Skip to main content
SpringerLink
Log in

HLA-B27-positive anterior uveitis

Clinical aspects, diagnostics, interdisciplinary management, and treatment

HLA-B27-positive Uveitis anterior

Klinik, Diagnostik, interdisziplinäres Management und Therapie. Englische Version

  • Übersicht
  • Published:
Die Ophthalmologie Aims and scope Submit manuscript

The Original Article was published on 12 January 2023

Abstract

Acute anterior uveitis (AAU) associated with human leukocyte antigen (HLA) B27 is the most common form of noninfectious intraocular inflammation and is considered to be a separate clinical entity. Young adults between the ages of 20 and 40 years are predominantly affected. The HLA-B27 positive AAU typically presents as a unilateral, fulminant disruption of the blood-aqueous humor barrier, which is accompanied by pronounced cellular infiltration and fibrinous exudation. Other characteristics are reduced intraocular pressure and a high tendency to relapse, which can also involve the partner eye. Patients with HLA-B27 positive AAU share a high risk for other genetically associated diseases, especially spondylarthritis, chronic inflammatory bowel diseases and psoriasis. As up to 40% of those affected have a systemic disease that has not yet been diagnosed, the ophthalmologist is of major importance for early detection.

Zusammenfassung

Die mit dem humanen Leukozytenantigen(HLA)-B27 assoziierte, akute anteriore Uveitis (AAU) ist die häufigste Form nichtinfektiöser intraokulärer Entzündungen und wird als eigene klinische Entität gesehen. Es sind überwiegend junge Erwachsene im Alter zwischen 20 und 40 Jahren betroffen. Die HLA-B27-positive AAU präsentiert sich typischerweise als einseitige, fulminante Störung der Blut-Kammerwasser-Schranke, die mit einer ausgeprägten zellulären Infiltration und fibrinösen Exsudation einhergeht. Weitere Charakteristika sind ein verminderter Augeninnendruck und eine hohe Rezidivneigung, die auch das 2. Auge einbeziehen kann. Patienten mit HLA-B27-positiver AAU teilen ein hohes Risiko zu weiteren genetisch assoziierten Erkrankungen, insbesondere zu Spondyloarthritis, chronischer Darmerkrankung und Psoriasis. Da bei bis zu 40 % der Betroffenen eine bisher nicht diagnostizierte Systemerkrankung vorliegt, kommt dem Ophthalmologen eine wichtige Bedeutung bei der Früherkennung zu.

Graphic abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Jabs DA, Nussenblatt RB, Rosenbaum JT, Standardization of Uveitis Nomenclature (SUN) Working Group (2005) Standardization of uveitis nomenclature for reporting clinical data. Results of the first international workshop. Am J Ophthalmol 140(3):509–516

    Article  PubMed  Google Scholar 

  2. Lenglinger M, Pohlmann D, Pleyer U (2020) Anteriore virale Uveitis. Klinik, diagnostisches Vorgehen und Behandlungsoptionen. Ophthalmologe 117(1):83–92

    Article  PubMed  Google Scholar 

  3. Chen B, Li J, He C, Li D, Tong W, Zou Y et al (2017) Role of HLA-B27 in the pathogenesis of ankylosing spondylitis (Review). Mol Med Rep 15(4):1943–1951

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Rademacher J, Mullner H, Diekhoff T, Haibel H, Igel S, Pohlmann D et al (2022) Keep an eye on the back: spondyloarthritis in patients with acute anterior uveitis. Arthritis Rheumatol. https://doi.org/10.1002/art.42315

    Article  PubMed  Google Scholar 

  5. Sibley CH (2016) Autoinflammation and HLA-B27: beyond antigen presentation. Ocul Immunol Inflamm 24(4):460–469

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Roberts RL, Wallace MC, Jones GT, van Rij AM, Merriman TR, Harrison A et al (2013) Prevalence of HLA-B27 in the New Zealand population: effect of age and ethnicity. Arthritis Res Ther 15(5):R158

