Ocular manifestations in Chinese adult patients with NLRP3-associated autoinflammatory disease.
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ABSTRACT:
SUBMITTER: Meng T
PROVIDER: S-EPMC8184759 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:PurposeTo determine whether the rare NLRP3-Associated Autoinflammatory Disease (NLRP3-AID) is associated with retinal changes and to assess the ocular involvement.MethodsA retrospective cohort study of 20 patients(40 eyes) diagnosed with rare NLRP3-AID at Peking Union Medical College Hospital, from April 2015 to August 2022. Patients underwent a comprehensive ophthalmological examination, including visual acuity, intraocular pressure examination, slit-lamp examination, fundus photography, optical coherence tomography(OCT), and fluorescence angiography (FA). Some patients also underwent optical coherence tomography angiography (OCTA).ResultsThis study analyzed 40 eyes of 20 patients (11 [55.0%] male; median age, 25.0 years [range, 12-52 years]) and 13 patients (26 eyes, 65%) demonstrated ocular involvement. The most common ophthalmologic manifestation was conjunctivitis (22 eyes, 84.6%), followed by papilledema (14 eyes, 53.8%), retinopathy (10 eyes, 38.5%), optic atrophy (6 eyes, 23.1%), uveitis (4 eyes, 15.4%), reduced pupil light reflex (3 eyes, 11.5%) and cataracts (2 eyes, 7.7%). Ocular involvement was bilateral in 11 patients (55.0%). Five kinds of retinal lesions were seen in 5 patients (10 eyes, 25%) with NLRP3-AID, including peripheral retinal vascular leakage, microaneurysms, macular ischemia, macular epiretinal membrane formation and drusen.ConclusionsPeripheral retinal vascular leakage, macular ischemia, microaneurysms and drusen are newly identified retinal findings in patients with NLRP3-AID, which suggests the importance of detailed retinal examination in these patients.
| S-EPMC10362747 | biostudies-literature
Project description:Objectives: NLRP3-associated autoinflammatory disease (NLRP3-AID) and Behçet's syndrome (BS) both belong to autoinflammatory diseases and rarely co-occur. Here we reported a Chinese pedigree of NLRP3-AID presented with BS. Methods: We recorded a Chinese pedigree of NLRP3-AID presented with BS. Whole-exome sequencing was performed to find the hereditary susceptibility gene, and Sanger sequencing was performed on a consecutive cohort of 30 BS patients. We also reviewed the English literature on vasculitis associated with NLRP3-AID. Results: The proband was a 45-year-old Chinese Han woman. She and her 12-year-old daughter presented with recurrent fevers, cold-induced urticaria, oral, and genital ulcers, conjunctivitis, uveitis, optic atrophy, erythema nodosum, headache, and hearing loss. They were initially suspected of having BS, and both responded poorly to corticosteroids and immunosuppressants, while anti-TNF therapy was moderately effective. Pedigree analysis revealed another four relatives with similar symptoms, and a heterozygous NLRP3 gene mutation c.1316C>T, p.Ala439Val was identified by whole-exome sequencing and Sanger sequencing. However, we did not discover NLRP3 gene mutation by Sanger sequencing in a confirmative cohort of 30 BS cases. A few case reports of vasculitis coexisting with NLRP3-AID, including a case of glomerulonephritis, and five cases of retinal vasculitis, were summarized through literature review. Conclusions: Our study is the first report of NLRP3-AID associated with BS. The coexistence of NLRP3-AID and BS reveals the extensive heterogeneity of the pathogenesis of systemic autoinflammatory diseases and calls for specific therapeutics.
| S-EPMC8264138 | biostudies-literature
Project description:ObjectivesANCA-associated vasculitis (AAV) is a group of multisystem diseases that can have several ocular manifestations. There are published data on ocular manifestations of granulomatosis with polyangiitis (GPA), but few for eosinophilic granulomatosis with polyangiitis (EGPA) or microscopic polyangiitis (MPA). There is little information concerning chronicity, complications, and association with other cranial manifestations of AAV.MethodsThis study retrospectively analysed longitudinal multicentre cohorts of individuals with AAV followed between 2006 and 2022. Data included diagnosis, demographics, cranial manifestations of disease, presence of manifestations at onset of disease and/or follow-up, and ocular complications of disease. Univariate and multivariable logistic regression analysis assessed associations across disease manifestations.ResultsData from 1441 patients were analysed, including 395 with EGPA, 876 with GPA, and 170 with MPA. Ocular manifestations were seen within 23.1% of patients: 39 (9.9%) with EGPA, 287 (32.7%) with GPA, and 12 (7.1%) with MPA at any time in the disease course. There were more ocular manifestations at onset (n = 224) than during follow-up (n = 120). The most common disease-related manifestations were conjunctivitis/episcleritis and scleritis. In multivariable analysis, dacryocystitis, lacrimal duct obstruction, and retro-orbital disease were associated with sinonasal manifestations of GPA; ocular manifestations were associated with hearing loss in MPA. The most common ocular complications and/or damage seen were cataracts (n = 168) and visual impairment (n = 195).ConclusionOcular manifestations occur in all forms of AAV, especially in GPA. Clinicians should be mindful of the wide spectrum of ocular disease in AAV, caused by active vasculitis, disease-associated damage, and toxicities of therapy.
