HLA-B27 positive juvenile idiopathic arthritis associated uveitis presenting with an acute onset and a chronic course

HLA-B27 positive juvenile idiopathic arthritis associated uveitis presenting with an acute onset and a chronic course | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report HLA-B27 positive juvenile idiopathic arthritis associated uveitis presenting with an acute onset and a chronic course Arash Maleki This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5769844/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose The occurrence of Human leukocyte antigen-(HLA-) B27-associated bilateral granulomatous panuveitis in a pediatric patient ultimately diagnosed with oligoarticular juvenile idiopathic arthritis JIA. Methods A case report. Case Presentation: A 10-year-old girl was evaluated for redness, pain, and photophobia in both eyes (OU) with no other ocular or systemic symptoms. Her best-corrected visual acuity was measured at 20/20 and 20/40 right (OD) and 20/40 left (OS) eyes, respectively. A slit lamp examination revealed mutton-fat keratic precipitates OU, anterior chamber reaction 1 + and 4 + cells OD and OS, respectively, and anterior vitreous 2 + cells OU. During dilated fundoscopy, 1 + OS haze was observed. Intravenous fluorescein angiography depicted mild disc OS and peripheral vascular leakage OU. Indocyanine green angiography revealed hypocyanescent lesions in choroid OU indicating of choroiditis. All lab work-up were negative or within the normal limits except positive HLA-B27. She was started on aggressive corticosteroids therapy, followed by a gradual taper. A flare-up occurred while she was on a regimen of 10 mg oral prednisolone and two drops of prednisolone OU. Then, immunomodulatory therapy was initiated with adalimumab and oral methotrexate. The eyes remained in remission with this regimen until she developed arthritis in the left knee and wrist, along with bilateral sacroiliitis. The pediatric rheumatology team decided to transition to golimumab, concurrently increasing the dosage of methotrexate. Conclusion Chronic bilateral panuveitis with an acute onset granulomatous anterior uveitis component may be indicative of HLA-B27 associated JIA. It can be coupled with a delayed onset oligoarticular JIA. adalimumab golimumab HLA-B27 juvenile idiopathic arthritis panuveitis Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Summary Statement Uveitis can be the first presentation of juvenile idiopathic arthritis (JIA) in 3-7% of the patients. HLA-B27 positive JIA typically presenting as unilateral acute anterior uveitis. Chronic bilateral granulomatous panuveitis may be indicative of HLA-B27 associated JIA. It can be coupled with a delayed onset oligoarticular JIA. Introduction Juvenile idiopathic arthritis (JIA) is a chronic rheumatologic condition with an unknown origin, characterized by arthritis lasting more than six weeks in children and adolescents before the age of sixteen. 1 Uveitis represents the most prevalent extra-articular manifestation observed in JIA. 2 The reported incidence of uveitis in JIA shows significant variation across different studies; however, the point prevalence is frequently documented to range between 10% and 15%. 2 Currently, HLA-B27 holds a central role in the classification of JIA and serves as one of the inclusion criteria for the enthesitis-related arthritis (ERA) category. The presence of HLA-B27 has been demonstrated to predict a more prolonged disease course, associated with an older age at disease onset in male patients. 3 To the best of our knowledge, bilateral granulomatous panuveitis hasn't been documented in the ophthalmology literature in association with HLA-B27 JIA. This study details the occurrence of HLA-B27-associated bilateral granulomatous panuveitis in a 10-year-old female ultimately diagnosed with oligoarticular JIA. Materials and Methods This study is a case report. The written informed consent was obtained from the mother of the patient for publication. Results A 10-year-old girl was evaluated at our clinic due to redness, pain, and photophobia in both eyes (OU), but more severely in the left eye (OS). The symptoms had started two weeks before the initial visit with us. Initially, erythromycin ointment was administered at the onset of the symptoms, and later switched to ofloxacin drops, leading to slight improvement in the right eye (OD). The patient denied experiencing loss of vision, photopsia, floaters, headache, recent flu-like symptoms and any systemic illnesses, skin and joint issues, headache, and hearing problems. Her best-corrected visual acuity (BCVA) was measured at 20/20 OD and 20/40 OS. Intraocular pressure (IOP) was 21 mmHg OD and 19 mmHg OS. A slit lamp examination revealed mild conjunctival injection (OU), mutton-fat and fine keratic precipitates (KPs) OU in Artl’s triangle, anterior chamber reaction 1 + cells OD and 4 + cells OS, and anterior vitreous 2 + cells OU. During dilated fundoscopy, no haze OD and 1 + haze OS in the media, otherwise normal ( Fig. 1 A, B ) . Optical coherence tomography (OCT) of the macula showed a normal structure and contour OU without significant choroidal thickening OU ( Fig. 2 A, B ) . Optic nerve head OCT retinal nerve fiber layer (rNFL) thickness mapping demonstrated slightly thickening of rNFL OS ( Fig. 3 A, B ) . Intravenous fluorescein angiography (IVFA) depicted mild peripheral vascular leakage OU and mild disc leakage and staining OS ( Fig. 4 A, B ) . Indocyanine green angiography (ICGA) revealed hypocyanescent lesions in choroid OU, mostly in the temporal choroid suggestive of choroiditis OU ( Fig. 5 A, B ) . Comprehensive blood work-up, including complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), antinuclear antibody (ANA), anti-neutrophilic cytoplasmic antibody (ANCA), urinalysis (U/A), interleukine-6 (IL-6), human leukocyte antigen- (HLA-) A29, B44, B51, DR1, DR4, DR15, angiotensin converting enzyme (ACE), lysozyme, 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D, quantiferon TB gold, rapid plasma regain (RPR), Lyme western blot, and treponema pallidum- particle agglutination (TP-PA) were within the normal range or negative; however HLA-B27 was positive. A pediatric rheumatology consultation was conducted and was reported normal. Chest CT scan, ordered by the pediatric rheumatology team, was reported normal with no lung involvement or hilar lymphadenopathy. Given the diagnosis of panuveitis and Harada-like disease, the patient was started on 40 mg of prednisone (1 mg/kg), atropine 1% twice daily, and prednisolone acetate 1% every two hours with slow tapering schedule. One week later, the eye examination showed improvement. The topical steroid was initiated to taper on a weekly basis, and oral prednisone at a dose of 5 mg every two weeks. One month later, BCVA was 20/20 OU and IOP 20 mmHg OU. The anterior and posterior segments examination ( Fig. 1 C, D ) , OCT macula ( Fig. 2 C, D ) , OCT optic nerve ( Fig. 3 C, D ) , IVFA ( Fig. 4 C, D ) and ICG ( Fig. 5 C, D ) were normal. The eyes remained quiet until a recurrence occurred, marked by 2 + AC reaction in both eyes and 1 + vitreous haze in the left eye despite the patient being on a regimen of 10 mg oral prednisolone and two drops of prednisolone OU. At this point, immunomodulatory was initiated and she commenced adalimumab at a dosage of 40 mg biweekly, including two loading doses, along with weekly orally administered methotrexate at a dosage of 15 mg. Corticosteroid therapy remained unchanged for a month before gradually tapering and being discontinued entirely within the following month. The eyes remained in remission with this regimen until, after nine months, she developed arthritis in the left knee and left wrist, along with bilateral sacroiliitis confirmed by ultrasound and magnetic resonance imaging (MRI). Given adalimumab ineffectiveness and the superior impact of golimumab on joints, the pediatric rheumatology team opted to transition to golimumab, concurrently increasing the dosage of methotrexate to 20 mg of through subcutaneous injections. The latest eye examination conducted two months later revealed remission in anterior and posterior ( Fig. 1 E, F ) exams, accompanied by an improvement in joint signs and symptoms. OCT macula and optic nerve ( Fig. 2 E, 2 F, 3 E, and 3 F ) , IVFA ( Fig. 4 D, F ) , and ICGA ( Fig. 5 E, F ) were normal. Discussion JIA associated uveitis is recognized for its challenging prognosis and elevated risk of complications. The condition imposes significant consequences on patients and their families. Timely diagnosed and prompt treatment are paramount for ensuring a favorable long-term prognosis. 4 Anterior uveitis associated with JIA typically manifests as a chronic, non-granulomatous anterior uveitis. Uveitis can be the first presentation of JIA in 3–7% of the patients, even though it may be asymptomatic. 4 Juvenile seronegative spondyloarthropathies (JSpA) is a subtype of JIA which that is linked with uveitis. It compasses conditions such as psoriatic arthritis, ankylosing spondylitis, enthesitis-related arthritis, reactive arthritis and enthropathic artritis. Two cohorts of JSpA exhibited that enthesitis-related arthritis had a high rate of HLA-B27 positivity. 5 The arthritis typically exhibit asymmetry, oligoarticular, and predominantly affects larger joints in lower extremities. Hip arthritis indicates the diagnosis and axial involvement has been documented in up to 30% of children within 15 months of diagnosis. 6 Acute anterior uveitis is one of the extra-articular manifestations of JSpA. Uveitis is characterized by unilateral, sudden inflammation accompanied redness, pain, photophobia and it is observed in approximately one-quarter of children with JSpA 7 ; however, uveitis can be asymptomatic. 8 Zuber and colleagues 9 diagnosed uveitis in 5.6% of their patients, predominantly in those with oligoarthritic arthritis and enthesis-related arthritis. Among these children, 64.3% tested positive for HLA-B27 antigen. The median age of onset of JIA in these individuals was 13.5 years. Heiligenhaus and colleagues 10 reported that acute symptomatic uveitis alternated between two eyes in 20% of patients with enthesitis-related JIA. Ryptal et al. 3 documented intermediate uveitis and panuveitis in one (1.4%) and two (2.8%) of their patients, respectively. In their study, six out of nine patients with an acute course of uveitis were positive for HLA-B27, and among them, five patients exhibited HLA positive enthesitis-related arthritis. While these study offers invaluable insights into the characteristics of HLA-B27 positive patients with JIA and JIA-associated uveitis, it lacks more detailed information about their uveitis. We ruled out sarcoidosis as a diagnosis for our patient, as all relevant blood tests, including ACE, lysozyme, 25-hydroxy vitamin D, and 1,25-hydroxy vitamin D, returned negative results. Furthermore, a chest CT scan showed no abnormalities. Additionally, as the course progressed, the patient fulfilled the criteria for JIA along with its associated uveitis, characterized by arthritis in one or more joints persisting for at least 6 weeks, commencing prior to the age of 16, notably accentuated by her HLA-B27 positivity. Our patient was unique since both axial and peripheral joints were involved without any signs of enthesitis. 