Downloaded from http://bjo.bmj.com/ on August 30, 2016 - Published by group.bmj.com Clinical science Clinical manifestations and outcome of tuberculous sclerokeratitis Samir S Shoughy,1 Mahmoud O Jaroudi,1 Khalid F Tabbara1,2,3

1The Eye Center and The Eye ABSTRACT uncommon.4 of the anterior segment Foundation for Research in Aim To study the clinical manifestations and outcome of the eye may lead to a variety of clinical manifes- Ophthalmology, Riyadh, Saudi Arabia of patients with tuberculous sclerokeratitis treated with tations and may affect the eyelids, the orbit, the lac- 2Department of antituberculous therapy without concomitant use of rimal gland, the , the sclera or the Ophthalmology, College of systemic steroids. conjunctiva.35 Medicine, King Saud Methods We reviewed retrospectively the medical Tuberculosis may affect the cornea leading to University, Riyadh, Saudi records of eight consecutive patients with tuberculous interstitial or disciform keratitis.67 Arabia 3The Wilmer Ophthalmological sclerokeratitis. Patients were treated unsuccessfully with Similarly, scleral involvement in tuberculosis may Institute of The Johns Hopkins topical and/or systemic steroids. They underwent occur as a localised lesion. Tuberculosis may affect University, School of Medicine, complete ophthalmic examination, systemic evaluation, the sclera and the adjacent corneal periphery Baltimore, Maryland, USA laboratory investigations and imaging. Tuberculin skin leading to sclerokeratitis, which may occur in other fi Correspondence to test was done with puri ed protein derivative (PPD) on systemic immune-mediated disorders such as in Dr Samir S Shoughy, all patients. The diagnosis of tuberculous sclerokeratitis patients with granulomatosis with polyangitis. Department of Ophthalmology, was made based on clinical findings of scleritis with We describe, herewith, eight cases of tuberculous The Eye Center and The Eye adjacent peripheral corneal stromal keratitis, positive PPD sclerokeratitis that were initially diagnosed as Foundation for Research in test of 15 mm of induration or more, response to immune-mediated disease and the inflammation Ophthalmology, The Eye Center, P. O. Box 55307, antituberculous treatment (ATT) within 4 weeks and deteriorated or did not respond to topical or sys- Riyadh 11534, Saudi Arabia; exclusion of other causes of sclerokeratitis. temic immunological suppression. They were later [email protected] Antituberculous drugs were given for a minimum of diagnosed as tuberculous sclerokeratitis and 6 months without concomitant use of corticosteroids. responded to antituberculous drugs without con- Received 11 August 2015 Revised 4 November 2015 The outcome measure was resolution of the ocular comitant use of oral corticosteroids or immunosup- Accepted 28 November 2015 surface inflammation of the sclera and cornea. pressive agents. Published Online First Results Eight consecutive patients with a diagnosis of 23 December 2015 tuberculous sclerokeratitis were included. There were one PATIENTS AND METHODS male and seven female patients. The mean age was The clinical findings of eight consecutive patients 29 years with an age range of 7–43 years. The with tuberculous sclerokeratitis were reviewed involvement of the sclera was nodular in six patients and retrospectively. Each patient underwent complete diffuse in two. The involvement of the cornea consisted ophthalmic examination, systemic evaluation, of peripheral corneal stromal inflammation adjacent to imaging and laboratory investigations. Ophthalmic the area of scleritis. Patients responded to evaluation included visual acuity testing, applana- antituberculous medications with complete resolution of tion tonometry and anterior and posterior segment the sclerokeratitis without topical or systemic anti- biomicroscopy. All patients had laboratory investi- inflammatory agents. gations, which included complete blood counts, Conclusions Antituberculous medications can lead to erythrocyte sedimentation rate and chest X-ray, to complete resolution of the sclerokeratitis without rule out systemic diseases that are associated with concomitant use of steroids, or other anti-inflammatory sclerokeratitis. Tuberculin skin test using purified agents. protein derivative (PPD) was done on all patients. Antinuclear antibody (ANA), cytoplasmic antineu- trophil cytoplasmic autoantibody (cANCA), peri- Tuberculosis remains a leading cause of morbidity nuclear antineutrophil cytoplasmic autoantibody and mortality worldwide. It is common in develop- (pANCA), anticyclic citrullinated peptide ing countries, and among immigrant populations (anti-CCP) and serum uric acid tests were done to and immunocompromised patients in developed exclude other causes of sclerokeratitis. We ruled countries. Tuberculosis primarily affects the lungs out by serology. but may also lead to extrapulmonary tissue involve- The presumptive diagnosis of tuberculous sclero- ment including the eye. It is estimated that 90% of keratitis was made based on the clinical findings of patients with tuberculosis may show no signs or scleritis with adjacent peripheral corneal stromal symptoms of the disease. Ocular tuberculosis is an keratitis, positive PPD of 15 mm of induration or 1 extrapulmonary form of the disease. The inci- more, response to a 4-week course of antitubercu- dence of ocular involvement among patients in a lous treatment (ATT) without anti-inflammatory 2 tuberculosis sanatorium was 1.4%. Mycobacterium agents and exclusion of other causes of sclerokerati- tuberculosis may affect any structure of the eye and tis. Two cases had isolation of M. tuberculosis from To cite: Shoughy SS, the clinical manifestations are insidious at onset. a draining preauricular lymph node. Patients were Jaroudi MO, Tabbara KF. Extraocular and intraocular involvements are sec- given a four-drug antituberculous therapy (etham- Br J Ophthalmol ondary to endogenous dissemination of the organ- butol, pyrizinamide, isoniazid, rifamycin) for – 3 2016;100:1301 1303. ism. Exogenous spread of the infection is 2 months, and a three-drug antituberculous therapy