    Article  PubMed  PubMed Central  Google Scholar 

  7. Pathanapitoon K, Dodds EM, Cunningham ET Jr., Rothova A (2017) Clinical spectrum of HLA-B27-associated ocular inflammation. Ocul Immunol Inflamm 25(4):569–576

    Article  CAS  PubMed  Google Scholar 

  8. Wakefield D, Clarke D, McCluskey P (2020) Recent developments in HLA B27 anterior uveitis. Front Immunol 11:608134

    Article  CAS  PubMed  Google Scholar 

  9. Rosenbaum JT, Asquith M (2018) The microbiome and HLA-B27-associated acute anterior uveitis. Nat Rev Rheumatol 14(12):704–713

    Article  PubMed  PubMed Central  Google Scholar 

  10. Rothova A, van Veenedaal WG, Linssen A, Glasius E, Kijlstra A, de Jong PT (1987) Clinical features of acute anterior uveitis. Am J Ophthalmol 103(2):137–145

    Article  CAS  PubMed  Google Scholar 

  11. Braakenburg AM, de Valk HW, de Boer J, Rothova A (2008) Human leukocyte antigen-B27-associated uveitis: long-term follow-up and gender differences. Am J Ophthalmol 145(3):472–479

    Article  CAS  PubMed  Google Scholar 

  12. Chang JH, McCluskey PJ, Wakefield D (2005) Acute anterior uveitis and HLA-B27. Surv Ophthalmol 50(4):364–388

    Article  PubMed  Google Scholar 

  13. Sieper J, van der Heijde D, Landewe R, Brandt J, Burgos-Vagas R, Collantes-Estevez E et al (2009) New criteria for inflammatory back pain in patients with chronic back pain: a real patient exercise by experts from the assessment of spondyloarthritis international society (ASAS). Ann Rheum Dis 68(6):784–788

    Article  CAS  PubMed  Google Scholar 

  14. Sieper J, Poddubnyy D (2017) Axial spondyloarthritis. Lancet 390(10089):73–84

    Article  PubMed  Google Scholar 

  15. Molto A, Sieper J (2018) Peripheral spondyloarthritis: concept, diagnosis and treatment. Best Pract Res Clin Rheumatol 32(3):357–368

    Article  PubMed  Google Scholar 

  16. Magrey MN, Danve AS, Ermann J, Walsh JA (2020) Recognizing axial spondyloarthritis: a guide for primary care. Mayo Clin Proc 95(11):2499–2508

    Article  CAS  PubMed  Google Scholar 

  17. Torres J, Mehandru S, Colombel JF, Peyrin-Biroulet L (2017) Crohn’s disease. Lancet 389(10080):1741–1755

    Article  PubMed  Google Scholar 

  18. Ungaro R, Mehandru S, Allen PB, Peyrin-Biroulet L, Colombel JF (2017) Ulcerative colitis. Lancet 389(10080):1756–1770

    Article  PubMed  Google Scholar 

  19. Rogler G, Singh A, Kavanaugh A, Rubin DT (2021) Extraintestinal manifestations of inflammatory bowel disease: current concepts, treatment, and implications for disease management. Gastroenterology 161(4):1118–1132

    Article  CAS  PubMed  Google Scholar 

  20. Troncoso LL, Biancardi AL, de Moraes HV Jr., Zaltman C (2017) Ophthalmic manifestations in patients with inflammatory bowel disease: a review. World J Gastroenterol 23(32):5836–5848

    Article  PubMed  PubMed Central  Google Scholar 

  21. Rademacher J, Pleyer U, Winterhalter S (2021) Spondylarthritis. In: Pleyer U (ed) Entzündliche Augenerkrankungen. Springer, Berlin, Heidelberg, pp 503–517