9 , 10 To the best of our knowledge, bilateral, granulomatous, and acute initiation with chronic course has not been reported in the literature for HLA-B27 positive JIA-associated uveitis. Considering the extensive eye involvement in our patient, it may be justifiable to conduct a more comprehensive evaluation of the retina, retinal vessels, and choroid using OCT, IVFA, and ICG in patients with HLA-B27 JIA-associated uveitis. Moreover, given the fact that her eyes responded to initial immunomodulatory therapy, but later showed involvement of axial and extra-axial joints suggest the need for a more thorough evaluation of joints using sophisticated techniques such as ultrasound and MRI of larger peripheral and axial joints. This proactive approach aims to detect joint involvement before symptoms manifest in HLA-B27 patients with uveitis. These facts seem to be crucial since extensive eye and possible systemic involvement may necessitate earlier initiation of IMT with more potent agents, which could be delayed in IMT in cases of isolated limited eye involvement. However, these hypotheses should be proven with more potent studies. We might face criticism for not initiating IMT promptly after diagnosing her with bilateral panuveitis with a granulomatous anterior uveitis component. Despite admitting this criticism after this case report, first, our comprehensive blood work-up revealed no abnormalities except for a positive HLA-B27 antigen. We consulted our pediatric rheumatology team to assess the patient for extraocular active and inactive signs of positive HLA-B27 in this age group and the evaluation yielded negative results. Second, there were no other symptoms and signs of vogt-Koyanagi-Harada (VKH) disease in our patient, and there was no recent history of flu-like symptoms. Hence, we diagnosed the patient with Harada-like disease. Recognizing the requirement for long-term aggressive IMT in Vogt-Koyanagi-Harada (VKH) or Harada disease, we opted to initiate treatment with oral steroids and implement a gradual taper before deciding on the use of IMT especially given the fact that her family was not prepared for long-term IMT therapy or aggressive procedure such as lumbar puncture for evaluation of cerebrospinal fluid (CSF). Conclusion bilateral panuveitis with granulomatous anterior uveitis component, characterized by an acute onset and chronic course, coupled with a delayed onset of oligoarticular JIA involving both axial and extra-axial components, can be indicative of HLA-B27 associated JIA. The significance of this case lies in the distinctive presentation, underscoring the need for thorough systemic and ocular investigations in similar patients. Declarations Statement of Ethics : Ethics approval was not required in accordance with local guidelines and University of Florida Intuitional Review Board. Conflict of interest Statement: The authors have no conflicts of interest to declare. Consent for publication T he written informed consent was obtained from the mother of the patient for publication. Funding Sources: This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors. Author Contribution Arash Maleki contribution in this study included conception and design of the study, data analysis and interpretation, drafting of the manuscript, and approval of the final version of the manuscript. Acknowledgement The authors express their gratitude to Dr. Ibrahim Sacit Tuna, MD and Bryce E. Buchowicz, MD for the interpretation of the MRI images. Data Availability Data is provided within the manuscript or supplementary information files References Petty RE, Southwood TR, Manners P, et al. International League of Associations for Rheumatology. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol. 2004;31(2):390–2. Rypdal V, Glerup M, Songstad NT, et al. Nordic Study Group of Pediatric Rheumatology. Uveitis in Juvenile Idiopathic Arthritis: 18-Year Outcome in the Population-based Nordic Cohort Study. Ophthalmology. 2021;128(4):598–608. 10.1016/j.ophtha.2020.08.024 . Berntson L, Nordal E, Aalto K, Peltoniemi S, Herlin T, Zak M, Nielsen S, Rygg M, Nordic Study Group of Paediatric Rheumatology. HLA-B27 predicts a more chronic disease course in an 8-year followup cohort of patients with juvenile idiopathic arthritis. J Rheumatol. 2013;40(5):725–31. 10.3899/jrheum.121257 . Heiligenhaus A, Heinz C, Edelsten C, Kotaniemi K, Minden K. Review for disease of the year: epidemiology of juvenile idiopathic arthritis and its associated uveitis: the probable risk factors. Ocul Immunol Inflamm. 2013;21(3):180–91. 10.3109/09273948.2013.791701 . Weiß A, Minden K, Listing J, Foeldvari I, Sieper J, Rudwaleit M. Course of patients with juvenile spondyloarthritis during 4 years of observation, juvenile part of GESPIC. RMD Open., Weiss PF, Klink AJ, Behrens EM, Sherry DD, Finkel TH, Feudtner C, Keren R. Enthesitis in an inception cohort of enthesitis-related arthritis. Arthritis Care Res (Hoboken). 2011;63(9):1307-12. 10.1002/acr.20508 Pagnini I, Savelli S, Matucci-Cerinic M, Fonda C, Cimaz R, Simonini G. Early predictors of juvenile sacroiliitis in enthesitis-related arthritis. J Rheumatol. 2010;37(11):2395–401. 10.3899/jrheum.100090 . Zeboulon N, Dougados M, Gossec L. Prevalence and characteristics of uveitis in the spondyloarthropathies: a systematic literature review. Ann Rheum Dis. 2008;67(7):955–9. 10.1136/ard.2007.075754 . Rychwalski PJ, Cruz OA, Alanis-Lambreton G, Foy TM, Kane RE. Asymptomatic uveitis in young people with inflammatory bowel disease. J AAPOS. 1997;1(2):111–14. 10.1016/s1091-8531(97)90009-4 . Żuber Z, Turowska-Heydel D, Sobczyk M, Chudek J. Prevalence of HLA-B27 antigen in patients with juvenile idiopathic arthritis. Reumatologia. 