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Approach to the Laboratory, Imaging, and Molecular Work-up for Uveitis

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Uveitis

Abstract

The work-up and diagnosis of uveitic diseases can be a challenge. Evolving nomenclature and classifications as well as a limited understanding of the utility and limitations of diagnostic tests may lead to confusion, unnecessary testing, and inaccurate or delayed diagnosis. In this chapter, we hope to clarify the goals of diagnosis and present a systematic approach for the diagnostic work-up in patients with uveitis. In order to appropriately discuss this work-up, we will briefly review current nomenclature, emphasize the importance of history, present a few important discriminating exam findings, and highlight the utilization of an anatomic classification system. In addition, we will highlight the utility, indications, and complementary role of laboratory, radiographic, and molecular testing. With this review, we hope to remove some of the uncertainty that comes when approaching these often complicated patients.

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References

  1. Jabs DA, Busingye J. Approach to the diagnosis of the uveitidies. Am J Ophthalmol. 2013;156:228–36.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Silverstein, et al. Changing trends in the etiologic diagnosis of uveitis. Doc Ophthalmol. 1997;94(1–2):25–37.

    Article  CAS  PubMed  Google Scholar 

  3. Smith NE, Nozik RA. Uveitis: a clinical approach to diagnosis and management. 3rd ed. Michigan: Lippincott Williams & Wilkins; 2003.

    Google Scholar 

  4. 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(3):509–16.

    Article  PubMed  Google Scholar 

  5. Rosenbaum JT, Holland GN. Uveitis and the tower of babel. Arch Ophthalmol. 1996;114(5):604–5.

    Article  CAS  PubMed  Google Scholar 

  6. Bloch-Michael E, Nussenblatt RB. International uveitis study group recommendations for the evaluation of intraocular inflammatory disease. Am J Ophthalmol. 1987;103:234–5.

    Article  Google Scholar 

  7. 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.

    Article  PubMed  Google Scholar 

  8. Deschenes J, Murray PI, Rao NA, Nussenblatt RB. International uveitis study group. International uveitis study group (IUSG): clinical classification of uveitis. Ocul Immunol Inflamm. 2008;16:1–2.

    Article  PubMed  Google Scholar 

  9. Okada AA, Jabs DA. The standardization of uveitis nomenclature project: the future is here. JAMA Ophthalmol. 2013;131(6):787–9.

    Article  PubMed  Google Scholar 

  10. Trusko B, Thorne J, Jabs D, et al. The standardization of uveitis nomenclature (SUN) project. Development of a clinical evidence base utilizing informatics tools and techniques. Methods Inf Med. 2013;52(3):259–65 Epub 8 Feb 2013.

    Article  CAS  PubMed  Google Scholar 

  11. Cunningham ET, Nozik RA. Duane’s clinical ophthalmology. Vol. 37. Philadelphia: Lippincott-Raven; 1997. Uveitis: Diagnostic approach and ancillary analysis. p. 58–68.

    Google Scholar 

  12. Harper SL, Chorich LJ, Foster CS. Diagnosis of uveitis. In: Foster CS, Vitale AT, editors. Diagnosis and treatment of uveitis. Philadelphia: W.B. Saunders; 2002. p. 79–103.

    Google Scholar 

  13. Cunningham ET. Uveitis in children. Ocul Immunol Inflamm. 2000;8:251–61.

    Article  PubMed  Google Scholar 

  14. Rathinam SR, Namperumalsamy P. Global variation and pattern changes in epidemiology of uveitis. Indian J Ophthalmol. 2007;55:173–83.

    Article  CAS  PubMed  Google Scholar 

  15. Jones NP. The manchester uveitis clinic: the first 3000 patients-epidemiology and casemix. Ocul Immunol Inflamm. 2013;23:118–26.

    Google Scholar 

  16. Rathinam SR, Babu M. Algorithmic approach in the diagnosis of uveitis. Indian J Ophthalmol. 2013;61(6):255–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Chang JH, McCluskey PJ, Wakefield D. Acute anterior uveitis and HLA-B27. Surv Ophthalmol. 2005;50:364–88.

    Article  PubMed  Google Scholar 

  18. McCannel CA, Holland GN, Helm CJ, et al. Causes of uveitis in the general practice of ophthalmology. UCLA community-based uveitis study group. Am J Ophthalmol. 1996;121:35–46.

    Article  CAS  PubMed  Google Scholar 

  19. Reeves SW, Sloan FA, Lee PP, Jaffe GJ. Uveitis in the elderly. Epidemiological data from the national long-term care survey medicare cohort. Ophthalmology. 2006;113:302–7.

