ABSTRACT
In this study, a case with tubercular choroiditis showing severe macular edema and progression of choroidal lesions following initiation of antitubercular treatment is presented and the management of posterior uveitis associated with tuberculosis is evaluated. A 40-year-old female patient was admitted with decreased vision in her right eye and her fundoscopic examination revealed serpiginous choroiditis. It was learned from her medical history that she had taken antitubercular therapy 9 years ago. Mantoux tuberculin skin test showed an area of induration measuring 15 mm and a positive interferon-gamma release assay was documented. Additionally, sequelae lesions due to previous tubercular infection were remarkable on her chest imaging. By excluding other causes of uveitis, the patient was considered presumed ocular tuberculosis and a full standard course of 4-drug antitubercular therapy was initiated. On the seventh day of the treatment existing choroidal lesions showed progression, new foci of choroiditis appeared and severe macular edema occurred. After adding systemic corticosteroid to the treatment, the macular edema resolved and choroidal lesions began to deactivate. In patients with tubercular choroiditis, continued progression may develop after initiation of antitubercular therapy. This paradoxical worsening is thought to be a hyperacute immunologic reaction occurring against antigen load released after antitubercular therapy. This phenomenon may be suppressed by the addition of systemic corticosteroids to the treatment.
Introduction
Serpiginous choroiditis is a rare, idiopathic, chronic inflammatory disease. It is characterized by geographic lesions affecting the choroid and the neighboring retinal pigment epithelium (RPE) and outer retinal layers. There are reports in the literature that patients with tuberculosis (TB) infection exhibit similar choroidal signs and it has been emphasized that the two entities must be evaluated separately. The clinical presentation of patients with definite or presumed ocular TB diagnosis has been termed ‘serpiginous-like choroiditis’.1Serpiginous 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 systemic and local complications if not accompanied by antitubercular therapy (ATT).
In patients with tuberculous choroiditis, ATT accelerates the healing process and reduces recurrence risk by decreasing the number of bacilli.2In some patients, the rapid destruction of bacilli that occurs with 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 reported in a few cases of ocular TB. Here we present a case of TB-related choroiditis that exhibited choroidal lesion progression and severe macular edema following initiation of ATT.
Discussion
A definite ocular TB diagnosis is usually not possible because the direct demonstration of TB bacilli in ocular tissues is difficult. Ocular findings alone are not sufficient to diagnose ocular TB due to the many clinical conditions that can simulate it. When other causes of uveitis have been ruled out, a patient with signs of active or latent TB is referred to as presumed ocular TB.3Especially in endemic areas, patients with findings suggestive of TB uveitis such as granulomatous uveitis, choroiditis, retinal vasculitis, retinal granuloma, and panuveitis should have TB tests included in their systemic evaluation. A TST result of 15 mm or larger is considered positive in vaccinated patients. However, this does not always correspond to a real infection, as the TST can give false positive results, especially in vaccinated individuals. In populations with routine vaccination, the QuantiFERON TB-Gold®(Cellestis Limited, Carnegie, Australia) test may be preferable because it analyzes interferon gamma release and only returns positive results for patients infected with Mycobacterium tuberculosis bacilli.4Like the TST, however, this test cannot discriminate between active and latent infections. Together with medical history and clinical findings, we also confirmed our patient’s infection with TB bacilli using the QuantiFERON test.
Posterior uveitis is the most common clinical manifestation of ocular TB. One of the clinical findings of this manifestation is serpiginous-like choroiditis, which is believed to result from an immune-mediated hypersensitivity reaction against TB bacilli.2This reaction can arise against both bacilli found in the ocular tissue and against remote Mycobacterium tuberculosis antigens.5Treatment response in these patients is relatively slow; it is therefore recommended to start treatment with a 4-drug regimen for 2 months, then continue for 9-12 months with a 2-drug regimen.
When ATT begins destroying TB bacilli, the tubercular antigen load increases and this may further exacerbate the reaction. This paradoxical presentation is the ocular form of Jarisch-Herxheimer reaction that emerges in systemic TB infections like TB meningitis, intracranial tuberculoma, pleural effusion and abdominal TB.2Worsening of clinical findings may be observed in the form of progression of existing lesions and the formation of new lesions. Paradoxical worsening can also occur upon initiation of antibiotic therapy in other ocular infections like syphilis, Lyme’s disease, and leptospirosis. There are other case reports in the literature of ATT inducing clinical exacerbation of ocular TB, similar to our case.2,6,7,8These patients were managed by adding systemic steroids to treatment, increasing the dose of steroid started with ATT, or adding immunosuppressant therapy. Our patient responded well to a high dose of oral steroid and her inflammation rapidly regressed.
There is no standard treatment protocol for TB-related posterior uveitis. Although successful outcomes have been reported with the use of ATT alone, the more common approach is to begin systemic steroid with ATT.2,9,10,11This approach is believed to reduce late stage hypersensitivity-related tissue damage and yield better visual and anatomic improvement. However, it should be noted that steroids can reactivate a latent infection or cause an intraocular infection to spread. Some studies have recommended adding systemic steroids at least 2 weeks after starting ATT.12Treating TB is a long process which requires patience. Especially for the first 2 months, patients must take quite a few pills each day. For patients who have difficulty complying with treatment, the addition of oral steroids may further reduce their compliance with the ATT. For such patients, it may be prudent to make decisions about steroid therapy based on the patient’s clinical course.
Paradoxical worsening may also occur in patients started on both ATT and systemic steroid simultaneously. One reason for this is the very severe inflammation and inadequate suppression. Another reason may be that rifampicin increases steroid metabolism.13In that case, increasing the steroid dose or adding immunosuppressive therapy may resolve the issue. In our patient, new foci of inflammation developed at the steroid maintenance dose of 24 mg/day and the lesions regressed when the dose was increased.
Conclusion
The possibility of the paradoxical phenomenon upon ATT initiation should be kept in mind, particularly for patients with TB-related posterior uveitis, and ATT should not be discontinued with the assumption that the treatment is not effective. Systemic steroid therapy may be beneficial to suppress inflammation and control progression.
