Post-Streptococcal Uveitis
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Disease Entity
Post-streptococcal uveitis (PSU) is an uncommon cause of bilateral non-granulomatous anterior uveitis that was initially described as a disease entity in 1991.[1] Since then, a limited number of case reports further characterizing the condition have been published.[2][3][4][5][6][7][8][9][10][11][12][13]
Etiology
PSU occurs following infection with β-hemolytic (Group A) streptococci. The pathophysiology of the condition remains obscure. However, it has been suggested that there is an immune-mediated reaction involving the production of cross-reactive antibodies following an acute infection which eventually activates CD4-positive T cells.[14] Subsequently, a component of molecular mimicry between beta-hemolytic streptococcal antigens and retinal soluble antigen (S), present in rod outer segments, likely further contributes to ocular involvement.[15]
Epidemiology
Group A streptococcal (GAS) infection is common. There are more than 600 million cases of GAS pharyngitis and 100 million cases of GAS pyoderma reported annually.[16] Post-streptococcal uveitis, however, is not common. As such, literature describing the entity is scarce. The condition predominantly affects younger populations, with most cases occurring in patients younger than 15 years of age.[3][7][13] Patients generally present in the winter and spring months,[13] which is consistent with trends for GAS infection.[17]
Risk Factors
As with other post-streptococcal syndromes, including rheumatic fever, glomerulonephritis, and polyarthritis, the most significant risk factor for the development of PSU is prior untreated GAS infection.[7] In children, risk factors for infection with GAS include sore throats and skin infections within the preceding 12 months, household crowding, and eczema.[18] In adults, GAS infections are substantially more common among those who are age ≥65 years, live in long-term care facilities, have a chronic illness or underlying skin condition, and are immunosuppressed.[17][19]
General Pathology
GAS is a gram-positive β-hemolytic bacteria with three cell wall proteins that make up the key virulence factors: M, T, and R. The M protein is thought to be the primary virulence factor, as it aids in evasion from phagocytosis. Furthermore, the protein is speculated to have super antigenic properties, as suggested by experimental investigations demonstrating a robust stimulatory effect on T-cell proliferation.[20]
The mechanisms of post-streptococcal syndromes are diverse and largely unclear. However, across all sequelae, there appears to be a component of molecular mimicry, in addition to other processes, within the pathogenesis of the disease state. Acute rheumatic fever is posited to be secondary to the cross reaction of antibodies against the N-acetyl glucosamine component of the bacteria with human laminin and myosin. Similarly, post-streptococcal glomerulonephritis may partially occur as a result of antibodies against streptococcal antigens and human laminin, collagen, and glomerular basement membrane.[21]
Clinical signs
The median time lag between initial infection and ocular symptoms is 2 weeks, although reports range from 3 days to 3 years.[6] Note: a history of streptococcal infection may not be reported by the patient due to subclinical symptoms.[7]
The most common pathologic presentation of PSU is a bilateral nongranulomatous anterior uveitis with fine inferior keratic precipitates and anterior vitreous cells.[22] Unilateral involvement has been identified in up to 32% of cases. Posterior uveitis is a less common finding observed in roughly 37.5% of patients.[3]
The patient may present with decreased visual acuity that is location specific.[3][6][20] Anterior segment findings include bulbar conjunctival hyperemia, anterior scleritis, “mutton fat” keratic precipitates, and mild or fibrinous anterior chamber reaction with associated hypopyon. Posterior segment findings include synechiae, vitritis, vitreal cellular reaction (located anterior, inferior, or on the posterior lens surface), retinal periphlebitis, retinitis, retinal vasculitis, retinal pigment epithelium detachment, cystoid macular edema, secondary glaucoma, optic disc swelling, and choroiditis.[2][3][6][11][12]
Symptoms
Typical symptoms of PSU include successive days to weeks of painful blurred vision sometimes associated with photophobia. History of upper respiratory infection, flu-like illness, sore throat, or skin infection within the preceding weeks may be present.
Clinical Diagnosis
The diagnosis of PSU is highly indicated by the presence of ocular inflammation with antecedent symptoms of pharyngitis and tonsillitis, coupled with a positive throat culture.[6]
Diagnostic Procedures/Laboratory Testing
Anti-streptolysin O titer (ASOT) levels are widely variable depending on patient age, location, and season, thereby limiting its utility as a definitive diagnostic test.[6] However, ASOT should be considered in all individuals with suspicion of PSU, as an elevated reading is highly suggestive of infection. A combination of ASOT and anti-DNase B has been demonstrated as more helpful in diagnosis, with a high sensitivity (95.5%) and specificity (88.6%).[23] Other potentially useful labs include ESR, CRP, blood culture, and tuberculin skin test. Chest X-ray and angiotensin converting enzyme can be obtained to rule out sarcoidosis, which has a similar ocular presentation.[22] Additional serologic testing should be performed to rule out other causes of uveitis or vasculitis based on risk factors to ensure timely diagnosis.
