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Small Case Series
March 14, 2011

Interferon-γ Release Assay in Tuberculous Scleritis

Author Affiliations

Author Affiliations: Department of Ophthalmology, Kyorin University School of Medicine, Tokyo, Japan.

Arch Ophthalmol. 2011;129(3):360-371. doi:10.1001/archophthalmol.2011.27

Scleritis is a painful, often chronic, and potentially destructive ocular inflammation caused by either infectious agents or noninfectious immune reactions. Tuberculosis (TB) is one possible infectious cause of scleritis. In this report, we describe 3 patients in whom use of an interferon (IFN)-γ release assay assisted in the diagnosis of tuberculous scleritis.

Report of Cases
Case 1

A 29-year-old woman was referred for bilateral anterior scleritis refractory to topical corticosteroids. On examination, corrected visual acuities were 1.2 with normal intraocular pressure in both eyes. The sclera was markedly hyperemic in all 4 quadrants bilaterally (Figure 1A). Mild inflammatory cells were present in the anterior chambers in both eyes but the fundi were unremarkable. Laboratory investigations revealed normal chemistry results and blood cell counts; however, the erythrocyte sedimentation rate was elevated at 46 mm/h and results of a tuberculin skin test (TST) were positive with 38 mm of erythema and 18 mm of induration. The initial chest radiograph was unremarkable; however, subsequent chest computed tomography revealed multiple nodular lesions in the lung parenchyma. Results of testing using QuantiFERON-TB 2G (QFT) (Cellestis, Carnegie, Australia), an IFN-γ release assay, were found to be positive (defined as IFN-γ levels >0.35 IU/mL by the laboratory). The patient was diagnosed with tuberculous scleritis and treated with a 3-drug regimen (isoniazid, 300 mg/d; rifampicin, 450 mg/d; and ethambutol hydrochloride, 750 mg/d) for the initial 2 months, followed by the same doses of isoniazid and rifampicin for an additional 7 months. The bilateral scleritis resolved within 1 month after initiating anti-TB treatment (Figure 1B). No recurrences of scleritis were observed over 6 months of follow-up since completing therapy.

Figure 1.
Slitlamp photographs for case 1. A, Slitlamp photograph of the right eye in case 1, revealing severely hyperemic sclera. B, Photograph of the same eye 1 month after initiation of antituberculosis therapy, showing a marked decrease in inflammation but some mild thinning of the sclera.

Slitlamp photographs for case 1. A, Slitlamp photograph of the right eye in case 1, revealing severely hyperemic sclera. B, Photograph of the same eye 1 month after initiation of antituberculosis therapy, showing a marked decrease in inflammation but some mild thinning of the sclera.

Case 2

A 72-year-old man was referred for unilateral scleritis refractory to topical corticosteroid therapy. His history was remarkable for having been diagnosed with unilateral uveitis in the left eye in 2005 at another hospital, the details of which were unknown. On examination, the corrected visual acuities were 0.5 OU, with normal intraocular pressure. The right eye was entirely normal, but the left eye exhibited marked scleral hyperemia in all 4 quadrants (Figure 2A). In addition, although the vitreous was clear, retinal and choroidal folds in the superior macular area were noted. Laboratory investigation results were positive for the presence of perinuclear antineutrophil cytoplasmic antibodies and an elevated erythrocyte sedimentation rate of 41 mm/h. The TST results showed 40 mm of erythema and 10 mm of induration; however, chest radiography examination was normal. Results of subsequent QFT testing were positive. An orbital computed tomographic scan confirmed diffuse thickening of the posterior eye wall and unilateral anterior and posterior scleritis was diagnosed, possibly due to TB. The patient was treated with a 4-drug regimen (isoniazid, 300 mg/d; rifampicin, 450 mg/d; ethambutol hydrochloride, 750 mg/d; and pyrazinamide, 1500 mg/d) for the first 2 months, followed by the same doses of isoniazid and rifampicin for 7 months. The scleritis improved within 2 months of initiating anti-TB therapy, and no recurrences were observed over 3 months of follow-up since completing treatment (Figure 2B).

Figure 2.
Slitlamp photographs for case 2. A, Slitlamp photograph of the left eye in case 2, revealing hyperemic sclera. B, Photograph of the same eye 6 months after initiation of antituberculosis therapy, showing no active inflammation.

Slitlamp photographs for case 2. A, Slitlamp photograph of the left eye in case 2, revealing hyperemic sclera. B, Photograph of the same eye 6 months after initiation of antituberculosis therapy, showing no active inflammation.

