Customize your JAMA Network experience by selecting one or more topics from the list below.
A 63-year-old white man with a history of cigarette use (≥80 pack-years) and alcohol dependence presented to the ophthalmology clinic with several weeks of left eye pain and redness. A review of systems was remarkable for unintentional weight loss, night sweats, and cough with scant sputum. On presentation, best-corrected visual acuity was 20/20 OU. Intraocular pressure, pupillary reaction, and ocular motility were normal. The right eye had normal anterior and posterior segment examination findings. The left eye was notable for mostly superior conjunctival and scleral hyperemia with dilated scleral vessels and associated scleral thinning with a conjunctival epithelial defect (Figure 1). The results of posterior examination of the left eye were normal. Results of serologic tests, including Treponema pallidum particle agglutination assay, HIV, hepatitis B and C, Lyme antibody, rheumatoid factor, and anticyclic citrullinated peptide, were negative. Angiotensin-converting enzyme level, uric acid level, erythrocyte sedimentation rate, complete blood cell count, and basic metabolic panel results were within normal limits. The results of proteinase 3–antineutrophil cytoplasmic antibody (ANCA) testing and interferon γ release assay using QuantiFERON-TB gold (QFT) (Qiagen) were positive. Chest computed tomography revealed tiny, scattered solid pulmonary nodules that were too small to characterize according to the radiology department. The patient was referred to the infectious diseases clinic, where the results of sputum culture and polymerase chain reaction for Mycobacteria tuberculosis were negative. Pulmonology evaluation determined that the pulmonary nodules were too small for biopsy via bronchoscopy.
Slitlamp photograph of the left eye shows diffuse hyperemia with dilated vessels and scleral thinning.
Perform an incisional biopsy
Prescribe oral prednisone
Initiate rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE) therapy
Inject sub-Tenon triamcinolone
Necrotizing anterior scleritis
C. Initiate RIPE therapy
Necrotizing scleritis can be vision-threatening and warrants investigation to determine the underlying cause and appropriate treatment. The cause could be idiopathic, infectious, or secondary to an underlying autoimmune disorder, such as rheumatoid arthritis or granulomatous polyangiitis.1 Positive serologic test results for proteinase 3–ANCA are present in approximately two-thirds of patients with granulomatous polyangiitis, and in the context of scleritis with positive ANCA results, the odds ratio of developing subsequent granulomatous polyangiitis is 22.91.2,3 This case was challenging because the patient also had positive QFT results and a history of positive tuberculin skin test results and exposure to a family member with active pulmonary tuberculosis. His QFT titer was high (>10 IU/mL; reference range, >1.09 IU/mL), but it still lacked the specificity to differentiate active vs latent tuberculosis.4
Scleral biopsy could help to differentiate the cause. However, surgical trauma to an inflamed sclera could exacerbate scleral necrosis, particularly if the cause is autoimmune related.5 Oral prednisone would be the treatment option if the cause was secondary to an autoimmune disease. Although the patient tested positive for proteinase 3–ANCA, initiating corticosteroid treatment orally or locally with sub-Tenon injection without ruling out an infectious cause could accelerate disease progression.
Although the patient had a negative sputum culture and polymerase chain reaction results, the combination of prior exposure, positive tuberculin skin test results, and a high QFT titer strongly suggests the diagnosis of tuberculosis scleritis.6 In a large cohort study of scleritis,7 9.4% of cases were infectious, and among these, 10% were related to tuberculosis. Ocular involvement secondary to systemic tuberculosis occurs in 1% to 2% of patients, and most have no history of pulmonary or systemic symptoms. Up to 50% can have normal chest radiography findings. Ocular manifestations may be secondary to direct invasion or a result of a hypersensitivity reaction to tuberculosis antigens. Tuberculosis scleritis typically presents as an anterior nodular scleritis but can be necrotizing and does not respond to topical corticosteroids.8 QuantiFERON-TB gold can be useful in guiding therapy because patients with higher titers respond better clinically to RIPE therapy.9
The patient was counseled for alcohol cessation and prescribed 6 months of RIPE therapy with close observation for clinical improvement. If the patient failed to improve, the treatment would be changed to systemic immunosuppression with oral corticosteroids and concomitant prophylaxis with oral isoniazid only.
After 2 days of RIPE therapy, the patient experienced acute worsening of symptoms and redness likely because of an ocular Jarisch-Herxheimer reaction secondary to lysis of the mycobacterium that exacerbated the inflammatory response.10 The patient was subsequently prescribed 40 mg of oral prednisone with a slow taper in conjunction with continuation of RIPE therapy. The patient noted an improvement of symptoms of redness on subsequent follow-up visits and at 4 months after initiation of RIPE therapy had complete resolution of the scleritis (Figure 2), which remained stable even after the discontinuation of oral prednisone therapy. The patient remained clinically stable without signs of inflammation after completing 6 months of RIPE therapy.
Photograph from 4 months after initiation of rifampin, isoniazid, pyrazinamide, and ethambutol therapy shows the resolution of the scleritis.
Corresponding Author: Julie M. Schallhorn, MD, MS, Department of Ophthalmology, University of California, San Francisco, 8 Koret Way, Room U-519, San Francisco, CA 94143-0644 (email@example.com).
Published Online: December 14, 2017. doi:10.1001/jamaophthalmol.2017.4167
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.
Hsia YC, Naseri A, Schallhorn JM. A Painful Red Eye. JAMA Ophthalmol. 2018;136(3):299–300. doi:10.1001/jamaophthalmol.2017.4167
Browse and subscribe to JAMA Network podcasts!
Create a personal account or sign in to: