Cochleovestibular Impairment in Pediatric Cogan's Syndrome Issa C

Cochleovestibular Impairment in Pediatric Cogan’s Syndrome

Issa C. Ndiaye, MD*; Simon J. Rassi, MD*; and Sylvette R. Wiener-Vacher, MD*

ABSTRACT. Cogan’s syndrome is a rare, chronic in- roids can prevent loss of inner-ear sensorial function flammatory disorder that typically targets the eyes and and limit ophthalmologic aftereffects. In 1934, Mor- vestibuloauditory apparatus, but it may also involve gan and Baumgartner1 published the first case of the other organs. Three pediatric cases of Cogan’s syndrome syndrome. In 1945, Cogan2 published the full de- (ages 5, 13, and 18 years) are reported with long-term scription of the syndrome as an inner-ear disorder in follow-up and complete and regular cochleovestibular its typical form. Several authors later reported atyp- functional evaluation and ophthalmologic and neuro- 3,4 logic examinations. One case was a typical form (charac- ical forms that differed from the typical presenta- terized by an interstitial keratitis and cochleovestibular tion by the type of ocular lesions, which can include impairment), whereas the other 2 cases were atypical superficial keratitis, scleritis, episcleritis, iritis, or forms with uveitis and polyarthritis. In all 3 cases, the choroiditis, as well as variable hearing impairment first clinical sign was nonspecific eye redness misdiag- and often systemic inflammation.5 Cogan’s syn- nosed as a banal conjunctivitis, initially or secondarily drome is generally considered an autoimmune dis- associated with bilateral endocochlear sensorineural ease despite the frequent lack of direct immunologic hearing loss and complete bilateral peripheral vestibular evidence.6,7 The efficacy of steroid treatment in the deficit. During the acute phase, early steroid treatment acute phase provides a compelling argument for this (prednisone, 1 mg/kg/day) was effective in treating the hypothesis. ocular lesions (3 of 3 cases) and improving hearing (2 of 3 cases) but less effective for the vestibular loss (2 of 3 Diagnosis of Cogan’s syndrome is often missed or cases). Adverse effects and dependence on the steroid delayed because it is a rare disease and its clinical occurred in 2 cases, and immunosuppressive drugs were signs at onset are not specific (banal conjunctivitis). necessary to avoid recurrences in 1 case. Over the long- This is dangerous for the patients because steroid term, the disease was controlled in 2 cases but continued treatment should begin as early as possible to allow to progress in the other. Cogan’s syndrome in childhood functional restoration of the inner ear and the eyes should be suspected in cases of conjunctivitis associated before irreversible lesions develop. Few pediatric with inner-ear symptoms; a prompt steroid treatment can cases have been reported in the literature, with no avoid progressive impairment of multiple sensorineural mention of long-term follow-up.5,8,9–14 functions (vision, balance, hearing). Long-term manage- We report 3 pediatric cases with long-term fol- ment involves limiting disease recurrences by adaptive therapies, screening for complications (aortitis in partic- low-up (4–9 years) and regular complete audiologic ular), and planning rehabilitation for the sensorial and vestibular testing to evaluate the sensorial defi- deficits. Pediatrics 2002;109(2). URL: http://www. cits. pediatrics.org/cgi/content/full/109/2/e38; children, Cogan’s syndrome, sudden hearing loss, imbalance, vertigo, con- PATIENTS AND METHODS junctivitis. Three cases of Cogan’s syndrome in children aged 5, 13, and 18 years at the onset of disease are presented. They were recruited from 950 children with balance problems referred to the vestibular ABBREVIATIONS. EVAR, earth vertical axis rotation; OVAR, off clinic over a 10-year period. Each patient underwent complete vertical axis rotation test; VOR, vestibuloocular responses; SNHL, testing including: audiologic tests (pure tone audiometry, speech sensorineural hearing loss; NSAID, nonsteroidal antiinflamma- recognition test, impedancemetry, and evoked otoacoustic emis- tory drugs; MRI, magnetic resonance imaging; EBV, Epstein-Barr sions), vestibular testing (clinical vestibular examination, caloric virus. bithermal test, earth vertical axis rotation [EVAR] test, off vertical axis rotation [OVAR], subjective vertical measurement, and vestibular evoked otolith myogenic potentials) and ophthalmologic ogan’s syndrome is a relatively rare inflam- examination. These tests were repeated over time to follow the matory disease characterized by nonsyphilitic evolution of the disease and evaluate the response to treatment. ocular interstitial keratitis associated with The vestibular test battery evaluated both canal and otolith C functions. The bithermal caloric test evaluated canal function by sudden hearing loss and vestibular impairment. successive irrigation of each ear canal with 30°C and 44°C water, However, its early diagnosis and treatment with ste- followed by a count of the quick phases of the vestibuloocular responses (VORs) through videoscopy from the 60th to 90th sec- onds after the beginning of the irrigation. From the *Otorhinolaryngology Department, Robert Debre´Pediatric Hos- Recordings of the VORs were performed with the electroocu- pital, Paris, France. lography technique. Measurements were made in complete dark- Received for publication Jul 16, 2001; accepted Sep 13, 2001. ness while patients kept their eyes open. Reprint requests to (S.R.W-V.) Otorhinolaryngology Department (Vestibu- Recordings of canal and otolith VORs were made during EVAR lar and Oculomotricity Exploration Unit), Robert Debre´Pediatric Hospital, and OVAR, respectively. Vertical and horizontal eye movements 48 Bld Se´rurier, 75019 Paris, France. E-mail: [email protected] were recorded with lightweight adhesive electrooculographic paris.fr electrodes. A computer-controlled rotating chair delivered the PEDIATRICS (ISSN 0031 4005). Copyright © 2002 by the American Acad- vestibular stimulation by applying at first a brief acceleration (of emy of Pediatrics. 40°/s2) achieving a constant velocity (60°/s) rotation about the http://www.pediatrics.org/cgi/content/full/109/2/Downloaded from www.aappublications.org/newse38 PEDIATRICSby guest on September Vol. 10926, 2021 No. 2 February 2002 1of7 earth vertical axis, and then inclining (at a 13° tilt) the axis of absence of fever spikes, cutaneous rash, swollen lymph nodes, and rotation; this is the rotation-tilt paradigm, a method previously hepatosplenomegaly. NSAIDs (aspirin and indomethacin) were described in detail.15,16 Canal and otolith vestibular functions again prescribed without clear improvement of symptoms. Slow were quantitatively evaluated by measuring the parameters of the intravenous injections of immunoglobulines (1 g/kg for 2 days) canal VORs (including time constant and maximal slow phase had no effect. One month after disease onset, the child reported, velocity) and from the parameters of the otolith VORs (modula- for the first time, tinnitus, hearing impairment, and a sensation of tion amplitude and bias for horizontal and vertical eye movement vertigo. These signs suggested an iatrogenic origin related to the slow-phase velocity). NSAID treatment. The child was then referred to our otorhinolar- The ophthalmologic examination included a measure of the yngology department for audiovestibular testing. Moderate to visual refraction and a slit-lamp examination. This was performed severe bilateral SNHL primarily in high frequencies was found initially to establish the diagnosis and then to follow the evolution with recruitment (characterized by stapedial reflex thresholds at of ocular lesions under treatment. 