Cogan Syndrome

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Cogan Syndrome:

Disease Entity:

Cogan’s syndrome (also Cogan syndrome) is an uncommon disease seen mostly in young adults that can severely affect vision and hearing.[1][2] Since 1945, only several hundred cases have been reported in the literature.[3] Cogan syndrome is characterized by recurrent ocular inflammation as well as hearing loss that can lead to deafness if left untreated.[4]

Systemic involvement can be seen in up to 80% of patients.[1] Hearing loss, headache, arthralgia, fever, arthritis, and myalgias are the most common systemic symptoms of Cogan syndrome, and up to 15% of patients develop vasculitis.[5][6] Cogan syndrome can also lead to cardiovascular complications such as aoritis, as well as gastrointestinal and neurologic manifestations.[7] Cogan syndrome most commonly affects young adults between 20-30 years old but can be seen at any age, and while the etiology is unknown, infectious triggers, such as upper respiratory tract infection, diarrhea, dental infection, or recent immunization have been reported.[1][8][9][10]

General Pathology:

Although the ocular pathogenesis of Cogan syndrome is not fully understood, it has been postulated to be an autoimmune disease in which autoantibodies target corneal, inner ear, and endothelial antigens.[1][7] Corneal tissue and cochlea from patients with CS have showed lymphocytic and plasma cell infiltration, indicating that Cogan syndrome is indeed an autoimmune disorder.[7][11]

Diagnosis:

There are two forms of Cogan syndrome that can be diagnosed based on the onset of symptoms and ocular pathophysiology: the classic form and the atypical form.[1][4]

Table 1: Hallmarks of Typical and Atypical Cogan Syndrome[1][2][4][7][12][13][14][15]
Cogan Syndrome Type Hallmark Features for Diagnosis Other Ocular Manifestations
The Classic Form
  • Peripheral subepithelial keratitis that rapidly evolves into interstitial keratitis
  • Vestibulo auditory symptoms that resemble Meniere’s disease such as nausea, vomiting, tinnitus, vertigo
  • Progressive hearing loss that progresses to deafness within 1-3 months
  • Vestibulo auditory symptoms within two years of eye symptoms
  • Iritis
  • Subconjunctival or conjunctival hemorrhage
  • Lacrimation
  • Eye redness
The Atypical Form
  • Inflammatory manifestations (episcleritis and choroiditis) with or without interstitial keratitis
  • Audiovestibular symptoms that are different from the Meniere-like symptoms seen in the typical form
  • 2+ years between ocular and vestibular auditory manifestations
  • Conjunctivitis
  • Scleritis
  • Uveitis
  • Optic disc edema
  • Closure angle glaucoma
  • Papillitis
  • Central vein occlusion
  • Vasculitic optic neuropathy
  • Retinal vasculitis

The Classic Form:

The classic form of Cogan syndrome is characterized by a nonsyphilitic, peripheral subepithelial keratitis that evolves rapidly into an interstitial keratitis with possible vascularization in the later stages of the disease.[2][4] Interstitial keratitis is the most commonly seen ocular manifestation of Cogan’s syndrome.[7] The symptoms of interstitial keratitis develop rapidly but then resolve slowly and can be either bilateral or unilateral.[2] The interstitial keratitis can lead to severe photophobia, lacrimation, eye pain, eye redness, blurred visions, and can flare up sporadically over many years before quieting.[1][2] Vestibulo-auditory symptoms resemble Meniere’s disease and appear as sudden episodes of nausea, vomiting, tinnitus, vertigo, and progressive hearing loss that usually progresses to deafness within 1 to 3 months.[2] The classic form of Cogan syndrome is diagnosed when a patient develops vestibular auditory symptoms within two years of ocular symptoms.[2] Iritis and subconjunctival or conjunctival hemorrhage are also possible features of the classic form.[2]

The Atypical Form:

