Paradoxical worsening of tuberculous chorioretinitis in a Chinese gentleman

In systemic tuberculosis, paradoxical worsening has been described as worsening of intracranial tuberculoma, meningeal disease, tuberculous meningeal radiculitis, pleural effusion and abdominal tuberculosis [1]. Paradoxical worsening after antibiotic therapy has been described in other conditions and is termed Jarisch-Herxheimer reaction (JHR) when associated with the treatment of secondary syphilis, manifesting with systemic symptoms 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 in other conditions such as Whipple’s disease [4] and Lyme disease [5].

The pathogenesis of paradoxical worsening in tuberculosis is not well understood. Proposed mechanisms include release of mycobacterial antigens after ATT and delayed hypersensitivity [1]. It can clinically manifest as rapid worsening of vitritis and chorioretinitis and has been reported to have good response to the addition of oral steroid [6–8] (Fig. 4).

In a case series published by Hamade et al. [9], 20 patients with presumed ocular tuberculosis treated with ATT only had complete resolution with no complication. On the other hand, although paradoxical worsening of ocular tuberculosis after treatment with ATT is rare, there have been a few cases reported so far [6–8, 10]. Interestingly, in a case series of 110 patients published by Gupta et al. [11], 14 % of patients with tubercular serpiginous-like choroiditis had continued progression while on treatment. One patient was on corticosteroids only, while the rest were on ATT and corticosteroids when they were observed to have continued progression. They were managed with increased immunosuppression either with increased dosage of corticosteroids or other immunosuppressants such as azathioprine, and these patients subsequently achieved clinical resolution. These studies demonstrate variability in response of ocular TB to different treatment regimes and highlight a need for future studies with a larger population of ocular tuberculosis to better evaluate the ideal treatment regime of ATT with or without adjunctive systemic steroids.

Our patient developed paradoxical worsening despite already being on oral steroid and ATT. In our case, oral steroid was initiated 1 week after the initiation of ATT. This is unique among other reported cases where steroid was only added to the treatment regime after development of ocular paradoxical worsening or started concurrently with ATT [11]. It is important to highlight that rifampicin, which is usually part of the standard regimen of ATT, may reduce bioavailability of prednisolone by 66 % [12]. This should be taken into consideration in order to achieve the therapeutic dose of systemic steroids in such patients. The benefit of starting oral steroids concurrently with ATT remains to be seen and needs further studies.

Ocular tuberculosis often poses a diagnostic and management challenge. Clinicians should be aware of the possibility of paradoxical worsening of ocular tuberculosis despite initiating ATT and consider starting systemic oral steroids concurrently and at the right dosage when managing ocular tuberculosis.