100 dB) (Fig. 1). The vestibular testing showed spontaneous nys- Complementary tests were performed for each case and fol- tagmus to the left, bilateral canal areflexia at the caloric test but lowed the initial diagnostic explorations. normal otolith responses to OVAR. Brain and inner-ear magnetic Table 1 lists the 3 reported cases, and Table 2 summarizes the resonance imaging ([MRI] with gadolinium injection) was normal. battery of tests performed and their results. Ophthalmologic follow-up was requested because of persistent eye redness. A slit-lamp examination revealed interstitial keratitis. CASE REPORTS This immediately suggested Cogan’s syndrome with systemic manifestation, and steroid therapy was instituted (prednisone, 1 Case 1 mg/kg/day). This treatment was quickly effective against the A 5-year-old boy suffered from bilateral conjunctivitis with fever and the arthralgia. Immunologic tests were negative except moderate uveitis 1 week after a second intradermic desensitiza- for the serodiagnosis of parvovirus B19 and the serodiagnosis of tion treatment against mite antigens. Two months later, he expe- hepatitis B, despite the absence of vaccination (Table 2). rienced vertigo lasting 24 hours without vomiting or tinnitus. The ophthalmologic signs improved after 1 month of steroid After 4 days, bilateral profound sensorineural hearing loss treatment, and no evidence of eye disease was found 9 weeks after (SNHL) occurred suddenly and predominantly at high frequen- treatment initiation. Improvement of the hearing thresholds was cies (Fig. 1). Evoked auditory brainstem responses confirmed the slower and incomplete. Hearing remained severely impaired on profound SNHL with no identifiable responses to 100-dB clicks. the left side (loss of 70 dB) and moderately impaired on the right The stapedius reflexes were absent at all frequencies. The neuro- side (loss of 30–40 dB) but stable. Seven years after disease onset, logic evaluation was normal. The ophthalmologic examination no other problems have occurred. Auditory and vestibular func- revealed uveitis secondary to probable viral conjunctivitis with tion have remained unchanged. after-effects of previous inflammatory episodes. Vestibular testing showed complete canal areflexia and some residual weak otolith Case 3 response to the OVAR test. The diagnosis of atypical Cogan’s syndrome was suggested An 18-year-old boy complained of sudden right-ear hearing because of the association of conjunctivitis and inner-ear lesions. loss and tinnitus without vertigo. He was hospitalized and treated All immunologic investigations were negative (Table 2). Steroid intravenously with steroids, mannitol, and vasodilators for 10 therapy was prescribed intravenously (prednisolone, 1 mg/kg/ days. This treatment normalized the hearing thresholds. Three day). After 1 week, hearing thresholds improved by 25 dB at all weeks later, he suffered from sudden left-ear hearing loss, bilateral frequencies on the left side. The uveitis remained without papil- tinnitus, headache, and ataxia without vertigo. He received the litis or keratitis. However, each attempt to decrease and eventually same treatment as before, but this time it was not effective. He stop the steroid treatment was associated with recurrent uveitis continued to complain of left-ear hearing loss and ataxia especially and a decrease in the hearing thresholds. This dependence on the in darkness. Three months later, he was referred to our depart- steroid was associated, 3 months after the beginning of the treatment for vestibular evaluation. ment, with ocular side effects—early-stage cataract (visual acuity The patient reported photophobia and eye redness before the of 2/10 in the right eye and 5/10 in the left eye) and acute first episode (right-ear hearing loss). His history revealed foot glaucoma that required surgical treatment (trabeculectomy on malformations (pes cavus) with limb jerk areflexia and familial both sides). Treatment with colchicine was attempted with relative neuropathy. Eight months earlier, he had received a second injec- success for the ophthalmologic status but not on hearing. Nine tion of vaccine for mumps (rubeole, oreillons, rougeole). Two years after the onset of the disease, this child required no medical months before the first episode of sudden hearing loss, his brother treatment but had bilateral profound deafness requiring special had mumps. His serology for Epstein-Barr virus (EBV) infection rehabilitation, vision that was stable and still compatible with was strongly positive, indicating a recent contact with the virus scholastic activity, and complete bilateral vestibular deficit that (Table 2). was well-compensated for. Cochlear implantation was suggested The results of neurophysiologic explorations (evoked visual but declined by the patient’s family for religious reasons. potentials, evoked somesthesic potentials of the upper and lower limbs, and electromyelogram) confirmed the diagnosis of heredi- tary polyneuropathy (Charcot-Marie-Tooth, type 1). Case 2 Hearing tests showed normal right tonal and vocal hearing During winter, a 13-year-old boy had fever (38°C–40°C) asso- thresholds with moderate left SNHL at lower frequencies (50 dB at ciated with myalgia, arthralgia, severe asthenia, headache, vomit- 125, 250, 750, and 500 Hz; 35 dB at 1 kHz) and normal threshold ing, and eye redness. At first, this suggested a viral infection, a for high frequencies (Ͼ2 kHz) (Fig. 1). Auditory brainstem-evoked reasonable diagnosis in the seasonal context. Treatment with responses were normal. Stapedial reflex thresholds were normal amoxicillin and nonsteroidal antiinflammatory drugs (NSAIDs) on the left side despite SNHL that indicated some recruitment and was not effective. an endocochlear disorder. The child was then hospitalized. His medical history revealed Vestibular testing revealed no spontaneous nystagmus and no that 1 month earlier he had experienced a severe reaction to a canal VORs during rotatory impulsions or caloric tests, whereas second vaccination for tuberculosis (BCG) with a large necrotic the otolith VORs were very weak bilaterally, indicating a severe ulceration at the injection site. bilateral vestibular deficit. The physical examination found cutaneous inflammatory signs Brainstem and inner-ear MRI showed no pathology of the at the level of the painful articulations (hands, ankles, the right cerebellopontine angle but an increased signal on T1 of the left elbow, and knee). The ophthalmologic examination was normal, inner ear, indicating a labyrinthitis. as were otorhinolaryngologic, cardiovascular, and neurologic Ophthalmologic evaluation showed corneal dystrophy with evaluations. loss of vision (right eye: 6/10; left eye: 8/10) and interstitial The results of the biological tests showed a nonspecific inflam- keratitis at the slit-lamp examination. mation (Table 2). This inflammatory syndrome associated with The diagnosis of a typical Cogan’s syndrome was then estab- joint pain suggested a dermatomyositis, but muscle, as well as lished, and intravenous steroid treatment (prednisone, 1 mg/kg/ liver, enzyme levels were normal. Joint radiographs were normal. day) was started. After 5 days of steroids, vestibular testing Juvenile arthritis with a systemic onset was diagnosed despite the showed a persistent complete bilateral vestibular deficit. Hearing

