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 Table of Contents  
CASE REPORT
Year : 2022  |  Volume : 2  |  Issue : 2  |  Page : 422-423

Low-dose rifabutin-induced uveitis with premature occurrence: A case series of rare presentation


1 Department of Ophthalmology, Armed Forces Clinic, New Delhi, India
2 Department of Ophthalmology, Command Hospital, Pune, Maharashtra, India
3 Department of Ophthalmology, Armed Forces Medical College, Pune, Maharashtra, India
4 Department of Ophthalmology, Base Hospital, New Delhi, India

Date of Submission06-Nov-2021
Date of Acceptance31-Jan-2022
Date of Web Publication13-Apr-2022

Correspondence Address:
Sumedha Vats
Department of Ophthalmology, Armed Forces Clinic, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijo.IJO_2814_21

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  Abstract 


Rifabutin is a known-drug prescribed for prophylaxis and treatment of Mycobacterium avium complex (MAC) and causes dose-related anterior uveitis in immunocompromised individuals, particularly, those infected with HIV. Previous studies have reported rifabutin-induced uveitis with high doses. It is infrequent with 300 mg/day or less; moreover, it takes weeks to months to develop. We report three HIV cases that on treatment with low-dose 300 mg rifabutin presented with anterior uveitis with early occurrence. Furthermore, one of the cases had rifabutin-induced panuveitis, another rarity. Thus, although rare, low-dose rifabutin-induced uveitis with early presentation should be kept as a differential diagnosis of unusual presentation of uveitis in HIV, early management of which prevents visual morbidity.

Keywords: Anterior uveitis, early presentation, panuveitis, rifabutin induced


How to cite this article:
Vats S, Agrawal M, Srikanth S, Kumar P, Goenka R. Low-dose rifabutin-induced uveitis with premature occurrence: A case series of rare presentation. Indian J Ophthalmol Case Rep 2022;2:422-3

How to cite this URL:
Vats S, Agrawal M, Srikanth S, Kumar P, Goenka R. Low-dose rifabutin-induced uveitis with premature occurrence: A case series of rare presentation. Indian J Ophthalmol Case Rep [serial online] 2022 [cited 2022 May 24];2:422-3. Available from: https://www.ijoreports.in/text.asp?2022/2/2/422/342982



Rifabutin is used for prophylaxis and treatment of Mycobacterium avium Scientific Name Search  complex (MAC) infection in AIDS.[1] A recognized rifabutin-induced complication is anterior uveitis with hypopyon. Though rare, intermediate, posterior, and panuveitis have also been reported.[2],[3] Its dose ranges from 300 to 1800 mg/day, but the association of uveitis with low-doses, precisely with 300 mg/day and less, is seldom reported. Another diagnostic dilemma is with immune recovery uveitis (IRU) in AIDS-related CMV retinitis patients on highly active antiretroviral therapy (HAART).[4],[5] Here, we report three HIV cases, on low-dose rifabutin for prophylaxis of MAC presented early with uveitis.


  Case Reports Top


Case-1

A 48-year-old male case of HIV, disseminated tuberculosis and disseminated cryptococcus, presented with ocular pain and redness in both eyes for a duration of one. The patient was on antiretroviral therapy (ART) since 2015 and oral rifabutin 300 mg/day for the last two weeks for prophylaxis of MAC infection. Lab tests revealed raised CD4-count from 64 per mm3 to 165 per mm3. Syphilis serology and inflammatory markers were negative; best corrected visual acuity (BCVA) of 20/30 and normal IOP in both eyes. Slit lamp examination revealed mild conjunctival-congestion, keratic precipitates (KPs), +2 cells in the anterior chamber (AC), and 0.3 mm hypopyon [Figure 1]a. Fundus examination was normal. In suspicion of RIU, the drug was discontinued and started on topical steroid and cycloplegics. Vision improved to 20/20 in both eyes with complete resolution of hypopyon in three weeks [Figure 1]b.
Figure 1: Slit lamp photographs of left eye of case1 (a), case 2 (c), and case 3 (e) showing rifabutin-induced anterior uveitis and hypopyon in anterior chamber. Following withdrawal of rifabutin, and starting steroids and cycloplegics in all the cases, there was resolution of uveitis with successful visual outcomes in case 1 (b), case 2 (d), and case 3 (f)

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Case-2

A 35-year-old male under anti-tubercular treatment and ART since 2018, presented with one-day history of pain, redness, and vision loss in both eyes. The patient was treated for CMV retinitis six months ago with intravitreal gancyclovir and oral valganciclovir 900 mg once a day both eyes. Patient was on oral rifabutin 300 mg once a day for last one week for prophylaxis of MAC. BCVA was perception of light in right eye and counting fingers close to the face in left eye with accurate projection of rays in both eyes. The CD4 count at presentation was 56 per mm3. Examination revealed circumcorneal congestion, +4 cells in the AC, +4 flare, and 2 mm hypopyon [Figure 1]c. Fundus could not be visualized due to obscuration of fundus by AC inflammation. The patient was suspected to have RIU; previous regimen was discontinued, and the patient was started on oral and topical steroids, and cycloplegic. There was complete resolution of uveitis with vision reaching 20/60 in both eyes [Figure 1]d. Later, fundus examination revealed resolved CMV retinitis.