Shoughy SS, et al. Br J Ophthalmol 2016;100:1301–1303. doi:10.1136/bjophthalmol-2015-307599 1301 Downloaded from http://bjo.bmj.com/ on August 30, 2016 - Published by group.bmj.com Clinical science

Table 1 Clinical and laboratory findings in cases of sclerokeratitis No. Age/gender Scleritis IK Lymph node involvement Pulmonary Tbc PPD induration (mm) Other ocular findings

1 31/F Nodular + No Inactive pulmonary Tbc >15 ANG chorioretinitis 2 33/F Nodular + Scrofula No >15 – 3 33/F Nodular + No No >15 ANG 4 43/F Sectorial + No No >15 – 5 18/M Nodular (multiple) + Scrofula No >15 – 6 22/F Sectorial + Scrofula No >15 AGU 7 42/F Nodular + No Inactive pulmonary Tbc >15 – 8 7/F Nodular + No No >15 – AGU, anterior granulomatous uveitis; ANG, anterior non-granulomatous uveitis; IK, interstitial keratitis; PPD, purified protein derivative; Tbc, tuberculosis.

(pyrizinamide, isoniazid, rifamycin) for 4 months. The protocol retinal vasculitis with multifocal chorioretinitis in one patient. was approved by the Institution Review Board (IRB) of The Eye Seven of the eight patients were treated elsewhere with topical Center, Riyadh, Saudi Arabia. The study design complied with and systemic corticosteroids and failed to respond. One patient the standards put forth by the Declaration of Helsinki. did not respond to topical steroids at presentation. Six had no radiological evidence of pulmonary tuberculosis. Two had evi- RESULTS dence of inactive pulmonary tuberculosis. Three had involve- There were one male and seven female patients. The mean age ment of the preauricular or cervical lymph nodes (Scrofula). was 29 years with an age range of 7–43 years (table 1). The One of the patients had a draining lymph node. PPD test was ocular involvement was unilateral in all cases. The involvement positive in all eight cases (more than 15 mm of induration) M. tuberculosis of the sclera was nodular in six patients and diffuse in two. The (table 1). was cultured and isolated from two M. tuberculosis involvement of the cornea consisted of peripheral corneal patients. One had positive culture for on – stromal inflammation adjacent to the area of scleritis in all cases. Löwenstein Jensen medium from vitreous biopsy and one had Associated ocular findings included uveitis in three patients, and positive culture from a draining cervical lymph node. All patients responded to antituberculous medications with complete resolution of the sclerokeratitis without the use of topical or systemic anti-inflammatory agents (figure 1A showing sclerokeratitis before treatment, and figure 1B shows resolution of inflammation 3 months after treatment). Signs of improve- ments were noted at 4 weeks after initiation of therapy. Patients showed progressive improvement in the signs and symptoms with complete resolution. In one patient, there was evidence of sclera thinning at the area of previous nodular scleritis. None of the patients were given topical or systemic corticosteroids or non-steroidal anti-inflammatory drugs during therapy with anti- tuberculous agents.

