Ocular Manifestations of Chronic Infantile Neurological Cutaneous and Articular Syndrome: A Case Report

Dear Editor,

Chronic infantile neurological cutaneous and articular (CINCA) syndrome, also known as neonatal-onset multisystem inflammatory disease, is a rare chronic inflammatory disease within the spectrum of cryopyrin-associated periodic syndrome [1]. It is caused by mutations in the NLRP3 gene, resulting in excessive interleukin-1β (IL-1β) production. The classic clinical triad includes neonatal-onset cutaneous rash, chronic meningitis, and recurrent arthritis. Ocular involvement, including recurrent uveitis, optic disc changes, and retinal complications, is less commonly described.

Herein, we present a case of a 23-year-old female patient who was genetically diagnosed with CINCA syndrome at another hospital (NLRP3 gene, c.1715A>G, p.Tyr572Cys) and presented with chronic bilateral uveitis and anomalies in the optic disc and retinal vasculature. Written informed consent for publication was obtained from the patient.

At the initial presentation at 21 years of age, she had a history of recurrent bilateral anterior uveitis and sensorineural hearing loss, treated with cochlear implantation six years earlier. Since age 14 years, she had been receiving anakinra, an IL-1 receptor antagonist, for the management of systemic inflammation. On ophthalmologic evaluation, best-corrected visual acuity was 20 / 40 in the right eye and 20 / 32 in the left eye. Intraocular pressure was normal. Slit-lamp examination showed quiet anterior chambers without inflammatory cells, and posterior subcapsular cataract was noted in the left eye. Fundus examination demonstrated bilateral optic disc swelling and peripheral perivascular sheathing (Fig. 1A–1D). Pupillary responses were normal without relative afferent pupillary defect. Macular optical coherence tomography (OCT) scans were unremarkable, but disc OCT scans revealed anterior angulation of Bruch’s membrane (Fig. 1E–1H). Ultrawide-field fundus fluorescein angiography showed good retinal perfusion bilaterally with mild peripheral retinal vascular leakage in the left eye and optic disc leakage in both eyes (Fig. 1I–1L). Electroretinography demonstrated preserved rod and cone function. Visual field testing was not possible due to limited cooperation. At subsequent follow-ups, visual acuity, intraocular pressure, and the status of the retina and optic nerve remained stable.

Fig. 1

Multimodal images of the patient. (A, B) Fundus photography shows bilateral disc edema. (C, D) Wide fundus photography shows peripheral vascular sheathing in both eyes, suggesting vasculitis affecting the peripheral retina. (E–H) Peripapillary optical coherence tomography scans showed anterior angulation of Bruch’s membrane. (I, J) Early-phase wide fluorescein angiography demonstrates optic disc leakage in both eyes. (K, L) Late-phase fluorescein angiography reveals marked leakage from the optic discs and peripheral retinal vessels.

In the multicenter study by Dollfus et al. [2], which evaluated 31 patients with CINCA syndrome, optic disc abnormalities, including optic disc edema, pseudopapilledema, and optic atrophy, were observed in 84% of patients. Anterior segment involvement was observed in 42% of patients, including perilimbal injection and conjunctivitis. Chronic anterior uveitis was present in 55% of cases. Posterior segment involvement was observed in 19% of patients. Moderate to severe visual acuity loss in at least one eye occurred in 26% of patients.

The retinal abnormalities observed in patients with CINCA syndrome are thought to result from chronic, uncontrolled systemic inflammation driven by NLRP3 gene gain-of-function mutations. These mutations activate the inflammasome pathway and cause overproduction of IL-1β, contributing to persistent inflammation involving multiple organ systems. In the posterior segment of the eye, this can manifest as posterior uveitis or optic disc swelling and may progress to structural retinal damage if left untreated. IL-1 blockade with agents such as anakinra has shown favorable systemic outcomes. Ophthalmologically, there has been a reported case in which anakinra led to sustained quiescence of uveitis, and resolution of vitritis and disc swelling, allowing tapering of systemic corticosteroids [3]. Reports of macular edema resolution and improvement of blepharitis further support the potential ocular benefits of IL-1 inhibition [1].

In our case, optic disc swelling was present bilaterally at presentation, with spectral-domain OCT revealing anterior angulation of Bruch’s membrane, suggesting prior optic nerve damage. Although some previous reports have suggested that optic nerve changes in CINCA syndrome may result from elevated intracranial pressure or recurrent intraocular inflammation, it was difficult to determine the exact cause in our patient due to limited past medical history and absence of neuroimaging data [4]. Despite controlled anterior chamber inflammation at the time of presentation, the presence of posterior subcapsular cataract and peripheral vascular leakage on wide-field angiography indicates chronic low-grade inflammation or prior inflammatory insults. Retinal involvement in CINCA syndrome has been reported to vary widely, from mild peripheral changes to severe retinal degeneration [5]. In our case, peripheral retinal vasculitis was observed without significant macular involvement, and visual acuity remained relatively preserved.

This case highlights the importance of comprehensive ophthalmologic evaluation, as CINCA syndrome can involve both the anterior and posterior segments including the optic disc. Thorough ophthalmologic evaluation upon diagnosis and regular surveillance are essential to prevent sight-threatening complications from uncontrolled chronic ocular inflammation.