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 Table of Contents  
Year : 2020  |  Volume : 15  |  Issue : 5  |  Page : 40-44

Uveitis in spondyloarthropathies: Current concepts

Division of Rheumatology, Southern Illinois University School of Medicine, Springfield, Illinois, USA

Date of Web Publication23-May-2020

Correspondence Address:
Dr. Krati Chauhan
801 N Rutledge St. Suite 1201, Springfield, Illinois 62702
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-3698.284750

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Uveitis is the inflammation of the middle layer of the eye, the Uvea. Spondyloarthropathies are systemic disorders with common clinical and pathological features. Uveitis is an important and frequent extraarticular manifestation of spondyloarthropathies. Recently, there has been a remarkable enhancement in the management of uveitis with the approval of biologics. This review discusses epidemiology, clinical features and management of uveitis associated with spondyloarthropathies.

Keywords: Immunosuppressive therapy, spondyloarthropathies, Uveitis

How to cite this article:
Chauhan K. Uveitis in spondyloarthropathies: Current concepts. Indian J Rheumatol 2020;15, Suppl S1:40-4

How to cite this URL:
Chauhan K. Uveitis in spondyloarthropathies: Current concepts. Indian J Rheumatol [serial online] 2020 [cited 2022 Nov 30];15, Suppl S1:40-4. Available from:

  Introduction Top

Eyes are the windows to the soul, and in spondyloarthropathies, uveitis becomes our gateway to these systemic conditions. Uveitis is inflammation of the uvea, the middle layer of the eye, present between the outer layer (sclera) and the inner layer (retina). Uvea comprises iris anteriorly, ciliary body in the middle, and choroid posteriorly. According to the Standardization of Uveitis Nomenclature criteria, uveitis is classified based on the anatomical location into anterior, intermediate, posterior, and panuveitis. The primary site of inflammation for the anterior uveitis is the anterior chamber (iritis, iridocyclitis, and anterior cyclitis), intermediate is the vitreous (pars planitis and posterior cyclitis), posterior is the choroid or retina (choroiditis, chorioretinitis, retinochoroiditis, retinitis, or neuroretinitis), and panuveitis is the inflammation of the anterior chamber, vitreous, and choroid or retina. Uveitis is termed acute when an episode is sudden in onset and lasts <3 months. Repeated episodes, with periods of no disease activity without treatment, lasting >3 months are termed recurrent. Moreover, uveitis which relapses in <3 months after discontinuing treatment is termed chronic. When no cells are present in the anterior chamber, the disease is considered inactive.[1]

  Epidemiology and Etiology Top

The incidence of uveitis is 17–52/10,000, and the prevalence is 100–150 cases/100,000 in the developed countries, affects around two million people worldwide,[2] and is associated with 10% of all cases of blindness.[3] Etiologically, it is generally classified into infectious and noninfectious causes, although it is often considered a simplified way of classifying a complex disease like uveitis. Noninfectious uveitis is more common in the Western world, and around 40% are associated with systemic autoimmune diseases such as spondyloarthropathies, Behcet's disease, and sarcoidosis.[4] About one-third of noninfectious uveitis are termed idiopathic, as these do not have an associated systemic disease. Infectious uveitis is common in developing countries, associated with tuberculosis, toxoplasmosis, syphilis, and onchocerciasis.[5]

  Clinical Features and Diagnosis Top

Anterior uveitis presents with pain, redness of the eye, and photophobia, whereas intermediate and posterior uveitis may be clinically silent initially or present with floaters, blind spots, and vision loss. Complications of uveitis include cataract, glaucoma, synechia formation, and macular edema. Inflammation in the eye is clinically recognized with the use of split lamp (these may show the presence of cells in the anterior chamber and in the vitreous) and indirect ophthalmoscope, and it may be further supplemented with the use of fluorescein angiography and optical coherence tomography. Diagnostic workup is guided by the history, physical examination, and anatomical location of the uveitis. It is recommended that all patients suspected of having uveitis get a complete blood count, erythrocyte sedimentation rate, C-reactive protein, tuberculin skin test or interferon-gamma release assay, syphilis serology, and chest X-ray (to evaluate the presence of tuberculosis and sarcoidosis). Human leukocyte antigen (HLA)-B27, Cytomegalovirus, and varicella-zoster virus serology may be obtained in patients presenting with acute anterior uveitis. HLA-B27 is particularly useful in patients with recurring anterior uveitis. Intraocular specimens obtained through anterior chamber tap, vitrectomy, or retinochoroidal biopsy may be obtained, depending on the individual patient, when the initial diagnostic tests are nonconclusive.[6]