2015;53(3):125–30. 10.5114/reum.2015.53133 . Heiligenhaus A, Minden K, Föll D, Pleyer U. Uveitis in juvenile idiopathic arthritis. Dtsch Arztebl Int. 2015;112(6):92–100, i. 10.3238/arztebl.2015.0092 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5769844","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":398310159,"identity":"003b1fb0-55cd-4c55-904a-0cbd21f01741","order_by":0,"name":"Arash Maleki","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABAUlEQVRIiWNgGAWjYJACZhDBx8DGcCDBwAbIZGw8QJQWNpCWDwVpIC0NxGthnPHhMFgErxb+2Ycffy5g2CbPxt6WeJjH4Lzd2vbDQFtqbKJxaZE4l2YmPYPhtmEbz7EDQC23k7edSQRqOZaW24BLzxkGM2YehtuMbRLpDWAtZgeAWhgbDuPUIn+G/fNnoBb7NvnnIC3nks3OP8SvxeAMj4E0UEtimwTbgYMzDA7Ymd0gYIvhGZ4yaZB72njSEg58MEhOMLsBtCUBj1/kzrBv/sxTcdu2n/2Y8YeEP3b2ZufTHz74UGOD2/sQ5yGYiWCVCXiVowF7UhSPglEwCkbByAAAdwBinfzbMT0AAAAASUVORK5CYII=","orcid":"","institution":"University of Florida","correspondingAuthor":true,"prefix":"","firstName":"Arash","middleName":"","lastName":"Maleki","suffix":""}],"badges":[],"createdAt":"2025-01-06 01:38:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5769844/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5769844/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":73269232,"identity":"ba754267-91c4-4ab0-98f7-9150448d3eb1","added_by":"auto","created_at":"2025-01-08 10:42:25","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":206548,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003e(A, B)\u003c/strong\u003e\u003c/em\u003e fundus photo of the right (OD) and left (OS) eyes, respectively. It shows 1+ haze in the media OS, otherwise normal. \u003cem\u003e\u003cstrong\u003e(C, D)\u003c/strong\u003e\u003c/em\u003efundus photo of OD and OS at one-month follow-up visit, respectively. No vitreous haze and other abnormalities are observed. \u003cem\u003e\u003cstrong\u003e(E, F)\u003c/strong\u003e\u003c/em\u003e fundus photo of OD and OS two months after starting golimumab infusions, respectively. Both eyes are normal.\u003c/p\u003e","description":"","filename":"Figure1300.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5769844/v1/f57d10a0ab839eba8e7ff670.jpg"},{"id":73269230,"identity":"2712940f-2a2d-491f-a6ac-83124d11a3b0","added_by":"auto","created_at":"2025-01-08 10:42:25","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":365001,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003e(A, B)\u003c/strong\u003e\u003c/em\u003e demonstrate optical coherence tomography (OCT) of macula at the initial visit OD and OS, respectively. These images show normal structure and contour of retina, along without significant choroidal thickening\u003cem\u003e. \u003c/em\u003e\u003cem\u003e\u003cstrong\u003e(C, D)\u003c/strong\u003e\u003c/em\u003e OCT of macula at one-month follow-up visit OD and OS, respectively. These images show normal structure and contour of retina. \u003cem\u003e\u003cstrong\u003e(E, F)\u003c/strong\u003e\u003c/em\u003eOCT of macula two months after starting golimumab OD and OS, respectively with normal structure and contour of macula OU.\u003c/p\u003e","description":"","filename":"Figure2300.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5769844/v1/7510560ce2cd60957d6d15ec.jpg"},{"id":73270399,"identity":"dd946b2f-c581-4c09-846f-5175f7b62b00","added_by":"auto","created_at":"2025-01-08 10:50:25","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":457730,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e(\u003c/strong\u003e\u003cem\u003e\u003cstrong\u003eA, B\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003e)\u003c/strong\u003e OCT of optic nerve at the initial visit in OD and OS, respectively. These images may indicate slightly thickening of retinal nerve fiber layer (rNFL) thickness OS, otherwise normal. \u003cem\u003e\u003cstrong\u003e(C, D)\u003c/strong\u003e\u003c/em\u003e OCT of optic nerve at one-month follow-up visit in OD and OS, respectively. These images indicate normal retinal nerve fiber layer (rNFL) thickness OU. \u003cem\u003e\u003cstrong\u003e(E, F)\u003c/strong\u003e\u003c/em\u003e OCT of optic nerve two months after starting golimumab therapy OD and OS, respectively. These images indicate normal retinal nerve fiber layer (rNFL) thickness OU.\u003c/p\u003e","description":"","filename":"Figure3300.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5769844/v1/01fc4bf4d7624c17e57df2c3.jpg"},{"id":73269243,"identity":"49300e09-78a3-4a13-b00a-36590bef0f5c","added_by":"auto","created_at":"2025-01-08 10:42:25","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":279452,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003e(A, B)\u003c/em\u003edemonstrate intravenous fluorescein angiography (IVFA) at the initial visit in the right and left eyes, respectively. These images show mild disc leakage and staining OS and mild peripheral vascular leakage and staining OU. \u003cem\u003e\u003cstrong\u003e(C, D)\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003e \u003c/strong\u003eshow IVFA at one-month follow-up visit. These images depict resolution of disc and vascular leakage and staining. \u003cem\u003e\u003cstrong\u003e(E, F)\u003c/strong\u003e\u003c/em\u003e IVFA two months after starting golimumab infusions. There is no optic nerve head leakage and staining OU.\u003c/p\u003e","description":"","filename":"Figure4300.