We report a case of bilateral anterior uveitis and ciliochoroidal effusions after isoniazid.
Case report
A healthy 47-year-old Malay man presented with 2 days of bilateral red eyes associated with pain and blurring of vision. This occurred a week after taking once-daily isoniazid 300 mg as anti-tuberculosis (TB) prophylaxis, prescribed due to a positive tuberculin skin test (TST, 15 mm) after his wife was diagnosed with active pulmonary TB. He was asymptomatic. Chest X-ray, HIV screen, and TB interferon-γ release assay (IGRA) (TB T-spot; Oxford Immunotec, Oxford, UK) were negative.
Presenting Snellen acuities were 6/12 OD and 6/9 OS. He had bilateral diffuse conjunctival congestion and deep anterior chambers with activity of 2+ cells. Fundus examination revealed bilateral, shallow, 360°, clear serous choroidal effusions, corroborated on ultrasound B scan imaging (Figure 1a). No other focal choroidal lesions were observed.
In view of his lack of symptoms and negative IGRA, isoniazid was stopped in consultation with his physician. Complete resolution of anterior uveitis and choroidal effusions was noted 3 days later (Figure 1b), with no further recurrences.
Discussion
Tuberculosis is a resurgent global disease. WHO's 2009 TB update estimates 33% of the world population is infected, 1.4 million of which have HIV.1
Isoniazid is widely used as prophylaxis or treatment against sensitive strains. Common adverse systemic reactions are hepatotoxicity and peripheral neuropathy. Established ocular side effects include toxic optic neuropathy, retrobulbar neuritis, and optic atrophy. Hypersensitivity reactions have rarely been reported and include rash, fever, lymphadenopathy, or vasculitis, which usually developed within 3–7 weeks of starting therapy.2
Isoniazid is metabolized in the liver mainly by acetylation and dehydrazination. This N-acetylhydrazine metabolite is believed to be responsible for the hepatotoxic effects of isoniazid. The rate of acetylation is genetically determined, being highest in Orientals and lowest in Caucasians. A previous study in Singapore reported 68% fast acetylators in a study sample of 68 Chinese subjects. Fast acetylation leads to accumulation of the acetylated metabolite with an increased risk of toxicity and side effects.3
In our TB-endemic Singapore population, a combined interpretation of clinical signs, TST, and IGRA is recommended to diagnose active TB.4 Our patient did not have evidence to support active TB. He was not on any other medications. Other drugs reported to cause choroidal effusions include topiramate,5 topical timolol, and dorzolamide.6
The sequential onset of bilateral choroidal effusions after starting isoniazid, with resolution upon discontinuation suggests a hypersensitivity response to isoniazid.
We acknowledge that to confirm drug causality, positive in vivo re-challenge is helpful. However, the temporal sequence and lack of other possible causes are highly supportive. A fast acetylator might also further strengthen our case. Unfortunately, we were not able to perform this test.
Physicians should consider the new onset of bilateral painful red eyes after starting isoniazid as a possible manifestation of drug hypersensitivity and prompt ophthalmological referral is encouraged for further evaluation.
References
World Health Organization, Stop TB Partnership. 2009 Update tuberculosis facts. http://www.who.int/tb/publications/2009/tbfactsheet_2009update_one_page.pdf. Accessed on 7 January 2010.
RxMed. The comprehensive resource for physicians, drug and illness information. Isoniazid. http://www.rxmed.com/b.main/b2.pharmaceutical/b2.1.monographs/CPS-%20Monographs/CPS-%20(General%20Monographs-%20I)/ISONIAZID.html. Accessed on 7 February 2010.
Lee EJD, Lim JME . A study of the acetylator phenotype in normal subjects. Singapore Med J 1981; 22 (3): 117–120.
Mazurek GH, Jereb J, Lobue P, Iademarco MF, Metchock B, Vernon A et al. Guidelines for using the QuantiFERON-TB Gold Test for detecting Mycobacterium tuberculosis infection, United States. MMWR Recomm Rep 2005; 54: 49–55.
Stangler F, Prietsch RF, Fortes Filho JB . Bilateral acute angle closure glaucoma in a young patient receiving oral topiramate: a case report. Arq Bras Oftalmol 2007; 70 (1): 133–136. Portugese.
Callahan C, Ayyala RS . Hypotony and choroidal effusion induced by topical timolol and dorzolamide in patients with previous glaucoma drainage device implantation. Ophthalmic Surg Lasers Imaging 2003; 34 (6): 467–469.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no conflict of interest.
Rights and permissions
About this article
Cite this article
Gan, N., Teoh, S. Isoniazid-related bilateral choroidal effusions. Eye 24, 1408–1409 (2010). https://doi.org/10.1038/eye.2010.57
Published:
Issue Date:
DOI: https://doi.org/10.1038/eye.2010.57