Cogan syndrome: Characteristics, outcome and treatment in a French nationwide retrospective study and literature review

doi:10.1016/j.autrev.2017.10.005

Autoimmunity Reviews

Volume 16, Issue 12, December 2017, Pages 1219-1223

https://doi.org/10.1016/j.autrev.2017.10.005 Get rights and content

Highlights

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Vestibulo-auditory response was similar with DMARDs and steroids alone.
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Infliximab could lead to vestibulo-auditory response in DMARDS and steroid-refractory Cogan syndrome.
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The 5 and 10-years incidence of relapse increased under steroids and DMARDS, while it stayed stable with infliximab.

Abstract

Background

Cogan syndrome is mainly treated with steroids. We aimed to determine the place of DMARDs and biologic-targeted treatments.

Patients and methods

We conducted a French nationwide retrospective study of patients with Cogan syndrome (n = 40) and a literature review of cases (n = 22) and analyzed the efficacy of disease-modifying anti-rheumatic drugs (DMARDs) and tumor necrosis factor α (TNF-α) antagonists.

Results

We included 62 patients (31 females) (median age 37 years [range 2–76]. At diagnosis, 61 patients (98%) had vestibulo-auditory symptoms, particularly bilateral hearing loss in 41% and deafness in 31%. Ocular signs were present in 57 patients (92%), with interstitial keratitis in 31 (51%). The first-line treatment consisted of steroids alone (n = 43; 70%) or associated with other immunosuppressive drugs (n = 18; 30%). Overall, 13/43 (30%) and 4/18 (22%) patients with steroids alone and with associated immunosuppressive drugs, respectively (p = 0.8), showed vestibulo-auditory response; 32/39 (82%) and 15/19 (79%) ocular response; and 23/28 (82%) and 10/14 (71%) general response. Overall 61 patients had used a total of 126 lines of treatment, consisting of steroids alone (n = 51 lines), steroids with DMARDs (n = 65) and infliximab (n = 10). Vestibulo-auditory response was significantly more frequent with infliximab than DMARDs or steroids alone (80% vs 39% and 35%, respectively), whereas ocular, systemic and acute-phase reactant response rates were similar. Infliximab was the only significant predictor of vestibulo-auditory improvement (odds ratio 20.7 [95% confidence interval 1.65; 260], p = 0.019).

Conclusion

Infliximab could lead to vestibulo-auditory response in DMARDS and steroid-refractory Cogan syndrome, but prospective studies are necessary.

Introduction

Cogan syndrome was first described in 1945 by an ophthalmologist, David G. Cogan, who reported on a “syndrome of non-syphilitic interstitial keratitis and vestibulo-auditory symptoms” that resembled Meniere's disease [1]. Other ocular signs such as conjunctivitis, uveitis, scleritis and choroiditis have been described recently and are considered atypical forms in the absence of interstitial keratitis.

Since 1945, > 250 cases of Cogan syndrome have been reported, and the disease seems to have an autoimmune origin; no easily available autoantibodies have been clearly associated with this syndrome [2], [3]. Alleviating the vestibulo-auditory symptoms, and in particular the hearing loss, remains challenging. Because of the rarity of the disease, no controlled study has been performed, with only small reported series, and the value of immunosuppressive treatment, particularly the place of disease-modifying anti-rheumatic drugs (DMARDs), remains to be determined. The 2 largest case-series, of 32 and 60 patients, mainly described the efficacy of steroids alone [2], [3]. Among the 60 patients, 57 (95%) received steroids, with vestibulo-auditory and ophthalmological improvements in 58% [3].

However, no studies have compared the benefit of DMARDs added to steroids and the potential efficacy of various DMARDs. Recently, a few case reports demonstrated the benefit of biologic targeted treatments, mainly infliximab, but larger studies are needed to determine their benefit for vestibulo-auditory involvement [4], [5], [6], [7], [8] [9]. A recent literature review analyzed treatment strategies in 141 patients, including various DMARDs and biologics, suggesting the value of immunosuppressive drugs but could not compare the efficacy of various regimen [10].