| S-EPMC10321114 | biostudies-literature
Project description:BackgroundCryopyrin-associated periodic syndromes (CAPS) have been considered autoinflammatory diseases resulting from NLRP3 gene mutations. In recent years, these conditions have been redefined as NLRP3-associated autoinflammatory diseases (NLRP3-AID). Our previous study highlighted a case of a Chinese individual carrying the de novo NLRP3 mutation.ResultsA female child carrying a de novo variant (c.1718T>G, p. L573W) in the NLRP3 gene was presented in this work. The patient manifested various symptoms, including recurrent fever, a rash resembling urticaria, arthritis, physical growth retardation, a notable prominence of the forehead, and a flat nose bridge. Additionally, inflammatory markers, like WBC count, PLT count, CRP, ESR, and IL-6 showed elevated levels. Additionally, we observed interstitial pulmonary disease in the patient, which is not frequently mentioned in previous studies. Notably, the proband did not present with any ocular, auditory, or neurological symptoms. After 12 weeks of subcutaneous canakinumab injection, there was a clear improvement in the patient's clinical manifestations and inflammatory markers.ConclusionOur study contributes to broadening the clinical spectrum of established pathogenic variants of NLRP3 gene, which are related to NLRP3-AID.
| S-EPMC10579556 | biostudies-literature
Project description:ObjectivesCryopyrin-associated periodic syndrome or NLRP3-associated autoinflammatory disease (NLRP3-AID) and NLRP12-AID are both Mendelian disorders with autosomal dominant inheritance. Both diseases are rare, primarily reported in the pediatric population, and are thought to be phenotypically indistinguishable. We provide the largest cohort of adult-onset patients and compared these diseases and the gene variant frequency to population controls.MethodsA cohort of adult patients with AIDs were retrospectively studied. All underwent molecular testing for periodic fever syndrome gene panels after extensive and negative workups for systemic autoimmune and other related diseases. Patients were divided into Group 1- NLRP3-AID patients with NLRP3 variants (N=15), Group 2- NLRP12-AID with NLRP12 variants (N=14) and Group 3- both NLRP3 and NLRP12 (N=9) variants. Exome sequence data of two large control populations including the ARIC study were used to compare gene variant distribution and frequency.ResultsAll 38 patients were Caucasian with women accounting for 82%. Median age at diagnosis was 41 ± 23 years and the disease duration at diagnosis was 14 ± 13 years. We identified statistically significant differences between the groups, notably that gastrointestinal symptoms as well as evaluations for same were significantly more frequent in patients with NLRP12 variants, and headaches/dizziness were less common among the NLRP12 patients. Livedo reticularis was noted in four patients, exclusively among NLRP12 carriers. Over 50% of patients in Groups 1 and 2 carry low-frequency disease-associated variants, while the remaining carry rare variants. We unprecedently identified digenic variants, i.e., the coexistence of NLRP3 and NLRP12, which were either both low frequency or low frequency/rare. Allele frequencies of all variants identified in our cohort were either absent or significantly lower in the control populations, further strengthening the evidence of susceptibility of these variants to SAID phenotypes.ConclusionOur comparative study shows that both NLRP3-AID and NLRP12-AID share similar clinical phenotypes, yet there are significant differences between them with regard to gastrointestinal and neurological symptoms. A spectrum of high to low genetic variations in both genes can contribute to SAID individually or in combination.
| S-EPMC10853347 | biostudies-literature
Project description:Extraintestinal manifestations of gastrointestinal disease can form an important aspect of the diagnosis, monitoring and management in these diseases. Ocular manifestations in particular are often disregarded and can, albeit rarely, present as an emergency.
| S-EPMC7043099 | biostudies-literature
Project description:BackgroundNLRP3-associated autoinflammatory disease (NLRP3-AID), caused by mutations of NLRP3, is one of the autoinflammatory diseases affecting inflammasomes. Since there are little cases of Chinese NLRP3-AID, we reported 14 Chinese NLRP3-AID patients in our center and summarized the clinical features of all Chinese patients by reviewing the literature.ResultsFourteen patients had been diagnosed as NLRP3-AID in our center. 12 different NLRP3 variants were identified, among which one is novel: p.Leu361Trp. Rash, recurrent fever, arthritis/arthralgia, uveitis, sensorineural deafness, symptoms of central neural systems (CNS), and increased inflammatory markers (including CRP, ESR, except Ferritin) were the common findings in Chinese patients. The frequencies of fever, neurological symptoms, musculoskeletal manifestations and ocular manifestations in Chinese patients might differ from that of patients from other regions. Besides, we also found clubbing fingers and optic neuritis in some NLRP3-AID patients, which were not commonly mentioned in previous reports.ConclusionIn our study, we expanded the clinical spectrum as well as the genetic pathogenic variants of NLRP3-AID. We also found that there were some differences between Chinese patients and patients from other regions, and that Chinese patients were more likely to develop severe symptoms.