Patients with the atypical form of Cogan syndrome typically present with inflammatory ocular manifestations, such as episcleritis and choroiditis, with or without interstitial keratitis along with audiovestibular symptoms that are different from the Meniere-like symptoms seen in the typical form of Cogan syndrome.[7] There is also a delay of more than two years between the ocular and vestibular auditory manifestations in the atypical form.[2] The atypical form can lead to manifestations such as conjunctivitis, anterior or posterior scleritis, uveitis, optic disc edema, closure angle glaucoma, papillitis, central vein occlusion, vasculitic optic neuropathy, and/or retinal vasculitis.[2][4][12][13][14][15]

Diagnostic Procedures:

There is no single and definitive test available to confirm the diagnosis of Cogan syndrome.[1] Therefore, understanding the ocular and systemic symptoms is critical for the diagnosis.[1] However, diagnosing the type of Cogan’s syndrome can be difficult because the timing and association of the ocular and vestibulo-auditory symptoms are highly variable, with some patients not developing interstitial keratitis at the onset of the disease and some even developing it years later.[7] Patients who present with signs suggestive of typical Cogan syndrome may later develop the hallmarks of atypical Cogan syndrome later on.[1] Systemic manifestations are more frequent in the atypical form and can be used in addition to the ocular manifestations to differentiate between the two types.[7]

Detecting the presence of corneal infiltrates with slit lamp examination is critical.[1] Cogan syndrome is a diagnosis of exclusion and if interstitial keratitis is detected, syphilis, herpes, chlamydia, tuberculosis, rubeola, mumps, Lyme disease, and parasitic etiologies must be ruled out before determining Cogan syndrome as the main cause for interstitial keratitis.[1] These other etiologies can be ruled out based on a detailed history, directed laboratory testing, and the knowledge that these typically do not cause the vestibular symptoms commonly seen in Cogan syndrome.[1]

There have been case reports of positive Chlamydia psittaci and Chlamydia trachomatis antibodies in the setting of Cogan syndrome.[9][10] Positive anti-heat shock protein antibodies, antineutrophil cytoplasmic antibody (ANCA), and rheumatoid factor (RF), antinuclear antibody (ANA), and anticardiolipin antibodies have been reported with Cogan syndrome. Fifty percent of Cogan syndrome patients may test positive for anti-heat shock protein antibodies.[10]

Management

Treatment

Patients with Cogan syndrome should be monitored closely and managed by ophthalmologists, internists, and otolaryngologists.[14] Treatment of Cogan syndrome depends on the severity and the degree of systemic involvement.[7]

Cogan syndrome is typically treated with steroids.[3] Topical corticosteroids, cycloplegics, and disease-modifying anti-rheumatic drugs (DMARDS) can be used to manage acute interstitial keratitis.[1][2][7] However, one must exercise caution when treating with steroids for ocular inflammation because it could lead to elevated intraocular pressure or premature formation of cataracts.[1] Topical Cyclosporin A may be effective in treating severe anterior segment inflammation in the setting of Cogan syndrome.[7][16]

Systemic corticosteroids may be considered (1-2mg/kg/day for 2-6 months) after the onset of hearing loss or when there is posterior involvement of the eye, such as retinal vasculitis, posterior scleritis, and posterior uveitis.[2][7][17] In addition, involvement of the inner ear, severe eye involvement, or development of systemic vasculitis may necessitate aggressive immunosuppressive therapy.[7][14] When a patient does not respond to steroids or there is a contraindication to steroid use, DMARDs or biologic agents are recommended.[1] Infliximab is now commonly used along with corticosteroids, especially in those who have failed combinations of steroids and DMARD therapy. This allows for tapering of corticosteroids in 86% of patients.[18]

Surgical Treatments:

Cochlear implants can be helpful in the treatment of hearing loss experienced by patients in the setting of Cogan syndrome.[5]