2of7 COCHLEOVESTIBULARDownloaded IMPAIRMENT from www.aappublications.org/news IN PEDIATRIC COGANby guest onЈ SSeptember SYNDROME 26, 2021 tests showed improvement of hearing thresholds for the frequencies 250, 500, and 1000 Hz (with normal thresholds for higher frequencies) on the left side. Steroids were continued orally with prednisolone (1 mg/kg/day). Two months later, hearing thresholds were normal for both ears. In contrast, vestibular function remained altered. Instability improved with regular physical therapy but remained disabling in darkness, probably because of the lack of somesthesic and proprioceptive information related to the familial polyneuropathy. At a ear functions eye lesions acuity deficit and conjunctivitis 4-year follow-up, hearing thresholds were normal, vestibular Ͼ 4 years No stabilization: Steroid dependence Recurrence of SNHL Ͼ 7 years Partial recovery of inner Complete remission of Ͼ 9 years Profound SNHL Low and stable visual Complete vestibular function was still impaired, and an ocular examination was normal. However, every attempt to decrease and stop the steroid treatment has been followed by fluctuating hearing loss and conjunctivitis. An immunosuppressive drug therapy (methotrexate) was started recently to improve the control of the disease with relatively good success, but after 5 months, attempts to decrease the dosage led to recurrence of eye and hearing impairments.