Case 3

A 54-year-old male with immunosurveillance on ART since 2009 and pulmonary Kochs since April 2020 presented with progressive vision loss associated with redness in left eye since two days. ART was changed to second-line-ART due to adverse reaction to efavirenz. The patient was on a continuation phase of ATT (rifabutin + isoniazid + ethambutol) since 1-month. The left eye showed circumcorneal-ciliary congestion with fine-KPs, hypopyon of 1.2 mm height, with +4 cells and +2 flare [Figure 1]e. Lens showed iris pigment dispersal over anterior lens capsule in the shape of a miotic pupil. Optic media was hazy with grossly normal fundus. He developed similar symptoms in the right eye after two days with BCVA 20/120, and anterior uveitis with retrolental cells and exudates in the all the retinal quadrants. The left eye also showed vitreous opacities then. In view of bilateral panuveitis, the patient was immediately started on oral steroids under anti-PCP/fungal prophylaxis. Rifabutin was stopped, considering it to be a potential contributor to the condition. The symptoms improved gradually, with vision reaching 20/30 in both eyes over a period of 10 days along with resolution of uveitis [Figure 1]f.


  Discussion Top


Uveitis may be associated with CMV retinitis, which is the commonest ocular manifestation in AIDS with profound immunodeficiency and a CD4 T-lymphocyte count of <50 per μL.[6] Studies attribute uveitis in CMV cases on HAART to the increased immunocompetence and calls it as IRU.[6] On the other hand, rifabutin-associated ocular inflammation as anterior uveitis is also seen in HIV infection.[4] Cases in this series were HIV positive, on ART, and on rifabutin for prophylaxis of MAC. The uveitis affected the anterior segment with AC cells, flare, and hypopyon. Though complete resolution occurred dramatically on discontinuation of rifabutin along with initiation of steroid and cycloplegic, it was difficult to rule out IRU. In view of merging clinical features, high index of suspicion towards both conditions should be kept in mind.

Prior studies have mentioned the onset of anterior uveitis between 2 weeks to 7 months after commencement of rifabutin.[7] RIU with dose of 600 mg/day reported an average of 65 days; while low-doses take even more time.[7] Concomitant use of drugs like clarithromycin and ethambutol are associated with increased risk of uveitis. Even low bodyweight causes increased frequency of uveitis.[8] Moreover, daily doses of rifabutin, ranging from more than 600 to 1800 mg, have been associated with uveitis, and its severity is influenced by the dose and duration of the treatment.[7],[8] To the best of our knowledge, our series is the one to report RIU with such a low dose of 300 mg, over and above, with early occurrence of initiation of rifabutin in all the cases. In addition to this, one case had panuveitis with early presentation, which is another rarity observed. Recently, only two case reports on rifabutin-induced panuveitis with untimely occurrence have been described.[9],[10] Our series seems to support the same. The bilaterality, improvement upon taking away the drug, and elimination of other likely causes of uveitis strongly link rifabutin as a cause of uveitis in all these cases. However, the possible pathogenic mechanisms warrant further study.


  Conclusion Top


Low-dose rifabutin-induced uveitis with premature presentation should be kept as a differential diagnosis in immunocompromised cases, timely management of which prevents visual morbidity.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Ebraert H, Salu P. Toxic uveitis caused by pharmacodynamic interactions of rifabutin and protease inhibitors: A case report. Bull Soc Belge Ophthalmol 2007;303:57-60.  Back to cited text no. 1
    
2.
Saran BR, Maguire AM, Nichols C, Frank I, Hertle RW, Brucker AJ, et al. Hypopyon uveitis in patients with acquired immunodeficiency syndrome treated for systemic Mycobacterium avium complex infection with rifabutin. Arch Ophthalmol 1994;112:1159-65.  Back to cited text no. 2
    
3.
Skolik S, Willermain F, Caspers LE. Rifabutin-associated panuveitis with retinal vasculitis in pulmonary tuberculosis. Ocul Immunol Inflamm 2005;13:483-5.  Back to cited text no. 3
    
4.
Khan M, Singh J, Dhillon B. Rifabutin-induced uveitis with inflammatory vitreous infiltrate. Eye 2000;14:344-6.  Back to cited text no. 4
    
5.
Urban B, Bakunowicz-Lazarczyk A, Michalczuk M. Immune recovery uveitis: Pathogenesis, clinical symptoms, and treatment. Mediators Inflamm 2014;2014:971417. doi: 10.1155/2014/971417.  Back to cited text no. 5
    
6.
Arevalo JF, Mendoza AJ, Ferretti Y. Immune recovery uveitis in AIDS patients with cytomegalovirus retinitis treated with highly active antiretroviral therapy in Venezuela. Retina 2003;23:495-502.  Back to cited text no. 6
    
7.
Cordero-Coma M, Salazar-Mendez R, Garzo-Garc I, Yilmaz T. Drug-induced uveitis. Expert Opin Drug Saf 2015;14:111-26.  Back to cited text no. 7
    
8.
Shafran SD, Deschênes J, Miller M, Phillips P, Toma E. Uveitis and pseudojaundice during a regimen of clarithromycin, rifabutin, and ethambutol. MAC Study Group of the Canadian HIV Trials Network. N Engl J Med 1994;330:438-9.  Back to cited text no. 8
    
9.
Biancardi AL, Freitas DF, Ridolfi FM, Sant'Anna FM, Curi AL. Rifabutin-induced severe panuveitis: An unusual case of early onset in a patient with AIDS. Arq Bras Oftalmol 2021;84:525-6.  Back to cited text no. 9
    
10.
Toomey CB, Lee J, Spencer DB. Rifabutin-cobicistat drug interaction resulting in severe bilateral panuveitis. Case Rep Ophthalmol 2020;11:156-60.  Back to cited text no. 10
    


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