituximab. Curr Opin Rheumatol 24(1):15–23

    Article  CAS  PubMed  Google Scholar 

  46. Miserocchi E, Modorati G (2012) Rituximab for noninfectious uveitis. Dev Ophthalmol 51:98–109

    Article  CAS  PubMed  Google Scholar 

  47. Orsoni JG, Laganà B, Rubino P, Zavota L, Bacciu S, Mora P (2010) Rituximab ameliorated severe hearing loss in Cogan’s syndrome: a case report. Orphanet J Rare Dis 5:18

    Article  PubMed Central  PubMed  Google Scholar 

  48. Wang JR, Yuen HW, Shipp DB et al (2010) Cochlear implantation in patients with autoimmune inner ear disease including cogan syndrome: a comparison with age- and sex-matched controls. Laryngoscope 120:2478–2483

    Article  PubMed  Google Scholar 

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Conflict of interest

The authors have no funding, financial relationships, or conflicts of interest to disclose.

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Authors and Affiliations

  1. Rheumatology Unit, Department of Medicine, Hadassah–Hebrew University Medical Center, Jerusalem, Israel

    Oshrat E. Tayer-Shifman

  2. Department of Otolaryngology/Head and Neck Surgery, Hadassah–Hebrew University Medical Center, Jerusalem, Israel

    Ophir Ilan & Hodaya Tovi

  3. Allergy and Clinical Immunology Unit, Department of Medicine, Hadassah–Hebrew University Medical Center, Jerusalem, 91120, Israel

    Yuval Tal

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  1. Oshrat E. Tayer-Shifman
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  2. Ophir Ilan
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  4. Yuval Tal
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Correspondence to Yuval Tal.

Additional information

Oshrat E. Tayer-Shifman and Ophir Ilan contributed equally.

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Tayer-Shifman, O.E., Ilan, O., Tovi, H. et al. Cogan's Syndrome—Clinical Guidelines and Novel Therapeutic Approaches. Clinic Rev Allerg Immunol 47, 65–72 (2014). https://doi.org/10.1007/s12016-013-8406-7

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  • DOI: https://doi.org/10.1007/s12016-013-8406-7

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