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5769844/v1/0e31b48185419e445b1e6c4d.jpg"},{"id":73269251,"identity":"1f16116f-de6e-41b5-94b2-f59d47d98601","added_by":"auto","created_at":"2025-01-08 10:42:26","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":275885,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003e(A, B)\u003c/strong\u003e\u003c/em\u003edemonstrate indocyanine green angiography (ICGA) at the initial visit OD and OS, respectively. These images show patches of choroiditis especially in the temporal choroid OU without any signs of choroidal vasculitis OU. \u003cem\u003e\u003cstrong\u003e(C, D)\u003c/strong\u003e\u003c/em\u003eshow ICGA at one-month follow-up visit. These images depict resolution of choroiditis OU. \u003cem\u003e\u003cstrong\u003e(E, F)\u003c/strong\u003e\u003c/em\u003e ICGA two months after starting golimumab infusions. Still, no signs of choroiditis or choroidal vasculitis.\u003c/p\u003e","description":"","filename":"Figure5300.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5769844/v1/8de0b946a97c58eed28ab103.jpg"},{"id":73305626,"identity":"9d9420b2-8787-49bc-b8b5-02718a0c85ea","added_by":"auto","created_at":"2025-01-08 16:53:59","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1910492,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5769844/v1/6a45b196-e842-482e-860f-68f2ab6e1cbe.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eHLA-B27 positive juvenile idiopathic arthritis associated uveitis presenting with an acute onset and a chronic course\u003c/p\u003e","fulltext":[{"header":"Summary Statement","content":"\u003cp\u003eUveitis can be the first presentation of juvenile idiopathic arthritis (JIA) in 3-7% of the patients. HLA-B27 positive JIA typically presenting as unilateral acute anterior uveitis. Chronic bilateral granulomatous panuveitis may be indicative of HLA-B27 associated JIA. It can be coupled with a delayed onset oligoarticular JIA.\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eJuvenile idiopathic arthritis (JIA) is a chronic rheumatologic condition with an unknown origin, characterized by arthritis lasting more than six weeks in children and adolescents before the age of sixteen.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e Uveitis represents the most prevalent extra-articular manifestation observed in JIA.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e The reported incidence of uveitis in JIA shows significant variation across different studies; however, the point prevalence is frequently documented to range between 10% and 15%.\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eCurrently, HLA-B27 holds a central role in the classification of JIA and serves as one of the inclusion criteria for the enthesitis-related arthritis (ERA) category. The presence of HLA-B27 has been demonstrated to predict a more prolonged disease course, associated with an older age at disease onset in male patients.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e To the best of our knowledge, bilateral granulomatous panuveitis hasn't been documented in the ophthalmology literature in association with HLA-B27 JIA.\u003c/p\u003e \u003cp\u003eThis study details the occurrence of HLA-B27-associated bilateral granulomatous panuveitis in a 10-year-old female ultimately diagnosed with oligoarticular JIA.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eThis study is a case report. The written informed consent was obtained from the mother of the patient for publication.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA 10-year-old girl was evaluated at our clinic due to redness, pain, and photophobia in both eyes (OU), but more severely in the left eye (OS). The symptoms had started two weeks before the initial visit with us. Initially, erythromycin ointment was administered at the onset of the symptoms, and later switched to ofloxacin drops, leading to slight improvement in the right eye (OD). The patient denied experiencing loss of vision, photopsia, floaters, headache, recent flu-like symptoms and any systemic illnesses, skin and joint issues, headache, and hearing problems. Her best-corrected visual acuity (BCVA) was measured at 20/20 OD and 20/40 OS. Intraocular pressure (IOP) was 21 mmHg OD and 19 mmHg OS. A slit lamp examination revealed mild conjunctival injection (OU), mutton-fat and fine keratic precipitates (KPs) OU in Artl\u0026rsquo;s triangle, anterior chamber reaction 1\u0026thinsp;+\u0026thinsp;cells OD and 4\u0026thinsp;+\u0026thinsp;cells OS, and anterior vitreous 2\u0026thinsp;+\u0026thinsp;cells OU. During dilated fundoscopy, no haze OD and 1\u0026thinsp;+\u0026thinsp;haze OS in the media, otherwise normal \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA, B\u003cb\u003e)\u003c/b\u003e. Optical coherence tomography (OCT) of the macula showed a normal structure and contour OU without significant choroidal thickening OU \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA, B\u003cb\u003e)\u003c/b\u003e. Optic nerve head OCT retinal nerve fiber layer (rNFL) thickness mapping demonstrated slightly thickening of rNFL OS \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA, B\u003cb\u003e)\u003c/b\u003e. Intravenous fluorescein angiography (IVFA) depicted mild peripheral vascular leakage OU and mild disc leakage and staining OS \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eA, B\u003cb\u003e)\u003c/b\u003e. Indocyanine green angiography (ICGA) revealed hypocyanescent lesions in choroid OU, mostly in the temporal choroid suggestive of choroiditis OU \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eA, B\u003cb\u003e)\u003c/b\u003e. Comprehensive blood work-up, including complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), antinuclear antibody (ANA), anti-neutrophilic cytoplasmic antibody (ANCA), urinalysis (U/A), interleukine-6 (IL-6), human leukocyte antigen- (HLA-) A29, B44, B51, DR1, DR4, DR15, angiotensin converting enzyme (ACE), lysozyme, 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D, quantiferon TB gold, rapid plasma regain (RPR), Lyme western blot, and treponema