    Article  Google Scholar 

  20. Yanoff M, Duker JS. Ophthalmology. 3rd ed. Elsevier; 2009. Uveitis and other intraocular inflammations; 7.3, p. 784.

    Google Scholar 

  21. Herbert HM, Viswanathan A, Jackson H, Lightman SL. Risk factors for elevated intraocular pressure in uveitis. J Glaucoma. 2004;13(2):96–9.

    Article  PubMed  Google Scholar 

  22. Bhagat N, Read RW, Rao NA, et al. Rifabutin-associated hypopyon uveitis in human immunodeficiency virus-negative immunocompetent individuals. Ophthalmol. 2001;108(4):750–2.

    Article  CAS  Google Scholar 

  23. Petrowski JT 3rd. Uveitis associated with rifabutin therapy: a clinical alert. J Am Optom Assoc. 1996;67(11):693–6.

    PubMed  Google Scholar 

  24. Tugwell P, Dennis DT, Weinstein A, Wells G, Shea B, Nichol G, et al. Laboratory evaluation in the diagnosis of Lyme disease. Ann Intern Med. 1997;127:1109–23.

    Article  CAS  PubMed  Google Scholar 

  25. Ledue TB, Collins MF, Craig WY. New laboratory guidelines for serologic diagnosis of Lyme disease: evaluation of the two-test protocol. J Clin Microbiol. 1996;34:2343–50.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Rosenbaum JT, Wernick R. The utility of routine screening of patients with uveitis for systemic lupus erythematosus or tuberculosis. A Bayesian analysis. Arch Ophthalmol. 1990;108(9):1291–3.

    Article  CAS  PubMed  Google Scholar 

  27. Albini TA, Karakousis PC, Rao NA. Interferon-gamma release assays in the diagnosis of tuberculosis uveitis. Am J Ophthalmol. 2008;146(4):486–8.

    Article  CAS  PubMed  Google Scholar 

  28. Streeton, JA, Desem N, Jones SL. Sensitivity and specificity of a gamma interferon blood test for tuberculosis infection. Int J Tuberc Lung Dis Off J Int Union Tuberc Lung Dis. 1998;2(6):443–50.

    Google Scholar 

  29. Mazurek GH, Jereb J, et al. Updated guidelines for using interferon gamma release assays to detect mycobacterium tuberculosis infection—centers for disease control. United states, 2010. MMWR Recomm Rep. 2010;59(RR05):1–25.

    Google Scholar 

  30. McMullen SE, Pegues DA, et al. Performance of QuantiFERON-TB gold and tuberculin skin test relative to subjects’ risk of exposure to tuberculosis. Clin Infect Dis. 2014;58(9):1260–6 Epub 27 Feb 2014.

    Article  PubMed  Google Scholar 

  31. Vasconcelos-Santos DV, Rao PK, et al. Clinical features of tuberculous serpiginous like choroiditis in contrast to classic serpiginous choroiditis. Arch Ophthalmol. 2010;128(7):853–8.

    Article  PubMed  Google Scholar 

  32. Kahn MA. Thoughts concerning the early diagnosis of ankylosing spondylitis and related diseases. Clin Exp Rheumatol. 2002;20(Suppl. 28):S6–10.

    Google Scholar 

  33. Patton ME, Su JR, Nelson R, et al. Primary and secondary syphilis—United states, 2005–2013. MMWR Morb Mortal Wkly Rep Cent Dis Control Prev. 2014;63(18):402–6.

    Google Scholar 

  34. Hong BK, Khanamiri HN, Bababeygy SR, Rao NA. The utility of routine tuberculosis screening in county hospital patients with uveitis. Br J Ophthalmol. 2014;98:1091–5.

    Article  PubMed  Google Scholar 

  35. Cush JJ, Winthrop K, Dao K, et al. Screening for mycobacterium tuberculosis infection: questions and answers for clinical practice. Drug Saf Quart. 2010; Spring 1(2):1–4.

    Google Scholar 

  36. National Health and Nutrition Examination Survey III (NHANES III), series 11 Data Files 1988–1994. Available online at http://www.cdc.gov/nchs/nhanes/nh3data.htm.

  37. Jones JL, Kruszon-Moran D, Sanders-Lewis K, et al. Toxoplasma gondii infection in the United states, 1999 2004, decline from the prior decade. Am J Trop Med Hyg. 2007;77(3):405–10.