In this largest French nationwide study and literature review, we report the long-term outcome of 62 patients with Cogan syndrome receiving steroids, DMARDs and/or tumor necrosis factor α (TNF-α) antagonists and compare their efficacy.

Section snippets

Materials and methods

We conducted a retrospective multicenter study in the French network of internal medicine (SNFMI) and the Club Rhumatisme and Inflammation (CRI) between July 2014 and 2016. Data were collected retrospectively from physicians in charge of patients. The physicians were asked to complete a standardized questionnaire online.

The inclusion criteria were 1) ocular signs consistent with non-syphilitic interstitial keratitis and/or conjunctivitis, episcleritis, scleritis or uveitis; 2) rapidly

Baseline characteristics of patients

We included 40 personal cases and 22 from the literature, for 62 patients (31 females; median age 37 years [range 2–76]). The median time from the first symptoms to diagnosis was 12 months [0 − 231]. At diagnosis, 61 patients (98%) had vestibulo-auditory symptoms, in particular, bilateral hearing loss for 41% and deafness for 31% (Supplementary Table 1). Ocular signs were present in 57 patients (92%), with interstitial keratitis in 31 (51%). The median time between vestibulo-auditory and ocular

Discussion

In our series of patients with Cogan syndrome, sex ratio, age at diagnosis, and prevalence of vestibulo-auditory, ocular and systemic signs were similar to previous data from the Mayo Clinic and French nationwide series [2], [3]. Associated autoimmune diseases were present in 8% of patients from the Mayo Clinic and in 10% of our patients [21]. Only one previous large series compared features of typical and atypical Cogan syndrome, mainly showing more frequent joint and neurological involvements

Conclusions

In DMARDs and steroids-refractory Cogan syndrome, infliximab can lead to vestibulo-auditory response, with 80% frequency of improvement at 6 months. Prospective studies are warranted to confirm these data and determine the place of associated drugs in this rare condition.

The following are the supplementary data related to this article.

. Cumulative incidence of relapse during follow-up of 129 lines treatment (n = 62 patients).

Acknowledgements

We thank the Club Rhumatismes et Inflammation (CRI) and the French National Society of Internal Medicine (SNFMI) for their help in the organization of this study.

Funding Sources

None.

Conflicts of interest

None.

Author contributions

All authors were involved in drafting the article. Arsene Mekinian had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of data analysis.

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Cited by (38)