  Management Top

The management of noninfectious uveitis is guided by the anatomic site. Anterior uveitis is generally treated with topical corticosteroids, intermediate uveitis with regional corticosteroid injections (periocular or intravitreal), or oral corticosteroids if required with immunosuppressive medications. Posterior and panuveitis are treated with oral corticosteroids and immunosuppressive medications. Topical steroids include prednisone acetate 1% and difluprednate. If a patient consistently requires 1–2 drops/day of topical steroids, it is considered an indication for either regional corticosteroid injections or systemic medications.[7] Immunosuppressive systemic medications include antimetabolites (azathioprine, mycophenolate mofetil, and methotrexate), calcineurin inhibitors (tacrolimus and cyclosporine), alkylating agents (cyclophosphamide and chlorambucil), and biologics. The management of noninfectious uveitis has been significantly enhanced with multiple studies addressing the systemic mediations and the side effects associated with these medications. The Systemic Immunosuppressive Therapy for Eye Diseases (SITE) was a retrospective cohort study. The primary outcome of the SITE was overall and malignancy-related mortality in patients using systemic immunosuppressive therapy. Patients taking oral steroids, methotrexate, mycophenolate mofetil, azathioprine, or cyclosporine had similar overall and cancer-related mortality rates as compared with patients not taking systemic immunosuppressive therapy. Patients taking cyclophosphamide had higher cancer-related mortality rates which were not statistically significant.[8]

The Multicenter Uveitis Steroid Treatment Trial compared the efficacy of systemic treatment to fluocinolone acetonide implant for the treatment of noninfectious intermediate uveitis, posterior uveitis, or panuveitis. Seven-year follow-up of this trial demonstrated that systemic therapy (corticosteroid along with immunosuppressive therapy) improved visual outcomes and reduced macular edema compared to fluocinolone acetonide implant.[9] First-line antimetabolites as steroid-sparing treatment uveitis trial, a randomized study, compared methotrexate and mycophenolate for achieving corticosteroid-sparing control of noninfectious intermediate uveitis, posterior uveitis, and panuveitis. This study concluded that mycophenolate mofetil was not superior to methotrexate as a first-line corticosteroid-sparing treatment in control of inflammation. Moreover, it suggested the need for further research to determine if mycophenolate mofetil or methotrexate is more effective based on the anatomical subtype of noninfectious uveitis.[10]

In 2016, tumor necrosis factor (TNF)-alpha inhibitor, adalimumab, became the first biologic to be approved for the treatment of noninfectious uveitis, following the VISUAL I and II trials.[11],[12] Etanercept, a fusion protein of the TNF-α receptor, has not been efficacious in managing noninfectious uveitis.[13] Secukinumab, a human antibody against interleukin-17A (IL-17A), was tested in three Phase III trials (INSURE, ENDURE, and SHIELD) and was found not be efficacious.[14] Ustekinumab, a human monoclonal antibody against IL-23 and IL-12, is being studied in two Phase II trials STELARA (NCT0291116) and STELABEC (NCT02648581).

