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Case Report
Open Access Peer-reviewed

Rifabutin Low Dose-Induced Intermediate Uveitis in a Patient with Acquired Immunodeficiency Syndrome

Agustina C. Palacio, Mercedes Cabrini, Graciela Ben, Emilio M. Dodds
American Journal of Medical Case Reports. 2017, 5(5), 116-118. DOI: 10.12691/ajmcr-5-5-3
Published online: June 03, 2017

Abstract

Intermediate uveitis is a relatively rare manifestation of Rifabutin induced uveitis. Rifabutin toxicity is unusual at doses of 300 mg daily or less. The purpose of this study is to report the case of an HIV+ patient with unilateral rifabutin induced intermediate uveitis after 4 months of treatment with low dose rifabutin (150 mg daily) in combination with ritonavir and fluconazole. The uveitis resolved after drug discontinuance and the use topical corticosteroids.

1. Background

Rifabutin is a semi-synthetic antimycobacterial from the rifamicin family agent mainly used in the treatment of Mycobacterium avium-complex (MAC) and tuberculosis in AIDS patients. Although anterior uveitis with hypopyon is the most common presentation, numerous cases of rifabutin induced uveitis associated with various degrees of vitritis have been reported previously 1, 2, 3, 4, 5. This side effect seems to be dose dependent and rapidly resolves after topical corticosteroid therapy and rifabutin discontinuation.

We report the case of a rifabutin-induced intermediate uveitis in an HIV+ patient with a low dose of rifabutin.

2. Case Report

A 48-year-old white man was referred to the uveitis clinic with decreased vision in his right eye. The patient reported red eye and blurry vision of 4 days of progress. His medical history was significant for HIV infection and pulmonary tuberculosis that had been treated with classic therapy for 2 months and then continued with maintenance therapy for over 4 months. For this condition, he was under highly active antiretroviral combination therapy (HAART) with tenofovir/emtricitabine/atazanavir/ritonavir. He was on isoniazid and rifabutin 150 mg/day as maintenance of the anti-tuberculosis treatment. He was also taking fluconazole 200 mg/week for onychomycosis. His past ocular history was insignificant.

His best-corrected acuity was counting fingers in the right eye and 20/20 in the left eye. His intraocular pressure was 4 mmHg OD and 10 mmHg OS. Anterior segment examination of right eye showed descemet folds, 3+ cells and flare (Figure 1). The right posterior segment examination revealed intense vitritis with snow balls and normal retina (Figure 2). The left eye was unremarkable.

Rifabutin associated uveitis was suspected and his medication was switched from rifabutin to levofloxacin. The patient was started on topical prednisolone acetate 1% every hour and phenylephrine 5%-tropicamide 0,5% every 8 hours.

One week later, his visual acuity improved to 20/100 OD, IOP was 9 mmHg, and there was a remarkable reduction in both anterior and posterior segment inflammation. Topical corticosteroids were indicated every 2 hours and dilating drops discontinued. The next week visual acuity of right eye was 20/50, IOP unchanged, anterior chamber showed +0.5 cells, and fundus examination showed less vitreous haze and vitreous condensation inferiorly with snow balls. (Figure 3). Prednisolone acetate 1% was tapered and discontinued in 15 days.

Two months after the beginning of symptoms, his visual acuity was 20/20 OU and the intraocular pressure 8 mmHg in both eyes. Anterior and posterior chamber showed a normal exam. (Figure 4).

3. Discussion

The most distinctive presentation of rifabutin-associated uveitis is an anterior uveitis with or without hypopyon 1, 2, 3, 4, There are some reported cases however of intermediate uveitis, although this is a relatively infrequent manifestation 6, 7, 8. Our patient presented with unilateral uveitis which showed a more severe inflammation in the vitreous than in the anterior chamber.

A characteristic of therapy with rifabutin is the dose related toxicity. The dose range of rifabutin associated with uveitis goes between 300 and 1800 mg daily 5, 9. Shafran and colleagues demonstrated that patients on 300 mg/day of rifabutin rarely developed uveitis, and when it occurred, it took at least 7 months of medication use for the uveitis to develop 3. Skinner and Blaschke later confirmed that drug related uveitis was unusual at the recommended dose of 300 mg/day 9. Our patient was on 150 mg daily of rifabutin for 4 months before he developed uveitis but he was also taking ritonavir 100 mg/d and fluconazole 200 mg/week. Both drugs interact in the metabolism of rifabutin through inhibition of hepatic cytochrome P450 and may increase the risk of rifabutin-associated uveitis.

