Siantar et al. Journal of Ophthalmic Inflammation and Infection (2015) 5:21 DOI 10.1186/s12348-015-0052-1

LETTER TO THE EDITOR Open Access

Paradoxical worsening of tuberculouschorioretinitis in a Chinese gentleman

Rosalynn Grace Siantar, Su Ling Ho and Rupesh Agrawal*

Abstract

We report a case of paradoxical worsening of tuberculous chorioretinitis after initiation of anti-tuberculous therapy(ATT). The patient had left panuveitis with tuberculous chorioretinitis and was started on systemic ATT and oral steroidsa week later. However, he developed paradoxical worsening 2 months after initiation of therapy. He was continued onATT, oral steroids and intravitreal amikacin with resolution of the chorioretinal lesion subsequently. Ocular tuberculosisoften poses a diagnostic challenge, and clinicians should be aware of the possibility of paradoxical worsening despiteappropriate ATT. Clinicians should strongly consider starting oral steroids concurrently with ATT when managing oculartuberculosis.

Keywords: Ocular tuberculosis; Chorioretinitis; Paradoxical worsening; Steroids

Correspondence/findingsIntroductionTuberculosis (TB), caused by Mycobacterium tuberculosis,can cause multi-systemic granulomatous inflammation,most commonly in the pulmonary system. Althoughocular involvement is relatively uncommon, it is still awell-known extrapulmonary manifestation [1]. It oftenposes a diagnostic challenge to ophthalmologists, andmanagement should be prompt as it can sight saving.The commonest manifestation of ocular tuberculosis is inthe uveal tract and usually presents as a posterior uveitis,of which choroidal tuberculomas are the commonest [1].With anti-tuberculous therapy (ATT), posterior uveitisis expected to resolve within 4 to 6 weeks [1]. We report arare case of paradoxical worsening of ocular TB after initi-ation of ATT.

ReportA 50-year-old man with past medical history of diabetesmellitus presented with 1 week history of left eye blurringof vision and mild discomfort. His Snellen visual acuitywas 6/7.5 in the right eye and 6/15 in the left eye. Anteriorsegment examination revealed signs of uveitis with

* Correspondence: rupeshttsh@gmail.comDepartment of Ophthalmology, Tan Tock Seng Hospital, Singapore 308433,Singapore

© 2015 Siantar et al. This is an Open Access art(http://creativecommons.org/licenses/by/4.0), wprovided the original work is properly credited

multiple keratic precipitates, anterior chamber cells 1+ andretrolental cells 2+. Fundus examination showed significantvitritis, vasculitis and a well defined yellowish-white chor-ioretinal lesion superior to the macula (Fig. 1a, b). Anteriorand posterior segment examination of the right eye wasnormal. He underwent a vitreous tap which identifiedmycobacterial DNA via polymerase chain reaction (PCR).The PCR test was the Probetec DTB assay (BectonDickinson), and the gene sequences targeted were IS6110and 16S rRNA. His Mantoux test measured 25 mm andchest X-ray was clear. Full blood count revealed lympho-cytosis, and other systemic investigations including HIVand syphilis were negative. The working diagnosis was thatof a left eye panuveitis with tuberculous chorioretinitis,and he was started on ATT (6 months course of oral ri-fampicin, isoniazid and ethambutol) by the infectiousdisease specialist. He was subsequently started on oralprednisolone 40 mg a week later. Fundus fluoresceinangiogram (Fig. 2a–c) revealed non-perfusion peripheralto the choroidal lesion representing a branch retinal veinocclusion, and he underwent a sectoral panretinal photo-coagulation. In the third month of treatment, the patientwas noted to have clinical deterioration with decrease invisual acuity to hand movement and progression of thechorioretinal lesion to the macula (Fig. 3). He underwent arepeat vitreous tap for which mycobacterial DNA PCR

icle distributed under the terms of the Creative Commons Attribution Licensehich permits unrestricted use, distribution, and reproduction in any medium,.

Fig. 1 a, b Fundus photos of left eye showing vitritis, vasculitis and chorioretinitis superior to the macula

Siantar et al. Journal of Ophthalmic Inflammation and Infection (2015) 5:21 Page 2 of 4

was now negative and received a dose of intravitreal amika-cin 0.4 mg/0.1 ml. The patient was continued on systemicoral ATT and steroids, and the lesion slowly resolved, be-coming smaller in size and developing fibrosis and laterscarring. The patient’s final visual acuity at last follow-upwas 6/120. The patient has given consent for the report tobe published.