    PubMed  Google Scholar 

  38. Ang M, Htoon HM, et al. Diagnosis of tuberculous uveitis: clinical application of an interferon-gamma release assay. Ophthalmology. 2009;116(7):1391–6.

    Article  PubMed  Google Scholar 

  39. Ang M, Wong WL, Kiew SY, et al. Prospective head-to-head study comparing 2 commercial interferon gamma release assays for the diagnosis of tuberculous uveitis. Am J Ophthalmol. 2014;157(6):1306–14.

    Google Scholar 

  40. McMullen SE, Pegues DA. Performance of QuantiFERON-TB gold and tuberculin skin test relative to subjects’ risk of exposure to tuberculosis. Clin Infect Dis. 2014;58(9):1260–6. doi:10.1093/cid/ciu119 Epub 27 Feb 2014.

    Article  PubMed  Google Scholar 

  41. Steffen RE, Caetano R, et al. Cost-effectiveness of quantiferon®-TB gold-in-tube versus tuberculin skin testing for contact screening and treatment of latent tuberculosis infection in Brazil. PLoS One. 2013;8(4). Print 2013.

    Google Scholar 

  42. U.S. Preventive Services Task Force. Screening for syphilis infection. Recommendation statement. 2004.

    Google Scholar 

  43. Larsen SA, Hambie EA, Wobig GH, Kennedy EJ. Cerebrospinal fluid serologic tests for syphilis: treponemal and nontreponemal tests. In: Morisset R, Kurstak E, editors. Advances in sexually transmitted diseases. Utrecht, The Netherlands: VNW Science Press; 1986. p. 157–62.

    Google Scholar 

  44. Tamesis RR, Foster CS. Ocular syphilis. Ophthalmology. 1990;97(10):1281–7.

    Article  CAS  PubMed  Google Scholar 

  45. Schmid GP. Serologic screening for syphilis. Rationale, cost, and realpolitik. Sex Transm Dis. 1996;23(1):45–50.

    Article  CAS  PubMed  Google Scholar 

  46. Reisner BS, Mann LM, Tholcken CA, et al. Use of the treponema pallidum-specific captia syphilis IgG assay in conjunction with the rapid plasma regain to test for syphilis. J Clin Microbiol. 1997;35(5):1141–3.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Wong EH, Klausner JD, Caguin-Grygiel G. Evaluation of an IgM/IgG sensitive enzyme immunoassay and the utility of index values for the screening of syphilis infection in a high-risk population. Sex Transm Dis. 2011;38(6):528–32.

    CAS  PubMed  Google Scholar 

  48. Fawcett PT, Rose CD, Budd SM, Gibney KM. Effect of immunization with recombinant OspA on serologic tests for Lyme borreliosis. Clin Diagn Lab Immunol. 2001;8(79–84):50.

    Google Scholar 

  49. Mogilyansky E, Loa CC, et al. Comparison of western immunoblotting and the C6 Lyme antibody test for laboratory detection of Lyme disease. Clin Diagn Lab Immunol. 2004;11(5):924–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Beneteau-Burnat B, Baudin B, Morgant G, Baumann FC, Giboudeau J. Serum angiotensin-converting enzyme activity in normal children and in those with sarcoidosis. Clin Chem. 1990;36:344–6.

    CAS  PubMed  Google Scholar 

  51. Tomita H, et al. Serum lysozyme levels and clinical features of sarcoidosis. Lung. 1999;177:161–7.

    Article  CAS  PubMed  Google Scholar 

  52. Weinreb RN, Tessler H. Laboratory diagnosis of ophthalmic sarcoidosis. Surv Ophthalmol. 1984;28:653–64.

    Article  CAS  PubMed  Google Scholar 

  53. Ainslie GM, Benatar SR. Serum angiotensin converting enzyme in sarcoidosis: sensitivity and specificity in diagnosis: correlations with disease activity, duration, extra-thoracic involvement, radiographic type and therapy. Q J Med. 1985;55(218):253–70.

    CAS  PubMed  Google Scholar 

  54. Baarsma GS, La Hey E. The predictive value of serum angiotensin converting enzyme and lysozyme levels in the diagnosis of ocular sarcoidosis. Am J Ophthalmol. 1987;104(3):211–7.

    Article  CAS  PubMed  Google Scholar 

  55. Power WJ, Neves RA, et al. The value of combined serum angiotensin-converting enzyme and gallium scan in diagnosing sarcoidosis. Ophthalmology. 1995;102(12):2007–11.