DISCUSSION The prevalence of infectious scleritis has been reported to be 9.4%. Tuberculosis accounted for 10.6% of the cases with infec- tious scleritis.8 Extrapulmonary tuberculosis including ocular tuberculosis may occur in the absence of pulmonary disease. In cases of sclerokeratitis. the corneal changes are usually related to or in the same quadrant as the active scleral disease and may or may not be associated with vascularisation of the cornea.9 Scleral involvement in tuberculosis is mostly anterior. Involvement of the posterior sclera is extremely rare and may present as a localised posterior scleritis or posterior scleral tuberculoma.10 11 Tuberculosis may affect the episclera causing nodular episcleritis.12 Tuberculous scleritis may result from either a direct invasion of the sclera by M. tuberculosis or an immune-mediated reaction to circulating mycobacterial antigens.13 The scleral involvement in our patients was nodular in six out of the eight patients and diffuse in two. Most of the cases previ- ously reported were nodular and localised lesions with elevation of the sclera. The lesion is focal and non-necrotising14 or may Figure 1 Tuberculous sclerokeratitis: (A) before treatment and (B) undergo scleral necrosis leading to scleral thinning.3 If not prop- 3 months after treatment. erly treated, the lesion may progress leading to scleral

1302 Shoughy SS, et al. Br J Ophthalmol 2016;100:1301–1303. doi:10.1136/bjophthalmol-2015-307599 Downloaded from http://bjo.bmj.com/ on August 30, 2016 - Published by group.bmj.com Clinical science

perforation.15 Diffuse scleritis may occur in patients with tuber- The recovery of the tuberculous sclerokeratitis without use of culosis but is less common than nodular scleritis.3 Scleritis may topical or systemic corticosteroids underscores the fact that be associated with adjacent keratitis leading to sclerokeratitis. tuberculous sclerokeratitis appears to resolve rapidly with antitu- The keratitis in cases of tuberculous sclerokeratitis is peripheral berculous therapy and no immunological suppression may be at the limbus with superficial corneal stromal inflammation adja- required. Tuberculous choroiditis and retinitis with vision- cent to the area of scleritis. threatening lesions may require a different approach and may Three of our patients had enlargement of the cervical lymph benefit from the concomitant use of systemic corticosteroids. nodes. Scrofula of the eye and neck has been described as a Non-steroidal anti-inflammatory drugs may have a limited role form of active extrapulmonary disease. One out of the three in the management of tuberculous sclerokeratitis. patients had draining lymph node and M. tuberculosis was iso- Early diagnosis and prompt treatment are mandatory for the lated from the lymph node. prevention of serious ocular complications of tuberculosis. The diagnosis of ocular tuberculosis is challenging and Patients presenting with sector or nodular sclerokeratitis should requires a high index of suspicion. The definitive diagnosis of be worked-up for tuberculosis. Immunomodulation or immuno- ocular tuberculosis relies on the isolation of the organism on suppressive therapy may lead to progressive worsening of the the Löwenstein–Jensen medium and histopathological staining condition. methods of ocular tissues or demonstration of M. tuberculosis DNA by PCR.16 17 The presumptive diagnosis of tuberculous Contributors All authors substantially contributed to the conception or design of fi the work; the acquisition, analysis or interpretation of data for the work; and sclerokeratitis is made based on the clinical ndings, positive drafting the work and final approval of the version to be published; and agreement PPD of 15 mm of induration or more, positive response to ATT to be accountable for all aspects of the work. fl 18 and exclusion of other causes of scleral in ammation. Competing interests None declared. The combination of a positive PPD test and a positive Ethics approval Institution Review Board of The Eye Center. QuantiFERON test result was found to increase the accuracy of diagnosis of tuberculous scleritis.19 The definitive diagnosis of Provenance and peer review Not commissioned; externally peer reviewed. tuberculous scleritis can be made by scleral biopsy. The histo- pathology of the scleral biopsy specimens shows mononuclear REFERENCES and epithelioid cells with caseating granuloma and acid-fast 1 Golden MP, Vikram HR. Extrapulmonary tuberculosis: an overview. Am Fam – bacilli.20 Physician 2005;72:1761 68. 2 Donahue HC. Ophthalmologic experience in a tuberculosis sanitarium. Am J Drug regimens for the treatment of ocular tuberculosis Ophthalmol 1967;64:742. including tuberculous sclerokeratitis are similar to those for pul- 3 Tabbara KF. Ocular tuberculosis: anterior segment. Int Ophthalmol Clin monary or extrapulmonary tuberculosis.21 The Centers for 2005;45:57–69. Disease Control (CDC) recommends the use of all four drugs 4 Alcolea A, Suarez MJ, Lizasoain M, et al. 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Shoughy SS, et al. Br J Ophthalmol 2016;100:1301–1303. doi:10.1136/bjophthalmol-2015-307599 1303 Downloaded from http://bjo.bmj.com/ on August 30, 2016 - Published by group.bmj.com

Clinical manifestations and outcome of tuberculous sclerokeratitis

Samir S Shoughy, Mahmoud O Jaroudi and Khalid F Tabbara

Br J Ophthalmol 2016 100: 1301-1303 originally published online December 23, 2015 doi: 10.1136/bjophthalmol-2015-307599

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