    Chapter  Google Scholar 

  22. Rudwaleit M, van der Heijde D, Landewe R, Akkoc N, Brandt J, Chou CT et al (2011) The assessment of spondyloarthritis international society classification criteria for peripheral spondyloarthritis and for spondyloarthritis in general. Ann Rheum Dis 70(1):25–31

    Article  CAS  PubMed  Google Scholar 

  23. Deutsche Ophthalmologische Gesellschaft e. V. (2010) Leitlinie Nr. 14a Uveitis anterior. https://www.dog.org/wp-content/uploads/2009/09/LL-Uveitis-anterior-2011-08-03-Endversion.pdf. Zugegriffen: 7. Okt. 2022

  24. Bernard A, Seve P, Abukhashabh A, Roure-Sobas C, Boibieux A, Denis P et al (2020) Lyme-associated uveitis: clinical spectrum and review of literature. Eur J Ophthalmol 30(5):874–885

    Article  PubMed  Google Scholar 

  25. Seve P, Cacoub P, Bodaghi B, Trad S, Sellam J, Bellocq D et al (2017) Uveitis: diagnostic work-up. A literature review and recommendations from an expert committee. Autoimmun Rev 16(12):1254–1264

    Article  PubMed  Google Scholar 

  26. Pleyer U, Quentin CD (2021) Virale anteriore Uveitis. In: Pleyer U (ed) Entzündliche Augenerkrankungen. Springer, Berlin, Heidelberg, pp 475–487

    Chapter  Google Scholar 

  27. Haroon M, O’Rourke M, Ramasamy P, Murphy CC, FitzGerald O (2015) A novel evidence-based detection of undiagnosed spondyloarthritis in patients presenting with acute anterior uveitis: the DUET (Dublin Uveitis Evaluation Tool). Ann Rheum Dis 74(11):1990–1995

    Article  PubMed  Google Scholar 

  28. Poddubnyy D, van Tubergen A, Landewé R, Sieper J, van der Heijde D (2015) Development of an ASAS-endorsed recommendation for the early referral of patients with a suspicion of axial spondyloarthritis. Ann Rheum Dis 74(8):1483–1487

    Article  PubMed  Google Scholar 

  29. Poddubnyy D, Rudwaleit M, Sieper J (2012) Frühe Spondyloarthritiden, Diagnostisches Vorgehen und Screening. Z Rheumatol 71(1):19–26

    Article  CAS  PubMed  Google Scholar 

  30. Heiligenhaus A, Kasper M, Grajewski R (2017) HLA-B27 positive acute anterior uveitis. Klin Monbl Augenheilkd 234(5):652–656

    Article  PubMed  Google Scholar 

  31. Rademacher J, Poddubnyy D, Pleyer U (2020) Uveitis in spondyloarthritis. Ther Adv Musculoskelet Dis 12:1759720X20951733

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Zu Hoerste MM, Walscheid K, Tappeiner C, Zurek-Imhoff B, Heinz C, Heiligenhaus A (2018) The effect of methotrexate and sulfasalazine on the course of HLA-B27-positive anterior uveitis: results from a retrospective cohort study. Graefes Arch Clin Exp Ophthalmol 256(10):1985–1992

    Article  CAS  PubMed  Google Scholar 

  33. Bouzid N, Jamilloux Y, Chapurlat R, Pradat P, De Parisot A, Kodjikian L et al (2020) Impact of systemic treatments on the course of HLA-B27-associated uveitis: a retrospective study of 101 patients. PLoS ONE 15(3):e230560

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Pacheco PA, Taylor SR, Cuchacovich MT, Diaz GV (2008) Azathioprine in the management of autoimmune uveitis. Ocul Immunol Inflamm 16(4):161–165

    Article  CAS  PubMed  Google Scholar 

  35. Jaffe GJ, Dick AD, Brezin AP, Nguyen QD, Thorne JE, Kestelyn P et al (2016) Adalimumab in patients with active noninfectious uveitis. N Engl J Med 375(10):932–943