DiscussionIn systemic tuberculosis, paradoxical worsening hasbeen described as worsening of intracranial tubercu-loma, meningeal disease, tuberculous meningeal radi-culitis, pleural effusion and abdominal tuberculosis[1]. Paradoxical worsening after antibiotic therapy hasbeen described in other conditions and is termed Jarisch-Herxheimer reaction (JHR) when associated with thetreatment of secondary syphilis, manifesting with systemicsymptoms such as fever, headache and sweating [2].Isolated intraocular JHR has been previously reported

in treatment of ocular syphilis with rapid visual loss [3].Worsening after initial therapy has also been described

Fig. 2 Fundus fluorescein angiography in early (a), mid (b) and late (c)

in other conditions such as Whipple’s disease [4] andLyme disease [5].The pathogenesis of paradoxical worsening in tubercu-

losis is not well understood. Proposed mechanisms in-clude release of mycobacterial antigens after ATT anddelayed hypersensitivity [1]. It can clinically manifest asrapid worsening of vitritis and chorioretinitis and hasbeen reported to have good response to the addition oforal steroid [6–8] (Fig. 4).In a case series published by Hamade et al. [9], 20 pa-

tients with presumed ocular tuberculosis treated withATT only had complete resolution with no complication.On the other hand, although paradoxical worsening ofocular tuberculosis after treatment with ATT is rare, therehave been a few cases reported so far [6–8, 10]. Interest-ingly, in a case series of 110 patients published by Guptaet al. [11], 14 % of patients with tubercular serpiginous-like choroiditis had continued progression while on treat-ment. One patient was on corticosteroids only, while therest were on ATT and corticosteroids when they were ob-served to have continued progression. They were managed

phases showing non-perfusion peripheral to area of chorioretinitis

Fig. 3 Fundus photo of the left eye showing progression of chorioretinitis to the macula

Siantar et al. Journal of Ophthalmic Inflammation and Infection (2015) 5:21 Page 3 of 4

with increased immunosuppression either with increaseddosage of corticosteroids or other immunosuppressantssuch as azathioprine, and these patients subsequentlyachieved clinical resolution. These studies demonstratevariability in response of ocular TB to different treatmentregimes and highlight a need for future studies with a largerpopulation of ocular tuberculosis to better evaluate theideal treatment regime of ATT with or without adjunctivesystemic steroids.Our patient developed paradoxical worsening despite

already being on oral steroid and ATT. In our case, oralsteroid was initiated 1 week after the initiation of ATT.This is unique among other reported cases where steroid

Fig. 4 Diagrammatic representation of clinical course ofocular tuberculosis

was only added to the treatment regime after developmentof ocular paradoxical worsening or started concurrentlywith ATT [11]. It is important to highlight that rifampicin,which is usually part of the standard regimen of ATT, mayreduce bioavailability of prednisolone by 66 % [12]. Thisshould be taken into consideration in order to achieve thetherapeutic dose of systemic steroids in such patients. Thebenefit of starting oral steroids concurrently with ATT re-mains to be seen and needs further studies.

ConclusionOcular tuberculosis often poses a diagnostic and manage-ment challenge. Clinicians should be aware of the possibil-ity of paradoxical worsening of ocular tuberculosis despiteinitiating ATT and consider starting systemic oral steroidsconcurrently and at the right dosage when managing oculartuberculosis.

AbbreviationsATT: anti-tubercular therapy; DNA: deoxyribonucleic acid; HIV: humanimmunodeficiency virus; JHR: Jarisch-Herxheimer reaction; PCR: polymerasechain reaction; TB: tuberculosis.

Competing interestsThe authors declare that they have no competing interests.

Authors’ contributionsRGS, SLH and RA wrote the main manuscript text. All authors read andapproved the final manuscript.

Authors’ informationRGS (MBBS) is a first year Ophthalmology resident. SLH (MB, BCh BAO, FRCS(Edinburgh)) is a Senior Consultant Ophthalmologist. RA (MBBS, FRCS (Glasg))is a Consultant Ophthalmologist. They are all working at the Department ofOphthalmology, Tan Tock Seng Hospital, Singapore.

Siantar et al. Journal of Ophthalmic Inflammation and Infection (2015) 5:21 Page 4 of 4

Received: 18 April 2015 Accepted: 26 June 2015

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