Case 3

A 68-year-old man was referred for unilateral anterior scleritis refractory to topical corticosteroid therapy. On examination, the corrected visual acuities were 1.2, with normal intraocular pressure in both eyes. The right eye was normal, but the left eye showed marked hyperemia of the sclera in 3 quadrants (Figure 3A) but no anterior chamber or posterior segment inflammation. Results of blood tests were unremarkable with a normal erythrocyte sedimentation rate. The chest radiograph was normal; however, the TST results showed 40 mm of erythema and 8 mm of induration. This raised our suspicion of possible TB, and QFT testing was subsequently performed and results were found to be positive. The patient received the same 4-drug regimen as in case 2, and the inflammation responded favorably within 1 month of starting anti-TB treatment, with no recurrences noted (Figure 3B).

Figure 3.
Slitlamp photographs for case 3. A, Slitlamp photograph of the left eye in case 3, revealing diffuse hyperemic sclera. B, Photograph of the same eye 6 months after initiation of antituberculosis therapy, showing a marked decrease in inflammation but thinning of the sclera.

Slitlamp photographs for case 3. A, Slitlamp photograph of the left eye in case 3, revealing diffuse hyperemic sclera. B, Photograph of the same eye 6 months after initiation of antituberculosis therapy, showing a marked decrease in inflammation but thinning of the sclera.

Comment

Pulmonary TB remains a major health concern in Japan, with an estimated incidence of 21 in 100 000 and an estimated prevalence of 35 767 for 2007, roughly 4 to 5 times that for the United States.1 Extrapulmonary disease accounts for about 20% of TB cases and can involve virtually any organ of the body, including the lymph nodes, central nervous system, skeletal system, pleura, liver, kidney, and skin.2 Although the TST has long been used to support a diagnosis of active or latent TB, it is believed to have low specificity in populations that routinely receive BCG vaccination such as in Japan.3 Recently, IFN-γ release assays have been developed to aid in the diagnosis of TB. The QFT assay measures IFN-γ released when whole blood is stimulated with 2 synthetic peptides, the early secreted antigenic target 6-kDa protein (ESAT-6) and the 10-kDa culture filtrate protein (CFP-10), both found in Mycobacterium tuberculosis but not in the BCG vaccine or in the vast majority of atypical mycobacterium.4

In the present report, the TST results were positive or with induration large enough to raise our suspicion of TB and warrant additional QFT testing. We have previously reported that the rate of TST result positivity (induration >10 mm) was roughly 20% among patients with uveitis referred to our Ocular Inflammation Service.3 Although the TST result positivity rate is not known for our patient population with scleritis, our experience in uveitis strongly suggests that a positive TST result alone is insufficient to diagnosis tuberculous ocular inflammation. Recently, Ang and colleagues5 have demonstrated that the combination of a positive TST result and a positive QFT result increases the accuracy of diagnosing tuberculous uveitis. The present report also supports the use of both TST and QFT in the diagnosis of tuberculous scleritis.

In summary, our 3 patients presented with scleritis refractory to topical corticosteroid therapy, standard community-based treatment for this condition in Japan. Based on positive TST and QFT results, anti-TB therapy was initiated, with all patients exhibiting improvement of inflammation within 1 to 2 months. Our experience highlights the difficulty in assessing TB as a possible cause of ocular inflammation and the potential of IFN-γ release assays for assisting in that assessment.

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Article Information

Correspondence: Dr Okada, Department of Ophthalmology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan (aokada@eye-center.org).

Financial Disclosure: None reported.

References
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 Global TB database. World Health Organization Web site. http://www.who.int/tb/country/global_tb_database/en/. Accessed May 2, 2010
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Torgersen  JDorman  SEBaruch  NHooper  NCronin  W Molecular epidemiology of pleural and other extrapulmonary tuberculosis: a Maryland state review. Clin Infect Dis 2006;42 (10) 1375- 1382
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Morimura  YOkada  AAKawahara  S  et al.  Tuberculin skin testing in uveitis patients and treatment of presumed intraocular tuberculosis in Japan. Ophthalmology 2002;109 (5) 851- 857
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Mori  TSakatani  MYamagishi  F  et al.  Specific detection of tuberculosis infection: an interferon-gamma-based assay using new antigens. Am J Respir Crit Care Med 2004;170 (1) 59- 64
PubMedArticle
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Ang  MHtoon  HMChee  SP Diagnosis of tuberculous uveitis: clinical application of an interferon-gamma release assay. Ophthalmology 2009;116 (7) 1391- 1396
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