Guidance on noncorticosteroid systemic immunomodulatory therapy in noninfectious uveitis: Fundamentals of Care of Uveitis (FOCUS) initiative” provides clinicians evidence based and practical information on systemic therapy for managing non-infectious uveitis.[7] These guidelines provide recommendations, when to start noncorticosteroid systemic immunomodulatory treatment and which medication to choose. Any information which is slight threatening presence of macular involvement or if the inflammation persists despite topical treatment; are indications for initiating systemic therapy. The choice of the medication is best, when it is individualized to the patient, depending on the patients' other medical comorbidities, ability of a patient to tolerate side effects associated with the medication, and the cost of the medication. Biologics are generally added after the patient has tried one of the nonbiologic medications.[7] Managing patients with uveitis requires close collaboration among specialists, as ophthalmologists assess uveitis activity and ocular complications and usually provide topical medications, and rheumatologists in majority of the cases manage systemic medications.

  Spondyloarthropathies Top

Spondyloarthropathies are a group of inflammatory disorders which share clinical, pathological, radiological, immunological, and genetic features. These include ankylosing spondylitis, reactive arthritis, psoriatic arthritis, inflammatory bowel disease (IBD), and undifferentiated spondyloarthropathies. Uveitis is the most common extra-articular manifestation of spondyloarthropathies. It is common in patients with the diagnosis of spondyloarthropathy for 10 years or more, who are HLA-B27 positive and have sacroiliitis.[15]

  Ankylosing Spondylitis and Uveitis Top

Ankylosing spondylitis is a chronic inflammatory disease that primarily affects the spine and the sacroiliac joints. It commonly presents during the second and third decades. Patients are generally males, who are HLA-B27 positive. Gradual onset back pain, relieved with activity, increased with rest and at night, and associated with morning stiffness, lasting for greater than an hour is the classic clinical presentation of ankylosing spondylitis. Acute anterior uveitis is the most common extra-articular presentation, occurring in 20%–30% of the patients.[16] There is no correlation of uveitis with joint disease severity and exacerbation. It is characterized as unilateral, sudden onset, and recurrent in nature. The patient presents with eye pain, redness, and photophobia. Slit-lamp examination shows cells in the anterior chamber and keratic precipitates on the cornea. Anterior uveitis responds well to topical corticosteroids, which controls the inflammation and a mydriatic agent which decreases ciliary muscle spasm and reduces eye pain. Acute anterior uveitis associated with ankylosing spondylitis has an excellent prognosis. Only patients who have a high recurrence of uveitis benefit from oral steroids or immunosuppressive drugs.[17] It has been reported that ankylosing spondylitis patients treated with anti-TNF-alpha agents show a significant decrease in the number of uveitis flares.[18]

  Inflammatory Bowel Diseases and Uveitis Top

IBD is a chronic inflammatory disorder of the gastrointestinal tract of unknown etiology. These include ulcerative colitis (UC) and Crohn's disease (CD). CD may affect any part of the gastrointestinal tract, whereas UC affects the colon and rectum. Lesions in UC are continuous and involve submucosa and mucosa. While CD is characterized by skip lesions and involvement of all the layers of the bowel wall.[19] Extraintestinal involvement in IBD may involve the joints, eye, skin, and liver. Ocular involvement is more common in CD, and it occurs in about 4%–10% of the patients.[20] It may occur before or after the diagnosis of IBD, and it is more common in patients with colitis, ileocolitis, and those with other extraintestinal involvements.[21]

The hypothesis for ocular involvement includes autoantibody production against cellular antigens shared by the colon and other organs.[22] Inflammation disrupts the mucosal lining, allowing proteins, or microorganisms to pass through the intestinal barrier and cause a reactive lymphoid tissue response. It results in the production of circulating antibodies or antigen–antibody complexes, causing ocular inflammation. These patients also have a higher prevalence of HLA-B27, indicating genetic involvement.[23]

Acute anterior uveitis is the most common uveitis associated with IBD, and posterior and panuveitis are less common. It may precede the diagnosis of IBD and may occur when IBD is active or quiescent. It is commonly associated with erythema nodosum and joint involvement and the presence of HLA-B27.[24] Anterior uveitis is managed with topical steroid drops or subtenon steroid injection and cycloplegics. Posterior and panuveitis are managed with the systemic steroids and use of immunosuppressive therapy such as azathioprine or biologics such as infliximab or adalimumab.[19]