    Article  CAS  PubMed  Google Scholar 

  36. Nguyen QD, Merrill PT, Jaffe GJ, Dick AD, Kurup SK, Sheppard J et al (2016) Adalimumab for prevention of uveitic flare in patients with inactive non-infectious uveitis controlled by corticosteroids (VISUAL II): a multicentre, double-masked, randomised, placebo-controlled phase 3 trial. Lancet 388(10050):1183–1192

    Article  CAS  PubMed  Google Scholar 

  37. Ramanan AV, Dick AD, Jones AP, McKay A, Williamson PR, Compeyrot-Lacassagne S et al (2017) Adalimumab plus methotrexate for uveitis in juvenile idiopathic arthritis. N Engl J Med 376(17):1637–1646

    Article  CAS  PubMed  Google Scholar 

  38. Rudwaleit M, Rodevand E, Holck P, Vanhoof J, Kron M, Kary S et al (2009) Adalimumab effectively reduces the rate of anterior uveitis flares in patients with active ankylosing spondylitis: results of a prospective open-label study. Ann Rheum Dis 68(5):696–701

    Article  CAS  PubMed  Google Scholar 

  39. van der Horst-Bruinsma I, van Bentum R, Verbraak FD, Rath T, Rosenbaum JT, Misterska-Skora M et al (2020) The impact of certolizumab pegol treatment on the incidence of anterior uveitis flares in patients with axial spondyloarthritis: 48-week interim results from C‑View. RMD Open 6(1):e1161. https://doi.org/10.1136/rmdopen-2019-001161

    Article  PubMed  PubMed Central  Google Scholar 

  40. van Bentum RE, Heslinga SC, Nurmohamed MT, Gerards AH, Griep EN, Koehorst C et al (2019) Reduced occurrence rate of acute anterior uveitis in ankylosing spondylitis treated with golimumab—the go-easy study. J Rheumatol 46(2):153–159

    Article  PubMed  Google Scholar 

  41. Lie E, Lindstrom U, Zverkova-Sandstrom T, Olsen IC, Forsblad-d’Elia H, Askling J et al (2017) Tumour necrosis factor inhibitor treatment and occurrence of anterior uveitis in ankylosing spondylitis: results from the Swedish biologics register. Ann Rheum Dis 76(9):1515–1521

    Article  CAS  PubMed  Google Scholar 

  42. DGRh (2019) Therapie mit Adalimumab. https://dgrh.de/dam/jcr:f0c50d32-101a-4905-99d2-87c816e2becf/Adalimumab%20ARZT%2011_2019.pdf. Zugegriffen: 19. Aug. 2022

  43. El-Shabrawi Y, Rath T, Heiligenhaus A (2022) Janus Kinase inhibitors: next-generation treatment for uveitis. Klin Monbl Augenheilkd 239(5):695–701

    Article  PubMed  Google Scholar 

  44. Deodhar AA, Miceli-Richard C, Baraliakos X, Marzo-Ortega H, Gladman DD, Blanco R et al (2020) Incidence of uveitis in secukinumab-treated patients with ankylosing spondylitis: pooled data analysis from three phase 3 studies. ACR Open Rheumatol 2(5):294–299

    Article  PubMed  PubMed Central  Google Scholar 

  45. Letko E, Yeh S, Foster CS, Pleyer U, Brigell M, Grosskreutz CL (2015) Efficacy and safety of intravenous secukinumab in noninfectious uveitis requiring steroid-sparing immunosuppressive therapy. Ophthalmology 122(5):939–948

    Article  PubMed  Google Scholar 

  46. Dick AD, Tugal-Tutkun I, Foster S, Zierhut M, Melissa Liew SH, Bezlyak V et al (2013) Secukinumab in the treatment of noninfectious uveitis: results of three randomized, controlled clinical trials. Ophthalmology 120(4):777–787

    Article  PubMed  Google Scholar 

  47. Park SC, Ham DI (2009) Clinical features and prognosis of HLA-B27 positive and negative anterior uveitis in a Korean population. J Korean Med Sci 24(4):722–728

