NLRP3-associated autoinflammatory disease (cryopyrin-associated periodic syndrome CAPS) is a rare autoinflammatory disorder most often caused by heterozygous gain-of-function variants in NLRP3 (CIAS1 on chromosome 1q44), leading to excessive inflammasome activation and overproduction of interleukin-1β. Diagnosis can be challenging because of phenotypic heterogeneity, somatic mosaicism, and low-penetrance variants.1 The patient, a 59-year-old woman with a history of seizure disorder, dry eye symptoms, and bilateral sensorineural hearing loss requiring hearing aids presented with one week of painless, progressive blurry vision in the right eye without previous episodes of vision loss, headache, or photophobia. On examination, she had a nonpruritic urticaria-like rash over the abdomen and limbs, which she reported having lifelong; episodes were triggered by cold exposure and, per patient report, fasting. Multiple relatives reportedly had similar episodic rashes. Ophthalmologic examination revealed a right relative afferent pupillary defect, mild optic nerve swelling, and conjunctival injection. Brain magnetic resonance imaging (MRI) demonstrated nonspecific white matter hyperintensities; the differential diagnosis included chronic microvascular change versus inflammatory or demyelinating pathology. Orbital MRI was interpreted as consistent with right posterior scleritis. Additional history revealed two first-degree relatives with genetically confirmed CAPS treated with interleukin-1 inhibitors. Initial laboratory results showed erythrocyte sedimentation rate of 33 mm/h (20 mm/h) and C-reactive protein 2.4 mg/dL (0.40–1 mg/dL). A glucocorticoid pulse was given for acute visual symptoms (3 days) without reported vision improvement. A broad evaluation for infectious, demyelinating, and immune-mediated etiologies was not supportive (Supplementary Table 1). Autoinflammatory genetic testing identified a pathogenic NLRP3 variant. Serum amyloid A (SAA) was elevated to 37 μg/mL, consistent with active systemic inflammation and an increased risk of AA amyloidosis. The pathophysiology and clinical spectrum of CAPS, and our patient's presentation, are summarized in Figure 1. Written informed consent was obtained from the patient for publication of this case report. CAPS spans a continuum commonly described as familial cold autoinflammatory syndrome, Muckle-Wells syndrome, and neonatal-onset multisystem inflammatory disease, with overlapping cutaneous, ocular, otologic, musculoskeletal, and neurologic features. Typical features include a recurrent urticaria-like rash that is often cold-triggered and nonpruritic, fatigue, musculoskeletal symptoms, and fever or subfebrile episodes; fever may be absent, particularly in milder phenotypes and in adulthood.2, 3 Most CAPS cases diagnosed in adulthood involve somatic NLRP3 mosaicism rather than inherited variants, reflecting the diagnostic challenges.1 Our patient, however, carried a pathogenic germline NLRP3 variant with lifelong symptoms yet was not diagnosed until age 59, underscoring the need for systematic screening of at-risk family members. In adult practice, neuro-ophthalmic manifestations can include headache or migraine, papilledema, and sensorineural hearing loss. Ocular involvement includes conjunctivitis and uveitis; conjunctivitis is the most frequently reported ocular lesion in large literature reviews. Posterior scleritis is a rare, potentially sight-threatening diagnosis; while usually painful, painless presentations occur, and imaging may assist diagnosis.4 To our knowledge, posterior scleritis has not been reported previously as an ocular manifestation of CAPS, making this case a novel addition to the recognized phenotypic spectrum of NLRP3-associated autoinflammatory disease. Evaluation relies on personal and family history, physical examination, and markers of inflammation during and between flares. SAA is particularly useful for detecting subclinical inflammation and stratifying amyloidosis risk.1 AA amyloidosis is a recognized complication, particularly when inflammation is undertreated, and may lead to renal failure. Interleukin-1 inhibition is central to disease control; SAA can monitor ongoing inflammatory activity relevant to amyloidosis risk.1, 3, 5 This case highlights the diagnostic complexity of CAPS in adults when childhood-onset symptoms go unrecognized. Lifelong cold-triggered urticaria-like rash, sensorineural hearing loss, seizures, and family history raised clinical suspicion, supported by identification of a pathogenic NLRP3 variant; elevated SAA further suggested active inflammation and amyloidosis risk. Early recognition is essential, because persistent inflammation can lead to severe complications, including AA amyloidosis. The authors thank the colleagues and collaborators for insightful discussions that contributed to the conceptual development of this paper. The authors used artificial intelligence (AI)–based tools to assist with language editing, grammar correction, and improvement of clarity in the manuscript. The AI tools were not used to generate scientific content, analyze data, or draw conclusions. All scientific content, interpretations, and conclusions are the sole responsibility of the authors. All authors contributed to at least one of the following manuscript preparation roles: conceptualization AND/OR methodology, software, investigation, formal analysis, data curation, visualization, and validation AND drafting or reviewing/editing the final draft. As corresponding author, Dr Kalemoglu confirms that all authors have provided the final approval of the version to be published and takes responsibility for the affirmations regarding article submission (eg, not under consideration by another journal), the integrity of the data presented, and the statements regarding compliance with institutional review board/Declaration of Helsinki requirements. Disclosure form. Supplementary Table 1: A broad evaluation for infectious, demyelinating, and immune-mediated etiologies were evaluated and they were all negative/ not supportive. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. 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Kalemoglu et al. (Fri,) studied this question.