  Psoriatic Arthritis and Uveitis Top

Psoriasis is an inflammatory skin condition, presenting as scaly erythematous plaques, involving the extensor surface of elbows and knees, affecting 2%–4% of the Western population. 20%–30% of the patients with psoriasis develop an inflammatory arthritis called psoriatic arthritis.[25] Uveitis occurs in about 6%–9% of the patients with psoriatic arthritis. It is more common in patients with axial joint involvement and who are HLA-B27 positive. Cytokines IL-17 and IL-23 are thought to play an important role in the pathogenesis of uveitis in psoriatic arthritis. It also been proposed that inflammation in psoriasis and psoriatic arthritis may result in a breakdown of the barrier between the blood and the aqueous humor. This breakdown allows inflammatory cells such as activated neutrophils to reach the aqueous humor and begin intraocular inflammation.[26] As compared to ankylosing spondylitis, uveitis associated with psoriatic arthritis is insidious in onset, continuous as compared to episodic, bilateral as compared to unilateral, and more common to be posterior, and it resembles uveitis seen in patients with IBD.[27] Management depends on the anatomical location, and anterior uveitis is managed with topical steroids and mydriatic agents. Posterior and panuveitis are managed with oral steroids and immunosuppressive therapy.

  Reactive Arthritis and Uveitis Top

Reactive arthritis is an inflammatory condition which occurs as a result of bacterial infection of the gastrointestinal tract or the genitourinary system.[28] The frequency of reactive arthritis after enteric infection is around 1%–4%. Common pathogens are Campylobacter,  Salmonella More Details, Shigella, and  Yersinia More Details.[29] 1%–3% of the patients with genitourinary system infections may develop reactive arthritis, though this percentage may be higher as genitourinary infections may not be recognized.[30] Reactive arthritis usually presents 1–4 weeks following the gastrointestinal tract or the genitourinary infection, which presents as asymmetric oligoarthritis localized to the large joints of the lower extremities. In general, the symptoms last for 4–5 months; sometimes, symptoms may persist for more than a year.[31] Acute anterior uveitis presenting as pain, photophobia, and redness may be seen in 5% of the patients, who are HLA-B27 positive, and some studies report a higher percentage of uveitis.[32] Uveitis in reactive arthritis is managed with topical steroids and cyloplegic agents, as detailed earlier in previous spondyloarthropathies.

  Uveitis in Pediatric Population Top

Uveitis is the most common extra-articular manifestation of juvenile idiopathic arthritis (JIA). Uveitis in JIA is chronic and is present in 10%–20% of the patients. It is rarely symptomatic and may not be detected till late in the course of the disease, hence the need for routine ophthalmologic screening for JIA patients. Undetected or untreated or undertreated chronic uveitis in JIA patients results in cataracts, glaucoma in 25%–50%, and vision loss in 10%–20%.[33]

In the year 2019, the American College of Rheumatology and Arthritis Foundation released new screening, monitoring, and treatment guidelines for JIA patients with uveitis.[33] JIA patients with oligoarthritis, antinuclear antibody positive, younger than 7 years at the time of JIA onset, JIA of <4 years, polyarthritis (rheumatoid factor negative), psoriatic arthritis, and undifferentiated arthritis should undergo ophthalmologic screening every 3 months. Guidelines recommend using prednisone acetate 1% over difluprednate, adding or increasing the dose of topical steroids over starting oral steroids for short-term control of uveitis. In patients who require systemic therapy, subcutaneous methotrexate is recommended over oral methotrexate as the first line therapy. Monoclonal antibody against TNF-alpha antibody may be started along with methotrexate for severe disease.[33] Like adults, children with spondyloarthropathies most commonly present with acute anterior uveitis which usually responds to topical steroids.[33]

  Conclusion Top

Uveitis is an important part of the clinical spectrum of spondyloarthropathies. It is a common extra-articular manifestation and may be the presenting symptom of spondyloarthropathies. It is best managed with close collaboration between ophthalmology and rheumatology. There has been advancement in the management, especially with the use of biologics. Novel research continuously adds to our understanding and management of uveitis.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Jabs DA, Nussenblatt RB, Rosenbaum JT, Standardization of Uveitis Nomenclature (SUN) Working Group. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. Am J Ophthalmol 2005;140:509-16.  Back to cited text no. 1
Gritz DC, Wong IG. Incidence and prevalence of uveitis in Northern California; the Northern California Epidemiology of Uveitis Study. Ophthalmology 2004;111:491-500.  Back to cited text no. 2
Suttorp-Schulten MS, Rothova A. The possible impact of uveitis in blindness: A literature survey. Br J Ophthalmol 1996;80:844-8.  Back to cited text no. 3
Rosenbaum JT. Uveitis in spondyloarthritis including psoriatic arthritis, ankylosing spondylitis, and inflammatory bowel disease. Clin Rheumatol 2015;34:999-1002.  Back to cited text no. 4
London NJ, Rathinam SR, Cunningham ET Jr., The epidemiology of uveitis in developing countries. Int Ophthalmol Clin 2010;50:1-7.  Back to cited text no. 5
Sève P, Cacoub P, Bodaghi B, Trad S, Sellam J, Bellocq D, et al. Uveitis: Diagnostic work-up. A literature review and recommendations from an expert committee. Autoimmun Rev 2017;16:1254-64.  Back to cited text no. 6
Dick AD, Rosenbaum JT, Al-Dhibi HA, Belfort R Jr., Brézin AP, Chee SP, et al. Guidance on Noncorticosteroid Systemic Immunomodulatory Therapy in Noninfectious Uveitis: Fundamentals Of Care for UveitiS (FOCUS) Initiative. Ophthalmology 2018;125:757-73.  Back to cited text no. 7
Kempen JH, Daniel E, Dunn JP, Foster CS, Gangaputra S, Hanish A, et al. Overall and cancer related mortality among patients with ocular inflammation treated with immunosuppressive drugs: Retrospective cohort study. BMJ 2009;339:b2480.  Back to cited text no. 8
Writing Committee for the Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study Research Group, Kempen JH, Altaweel MM, Holbrook JT, Sugar EA, Thorne JE, et al. Association between long-lasting intravitreous fluocinolone acetonide implant vs systemic anti-inflammatory therapy and visual acuity at 7 years among patients with intermediate, posterior, or panuveitis. JAMA 2017;317:1993-2005.  Back to cited text no. 9
Rathinam SR, Gonzales JA, Thundikandy R, Kanakath A, Murugan SB, Vedhanayaki R, et al. Effect of Corticosteroid-Sparing Treatment With Mycophenolate Mofetil vs Methotrexate on Inflammation in Patients With Uveitis: A Randomized Clinical Trial. JAMA 2019;322:936-45.  Back to cited text no. 10
Nguyen QD, Merrill PT, Jaffe GJ, Dick AD, Kurup SK, Sheppard J, et al. 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 2016;388:1183-92.  Back to cited text no. 11
Jaffe GJ, Dick AD, Brézin AP, Nguyen QD, Thorne JE, Kestelyn P, et al. Adalimumab in Patients with Active Noninfectious Uveitis. N Engl J Med 2016;375:932-43.  Back to cited text no. 12
Cordero-Coma M, Sobrin L. Anti-tumor necrosis factor-α therapy in uveitis. Surv Ophthalmol 2015;60:575-89.  Back to cited text no. 13
Dick AD, Tugal-Tutkun I, Foster S, Zierhut M, Melissa Liew SH, Bezlyak V, et al. Secukinumab in the treatment of noninfectious uveitis: Results of three randomized, controlled clinical trials. Ophthalmology 2013;120:777-87.  Back to cited text no. 14