    Article  PubMed  PubMed Central  Google Scholar 

  48. Loh AR, Acharya NR (2010) Incidence rates and risk factors for ocular complications and vision loss in HLA-B27-associated uveitis. Am J Ophthalmol 150(4):534–42.e2

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Universitätsaugenklinik Graz—LKH-Universitätsklinikum Graz, Medizinische Universität Graz, Auenbruggerplatz 4, 8036, Graz, Austria

    Peter Werkl

  2. Medizinische Klinik für Gastroenterologie, Infektiologie und Rheumatologie, Division of Gastroenterology, Infectious Diseases and Rheumatology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Hindenburgdamm 30, 12203, Berlin, Germany

    Judith Rademacher

  3. Berlin Institute of Health at Charité—Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany

    Judith Rademacher &  Uwe Pleyer FEBO

  4. Universitäts-Augenklinik, Charité, Campus Virchow Klinikum—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, und Berlin Institute of Health, 13355, Berlin, Germany

    Uwe Pleyer FEBO

Authors
  1. Peter Werkl
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Judith Rademacher
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Uwe Pleyer FEBO
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Uwe Pleyer FEBO.

Ethics declarations

Conflict of interest

In accordance with Springer Medicine guidelines, authors and scientific directors are requested to make a full declaration of their financial and non-financial interests as part of the manuscript preparation and manuscript approval process.

Authors

P. Werkl: A. Financial interests: P. Werkl declares no financial conflict of interest.—B. Non-financial interests: resident in special specialty training at the University Eye Hospital Graz—LKH-Universitätsklinikum Graz. J. Rademacher: A. Financial interests: congress attendance reimbursement: Novartis, UCB, AbbVie.—B. Non-financial interests: employed specialist in internal medicine, Charité Universitätsmedizin Berlin, Medical Clinic for Gastroenterology, Infectiology and Rheumatology; clinician scientist, BIH Berlin Institute of Health | Memberships: DGRh, DGfI, DGIM, ASAS. U. Pleyer: A. Financial interests: research funding: German Research Foundation, BMBF, European Union; speaker’s fees/travel reimbursement as passive participant: AbbVie, Alcon, Allergan, Alimera, Bausch and Lomb, Bayer, Novartis, Santen, Thea; I, my spouse/partner or child(ren) hold patent/share/stock or similar in a company active in the field of medicine: Bayer, Biontech (shares)—B. Non-financial interests: senior physician, Department of Ophthalmology, Charité Universitätsmedizin Berlin | Membership/function in Interest Groups: speaker of the section Uveitis/DOG since 2014 | Focus of scientific clinical activities: head of the consulting hours “Tertiary Center for Inflammatory Eye Diseases” from 1994 up to today | Secretary: Berlin-Brandenburg Ophthalmologists | Board member: German UVEITIS Working Group DUAG e. V. U. Pleyer is a member of the editorial board of Die Ophthalmologie. He was not involved in the review of this manuscript or in any decisions related to this manuscript.

Scientific director

The full conflict of interest statement for the scientific director can be found at the certified continuing education course at www.springermedizin.de/cme.

The publisher

declares that no sponsorship money will be paid to the publisher for the publication of this CME continuing education course.

For this article no studies with human participants or animals were performed by any of the authors. All studies mentioned were conducted in accordance with the ethical standards indicated in each case. Written consent has been obtained from patients and/or their legal representatives for images or other information within the manuscript by which patients can be identified.

The supplement containing this article is not sponsored by industry.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

figure qr

Scan QR code & read article online

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Werkl, P., Rademacher, J. & Pleyer, U. HLA-B27-positive anterior uveitis. Ophthalmologie 121 (Suppl 1), 12–22 (2024). https://doi.org/10.1007/s00347-023-01960-z

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00347-023-01960-z

Keywords

Schlüsselwörter

Search

Navigation