Although fluconazole inhibit cytochrome P-450 and increases serum availability of rifabutin 10, 11, the association with higher risk of rifabutin induced uveitis is controversial. Shafran and associates found no evidence that concomitant therapy with fluconazole can increase the incidence of uveitis 3. On the other hand, Havlir et al reported 4 cases of uveitis in patients receiving rifabutin 300 mg daily in combination with fluconazole 400 mg/week that developed uveitis after 7 months of therapy 12.

Ritonavir is a potent inhibitor of CYP3A and has been demonstrated that it can exacerbate the adverse reactions of rifabutin 13, 14. Subsequently, recent guidelines have proposed the use of intermittently administered rifabutin 150 mg 3 times per week or 150 mg daily with close monitoring of adverse effects when used in the combination with ritonavir. Investigators found that the serum concentration of rifabutin, when given at dosages of 150 mg every 3 days in combination with ritonavir, were comparable to concentrations achieved with rifabutin 300 mg once daily in patients not being treated with protease inhibitors 15.

There is only one reported case in the literature of an HIV+ cachectic patient with 150 mg/day of rifabutin combined with triple therapy for HIV causing panuveitis and retinal vasculitis after 6 months of treatment 5. Low body weight is another known risk factor for the development of rifabutin-induced uveitis 3.

We present a well-documented report of an HIV+ non-cachectic patient with unilateral rifabutin induced intermediate uveitis after 4 months of treatment with a low dose of rifabutin (150 mg qd) in combination with ritonavir and fluconazole. The uveitis resolved in 2 months with discontinuation of rifabutin and the use of intensive topical corticosteroids 1, 2, 4.

4. Conclusion

Rifabutin is a well-recognized cause of drug induced intraocular inflammation. Patients receiving rifabutin, even in low doses, with combinations of protease inhibitors and/or azoles should be warned about signs and symptoms of uveitis and be monitored closely for the development of rifabutin toxicity.

Conflict of Interest

No conflicting relationship exists for any author.

References

[1]  B. R. Saran, A. M. Maguire, C. Nichols, I. Frank, R. W. Hertle, A. J. Brucker, S. Goldman, M. Brown, and B. Van Uitert, “Hypopyon uveitis in patients with acquired immunodeficiency syndrome treated for systemic Mycobacterium avium complex infection with rifabutin,” Arch Ophthalmol, vol. 112, no. 9, pp. 1159-65, Sep, 1994.
In article      View Article  PubMed
 
[2]  M. O. Frank, M. B. Graham, and B. Wispelway, “Rifabutin and uveitis,” N Engl J Med, vol. 330, no. 12, pp. 868, Mar 24, 1994.
In article      View Article  PubMed
 
[3]  S. D. Shafran, J. Singer, D. P. Zarowny, J. Deschenes, P. Phillips, F. Turgeon, F. Y. Aoki, E. Toma, M. Miller, R. Duperval, C. Lemieux, and W. F. Schlech, 3rd, “Determinants of rifabutin-associated uveitis in patients treated with rifabutin, clarithromycin, and ethambutol for Mycobacterium avium complex bacteremia: a multivariate analysis. Canadian HIV Trials Network Protocol 010 Study Group,” J Infect Dis, vol. 177, no. 1, pp. 252-5, Jan, 1998.
In article      View Article  PubMed
 
[4]  D. S. Jacobs, P. J. Piliero, M. G. Kuperwaser, J. A. Smith, S. D. Harris, T. P. Flanigan, J. H. Goldberg, and D. V. Ives, “Acute uveitis associated with rifabutin use in patients with human immunodeficiency virus infection,” Am J Ophthalmol, vol. 118, no. 6, pp. 716-22, Dec 15, 1994.
In article      View Article
 
[5]  S. Skolik, F. Willermain, and L. E. Caspers, “Rifabutin-associated panuveitis with retinal vasculitis in pulmonary tuberculosis,” Ocul Immunol Inflamm, vol. 13, no. 6, pp. 483-5, Dec, 2005.
In article      View Article  PubMed
 
[6]  L. Akduman, L. V. Del Priore, H. J. Kaplan, and W. G. Powderly, “Rifabutin induced vitritis in AIDS patients,” Ocul Immunol Inflamm, vol. 4, no. 4, pp. 219-24, 1996.
In article      View Article  PubMed
 