Canouï-Poitrine F, Lekpa FK, Farrenq V, Boissinot V, Hacquard-Bouder C, Comet D, et al. Prevalence and factors associated with uveitis in spondylarthritis patients in France: Results from an observational survey. Arthritis Care Res (Hoboken) 2012;64:919-24.  Back to cited text no. 15
Martin TM, Smith JR, Rosenbaum JT. Anterior uveitis: Current concepts of pathogenesis and interactions with the spondyloarthropathies. Curr Opin Rheumatol 2002;14:337-41.  Back to cited text no. 16
Gouveia EB, Elmann D, Morales MS. Ankylosing spondylitis and uveitis: Overview. Rev Bras Reumatol 2012;52:742-56.  Back to cited text no. 17
Braun J, Baraliakos X, Listing J, Sieper J. Decreased incidence of anterior uveitis in patients with ankylosing spondylitis treated with the anti-tumor necrosis factor agents infliximab and etanercept. Arthritis Rheum 2005;52:2447-51.  Back to cited text no. 18
Mady R, Grover W, Butrus S. Ocular complications of inflammatory bowel disease. ScientificWorldJournal 2015;2015:438402.  Back to cited text no. 19
Mintz R, Feller ER, Bahr RL, Shah SA. Ocular manifestations of inflammatory bowel disease. Inflamm Bowel Dis 2004;10:135-9.  Back to cited text no. 20
Petrelli EA, McKinley M, Troncale FJ. Ocular manifestations of inflammatory bowel disease. Ann Ophthalmol 1982;14:356-60.  Back to cited text no. 21
Das KM. Relationship of extraintestinal involvements in inflammatory bowel disease: New insights into autoimmune pathogenesis. Dig Dis Sci 1999;44:1-3.  Back to cited text no. 22
Mallas EG, Mackintosh P, Asquith P, Cooke WT. Histocompatibility antigens in inflammatory bowel disease. Their clinical significance and their association with arthropathy with special reference to HLA-B27 (W27). Gut 1976;17:906-10.  Back to cited text no. 23
Knox DL, Schachat AP, Mustonen E. Primary, secondary and coincidental ocular complications of Crohn's disease. Ophthalmology 1984;91:163-73.  Back to cited text no. 24
Alinaghi F, Calov M, Kristensen LE, Gladman DD, Coates LC, Jullien D, et al. Prevalence of psoriatic arthritis in patients with psoriasis: A systematic review and meta-analysis of observational and clinical studies. J Am Acad Dermatol 2019;80:251-.65E+21.  Back to cited text no. 25
Sharma SM, Jackson D. Uveitis and spondyloarthropathies. Best Pract Res Clin Rheumatol 2017;31:846-62.  Back to cited text no. 26
Paiva ES, Macaluso DC, Edwards A, Rosenbaum JT. Characterisation of uveitis in patients with psoriatic arthritis. Ann Rheum Dis 2000;59:67-70.  Back to cited text no. 27
Parker CT, Thomas D. Reiter's syndrome and reactive arthritis. J Am Osteopath Assoc 2000;100:101-4.  Back to cited text no. 28
Porter CK, Choi D, Riddle MS. Pathogen-specific risk of reactive arthritis from bacterial causes of foodborne illness. J Rheumatol 2013;40:712-4.  Back to cited text no. 29
Rohekar S, Pope J. Epidemiologic approaches to infection and immunity: The case of reactive arthritis. Curr Opin Rheumatol 2009;21:386-90.  Back to cited text no. 30
Hannu T. Reactive arthritis. Best Pract Res Clin Rheumatol 2011;25:347-57.  Back to cited text no. 31
Bănicioiu-Covei S, Vreju AF, Ciurea PL. Correlations between infection patterns and eye damage in reactive arthritis. Rom J Morphol Embryol 2019;60:601-4.  Back to cited text no. 32
Angeles-Han ST, Ringold S, Beukelman T, Lovell D, Cuello CA, Becker ML, et al. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Screening, Monitoring, and Treatment of Juvenile Idiopathic Arthritis-Associated Uveitis. Arthritis Care Res (Hoboken) 2019;71:703-16.  Back to cited text no. 33


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