Paradoxical worsening of presumed tubercular serpiginous like choroiditis on anti-tubercular therapy

Choroidal tuberculosis may present as multifocal progressive or serpiginous like choroiditis. It is important to recognize these presentations as these eyes show good response to systemic antitubercular therapy. Paradoxical reaction in tuberculosis can occur in patients receiving anti tuberculous therapy (ATT). It consists of clinical or radiological worsening of pre existing tuberculous lesions or the development of new lesions in patients who initially improved on treatment. Intraocular tuberculosis presents most commonly as posterior uveitis, either as choroidal tubercles, choroidal tuberculoma, subretinal abscess or serpiginous-like choroiditis; however, it can also present, in order of decreasing prevalence, as granulomatous anterior uveitis, panuveitis and intermediate uveitis. We report, a case of paradoxical worsening of presumed tubercular serpiginous like choroiditis on antitubercular therapy. Through this interesting case we try to highlight the fact that continued progression of lesions may be noted inspite of ATT and systemic steroids but it is important to be aware of paradoxical worsening, so that one doesn’t interrupt ATT. Case Report


Introduction
Serpiginous like choroiditis (SLC) and serpiginous choroiditis (SC) are uveitic entities on the same spectrum but with different clinical morphologic features. Serpiginous choroiditis is believed to be an autoimmune disease and responds well to systemic steroids; in contrast, treating serpiginous-like choroiditis with steroids can lead to serious local and systemic complications if not accompanied by anti-tubercular therapy (ATT).Paradoxical reaction to anti-tubercular therapy has been observed in various forms of ocular tuberculosis including serpiginous-like choroiditis, granulomatous anterior uveitis, intermediate uveitis, panuveitis, retinal vasculitis and has been documented frequently in extrapulmonary tuberculosis (TB) [1][2][3]. It is believed to be mediated by the host's immune system due to an enhanced delayed hypersensitivity of the host, decreased suppressor mechanisms, and as a response to mycobacterial antigens.

Case Report
A man of age 37 year presented with complaints of diminution of vision in left eye since 15 days. He was previously diagnosed and treated by his local ophthalmologist, as acute retinal necrosis, had received 600 mg Acyclovir intravenous thrice daily for 1 week followed by oral Valacyclovir 1 gm thrice daily and oral steroid (60 mg for fi rst week followed

Discussion
Choroidal tuberculosis may present as multifocal progressive or serpiginous like choroiditis. Tubercular serpiginous-like choroiditis is considered as an immunemediated hypersensitivity reaction to the tubercular bacilli sequestrated in the retinal pigment epithelium layer. These eyes show good response to ATT [4]. Resolution of lesions in patients with serpiginous choroiditis can occur with combination therapy of systemic steroids and immunosuppressive agents [5]. In patients with tuberculous choroiditis, ATT accelerates theprocess of healing and reduces recurrence risk by decreasing the number of bacilli. In some patients, the rapid destruction of bacilli after initiation of ATT may cause existing lesions to worsen and new lesions to form. This paradoxical phenomenon occurs more often during the treatment of systemic TB infections, but has also been found in ocular TB. Paradoxical worsening may even occur in patients initiated on simultaneous ATT and systemic steroid. One reason for this may be very severe infl ammation and inadequate suppression. Another reason may be that rifampicin increases steroid metabolism [6]. In that case, increasing the steroid dose or adding immunosuppressive therapy may resolve the issue. The factor that could have contributed to the paradoxical reaction in our case was that our patient was also on rifampicin, which is reported to reduce the bioavailability of corticosteroids. Hawkey et al. found that a higher bacillary load or a persistent antigenic stimulus that is poorly cleared from the diseased site may be responsible for the development of paradoxical worsening [7]. The RPE shares many features with the macrophages, including phagocytosis of bacteria and expression of toll-like and complement receptors and     perturbed RPE produces a variety of infl ammatory substances, including interleukin-1 and granulocyte-macrophage colonystimulating factor [8]. Therefore, the RPE cells that have engulfed Mycobacteria may release cytokines triggered by mycobacterial LAM (lipoarabinomannan) thus causing continued progression.

Conclusion
The possibility of the paradoxical phenomenon upon ATT initiation should be kept in mind, so that one does not interrupt anti-tubercular treatment and think of drugresistant tubercular serpiginous-like choroiditis or investigate for other possible non tubercular aetiologies. To monitor the disease progression, recurrences, and involvement of the other eye, serial examination at regular intervals is recommended.
Systemic steroid and/or immunosuppressive therapy is useful to suppress infl ammation and control progression.