  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 Espinoza, Gabriela Mabel, et al. “Cogan’s Syndrome: Clinical Presentations and Update on Treatment.” Current Allergy and Asthma Reports, vol. 20, no. 9, 16 June 2020, doi:10.1007/s11882-020-00945-1.
  2. 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 Haynes, Barton F., et al. “Cogan Syndrome.” Medicine, vol. 59, no. 6, 1980, pp. 426–441., doi:10.1097/00005792-198011000-00003.
  3. 3.0 3.1 Durtette, Charlotte, et al. “Cogan Syndrome: Characteristics, Outcome and Treatment in a French Nationwide Retrospective Study and Literature Review.” Autoimmunity Reviews, vol. 16, no. 12, 2017, pp. 1219–1223., doi:10.1016/j.autrev.2017.10.005.
  4. 4.0 4.1 4.2 4.3 4.4 Orsoni, Jelka G., et al. “Cogan Syndrome.” Cornea, vol. 21, no. 4, 2002, pp. 356–359., doi:10.1097/00003226-200205000-00005.
  5. 5.0 5.1 Gluth, Michael B., et al. “Cogan Syndrome: A Retrospective Review of 60 Patients throughout a Half Century.” Mayo Clinic Proceedings, vol. 81, no. 4, 2006, pp. 483–488., doi:10.4065/81.4.483.
  6. Vollertsen RS. “Vasculitis and Cogan's syndrome.” Rheumatic Diseases Clinics of North America, vol. 16, no. 2, 1990, pp. 433-439.
  7. 7.00 7.01 7.02 7.03 7.04 7.05 7.06 7.07 7.08 7.09 7.10 7.11 7.12 Kessel, Aharon, et al. “Cogan Syndrome — Pathogenesis, Clinical Variants and Treatment Approaches.” Autoimmunity Reviews, vol. 13, no. 4-5, 2014, pp. 351–354., doi:10.1016/j.autrev.2014.01.002.
  8. Pagnini, Ilaria, et al. “Clinical Features and Outcome of Cogan Syndrome.” The Journal of Pediatrics, vol. 160, no. 2, 2012, doi:10.1016/j.jpeds.2011.07.051.
  9. 9.0 9.1 Iliescu, Daniela Adriana, et al. “COGAN'S SYNDROME.” Romanian journal of ophthalmology, vol. 59, no. 1, 2015, pp. 6-13.
  10. 10.0 10.1 10.2 Weisenthal RW. 2020-2021 Basic and Clinical Science Course (TM) (BCSC), Section 08: External Disease and Cornea. American Academy of Ophthalmology; 2020.
  11. St. Clair, E. William, and Rex M. McCallum. “COGANʼS Syndrome.” Current Opinion in Rheumatology, vol. 11, no. 1, 1999, pp. 47–52., doi:10.1097/00002281-199901000-00008.
  12. 12.0 12.1 Bennett, Fiona M. “Bilateral Recurrent Episcleritis.” American Journal of Ophthalmology, vol. 55, no. 4, 1963, pp. 815–818., doi:10.1016/0002-9394(63)92451-6.
  13. 13.0 13.1 Peeters, G. J., et al. “Atypical Cogan's Syndrome: An Autoimmune Disease?” Annals of Otology, Rhinology & Laryngology, vol. 95, no. 2, 1986, pp. 173–175., doi:10.1177/000348948609500213.
  14. 14.0 14.1 14.2 14.3 SHAH, P., et al. “Posterior Scleritis—an Unusual Manifestation of Cogan's Syndrome.” Rheumatology, vol. 33, no. 8, 1994, pp. 774–775., doi:10.1093/rheumatology/33.8.774.
  15. 15.0 15.1 Gluth, Michael B., et al. “Cogan Syndrome: A Retrospective Review of 60 Patients throughout a Half Century.” Mayo Clinic Proceedings, vol. 81, no. 4, 2006, pp. 483–488., doi:10.4065/81.4.483.
  16. Shimura, Masahiko, et al. “Effective Treatment with Topical Cyclosporin A of a Patient with Cogan Syndrome.” Ophthalmologica, vol. 214, no. 6, 2000, pp. 429–432., doi:10.1159/000027538.
  17. Graff JM, Freed N, Oetting TA: Cogan's Syndrome: 42-year-old Female with Interstitial Keratitis and Vertigo. EyeRounds.org. May 24, 2007; Available from: http://www.EyeRounds.org/69-CogansInterstitialKeratitisVestibuloauditory.htm
  18. Padoan, Roberto, et al. “Cogan’s Syndrome: New Therapeutic Approaches in the Biological Era.” Expert Opinion on Biological Therapy, vol. 19, no. 8, 2019, pp. 781–788., https://doi.org/10.1080/14712598.2019.1611779.
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