| S-EPMC9169254 | biostudies-literature
Project description:PURPOSE:This study aims to assess the evolution of ocular manifestations in a cohort of Fabry patients. METHODS:This is a prospective observational study conducted from 2013 to 2017 (5 consecutive exams). All subjects underwent a comprehensive ocular examination including oriented case history, refraction, corneal topography, biomechanical corneal properties and pachometry assessments, aberrometry, anterior segment evaluation, double-frequency visual field (FDT), intra-ocular pressure, and ocular fundus. At baseline, 41 subjects enrolled but 9 dropped-out and 4 files were not kept for analysis (missing data). Remaining 28 subjects were classified into: Group 1 -hemizygotes (HMZ), all on enzyme replacement therapy (ERT) (N = 10); Group 2 -heterozygotes (HTZ) actively ERT-treated (N = 8), and Group 3 -HTZ not treated (N = 10). RESULTS:There is a high intra and inter-subjects variability. At baseline, prevalence of the ocular manifestations found is similar to published data: cornea verticillata (89.2%), conjunctival vessels tortuosity (85.7%), corneal haze (67.8%), retinal vessels tortuosity (64.2%), anterior cataract (39.2%) and posterior cataract (28.5%). Prevalence for new elements are found: upper lid vessels toricity (96.4%) and micro-aneurysms (42.8%). At the end, micro-aneurysms (+82%), posterior cataract (+75%) corneal haze (+21%) anterior cataract (+17%) and retinal vessels tortuosities (+4%) evolved in prevalence and severity despite the fact that 68% of the patients were on ERT. Treated heterozygotes evolved more than other groups (p>0.05). CONCLUSION:ERT does not seem to halt the clinical evolution of several ocular manifestations. Longer observational time and objective grading systems may be required to fully confirm these findings.
| S-EPMC6597042 | biostudies-literature
Project description:The objective of this review is to describe the clinical manifestations of the growing spectrum of monogenic autoinflammatory diseases including recently described syndromes. The autoinflammatory diseases can be grouped based on clinical findings: 1. the three classic hereditary "periodic fever syndromes", familial Mediterranean Fever (FMF); TNF receptor associated periodic syndrome (TRAPS); and mevalonate kinase deficiency/hyperimmunoglobulinemia D and periodic fever syndrome (HIDS); 2. the cryopyrin associated periodic syndromes (CAPS), comprising familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS) and neonatal-onset multisystem inflammatory disease (NOMID) or CINCA, and; 3. pediatric granulomatous arthritis (PGA); 4. disorders presenting with skin pustules, including deficiency of interleukin 1 receptor antagonist (DIRA); Majeed syndrome; pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome; deficiency of interleukin 36 receptor antagonist (DITRA); CARD14 mediated psoriasis (CAMPS), and early-onset inflammatory bowel diseases (EO-IBD); 5. inflammatory disorders caused by mutations in proteasome components, the proteasome associated autoinflammatory syndromes (PRAAS) and 6. very rare conditions presenting with autoinflammation and immunodeficiency.
| S-EPMC3769788 | biostudies-literature
Project description:ObjectiveTrichothiodystrophy (TTD) is a rare, autosomal recessive disorder characterized by sulfur-deficient brittle hair and multisystem abnormalities. Many TTD patients have a defect in known DNA repair genes. This report systematically evaluates the ocular manifestations of the largest-to-date cohort of TTD patients and xeroderma pigmentosum (XP)/TTD patients.DesignCase series.ParticipantsThirty-two participants, ages 1 to 30 years, referred to the National Eye Institute for examination from 2001 to 2010; 25 had TTD and 7 had XP/TTD.MethodsComplete, age- and developmental stage-appropriate ophthalmic examination.Main outcome measuresVisual acuity (VA), best-corrected VA, ocular motility, state of the ocular surface and corneal endothelial cell density, corneal diameter, and lens assessment.ResultsDevelopmental abnormalities included microcornea (44% TTD), microphthalmia (8% TTD, 14% XP/TTD), nystagmus (40% TTD), and infantile cataracts (56% TTD, 86% XP/TTD). Corrective lenses were required by 65% of the participants, and decreased best-corrected VA was present in 28% of TTD patients and 71% of XP/TTD patients. Degenerative changes included dry eye (32% TTD, 57% XP/TTD) and ocular surface disease identified by ocular surface staining with fluorescein (32% TTD) that usually are exhibited by much older patients in the general population. The 2 oldest TTD patients exhibited clinical signs of retinal/macular degeneration. Four XP/TTD patients presented with corneal neovascularization.ConclusionsThese TTD and XP/TTD study participants had a wide variety of ocular findings including refractive error, infantile cataracts, microcornea, nystagmus, and dry eye/ocular surface disease. Although many of these can be ascribed to abnormal development--likely owing to abnormalities in basal transcription of critical genes--patients may also have a degenerative course.Financial disclosure(s)Proprietary or commercial disclosures may be found after the references.
| S-EPMC3230678 | biostudies-literature