Cogan's syndrome
2023, Revue du Rhumatisme (Edition Francaise)
Le syndrome de Cogan est rare avec environ 250 cas décrits dans la littérature. Il s’agit d’une maladie supposée auto-immune bien qu’aucun anticorps spécifique n’ait été identifié à ce jour. Elle est classée parmi les vascularites systémiques pouvant toucher les vaisseaux de différents calibres. Le syndrome de Cogan est défini dans sa forme typique par une kératite interstitielle non syphilitique associée à des manifestations audiovestibulaires comparables au syndrome de Ménière. Le délai entre l’apparition des deux symptômes est inférieur à 2 ans. Il est dit atypique lorsque le délai dépasse ces 2 ans et/ou s’il est associé à d’autres manifestations oculaires ou systémiques. Le pronostic visuel est le plus souvent favorable avec une réversibilité des lésions. À l’inverse, l’atteinte audio-vestibulaire peut être sévère et irréversible. Il n’existe à ce jour aucun consensus concernant la prise en charge du syndrome de Cogan. Le traitement repose sur une corticothérapie en association dans certaines formes avec un autre immunosuppresseur (DMARDs, biothérapie).
Cogan syndrome is rare with about 250 cases described in the literature. It is a suspected autoimmune disease although no specific antibodies have been identified to date. It is classified as a systemic vasculitis that can affect vessels of various sizes. Cogan's syndrome is typically defined as non-syphilitic interstitial keratitis associated with audio-vestibular manifestations comparable to Meniere's syndrome. The delay between the onset of the two symptoms is less than 2 years. It is said to be atypical when the delay exceeds 2 years and/or if it is associated with other ocular or systemic manifestations. The visual prognosis is usually favourable with reversibility of the lesions. Conversely, the audio-vestibular damage can be severe and irreversible. To date, there is no consensus on the management of Cogan syndrome. The treatment is based on corticosteroid therapy in association in certain forms with another immunosuppressant (DMARDs, biotherapy).
Isolated Aortitis: Workup and Management
2023, Rheumatic Disease Clinics of North America
Cogan syndrome masquerading as corneal ectasia
2021, American Journal of Ophthalmology Case Reports
Citation Excerpt :
Atypical ophthalmic findings reported include conjunctivitis, uveitis, scleritis and choroiditis.1 Aggressive immunosuppressive therapy and multi-specialty management of the disease is warranted owing to its systemic manifestations, including vasculitis.1–3 Despite more than 250 reports on Cogan syndrome in the literature, there is a paucity of data regarding the appearance of corneal topography and tomography in this syndrome.
To report a case of Cogan syndrome that presented with the appearance of bilateral asymmetric corneal ectasia on Scheimpflug tomography.
Case Report and Literature Review.
A 43-year-old woman previously diagnosed with keratoconjunctivitis sicca and presumed keratoconus presented with seven months of episodic eye pain and progressive bilateral blurry vision with new onset bilateral monocular diplopia. Review of symptoms were significant for tinnitus, vertigo, and sensorineural hearing loss that began many months after her initial presentation for visual symptoms. Scheimpflug tomography showed asymmetric focal steepening on anterior curvature with corresponding focal total corneal thinning, focal posterior elevation, and abnormal ARTMax (205 OD, 103 OS) and BAD-D (2.75 OD, 5.6 OS) values. Clinical examination was notable only for faint anterior corneal stromal inflammation without neovascularization, but there was significant corresponding focal hyperreflectivity on anterior segment optical coherence tomography (OCT) examination with focal epithelial hypertrophy rather than thinning. Given the combined findings of interstitial keratitis and sensorineural hearing loss the patient was diagnosed with Cogan syndrome. She responded well to topical steroids and systemic immunosuppressive therapy, with near resolution of her abnormal topographic and tomographic findings and resolution of monocular diplopia in both eyes.
Cogan syndrome should be suspected for any patient with corneal stromal findings and associated with vertigo and/or hearing loss. Anterior segment optical coherence tomography (OCT) can distinguish between ectatic and inflammatory diseases and may help make the appropriate diagnosis in subtle cases.
Cogan's syndrome
2021, Journal Francais d'Ophtalmologie
Cogan syndrome: Descriptive analysis and clinical experience of 7 cases diagnosed and treated in two third level hospitals
2021, Reumatologia Clinica
El síndrome de Cogan (SC) es una enfermedad inflamatoria clasificada como vasculitis de vaso variable. Se trata de una enfermedad rara con escasas series publicadas, por lo que revisamos nuestra experiencia en 2 centros en los últimos 10 años.
Descripción de 7 casos diagnosticados de SC, atendiendo a los criterios de clasificación (típico o atípico), sus manifestaciones clínicas, tratamientos utilizados y sus complicaciones. Se realizó un análisis comparativo con las series y casos descritos en la literatura.
