Do Naranjo Criteria Still Apply to Ipilimumab-induced Uveitis?

Drug-induced uveitis represents a rare class of heterogeneous uveitis. The probability that a drug may cause a side-effect, such as uveitis, has been defined by the Naranjo criteria [1], primarily including the concepts of challenge (uveitis occurs after the suspected drug has been administered), dechallenge (reversibility, i.e. resolution of uveitis after discontinuation of the drug), and rechallenge (relapse of uveitis when therapy with the suspected drug is resumed). Another important criterion is the increase of the side-effect with increased dosage of the suspected drug (dose-dependent effect). In the current issue of the Journal, Fierz et al. report a case series of 3 patients who presented with uveitis after initiation of immunotherapy with various agents for advanced cutaneous melanoma. With regard to ipilimumab-induced uveitis [2], a novel classification of ocular side effects should be proposed, since it is thought that ipilimumab-induced adverse events, including ocular inflammation, may be immune-mediated [3], and not directly dose-dependent, making Naranjo criteria less useful in clinical practice. Although pathogenic mechanisms of drug-induced uveitis are not understood, the role of melanin has been postulated [3], which in turn may explain a clinical picture suggesting a Vogt-Koyanagi-Harada-like uveitis.

• References

• 1 Naranjo CA, Fornazzari L, Sellers EM. Clinical detection and assessment of drug induced neurotoxicity. Prog Neuropsychopharmacol 1981; 5: 427-434
• 2 Weber JS, Kahler KC, Hauschild A. Management of immune-related adverse events and kinetics of response with ipilimumab. J Clin Oncol 2012; 30: 2691-2697
• 3 Moorthy RS, Valluri S, Jampol LM. Drug-induced uveitis. Surv Ophthalmol 1998; 42: 557-570