Management
Primary Prevention
Treatment of the precipitating streptococcal infection, typically with penicillin, is the primary prevention strategy for post-streptococcal syndromes. Data regarding prophylaxis of close contacts is conflicting. If a decision to treat the contact is reached, prophylaxis should be exclusively restricted to individuals who were exposed for more than 24 hours within a one week period.[24]
Medical Therapy
A multidisciplinary approach is recommended for management of patients with PSU. Active or residual streptococcal infection should be treated with one dose of intramuscular penicillin or one week of oral penicillin.[7] As with other uveitides, topical corticosteroids and mydriatics are the initial treatments, which may be escalated to topical or regional corticosteroids, and then systemic corticosteroids as the severity of disease progresses.[6] Systemic immunosuppressants such as methotrexate and adalimumab may be considered for disease refractory to the aforementioned treatment modalities.[13]
Monitoring
Close clinical follow-up of patients and serial monitoring of ASOT following diagnosis has been recommended by prior investigations.[6][7] ASOT levels peak at 3-5 weeks after infection, but can stay benignly elevated for more than 8 weeks.[25] In the setting of rising ASOT levels with a worsening clinical picture, further antibiotic management may be necessary for treatment.[6][7]
Prophylaxis
At this time, medical prophylaxis against GAS pharyngitis or tonsillitis with penicillin is not generally recommended for patients provided the risks associated with long-term antibiotics. Nonetheless, individual patients with recurrent episodes of vision-threatening uveitis may benefit from such an option.[7]
Surgical prophylaxis in the form of tonsillectomy has been used in some patients to reduce the number of recurrent episodes of GAS pharyngitis, although the benefits associated with this approach are speculative and it is unknown whether this decreases future risk of PSU.[6][7][13] Ultimately, treatment regimens should be specific to each case.[26]
References
- ↑ Cokingtin CD, Han DP. Bilateral nongranulomatous uveitis and a poststreptococcal syndrome. Am J Ophthalmol. 1991;112(5):595-6. doi:10.1016/s0002-9394(14)76865-5.
- ↑ 2.0 2.1 Filloy A, Comas C, Català-Mora J. Anterior and Intermediate Uveitis with Retinal Vasculitis: An Unusual Manifestation of Post-Streptococcal Uveitis Syndrome. Ocul Immunol Inflamm. 2016;24(6):607-609. doi:10.3109/09273948.2015.1094094
- ↑ 3.0 3.1 3.2 3.3 3.4 Tinley C, Van Zyl L, Grötte R. Poststreptococcal syndrome uveitis in South African children. Br J Ophthalmol. 2012; 96(1):87-9. doi:10.1136/bjo.2010.199315
- ↑ Fretzayas A, Moustaki M, Stefos E, Dermitzaki E, Nicolaidou P. Uveitis: an isolated complication of post-streptococcal syndrome. Ann Trop Paediatr. 2010;30(2):153-5. doi: 10.1179/146532810x12703902516329
- ↑ de Smet MD. Papillophlebitis and uveitis as a manifestation of post-streptococcal uveitis syndrome. Eye. 2009;23(4):985-987. doi:10.1038/sj.eye.6703039
- ↑ 6.0 6.1 6.2 6.3 6.4 6.5 6.6 6.7 6.8 6.9 Gallagher MJ, Muqit MM, Jones D, Gavin M. Post-streptococcal uveitis. Acta Ophthalmologica Scandinavica. 2006;84(3):424-8. doi:10.1111/j.1600-0420.2005.00594
- ↑ 7.0 7.1 7.2 7.3 7.4 7.5 7.6 7.7 7.8 Ur Rehman S, Anand S, Reddy A, Backhouse OC, Mohamed M, Mahomed I, Atkins AD, James T. Poststreptococcal syndrome uveitis: a descriptive case series and literature review. Ophthalmology. 2006;113(4):701-6. doi:10.1016/j.ophtha.2005.12.024
- ↑ Kobayashi S, Tamura N, Ikeda M, Sakuraba K, Matsumoto T, Hashimoto H. Uveitis in adult patients with poststreptococcal reactive arthritis: the first two cases reported associated with uveitis. Clinical Rheumatology. 2002;21(6):533-5. doi:10.1007/s100670200130
- ↑ Besada E, Schatz S, Saremi SS. Post-streptococcal uveitis. Optometry. 2000;71(4):233-8.