pallidum- particle agglutination (TP-PA) were within the normal range or negative; however HLA-B27 was positive. A pediatric rheumatology consultation was conducted and was reported normal. Chest CT scan, ordered by the pediatric rheumatology team, was reported normal with no lung involvement or hilar lymphadenopathy. Given the diagnosis of panuveitis and Harada-like disease, the patient was started on 40 mg of prednisone (1 mg/kg), atropine 1% twice daily, and prednisolone acetate 1% every two hours with slow tapering schedule. One week later, the eye examination showed improvement. The topical steroid was initiated to taper on a weekly basis, and oral prednisone at a dose of 5 mg every two weeks. One month later, BCVA was 20/20 OU and IOP 20 mmHg OU. The anterior and posterior segments examination \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC, D\u003cb\u003e)\u003c/b\u003e, OCT macula \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC, D\u003cb\u003e)\u003c/b\u003e, OCT optic nerve \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eC, D\u003cb\u003e)\u003c/b\u003e, IVFA \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eC, D\u003cb\u003e)\u003c/b\u003e and ICG \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eC, D\u003cb\u003e)\u003c/b\u003e were normal. The eyes remained quiet until a recurrence occurred, marked by 2\u0026thinsp;+\u0026thinsp;AC reaction in both eyes and 1\u0026thinsp;+\u0026thinsp;vitreous haze in the left eye despite the patient being on a regimen of 10 mg oral prednisolone and two drops of prednisolone OU. At this point, immunomodulatory was initiated and she commenced adalimumab at a dosage of 40 mg biweekly, including two loading doses, along with weekly orally administered methotrexate at a dosage of 15 mg. Corticosteroid therapy remained unchanged for a month before gradually tapering and being discontinued entirely within the following month. The eyes remained in remission with this regimen until, after nine months, she developed arthritis in the left knee and left wrist, along with bilateral sacroiliitis confirmed by ultrasound and magnetic resonance imaging (MRI). Given adalimumab ineffectiveness and the superior impact of golimumab on joints, the pediatric rheumatology team opted to transition to golimumab, concurrently increasing the dosage of methotrexate to 20 mg of through subcutaneous injections. The latest eye examination conducted two months later revealed remission in anterior and posterior \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eE, F\u003cb\u003e)\u003c/b\u003e exams, accompanied by an improvement in joint signs and symptoms. OCT macula and optic nerve \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eE, \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eF, \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eE, and \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eF\u003cb\u003e)\u003c/b\u003e, IVFA \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eD, F\u003cb\u003e)\u003c/b\u003e, and ICGA \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eE, F\u003cb\u003e)\u003c/b\u003e were normal.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eJIA associated uveitis is recognized for its challenging prognosis and elevated risk of complications. The condition imposes significant consequences on patients and their families. Timely diagnosed and prompt treatment are paramount for ensuring a favorable long-term prognosis.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e Anterior uveitis associated with JIA typically manifests as a chronic, non-granulomatous anterior uveitis. Uveitis can be the first presentation of JIA in 3–7% of the patients, even though it may be asymptomatic.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eJuvenile seronegative spondyloarthropathies (JSpA) is a subtype of JIA which that is linked with uveitis. It compasses conditions such as psoriatic arthritis, ankylosing spondylitis, enthesitis-related arthritis, reactive arthritis and enthropathic artritis. Two cohorts of JSpA exhibited that enthesitis-related arthritis had a high rate of HLA-B27 positivity.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e The arthritis typically exhibit asymmetry, oligoarticular, and predominantly affects larger joints in lower extremities. Hip arthritis indicates the diagnosis and axial involvement has been documented in up to 30% of children within 15 months of diagnosis.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e Acute anterior uveitis is one of the extra-articular manifestations of JSpA. Uveitis is characterized by unilateral, sudden inflammation accompanied redness, pain, photophobia and it is observed in approximately one-quarter of children with JSpA\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e; however, uveitis can be asymptomatic.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eZuber and colleagues\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e diagnosed uveitis in 5.6% of their patients, predominantly in those with oligoarthritic arthritis and enthesis-related arthritis. Among these children, 64.3% tested positive for HLA-B27 antigen. The median age of onset of JIA in these individuals was 13.5 years. Heiligenhaus and colleagues\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e reported that acute symptomatic uveitis alternated between two eyes in 20% of patients with enthesitis-related JIA. Ryptal et al.