Se incluyeron 7 casos, 3 varones y 4 mujeres, con una edad media al diagnóstico de 43 años, y un tiempo de evolución medio de 47 meses. Cinco pacientes cumplían las características típicas según los criterios clásicos de 1980, siendo el resto casos atípicos, uno por ausencia de queratitis intersticial y otro por un periodo entre la aparición de clínica ocular y auditivo-vestibular mayor de 2 años. Todos recibieron inmunosupresores, siendo el más utilizado el metotrexato, seguido de la azatioprina. En 5 casos se utilizaron fármacos biológicos: infliximab en 4 ocasiones y en 2 tocilizumab. Un paciente falleció por endocarditis bacteriana y shock séptico.
Las características de la serie presentada son similares a las publicadas hasta ahora, con diferencias clínicas fundamentalmente en la afectación de grandes vasos. Ante la escasa casuística, parece necesario la creación de registros multicéntricos para mejorar la evidencia en cuanto al manejo de pacientes con SC.
Cogan's syndrome (CS) is an inflammatory disease classified as variable vessel vasculitis. It is a rare disease with few published series, and therefore we reviewed our experience in the last ten years in two centres.
Description of 7 diagnosed cases of CS, according to the classification criteria (typical or atypical), their clinical manifestations, treatments used and their complications. A comparative analysis was performed with the series and cases described in the literature.
Seven cases were included, three men and four women, with a mean age at diagnosis of 43 years, and an average disease duration of 47 months. Five patients met the typical characteristics according to the 1980 classical criteria, the rest being atypical cases, one due to the absence of interstitial keratitis and another due to a period between the onset of ocular and auditory-vestibular clinical symptoms greater than two years. All received immunosuppressants, methotrexate being the most commonly used, followed by azathioprine. In 5 cases, biological drugs were used, infliximab in 4 times and 2 tocilizumab. One patient died from bacterial endocarditis and septic shock.
The characteristics of the series presented are like those published to date, with clinical differences mainly in the involvement of large vessels. Given the low frequency, it seems necessary to create multicentre records to improve the evidence regarding the management of patients with CS.
Syndrome de Cogan
2021, Revue de Medecine Interne
Le syndrome de Cogan « typique » est défini par une kératite interstitielle non-syphilitique associée à une atteinte audio-vestibulaire proche du syndrome de Ménière avec un délai maximum de 2 ans entre les atteintes. Le syndrome de Cogan est dit « atypique » en présence d'une atteinte oculaire inflammatoire autre que la kératite interstitielle, d'un tableau audio-vestibulaire différent de celui évoquant un syndrome de Ménière, ou d'un délai de plus de 2 ans entre les atteintes ophtalmologiques et audio-vestibulaires. D'autres manifestations sont possibles, principalement des signes généraux et une vascularite le plus souvent des gros vaisseaux touchant volontiers l'aorte thoracique. La présence d'un syndrome inflammatoire est habituelle, et aucun test biologique spécifique n'est disponible. Le pronostic est dominé par l'atteinte audio-vestibulaire et en particulier le risque de surdité définitive, d'autres complications en particulier les complications vasculaires étant rares. Le traitement fait appel à la corticothérapie et le recours aux autres immunosuppresseurs ou aux biothérapies reste mal codifié.
“Typical” Cogan's syndrome is defined as a non-syphilitic interstitial keratitis associated with audio-vestibular resembling Ménière's disease with a 2-year maximum delay between these 2 organ impairment. Cogan syndrome is classified as “atypical” in the absence of interstitial keratitis and the presence of other inflammatory eye manifestations, an audio-vestibular impairment different from typical Menière-like disease, or a delay longer than 2 years between eye and audio-vestibular manifestations. Constitutional signs and large-vessel vasculitis is also possible, mostly affecting the thoracic aorta. The presence of acute-phase reactants is common, but no specific laboratory tests are available. The prognosis is dominated by the audio-vestibular impairment and in particular the risk of deafness, while other complications especially vascular complications being rare. Treatment with glucocorticoids is usually necessary and the combination to other immunosuppressive therapies or biological-targeted drugs needs to be determined.

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ReviewCogan syndrome: Characteristics, outcome and treatment in a French nationwide retrospective study and literature review

Highlights

Abstract

Background

Patients and methods

Results

Conclusion

Introduction

Section snippets

Materials and methods

Baseline characteristics of patients

Discussion

Conclusions

Acknowledgements

Funding Sources

Conflicts of interest

Author contributions

Mayo Clin Proc

Autoimmun Rev

Am J Med

Int J Pediatr Otorhinolaryngol

Am J Otolaryngol

Am J Ophthalmol

Autoimmun Rev

Typical and atypical Cogan's syndrome: 32 cases and review of the literature

Rheumatology (Oxford)

Rituximab ameliorated severe hearing loss in Cogan's syndrome: a case report

Orphanet J Rare Dis

Review
Cogan syndrome: Characteristics, outcome and treatment in a French nationwide retrospective study and literature review