DISCUSSION

drugs Cogan’s syndrome is a rare chronic inflammatory 1-prednisolone 2-immunosuppressive 1-NSAID 2-immunoglobulins 3-prednisolone 1-prednisolone 2-colchicine disease that can be successfully treated if it is recog- nized early in its course. Children may present with signs identical to those of adults with typical Cogan’s syndrome (as in case 3) such as associated nonsyphilitic interstitial keratitis and cochleovestibular deficits (including vertigo and SNHL); or pediatric cases may involve atypical forms (case 1 with uveitis and case 2 with polyarthritis). Vollertsen et al17 reported that adult cases consist of 70% typical forms and 30% complete vestibular areflexia vestibular canal areflexia, normal otolith responses canal areflexia, otolith partial impairement atypical. Published data emphasize that in atypical forms the inflammation can involve the cornea as well as other parts of the eye.3 Audiovestibular symptoms may appear before or after ocular involvement (with as much as a 2-year interval).9 Our 2 cases of atypical Cogan’s syndrome involved bilateral uveitis 15 days after conjunctivitis with no associated interstitial karatitis. In one case, a severe flu-like syndrome Interstitial keratitis Bilateral sudden SNHL, Interstitial keratitis Bilateral fluctuating SNHL, Conjunctivitis, uveitis Bilateral SNHL, vestibular preceded by approximately 4 weeks the onset of ocular and cochleovestibular disorders.