    Article  CAS  PubMed  Google Scholar 

  56. Newman LS, Rose CS, Maier LA. Sarcoidosis. N Engl J Med. 1997;336:1224–34.

    Article  CAS  PubMed  Google Scholar 

  57. Cassidy JT, Levinson JE, Bass JC, et al. A study of classification criteria for a diagnosis of juvenile rheumatoid arthritis. Arthritis Rheum. 1986;29:274–81.

    Article  CAS  PubMed  Google Scholar 

  58. Tan EM, Feltkamp TE, et al. Range of antinuclear antibodies in “healthy” individuals. Arthritis Rheum. 1997;40(9):1601.

    Article  CAS  PubMed  Google Scholar 

  59. Hettinga YM, Scheerlinck LME, Lilein MR, et al. The value of measuring urinary β2-microglobulin and serum creatinine for detecting tubulointerstitial nephritis and uveitis syndrome in young patients with uveitis. JAMA Ophthalmol. Published online, 30 Oct 2014. doi;10.1001/jamaophthalmol.2014.4401.

  60. Reed JB, Scaled DK, Wong MT, et al. Bartonella henselae neuroretinitis in cat scratch disease. Diagnosis management and sequelae. Ophthalmology. 1998;105(3):459–66.

    Article  CAS  PubMed  Google Scholar 

  61. Zamecki KJ, Jabs DA, et al. HLA typing in uveitis: use and misuse. Am J Ophthalmol. 2010;149:189–93.

    Article  CAS  PubMed  Google Scholar 

  62. Rosenbaum JT. Characterization of uveitis associated with spondyloarthritis. J Rheumatol. 1989;16:792–6.

    CAS  PubMed  Google Scholar 

  63. Monnet D, Breban M, et al. Ophthalmic findings and frequency of extraocular manifestations in patients with HLA-B27 uveitis: a study of 175 cases. Ophthalmology. 2004;111:802–9.

    Article  PubMed  Google Scholar 

  64. Linssen A, Meenken C, et al. Outcomes of HLA-B27 positive and HLA-B27 negative acute anterior uveitis. Am J Ophthalmol. 1995;120:351–61.

    Article  CAS  PubMed  Google Scholar 

  65. Tay-Kearney ML, Schwam BL, et al. Clinical features and associated systemic diseases of HLA-B27 uveitis. Am J Ophthalmol. 1996;121:47–56.

    Article  CAS  PubMed  Google Scholar 

  66. Nussenblatt RB, Mittal KK. Birdshot retinochoroidopathy associated with HLA-A29 antigen and immune responsiveness to retinal s-antigen. Am J Ophthalmol. 1982;94(2):147–58.

    Article  CAS  PubMed  Google Scholar 

  67. Miller BH, Rosado-de-christenson ML, Mcadams HP, et al. Thoracic sarcoidosis: radiologic-pathologic correlation. Radiographics. 1995;15(2):421–37.

    Article  CAS  PubMed  Google Scholar 

  68. Müller NL, Franquet T, Lee KS, et al. Imaging of pulmonary infections. Lippincott Williams & Wilkins; 2007.

    Google Scholar 

  69. Yeager H, Rossman MD. Pulmonary and psychosocial findings at enrollment in the ACCESS study. Sarcoidosis Vasc Diffuse Lung Dis. 2005; 22(2):147–53.

    Google Scholar 

  70. Disayabutr S, Pattanaprichakul P. A case series of sarcoidosis with pulmonary involvement: various clinical and radiographic manifestations. J Med Assoc Thai. 2013;96(8):888–97.

    PubMed  Google Scholar 

  71. Criado E, Sanchez M. Pulmonary sarcoidosis: typical and atypical manifestations at high-resolution CT with pathologic correlation. Radiographics. 2010;30(6):1567–86.

    Article  PubMed  Google Scholar 

  72. Klech H, Kohn H, Pohl W, et al. Diagnosis in sarcoidosis. Sensitivity and specificity of 67-gallium scintigraphy, serum angiotensin converting enzyme levels, thoracic radiography and blood lymphocyte subpopulations. Wien Med Wochenschr. 1983;133(17):425–32 (article in German).

    Google Scholar 

  73. Silva M, Nunes H, Valeyre D, et al. Imaging of sarcoidosis. Clin Rev Allergy Immunol. 2015;49(1)1:45–53.

    Google Scholar 

  74. Van’t Hoog AH, Langendam MW, et al. A systematic review of the sensitivity and specificity of symptom- and chest-radiography screening for active pulmonary tuberculosis in HIV-negative persons and persons with unknown HIV status. Cochrane Database Syst Rev Infect Dis Group. Published online, 2 Jan 2014.