- ↑ Leiba H, Barash J, Pollack A. Poststreptococcal uveitis. American Journal of Ophthalmology. 1998;126(2):317-8. doi:10.1016/s0002-9394(98)00159-7
- ↑ 11.0 11.1 Benjamin A, Tufail A, Holland GN. Uveitis as the only clinical manifestation of poststreptococcal syndrome. American Journal of Ophthalmology. 1997;123(2):258-60. doi:10.1016/s0002-9394(14)71047-5
- ↑ 12.0 12.1 Ortiz JM, Kamerling JM, Fischer D, Baxter J. Scleritis, uveitis, and glaucoma in a patient with rheumatic fever. American Journal of Ophthalmology. 1995;120(4):538-9. doi:10.1016/s0002-9394(14)72676-5
- ↑ 13.0 13.1 13.2 13.3 13.4 Curragh DS, McAvoy CE, Rooney M, McLoone E. Post-streptococcal uveitis syndrome in a Caucasian population: a case series. Eye. 2019;33(3):380-384. doi:10.1038/s41433-018-0214-0
- ↑ Shulman ST, Bisno AL. Nonsuppurative poststreptococcal sequelae: rheumatic fever and glomerulonephritis. In Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases, Eighth Edition. Elsevier. 2015;1:2300-2309. doi:10.1016/B978-1-4557-4801-3.00200-9
- ↑ Cunningham MW. Pathogenesis of group A streptococcal infections. Clinical Microbiology Reviews. 2000;13(3):470-511. doi:10.1128/CMR.13.3.470
- ↑ Carapetis JR, Steer AC, Mulholland EK, Weber M. The global burden of group A streptococcal diseases. Lancet Infectious Diseases. 2005;5(11):685-694. doi:10.1016/S1473-3099(05)70267-X
- ↑ 17.0 17.1 O'Loughlin RE, Roberson A, Cieslak PR, Cieslak PR, Lynfield R, Gershman K, Craig A, Albanese BA, Farley MM, Barrett NL, Spina NL, Beall B, Harrison LH, Reingold A, Beneden CV, Active Bacterial Core Surveillance Team. The epidemiology of invasive group A streptococcal infection and potential vaccine implications: United States, 2000-2004. Clinical Infectious Diseases. 2007;45(7):853-62. doi:10.1086/521264
- ↑ Bennett J, Moreland NJ, Zhang J, Crane J, Sika-Patonu D, Carapetis J, Williamson DA, Baker MG. Risk factors for group A streptococcal pharyngitis and skin infections: A case control study. Lancet Regional Health - Western Pacific. 2022;26:100507. doi:10.1016/j.lanwpc.2022.100507
- ↑ Nelson GE, Pondo T, Toews KA, Farley M, Lindegren ML, Lynfield R, Aragon D, Zansky SM, Watt JP, Cieslak PR, Angeles K, Harrison LH, Petit S, Beall B, Van Beneden CA. Epidemiology of Invasive Group A Streptococcal Infections in the United States, 2005-2012. Clinical Infectious Diseases. 2016;63(4):478-86. doi:10.1093/cid/ciw248
- ↑ 20.0 20.1 Kotb M, Courtney HS, Dale JB, Beachey EH. Cellular and biochemical responses of human T lymphocytes stimulated with streptococcal M proteins. Journal of Immunology. 1989;142(3):966-970. doi:10.4049/jimmunol.142.3.966
- ↑ Ivory D, Folzenlogen D. Post streptococcal syndromes, a rheumatologist perspective. The Internet J of Rheumatology. 2009;6:2.
- ↑ 22.0 22.1 Abderrahim K, Chebil A, Falfoul Y, Bouladi M, El Matri L. Granulomatous uveitis and reactive arthritis as manifestations of post-streptococcal syndrome. International Ophthalmology. 2015;35(5):641-3. doi:10.1007/s10792-012-9626-1
- ↑ Blyth CC, Robertson PW. Anti-streptococcal antibodies in the diagnosis of acute and post-streptococcal disease: streptokinase versus streptolysin O and deoxyribonuclease B. Pathology. 2006;38(2):152-6. doi:10.1080/00313020600557060
- ↑ de Almeida Torres RS, dos Santos TZ, de Almeida Torres RA, de Manuel Petrini LMC, Burger M, Steer AC, Smeesters PR. Management of Contacts of Patients With Severe Invasive Group A Streptococcal Infection. Journal of the Pediatric Infectious Disease Society. 2016;5(1):47-52. doi:10.1093/jpids/piu107
- ↑ Steer AC, Vidmar S, Ritika R, Kado J, Batzloff M, Jenney AW, Carlin JB, Carapetis JR. Normal ranges of streptococcal antibody titers are similar whether streptococci are endemic to the setting or not. Clinical and Vaccine Immunology. 2009;16(2):172-5. doi: 10.1128/CVI.00291-08.
- ↑ Holland GN. Recurrent anterior uveitis associated with streptococcal pharyngitis in a patient with a history of poststreptococcal syndrome. American Journal of Ophthalmology. 1999;127(3):346-7. doi:10.1016/S0002-9394(98)00341-9