Arguments Supporting an Autoimmune Origin for Cogan’s Syndrome The exact cause of Cogan’s syndrome remains un- known although several hypotheses have been suggested. The most commonly accepted hypothe- Symptoms Eye Lesions Inner-Ear Damage Treatments Follow-up sis—an autoimmune mechanism6,7,17,18—is supported by the frequently successful remission of hearing loss unsteadiness polyarthritis, fluctuating hearing loss, eye redness, unsteadiness sudden hearing loss Sudden hearing loss, Flu-like syndrome, juvenile Eye redness, vertigo, after steroid administration, the positive transfor- mation of the lymphoblastic test regarding cochlear antigen in some cases,19,20 and the association of Cogan’s syndrome with other autoimmune diseases such as rheumatoid arthritis.21–23 Schuknecht and Nadol24 published a histologic study of the temporal bone from a patient who had mumps (ROR) tuberculosis (BCG) mite antigens

Potential Trigger suffered from Cogan’s syndrome and later died of another pathology. The lesions observed in this case were similar to those usually found in other autoim-

Sex Past History, mune diseases: acute labyrinthitis with inner-ear tis- sue atrophy, endolymphatic hydrops, diffuse fibro- sis, and neural degeneration. In case 3 of our series, Age

Summary of the 3 Reported Cases of Cogan ’ s Syndrome MRI also revealed signs of labyrinthitis on 1 side (Year) (hypersignal on T1).18 The presence of abnormal antibodies in Cogan’s 3 18 Male Second vaccine for 2 13 Male Second vaccine for 1 5 Male Desensitization to syndrome is an argument for its immunologic origin;

Patient however, this is not consistently found. In a recent Number 25 TABLE 1. ROR indicates tri-vaccine for rubella – mumps measles. study, Casoli and Tumiati found elevated antibody

Downloaded from www.aappublications.org/newshttp://www.pediatrics.org/cgi/content/full/109/2/ by guest on September 26, 2021 e38 3of7 TABLE 2. Biological Tests Results for the 3 Reported Cases of Cogan’s Syndrome Blood Tests Results Case 1 Case 2 Case 3 Blood count Hypereosinophilia Normal Normal Erythrocyte sedimentation test 25 mm/h 125 mm/h C-reactive protein 205 mg/L 5 mg/L Syphilis serology Negative Negative Negative EBV serology Negative Negative Anti-VCA:670 UA Anti-EBNA:499 UA Mumps serology Negative Immunoglobulin G ϩ (2219 U) Immunoglobulin-negative HIV serology Negative Negative Negative Coxsakies A-B serology Negative Parvovirus B 19 serology Positive immunoglobulin G Positive immunoglobulin G and immunoglobulin M Hepatitis serology Negative Positive virus B Positive virus B Antiphospholipid antibodies Negative Antithymus antibodies Negative Antinuclear antibodies Negative Negative Rhumatoid factors Negative Negative Proteins electrophoresis Normal Normal Normal Histocompatibility leukocyte A28, A29, B5, B35 A1, A25, B18 B40, BW6 A2, B51, B8 antigens Cw4, Bw4, Bw6 Cryoglobulinemia Negative Ophthalmological slip Uveitis Interstitial keratitis Interstitial keratitis Cardiac echography Normal Normal Normal Abdominal echography Normal Lumbar puncture Normal

Fig 1. Hearing thresholds at onset of Cogan’s syndrome for the 3 reported cases. In cases 2 and 3 the SNHL is associated with recruitment (gap between the thresholds of the stapedial reflexes [Cϩ] and the air conduction hearing thresholds is clearly inferior to 70 dB). immunoglobulin G and immunoglobulin M an- ibility leukocyte antigen system are also described in tiphospholipid at 53.5 U/mL (normal value: Ͻ10U/ Cogan’s syndrome: haplotypes A9, Bw17, Bw35, and mL) and 41.5 U/mL (normal value: Ͻ6 U/mL), re- Cw4.26,27 We found haplotype Cw4 in our case 1. spectively, in a patient with Gougerot-Sjo¨gren Some authors consider vaccinations and infections syndrome, who presented with Cogan’s syndrome 6 to be triggering factors for Cogan’s syndrome.28–30 In years later.25 These authors suggest a correlation be- our study, the serology of parvovirus B19 was in- tween the presence of the anticardiolipid antibody creased in case 2, and the serology of EBV in case 3 and Cogan’s syndrome. Yamanishi et al26 described indicated recent infection with EBV. In cases 2 and 3, a case with atypical Cogan’s syndrome associated a second vaccination (for tuberculosis and mumps, with antineutrophil cytoplasmic antibody. In our respectively) could be related to the onset of Cogan’s case 3, assays for this antibody were negative. In syndrome. In case 1, the second injection of desensi- published papers, some antigens of the histocompat- tization against mite antigens was followed 15 days