    Google Scholar 

  75. Takada K, Matsumoto S, et al. Diagnostic management of patients with suspected ocular sarcoidosis. J Thorac Dis. 2013;5(2):135–40.

    Google Scholar 

  76. Mana J, Teirstein AS, et al. Excessive thoracic computed tomographic scanning in sarcoidosis. Thorax. 1995;50(12):1264–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Kaiser PK, Lowder CY, Sullivan P, et al. Chest computerized tomography in the evaluation of uveitis in elderly women. Am J Ophthalmol. 2002;133(4):499–505.

    Article  PubMed  Google Scholar 

  78. Statement on sarcoidosis. Joint statement of the american thoracic society (ATS), the European respiratory society (ERS), and the world association of sarcoidosis and other granulomatous disorders (WASOG) adopted by the ATS board of directors and by the ERS executive committee, February 1999. Am J Respir Crit Care Med. 1999;160:736–55.

    Article  Google Scholar 

  79. Nunes H, Brillet PY, et al. Imaging in sarcoidosis. Semin Respir Crit Care Med. 2007;28(1):102–20.

    Article  PubMed  Google Scholar 

  80. Noyes K, Weinstock-Guttman B, et al. Impact of diagnosis and early treatment on the course of multiple sclerosis. Am J Manag Care. 2013;19(Suppl. 17):s321–31.

    PubMed  Google Scholar 

  81. Zhao Y, Xu L, Ma W, et al. Shell-engineered chiroplasmonic assemblies of nanoparticles for zeptomolar DNA detection. Nano Lett. 2014;14(7):3908–13.

    Article  CAS  PubMed  Google Scholar 

  82. Rothova A, de Boer JH, Ten Dam-van Loon NH, et al. Usefulness of aqueous humor analysis for the diagnosis of posterior uveitis. Ophthalmology. 2008;115(2):306–11.

    Article  PubMed  Google Scholar 

  83. Knox CM, Chandler D, Short GA, et al. Polymerase chain reaction-based assays of vitreous samples for the diagnosis of viral retinitis. Use in diagnostic dilemmas. Ophthalmology. 1998;105:37–44.

    Article  CAS  PubMed  Google Scholar 

  84. Chan CC, Shen D, Tuo J, et al. Polymerase chain reaction in the diagnosis of uveitis. Int Ophthalmol Clin. 2005;45(2):41–55.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Balne PK, Barik MR, Sharma S, et al. Development of a loop-mediated isothermal amplification assay targeting the mpb64 gene for the diagnosis of intraocular tuberculosis. J Clin Microbiol. 2013;51(11):3839–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Fanburg BL: Sarcoidosis. In: Wyngaarden JB, Smith LH, Jr., Bennett JC, editors. Cecil textbook of medicine. 19th ed. Philadelphia: W.B. Saunders; 1992:430–5.

    Google Scholar 

  87. Nichols CW, Eagle RC, Yanoff M, et al. Conjunctival biopsy as an aid in the evaluation of the patient with suspected sarcoidosis. Ophthalmology. 1980;87:287–91.

    Article  CAS  PubMed  Google Scholar 

  88. Bui KM, Garcia-Gonzales JM, Pael SS, et al. Directed conjunctival biopsy and impact of histologic sectioning methodology on the diagnosis of ocular sarcoidosis. J Ophthalmic Inflam Infect. 2014;4:8.

    Article  Google Scholar 

  89. Karcioglu AZ, Brear R. Conjunctival biopsy in sarcoidosis. Am J Ophthal. 1985;99:68–73.

    Article  CAS  PubMed  Google Scholar 

  90. Spaide RF, Ward DL. Conjunctival biopsy in the diagnosis of sarcoidosis. Br J Ophthalmol. 1990;74:469–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Sulavik SB, Palestro CF, et al. Extrapulmonary sites of radiogallium accumulation in sarcoidosis. Clin Nucl Med. 1990;15:876–8.

    Article  CAS  PubMed  Google Scholar 

  92. Davatchi F, Chams-Davatchi C, et al. Diagnostic value of pathergy test in Behcet’s disease according to the change of incidence over the time. Clin Rheumatol. 2011;30(9):1151–5.

    Article  PubMed  Google Scholar 

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Hansen, B.A., Soukiasian, S.H. (2017). Approach to the Laboratory, Imaging, and Molecular Work-up for Uveitis. In: Papaliodis, G. (eds) Uveitis. Springer, Cham. https://doi.org/10.1007/978-3-319-09126-6_2

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