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e documented intermediate uveitis and panuveitis in one (1.4%) and two (2.8%) of their patients, respectively. In their study, six out of nine patients with an acute course of uveitis were positive for HLA-B27, and among them, five patients exhibited HLA positive enthesitis-related arthritis. While these study offers invaluable insights into the characteristics of HLA-B27 positive patients with JIA and JIA-associated uveitis, it lacks more detailed information about their uveitis.\u003c/p\u003e \u003cp\u003eWe ruled out sarcoidosis as a diagnosis for our patient, as all relevant blood tests, including ACE, lysozyme, 25-hydroxy vitamin D, and 1,25-hydroxy vitamin D, returned negative results. Furthermore, a chest CT scan showed no abnormalities. Additionally, as the course progressed, the patient fulfilled the criteria for JIA along with its associated uveitis, characterized by arthritis in one or more joints persisting for at least 6 weeks, commencing prior to the age of 16, notably accentuated by her HLA-B27 positivity.\u003c/p\u003e \u003cp\u003eOur patient was unique since both axial and peripheral joints were involved without any signs of enthesitis.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e To the best of our knowledge, bilateral, granulomatous, and acute initiation with chronic course has not been reported in the literature for HLA-B27 positive JIA-associated uveitis.\u003c/p\u003e \u003cp\u003eConsidering the extensive eye involvement in our patient, it may be justifiable to conduct a more comprehensive evaluation of the retina, retinal vessels, and choroid using OCT, IVFA, and ICG in patients with HLA-B27 JIA-associated uveitis. Moreover, given the fact that her eyes responded to initial immunomodulatory therapy, but later showed involvement of axial and extra-axial joints suggest the need for a more thorough evaluation of joints using sophisticated techniques such as ultrasound and MRI of larger peripheral and axial joints. This proactive approach aims to detect joint involvement before symptoms manifest in HLA-B27 patients with uveitis. These facts seem to be crucial since extensive eye and possible systemic involvement may necessitate earlier initiation of IMT with more potent agents, which could be delayed in IMT in cases of isolated limited eye involvement. However, these hypotheses should be proven with more potent studies.\u003c/p\u003e \u003cp\u003eWe might face criticism for not initiating IMT promptly after diagnosing her with bilateral panuveitis with a granulomatous anterior uveitis component. Despite admitting this criticism after this case report, first, our comprehensive blood work-up revealed no abnormalities except for a positive HLA-B27 antigen. We consulted our pediatric rheumatology team to assess the patient for extraocular active and inactive signs of positive HLA-B27 in this age group and the evaluation yielded negative results. Second, there were no other symptoms and signs of vogt-Koyanagi-Harada (VKH) disease in our patient, and there was no recent history of flu-like symptoms. Hence, we diagnosed the patient with Harada-like disease. Recognizing the requirement for long-term aggressive IMT in Vogt-Koyanagi-Harada (VKH) or Harada disease, we opted to initiate treatment with oral steroids and implement a gradual taper before deciding on the use of IMT especially given the fact that her family was not prepared for long-term IMT therapy or aggressive procedure such as lumbar puncture for evaluation of cerebrospinal fluid (CSF).\u003c/p\u003e "},{"header":"Conclusion","content":"\u003cp\u003ebilateral panuveitis with granulomatous anterior uveitis component, characterized by an acute onset and chronic course, coupled with a delayed onset of oligoarticular JIA involving both axial and extra-axial components, can be indicative of HLA-B27 associated JIA. The significance of this case lies in the distinctive presentation, underscoring the need for thorough systemic and ocular investigations in similar patients.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003e \u003cb\u003eStatement of Ethics\u003c/b\u003e:\u003c/h2\u003e \u003cp\u003e \u003cstrong\u003eEthics approval\u003c/strong\u003e \u003cp\u003ewas not required in accordance with local guidelines and University of Florida Intuitional Review Board.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConflict of interest Statement:\u003c/strong\u003e \u003cp\u003eThe authors have no conflicts of interest to declare.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eConsent for publication\u003c/h2\u003e \u003cp\u003e \u003cb\u003eT\u003c/b\u003ehe written informed consent was obtained from the mother of the patient for publication.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding Sources:\u003c/h2\u003e \u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eArash Maleki contribution in this study included conception and design of the study, data analysis and interpretation, drafting of the manuscript, and approval of the final version of the manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e \u003cp\u003eThe authors express their gratitude to Dr. Ibrahim Sacit Tuna, MD and Bryce E. Buchowicz, MD for the interpretation of the MRI images.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eData is provided within the manuscript or supplementary information files\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003ePetty RE, Southwood TR, Manners P, et al. International League of Associations for Rheumatology. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol. 2004;31(2):390\u0026ndash;2.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRypdal V, Glerup M, Songstad NT, et al. Nordic Study Group of Pediatric Rheumatology. Uveitis in Juvenile Idiopathic Arthritis: 18-Year Outcome in the Population-based Nordic Cohort Study. Ophthalmology. 2021;128(4):598\u0026ndash;608. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ophtha.2020.08.024\u003c/span\u003e\u003cspan address=\"10.1016/j.ophtha.2020.08.024\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBerntson L, Nordal E, Aalto K, Peltoniemi S, Herlin T, Zak M, Nielsen S, Rygg M, Nordic Study Group of Paediatric Rheumatology. HLA-B27 predicts a more chronic disease course in an 8-year followup cohort of patients with juvenile idiopathic arthritis. J Rheumatol. 2013;40(5):725\u0026ndash;31. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3899/jrheum.121257\u003c/span\u003e\u003cspan address=\"10.3899/jrheum.121257\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHeiligenhaus A, Heinz C, Edelsten C, Kotaniemi K, Minden K. Review for disease of the year: epidemiology of juvenile idiopathic arthritis and its associated uveitis: the probable risk factors. Ocul Immunol Inflamm. 2013;21(3):180\u0026ndash;91. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3109/09273948.2013.791701\u003c/span\u003e\u003cspan address=\"10.3109/09273948.2013.791701\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWei\u0026szlig; A, Minden K, Listing J, Foeldvari I, Sieper J, Rudwaleit M. Course of patients with juvenile spondyloarthritis during 4 years of observation, juvenile part of GESPIC. RMD Open., Weiss PF, Klink AJ, Behrens EM, Sherry DD, Finkel TH, Feudtner C, Keren R. Enthesitis in an inception cohort of enthesitis-related arthritis. Arthritis Care Res (Hoboken). 2011;63(9):1307-12. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/acr.20508\u003c/span\u003e\u003cspan address=\"10.1002/acr.20508\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePagnini I, Savelli S, Matucci-Cerinic M, Fonda C, Cimaz R, Simonini G. Early predictors of juvenile sacroiliitis in enthesitis-related arthritis. 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J AAPOS. 1997;1(2):111\u0026ndash;14. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/s1091-8531(97)90009-4\u003c/span\u003e\u003cspan address=\"10.1016/s1091-8531(97)90009-4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eŻuber Z, Turowska-Heydel D, Sobczyk M, Chudek J. Prevalence of HLA-B27 antigen in patients with juvenile idiopathic arthritis. Reumatologia. 2015;53(3):125\u0026ndash;30. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.5114/reum.2015.53133\u003c/span\u003e\u003cspan address=\"10.5114/reum.2015.53133\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHeiligenhaus A, Minden K, F\u0026ouml;ll D, Pleyer U. Uveitis in juvenile idiopathic arthritis. Dtsch Arztebl Int. 2015;112(6):92\u0026ndash;100, i. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3238/arztebl.2015.0092\u003c/span\u003e\u003cspan address=\"10.3238/arztebl.2015.0092\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"adalimumab, golimumab, HLA-B27, juvenile idiopathic arthritis, panuveitis","lastPublishedDoi":"10.21203/rs.3.rs-5769844/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5769844/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eThe occurrence of Human leukocyte antigen-(HLA-) B27-associated bilateral granulomatous panuveitis in a pediatric patient ultimately diagnosed with oligoarticular juvenile idiopathic arthritis JIA.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA case report.\u003c/p\u003e\u003ch2\u003eCase Presentation:\u003c/h2\u003e \u003cp\u003eA 10-year-old girl was evaluated for redness, pain, and photophobia in both eyes (OU) with no other ocular or systemic symptoms. Her best-corrected visual acuity was measured at 20/20 and 20/40 right (OD) and 20/40 left (OS) eyes, respectively. A slit lamp examination revealed mutton-fat keratic precipitates OU, anterior chamber reaction 1\u0026thinsp;+\u0026thinsp;and 4\u0026thinsp;+\u0026thinsp;cells OD and OS, respectively, and anterior vitreous 2\u0026thinsp;+\u0026thinsp;cells OU. During dilated fundoscopy, 1\u0026thinsp;+\u0026thinsp;OS haze was observed. Intravenous fluorescein angiography depicted mild disc OS and peripheral vascular leakage OU. Indocyanine green angiography revealed hypocyanescent lesions in choroid OU indicating of choroiditis. All lab work-up were negative or within the normal limits except positive HLA-B27. She was started on aggressive corticosteroids therapy, followed by a gradual taper. A flare-up occurred while she was on a regimen of 10 mg oral prednisolone and two drops of prednisolone OU. Then, immunomodulatory therapy was initiated with adalimumab and oral methotrexate. The eyes remained in remission with this regimen until she developed arthritis in the left knee and wrist, along with bilateral sacroiliitis. The pediatric rheumatology team decided to transition to golimumab, concurrently increasing the dosage of methotrexate.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eChronic bilateral panuveitis with an acute onset granulomatous anterior uveitis component may be indicative of HLA-B27 associated JIA. It can be coupled with a delayed onset oligoarticular JIA.\u003c/p\u003e","manuscriptTitle":"HLA-B27 positive juvenile idiopathic arthritis associated uveitis presenting with an acute onset and a chronic course","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-08 10:42:20","doi":"10.21203/rs.3.rs-5769844/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e4d96388-203f-46f8-b934-54b59b7242c4","owner":[],"postedDate":"January 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-01-08T16:53:42+00:00","versionOfRecord":[],"versionCreatedAt":"2025-01-08 10:42:20","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5769844","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5769844","identity":"rs-5769844","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}