[7]  M. J. Chaknis, S. E. Brooks, K. T. Mitchell, and D. M. Marcus, “Inflammatory opacities of the vitreous in rifabutin-associated uveitis,” Am J Ophthalmol, vol. 122, no. 4, pp. 580-2, Oct, 1996.
In article      View Article
 
[8]  C. Pochat-Cotilloux, F. De Bats, A. M. Nguyen, F. Benbouzid, A. Malcles, P. Denis, and L. Kodjikian, “[Rifabutin-associated bilateral uveitis: a case report],” J Fr Ophtalmol, vol. 37, no. 8, pp. e115-7, Oct, 2014.
In article      View Article  PubMed
 
[9]  M. H. Skinner, and T. F. Blaschke, “Clinical pharmacokinetics of rifabutin,” Clin Pharmacokinet, vol. 28, no. 2, pp. 115-25, Feb, 1995.
In article      View Article  PubMed
 
[10]  P. K. Narang, C. B. Trapnell, J. R. Schoenfelder, J. P. Lavelle, and J. R. Bianchine, “Fluconazole and enhanced effect of rifabutin prophylaxis,” N Engl J Med, vol. 330, no. 18, pp. 1316-7, May 05, 1994.
In article      View Article  PubMed
 
[11]  C. B. Trapnell, P. K. Narang, R. Li, and J. P. Lavelle, “Increased plasma rifabutin levels with concomitant fluconazole therapy in HIV-infected patients,” Ann Intern Med, vol. 124, no. 6, pp. 573-6, Mar 15, 1996.
In article      View Article  PubMed
 
[12]  D. Havlir, F. Torriani, and M. Dube, “Uveitis associated with rifabutin prophylaxis,” Ann Intern Med, vol. 121, no. 7, pp. 510-2, Oct 01, 1994.
In article      View Article  PubMed
 
[13]  A. Cato, 3rd, J. Cavanaugh, H. Shi, A. Hsu, J. Leonard, and R. Granneman, “The effect of multiple doses of ritonavir on the pharmacokinetics of rifabutin,” Clin Pharmacol Ther, vol. 63, no. 4, pp. 414-21, Apr, 1998.
In article      View Article
 
[14]  H. C. Lin, P. L. Lu, and C. H. Chang, “Uveitis associated with concurrent administration of rifabutin and lopinavir/ritonavir (Kaletra),” Eye (Lond), 12, pp. 1540-1, England, 2007.
In article      View Article
 
[15]  J. I. Kuper, and M. D'Aprile, “Drug-Drug interactions of clinical significance in the treatment of patients with Mycobacterium avium complex disease,” Clin Pharmacokinet, vol. 39, no. 3, pp. 203-14, Sep, 2000.
In article      View Article  PubMed
 

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Cite this article:

Normal Style
Agustina C. Palacio, Mercedes Cabrini, Graciela Ben, Emilio M. Dodds. Rifabutin Low Dose-Induced Intermediate Uveitis in a Patient with Acquired Immunodeficiency Syndrome. American Journal of Medical Case Reports. Vol. 5, No. 5, 2017, pp 116-118. http://pubs.sciepub.com/ajmcr/5/5/3
MLA Style
Palacio, Agustina C., et al. "Rifabutin Low Dose-Induced Intermediate Uveitis in a Patient with Acquired Immunodeficiency Syndrome." American Journal of Medical Case Reports 5.5 (2017): 116-118.
APA Style
Palacio, A. C. , Cabrini, M. , Ben, G. , & Dodds, E. M. (2017). Rifabutin Low Dose-Induced Intermediate Uveitis in a Patient with Acquired Immunodeficiency Syndrome. American Journal of Medical Case Reports, 5(5), 116-118.
Chicago Style
Palacio, Agustina C., Mercedes Cabrini, Graciela Ben, and Emilio M. Dodds. "Rifabutin Low Dose-Induced Intermediate Uveitis in a Patient with Acquired Immunodeficiency Syndrome." American Journal of Medical Case Reports 5, no. 5 (2017): 116-118.
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[1]  B. R. Saran, A. M. Maguire, C. Nichols, I. Frank, R. W. Hertle, A. J. Brucker, S. Goldman, M. Brown, and B. Van Uitert, “Hypopyon uveitis in patients with acquired immunodeficiency syndrome treated for systemic Mycobacterium avium complex infection with rifabutin,” Arch Ophthalmol, vol. 112, no. 9, pp. 1159-65, Sep, 1994.
In article      View Article  PubMed
 
