Cogan's Syndrome With Neurological Manifestations and Concurrent Axial Spondyloarthritis: A Case Report

Cogan's syndrome is a rare, inflammatory disorder of unknown etiology characterized by ocular involvement and vestibuloauditory dysfunction [1]. The detection of antibodies against corneal, inner ear, and endothelial antigens is thought to be associated with an autoimmune pathogenesis [2]. Systemic manifestations such as headache, arthralgia, myalgia, fever, and arthritis are present in approximately half of the patients. The underlying cause of systemic symptoms is considered variable vessel vasculitis, which leads to organ and system involvement. We report a diagnostically challenging case of Cogan's syndrome with neurological manifestations and concurrent axial spondyloarthritis, successfully managed with immunosuppressive therapy. The patient was a 52-year-old male who presented with a 3-month history of persistent headache, bilateral red eyes, back pain, progressive hearing loss, dizziness, and significantly elevated inflammatory markers. Laboratory tests showed an erythrocyte sedimentation rate (ESR) of 80 mm/h, a CRP level of 81 mg/L (0–5 mg/L), as well as neutrophilic leukocytosis and microcytic anemia. Blood and urine cultures, as well as microbiological examinations including syphilis and brucella, were negative. Physical examination showed conjunctival redness, ataxic gait, and a positive Romberg test. Audiometric evaluation revealed moderate sensorineural hearing loss (SNHL) in the right ear and severe SNHL in the left ear, while the otoscopic examination showed normal findings. The ophthalmological examination indicated bilateral hyperemic conjunctiva, photophobia, clear corneas, and firm exudates in the bilateral papillomacular bands. The first cranial Magnetic Resonance Imaging (MRI) showed no abnormalities. Due to persistent headache, fever, eye symptoms, and tenderness of the thoracic vertebrae, a lumbar puncture was performed to investigate a possible central nervous system (CNS) infection. Cerebrospinal fluid (CSF) analysis showed pleocytosis and elevated protein levels with sterile culture results. Empirical anti-tuberculous therapy and dexamethasone were started based on a preliminary diagnosis of CNS tuberculosis. Doxycycline was also added due to positive Borrelia IgG and Bartonella IgG results, although confirmation tests for Borrelia were negative. Despite antimicrobial therapy, the patient's neurological and ocular symptoms progressed, with worsening ataxia and hearing loss. Follow-up cranial MRI showed large T2-weighted and FLAIR hyperintense lesions, up to 12 × 9 mm in size, in the right frontotemporal lobe and periventricular white matter, as shown in Figure 1. Diffusion-weighted imaging revealed diffusion-restricting patterns consistent with acute infarcts in the related areas and in the posterior crus of the right internal capsule. Grades 1–2 papilledema was observed during the ophthalmologic examination. Acetylsalicylic acid and clopidogrel were prescribed after the neurological consultation. Rheumatoid factor was positive at 35 IU/mL, while anti-citrullinated peptide antibodies, anti-nuclear antibodies, anti-neutrophil cytoplasmic antibodies, and antiphospholipid antibodies were all negative. Anti-tuberculous treatment was discontinued on the 38th day, following negative tuberculosis culture results and lack of clinical improvement. Color Doppler ultrasonography of the carotid and vertebral arteries was unremarkable, and transthoracic echocardiography revealed no vegetations or intracardiac masses. 18-Fluorodeoxyglucose-positron emission tomography (FDG-PET) was performed due to elevated ESR, cervical, and inguinal lymphadenomegaly and malignancy was ruled out, but mild FDG uptake was noted in the left carotid artery, raising suspicion for localized vasculitis. Despite antimicrobial and antiplatelet treatments, the patient continued to experience severe headache, ocular inflammation, progressive hearing loss, fatigue, vertigo, and persistent elevation of inflammatory markers. He was subsequently referred to the rheumatology department, where, after the exclusion of infectious diseases, a diagnosis of Cogan's syndrome was established. The patient was treated with intravenous pulses of glucocorticoids (1 g of methylprednisolone for 3 days), followed by 60 mg/day, and cyclophosphamide 1 g monthly. Significant clinical improvement was observed, including resolution of headache, weakness, vertigo, and ataxia. Inflammatory markers normalized, and partial hearing recovery was noted. Additionally, the patient had a three-year history of inflammatory low back pain. Sacroiliac joint MRI demonstrated bilateral active and chronic inflammatory changes, and HLA-B27 positivity supported the diagnosis of axial spondyloarthritis according to the Assessment of SpondyloArthritis International Society (ASAS) classification criteria [3]. Cogan's syndrome may present with systemic and neurological symptoms that complicate its diagnosis, especially in atypical cases. Neurological involvement of Cogan's syndrome has been reported in cases presenting with ischemic stroke, encephalitis, aseptic meningitis, and peripheral and cranial neuropathy [4]. CSF examination of Cogan's syndrome revealed pleocytosis, elevated protein levels, and sterile cultures [4]. In our patient, cranial MRI revealed both acute infarcts and multiple hyperintense lesions, while CSF analysis showed pleocytosis without evidence of infection. These findings strongly suggested CNS vasculitis, consistent with previously reported neurological involvement in Cogan's syndrome. In addition to neurological features, ocular findings are also variable in Cogan's syndrome. While interstitial keratitis is the most commonly described manifestation, other reported ocular presentations in Cogan's syndrome include conjunctivitis, uveitis, scleritis, and choroiditis [5]. The patient exhibited bilateral conjunctival hyperemia and photophobia, findings consistent with conjunctivitis. The patient fulfilled the ASAS classification criteria [3] for axial spondyloarthritis, based on inflammatory back pain, HLA-B27 positivity, and MRI findings of sacroiliitis. Cogan's syndrome coexisting with axial spondyloarthritis is extremely rare; only one similar case has been reported to date [6]. To date, no consistent association has been established between Cogan's syndrome and any specific HLA allele. In fact, the largest available HLA-typing study involving 10 well-characterized patients with Cogan's syndrome failed to demonstrate any significant correlation [7]. Therefore, the HLA-B27 positivity in our patient is more likely attributable to the coexisting axial spondyloarthritis. The management of Cogan's syndrome generally involves a combination of strategies aimed at controlling inflammation and related symptoms. Glucocorticoid therapy is often the first-line treatment and typically improves vestibulocochlear and ocular symptoms [8, 9]. Biological agents such as infliximab offer an alternative treatment for glucocorticoid or conventional immunosuppressive refractory patients [10]. This case highlights the diagnostic and management challenges of Cogan's syndrome, particularly when symptoms overlap. Although the patient met ASAS criteria for spondyloarthritis [3]; as the inflammatory back pain was resolved at the time of the diagnosis, he was given nonsteroidal anti-inflammatory drugs on demand. Early recognition and prompt initiation of immunosuppressive therapy are essential in preventing irreversible complications in Cogan's syndrome. Writing: Tugce Bozkurt, Data collection: Tugce Bozkurt and Sevilay Batibay, Review and editing: Elif Dincses-Nas and Esen Kasapoglu. The authors declare no conflicts of interest. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.