HLA-B27 associated acute anterior uveitis

From EyeWiki


Uveitis is a common form of intraocular inflammation of the iris, ciliary body, or choroid, which presents predominantly as anterior uveitis (80-85%). Approximately 50% of acute anterior uveitis (AAU) cases are associated with the allele Human Leukocyte Antigen B27 (HLA-B27).

Background

The HLA-B locus encodes a class I Major Histocompatibility Complex surface antigen which presents antigens to CD8+ T-cells.

HLA-B27:

  • changes amino acids in the antigen-binding cleft
  • highly polymorphic
  • 105 subtypes, 132 genetic alleles

Epidemiology

HLA-B27 Prevalence:

  • Varies between ethnic populations
    • Pawaia tribe of Papua New Guinea (53%)
    • Haida natives of western Canada (50%)
    • Chukotka Eskimos of eastern Russia (40%)
    • Northern Scandinavia (14-16%)
    • Caucasians (8-10%)
  • HLA-B27 Prevalence in the United States:
    • 7.5% in non-Hispanic whites
    • 4.6% in Mexican-Americans
    • 2-4% in African-Americans

Clinical Presentation

  • Age of onset: 20-40 years
  • Males 1.5-2.5 times more likely than women
  • Systemic associations: Psoriasis, Ankylosing Spondylitis, Inflammatory Bowel Disease, and Reactive Arthritis
  • Frequency:
    • Recurrent, averaging 1-2 episodes per year
    • Common episodes of inflammation alternate between eyes; rarely if ever bilateral simultaneously
    • Usually resolves within two months
    • Recurrence may become less frequent with longer duration
  • Unilateral
    • Sudden onset
    • Photophobia
    • Ocular pain
    • Eye redness
    • Non-granulomatous
    • Severe inflammation potentially resulting in:
      • Hypopyon
      • Anterior chamber fibrin
    • Rarely:
      • Papillitis
      • Vitritis

[1]Potential Ocular Complications

  • Posterior synechiae
  • Ocular hypertension or glaucoma
  • Posterior subcapsular cataract
  • Epiretinal membrane
  • Less commonly:
    • Cystoid macular edema
    • Band keratopathy
    • Ocular hypotony
  • Mixed results whether complication rates differ between HLA-B27 and other uveitis etiologies

Diagnostic Testing

  • Careful review of systems and systemic evaluation to look for joint, skin or bowel involvement
  • HLA-B27 typing
  • Consider Rheumatology referral and/or xray of sacroiliac joint
  • Consider Syphilis serology, Chest xray, ACE, lysozyme to rule out other causes of uveitis


Management

  • Corticosteroids (topical drops, periocular/intraocular injection, oral) based on the amount of inflammation present; Start with high dose/frequency (such as prednisolone acetate 1% every 1-2 hours, or difluprednate 4-6 x/day or 1 mg/kg oral prednisone then taper over several weeks)
  • Cycloplegia for comfort and to prevent posterior synechiae (cyclopentolate 1% twice daily for example)
  • Systemic immunosuppressive medications in patients with multiple vision threatening flares and systemic diseases (anti-metabolites, biologics) [2][2]
  • Adalimumab approved only for AAU patients with spondyloarthropathy
    • FDA approval for non-infectious posterior or panuveitis (not anterior uveitis)

References

  1. Seve P, Cacoub P, Bodaghi B, Trad S, Sellam J, Bellocq D, Bielefeld P, Sene D, Kaplanski G, Monnet D, Brezin A, Weber M, Saadoun D, Chiquet C, Kodjikian L. Uveitis: Diagnostic work-up. A literature review and recommendations from an expert committee. Autoimmun Rev. 2017;16:1254-1264.
  2. Rosenbaum JT. New developments in uveitis associated with HLA B27. Curr Opin Rheumatol. 2017;29:298-303.
  3. Kopplin LJ, Mount G, Suhler EB. Review for Disease of the Year: Epidemiology of HLA-B27 Associated Ocular Disorders. Ocul Immunol Inflamm. 2016;24:470-5.
  4. Chang JH, McCluskey PJ, Wakefield D. Acute anterior uveitis and HLA-B27. Surv Ophthalmol. 2005;50:364-88.
  5. Wakefield D. Management of HLA-B27 acute anterior uveitis. American Academy of Ophthalmology. https://www.aao.org/current-insight/management-of-hlab27-acute-anterior-uveitis. August 7, 2009. Accessed December 30, 2017.
    1. D'Ambrosio EM, La Cava M, Tortorella P, Gharbiya M, Campanella M, Iannetti L. Clinical Features and Complications of the HLA-B27-associated Acute Anterior Uveitis: A Metanalysis. Semin Ophthalmol. 2017;32(6):689-701. doi: 10.3109/08820538.2016.1170158. Epub 2016 Jul 12. Review. PubMed PMID: 27404944.
    2. 2.0 2.1 Zu Hoerste MM, Walscheid K, Tappeiner C, Zurek-Imhoff B, Heinz C, Heiligenhaus A. 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. 2018 Oct;256(10):1985-1992. doi: 10.1007/s00417-018-4082-x. Epub 2018 Aug 1. PubMed PMID: 30069748.