4of7 COCHLEOVESTIBULARDownloaded IMPAIRMENT from www.aappublications.org/news IN PEDIATRIC COGANby guest onЈ SSeptember SYNDROME 26, 2021 later by conjunctivitis and uveitis, whereas hearing Ophthalmologic Abnormalities and vestibular loss appeared 2 months later. These Initially, clinical ocular signs—including conjunc- events in our 3 cases could correspond to an over- tivitis, photophobia, and eye redness—are appar- stimulation of a fragile immune system triggering ently benign. However, these symptoms must alert the onset of Cogan’s syndrome. This evidence argues the ophthalmologist, especially if there is no obvious for extreme prudence in managing immunizations in history of allergy. Interstitial keratitis represents the potentially vulnerable patients. most typical lesion of ocular disease in Cogan’s syndrome; however, a slit-lamp examination is required to confirm the diagnosis. Inflammation may involve Cochleovestibular Lesions: Labyrinthitis other tissues in the atypical forms, whether or not In the literature, the vestibular system in Cogan’s associated with interstitial keratitis.3 Uveitis associ- syndrome is affected before the cochlear system is by ated with SNHL may be confused with Vogt-Koy- an interval of days or weeks.7,28 Most often vestibu- anagi-Harada syndrome. The latter is an uveoen- lar damage is detected by clinical examination only, cephalitis characterized by meningitis signs, a and instrumental vestibular testing is seldom real- decrease of visual acuity with possible retinal sepa- ized, particularly in children. Cochlear damage is ration and blindness, SNHL, and discoloration of usually better documented.30 hairs (poliosis) or alopecia. Poliosis and alopecia do In Cogan’s syndrome the hearing loss may have a not occur in Cogan’s syndrome, even if meningism is sudden onset, as was the case with 2 patients in our sometimes present.32,33 Iritis, scleritis,4 episcleritis, series (cases 1 and 3). Fluctuating hearing loss may and chorioretinitis are rarely found in Cogan’s syn- occur during the course of the disease,29,31 like in drome. case 2. Without steroid treatment, it can rapidly progress to complete and definitive SNHL. In 2 cases Systemic Manifestations (2 and 3) the gap between thresholds of hearing (air Cogan’s syndrome is an inflammatory disease not conduction) and the thresholds of the stapedial reflex always restricted to the eyes and the inner ear. Sys- (Fig. 1) was smaller than found in normal subjects. temic manifestations occurred in 63% of the cases of This indicates recruitment and an endocochlear Yamanishi26 and 72% for Cheson.35 In 37% and 28% mechanism of the SNHL supporting the hypothesis [respectively 26, 35], the disease is only localized to of labyrinthitis in these 2 cases. the eyes and inner ear, as in our cases 1 and 3. The In our study, we evaluated vestibular and cochlear systemic manifestations can occur from 2 months to function over the course of several years of follow- 7 years32,33,36 after the first signs of Cogan’s syn- up. In case 2, vestibular function fluctuated as did drome. This illustrates the interest of long-term fol- cochlear function. In this case the vestibular damage low-up and the difficulties in the detection of these affected only semicircular canals but otolithic func- delayed lesions. Symptoms such as fever, arthralgia, tion was spared. In the other 2 cases vestibular func- myalgia, and weight loss are reported.32,33 tion was more severely impaired, suggesting a lesion Systemic manifestation may be the first and only of the whole sensorial vestibular apparatus. manifestation of Cogan’s syndrome for a long pe- In cases 1 and 2, the complete bilateral vestibular riod, and this may delay diagnosis. This was the case deficit was not disabling because of possible propri- in our second patient, whose fever, myalgia, and oceptive and visual compensation. But in case 3 the arthralgia occurred 1 month before the onset of au- instability was disabling (particularly in darkness), diovestibular loss. likely because of the lack of proprioceptive and som- However, systemic manifestations are basically at- esthesic information attributable to the degenerative tributable to systemic vasculitis of small, medium, 37 polyneuropathy. and large vessels. The histologic characteristics of Radiologic investigations were often done in the these lesions help rule out other causes of vasculitis, such as polyarteritis nodosa, Wegener’s granuloma- cases reported in the literature. Computed tomo- 5,37 graphic scans are typically normal, whereas MRI tosis, Takayasu’s disease, and Behc¸et’s disease. Vascular lesions with thrombosis, stenosis, and with gadolinium may reveal lesions consistent with bleeding can affect all organs. Cardiovascular mani- labyrinthitis, such as in case 3. This sign, although festations are the most serious and represent 10% of only rarely found, may depend on the stage of the cases of Cogan’s syndrome.17,35 Aortic insufficiency, inflammation at the level of the inner ear and could coronary stenosis,34,38 pericarditis, and arrhythmia be a very temporary sign. In case 3, which involved are the most common cardiac lesions. According to 2 successive sudden hearing loss episodes at a Haynes et al,3 aortic insufficiency is most common in 3-week interval (the first one on the right side and typical Cogan’s syndrome, whereas systemic vascu- the second on the left), the MRI showed increased litis occurs in the atypical form. This would suggest signal on T1 in the left ear (the side of sudden hear- that typical Cogan’s syndrome should not be consid- ing loss at that time) but the MRI was normal for the ered as a disorder strictly limited to the eyes and other side. Although many authors propose repeated inner ear and that in a long-term follow-up a regular MRI to better evaluate the progression of the dis- cardiac examination should be performed to ease,32–34 this costly strategy may be less informative promptly detect such complications for appropriate and effective than cochleovestibular functional eval- treatment.35 uations. Respiratory symptoms—including thoracic pain,

