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Mycobacterium tuberculosis is an uncommon cause of scleritis in the developed world. Definitive diagnosis is usually made by identification of acid-fast bacilli (AFB) using microscopy or culture techniques.1 We report a case of tuberculous scleritis in which diagnosis was made only after quantitative polymerase chain reaction (PCR) on tissue specimens.
A 54-year-old woman originally from Mexico had redness and pain in her right eye for 6 months and was diagnosed with nodular scleritis. She was referred to the University of Illinois at Chicago when her symptoms did not resolve with oral prednisone. Her medical history was significant for diabetes, hypertension, hypercholesterolemia, and atrial fibrillation. Her best-corrected visual acuity was 20/80 OD and 20/25 OS. Examination revealed marked scleral injection with 2 scleral nodules superiorly in the right eye. The rest of the ocular examination was unremarkable. She was taking 10 mg/d of prednisone on presentation. Methotrexate (15 mg/wk) was added.
When workup revealed a positive Quantiferon-TB Gold test result (Cellestis Inc, Valencia, California) and calcified granulomas in bilateral hila on chest radiography and chest computed tomography, the patient was referred to the infectious disease service and began treatment with quadruple antituberculosis therapy (rifampin, isoniazid, pyrazinamide, and ethambutol hydrochloride). Methotrexate was stopped, and she self-discontinued prednisone treatment without taper. The scleritis worsened 1 week later, so prednisone treatment (30 mg/d) was restarted; the dosage was later increased (60 mg/d) owing to continued deterioration. Despite 3 months of tuberculosis therapy and treatment with oral prednisone, new nodules developed (Figure 1A). Because the infectious disease service was convinced that the scleritis did not represent infection with tuberculosis, treatment with cyclophosphamide (150 mg/d) was started but was discontinued after 10 days because of worsened scleritis. Scleral biopsy was recommended to rule out multidrug-resistant Mycobacterium, but the patient refused and sought another opinion. She continued receiving prednisone (40 mg/d) with antituberculosis therapy elsewhere.
On return 2 months later, the number of nodules had increased and biopsy was performed. Gram stains, AFB stain, and bacterial cultures had negative results. Microscopy revealed extensive scleral necrosis without classic granuloma formation (Figure 1B and C). Results for tissue Gram stain and stains for AFB (Ziehl-Nielson and Fite stains) were negative. Immunohistochemical staining results were positive for herpes simplex virus type 1. Valacyclovir hydrochloride (1 g 3 times daily) was added.
External photograph and photomicrographs. A, External photograph showing scleral nodules nasally and superiorly in the right eye. B, Mixed inflammatory infiltrate in the sclera consisting of lymphocytes, plasma cells, and polymorphonuclear leukocytes with scleral necrosis (hematoxylin-eosin, original magnification ×10). C, Note areas of scleral collagen necrosis at higher magnification (hematoxylin-eosin, original magnification ×16).
When the patient was noted to have hyphema and retinal whitening on examination 9 days after the biopsy, vitreous tap and intravitreous ganciclovir sodium and foscarnet sodium injections were performed. Results from PCR were negative for herpes simplex virus, varicella zoster virus, and cytomegalovirus.
She became noncompliant with medications and anticoagulation clinic visits, and she presented to the emergency room in diabetic ketoacidosis with emesis, an extremely high international normalized ratio (INR), and bleeding from her right eye. Vision was no light perception with scleral rupture superonasally and extrusion of intraocular contents (Figure 2A). Once the patient was medically stabilized, enucleation was performed. Histopathologic analysis revealed extensive necrotizing scleral and uveal inflammation. Results from histochemical stains for AFB and cultures were negative (Figure 2B). Results from microbiological testing of bronchoalveolar lavage were negative.
External photograph and photomicrograph montage. A, External photograph showing the scleral rupture site superonasally in the right eye. B, Montage showing extensive areas of inflammatory infiltrate involving the sclera and uvea in the region of perforation (arrow). Note the areas of scleral necrosis (asterisk) (hematoxylin-eosin, original magnification ×4).
Specimens were sent to the Ocular Pathology Laboratory, Doheny Eye Institute, Los Angeles, California, for real-time PCR, which revealed M tuberculosis genome. There were 702 copies of mycobacteria in four 20-μm histologic sections (44.9 fg of M tuberculosis DNA/1 μg of total DNA). The method and primers used have been previously described.2
Ocular involvement with tuberculosis is rare.3 In this case, diagnosis was based on positive PCR results following negative results on multiple cultures and stains for AFB on tissue sections and body fluids. Histopathologic analysis may not always offer adequate sensitivity, especially when bacteria are few. This report exemplifies the importance of quantitative PCR in such cases. A confounding factor in this case was tissue immunoreactivity to herpes simplex virus type 1 antibody. Although the antibodies used have a high sensitivity, variable specificity and false-positive reactions may occur.4
This case also highlights the difficulty in treating multidrug-resistant tuberculous scleritis, which is more likely to have a dismal prognosis as has scleritis secondary to drug-resistant atypical mycobacteria.5
Correspondence: Dr Goldstein, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, 1855 W Taylor St, M/C 648, Chicago, IL 60612 (email@example.com).
Financial Disclosure: None reported.
This article was corrected online for typographical errors on 8/10/2009.
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