[2]  M. O. Frank, M. B. Graham, and B. Wispelway, “Rifabutin and uveitis,” N Engl J Med, vol. 330, no. 12, pp. 868, Mar 24, 1994.
In article      View Article  PubMed
 
[3]  S. D. Shafran, J. Singer, D. P. Zarowny, J. Deschenes, P. Phillips, F. Turgeon, F. Y. Aoki, E. Toma, M. Miller, R. Duperval, C. Lemieux, and W. F. Schlech, 3rd, “Determinants of rifabutin-associated uveitis in patients treated with rifabutin, clarithromycin, and ethambutol for Mycobacterium avium complex bacteremia: a multivariate analysis. Canadian HIV Trials Network Protocol 010 Study Group,” J Infect Dis, vol. 177, no. 1, pp. 252-5, Jan, 1998.
In article      View Article  PubMed
 
[4]  D. S. Jacobs, P. J. Piliero, M. G. Kuperwaser, J. A. Smith, S. D. Harris, T. P. Flanigan, J. H. Goldberg, and D. V. Ives, “Acute uveitis associated with rifabutin use in patients with human immunodeficiency virus infection,” Am J Ophthalmol, vol. 118, no. 6, pp. 716-22, Dec 15, 1994.
In article      View Article
 
[5]  S. Skolik, F. Willermain, and L. E. Caspers, “Rifabutin-associated panuveitis with retinal vasculitis in pulmonary tuberculosis,” Ocul Immunol Inflamm, vol. 13, no. 6, pp. 483-5, Dec, 2005.
In article      View Article  PubMed
 
[6]  L. Akduman, L. V. Del Priore, H. J. Kaplan, and W. G. Powderly, “Rifabutin induced vitritis in AIDS patients,” Ocul Immunol Inflamm, vol. 4, no. 4, pp. 219-24, 1996.
In article      View Article  PubMed
 
[7]  M. J. Chaknis, S. E. Brooks, K. T. Mitchell, and D. M. Marcus, “Inflammatory opacities of the vitreous in rifabutin-associated uveitis,” Am J Ophthalmol, vol. 122, no. 4, pp. 580-2, Oct, 1996.
In article      View Article
 
[8]  C. Pochat-Cotilloux, F. De Bats, A. M. Nguyen, F. Benbouzid, A. Malcles, P. Denis, and L. Kodjikian, “[Rifabutin-associated bilateral uveitis: a case report],” J Fr Ophtalmol, vol. 37, no. 8, pp. e115-7, Oct, 2014.
In article      View Article  PubMed
 
[9]  M. H. Skinner, and T. F. Blaschke, “Clinical pharmacokinetics of rifabutin,” Clin Pharmacokinet, vol. 28, no. 2, pp. 115-25, Feb, 1995.
In article      View Article  PubMed
 
[10]  P. K. Narang, C. B. Trapnell, J. R. Schoenfelder, J. P. Lavelle, and J. R. Bianchine, “Fluconazole and enhanced effect of rifabutin prophylaxis,” N Engl J Med, vol. 330, no. 18, pp. 1316-7, May 05, 1994.
In article      View Article  PubMed
 
[11]  C. B. Trapnell, P. K. Narang, R. Li, and J. P. Lavelle, “Increased plasma rifabutin levels with concomitant fluconazole therapy in HIV-infected patients,” Ann Intern Med, vol. 124, no. 6, pp. 573-6, Mar 15, 1996.
In article      View Article  PubMed
 
[12]  D. Havlir, F. Torriani, and M. Dube, “Uveitis associated with rifabutin prophylaxis,” Ann Intern Med, vol. 121, no. 7, pp. 510-2, Oct 01, 1994.
In article      View Article  PubMed
 
[13]  A. Cato, 3rd, J. Cavanaugh, H. Shi, A. Hsu, J. Leonard, and R. Granneman, “The effect of multiple doses of ritonavir on the pharmacokinetics of rifabutin,” Clin Pharmacol Ther, vol. 63, no. 4, pp. 414-21, Apr, 1998.
In article      View Article
 
[14]  H. C. Lin, P. L. Lu, and C. H. Chang, “Uveitis associated with concurrent administration of rifabutin and lopinavir/ritonavir (Kaletra),” Eye (Lond), 12, pp. 1540-1, England, 2007.
In article      View Article
 
[15]  J. I. Kuper, and M. D'Aprile, “Drug-Drug interactions of clinical significance in the treatment of patients with Mycobacterium avium complex disease,” Clin Pharmacokinet, vol. 39, no. 3, pp. 203-14, Sep, 2000.
In article      View Article  PubMed