Downloaded from www.aappublications.org/newshttp://www.pediatrics.org/cgi/content/full/109/2/ by guest on September 26, 2021 e38 5of7 dyspnea, and hemoptysis or pleurisy—may occur.33 physicians because delayed diagnosis can be delete- None of our patients had cardiovascular or respira- rious to inner ear and visual neurosensory organs tory problems. attributable to delayed steroid treatment. The choice Abdominal lesions such as gastrointestinal bleed- of therapy is difficult in the long-term because of the ing have been reported,20 and 1 case of Cogan’s frequent side effects of the steroids and the risks of syndrome was associated with Crohn’s disease.39 immunosuppressive drugs in children. In our expe- Neurologic manifestations are not specific, varying rience Cogan’s syndrome appears to have been trig- from headache to coma.40 Le Coz41 described 1 case gered by overstimulation of the immune system, of Cogan’s syndrome revealed by meningeal signs. which argues for caution regarding immunization, Renal artery stenosis and cutaneous lesions (urticar- especially booster injections. ia) have also been reported.42,43 Prognosis of Cogan’s syndrome is difficult to evaluate in pediatric cases, and long-term follow-up is Treatment and Prognosis required to detect delayed complications, especially cardiovascular lesions, and to avoid their deleterious Early diagnosis of Cogan’s syndrome is important consequences. It is important to plan for the manage- because prompt treatment may prevent permanent ment of auditory and visual sensorial deficits, fre- profound hearing loss. quent after-effects of the disease. The most effective treatment is oral steroids.31,33,44 Promptly prescribed steroids can permit recovery of hearing. The inefficacy of delayed treatment is con- ACKNOWLEDGMENTS troversial.44 In our cases prednisone was adminis- This work was supported by grants from the Fondation pour la tered at 1 mg/kg/day, the dose given in previously Recherche me´dicale, Fondation de France, Fondation Reuter, and published cases of Cogan’s syndrome. However, grant 951008 from the Direction de la De´le´gation pour la Recher- some authors3 suggest that a higher dose of steroids che Clinique de L’Assistance Publique des Hoˆpitaux de Paris. (up to 2 mg/kg/day) during the 2 first weeks after We thank Dr S. I. Wiener for helpful editorial comments. onset of the disease would be more effective. Intra- venous administration during the first week is rec- REFERENCES ognized as preferable. However, such a high dose of 1. Morgan RF, Baumgartner CJ. 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