Systemic complications of intravitreal bevacizumab: a case report and literature review

Abstract Background: Systemic complications of intravitreal bevacizumab (IVB) injections have been previously reported. We aimed to summarize the systemic complications reported in online primary studies. Moreover, we describe a patient experiencing simultaneous renal and cutaneous drug-induced adverse effects, with exacerbation of chronic renal insufficiency and granulomatous skin lesions, after receiving several IVB injections to manage bilateral ischemic branch retinal vein occlusion (BRVO). Case Presentation: A ۶۹-year-old Hispanic diabetic man with chronic renal insufficiency due to polyclonal gammopathy received several IVB injections to treat bilateral ischemic BRVO. One week after the sixth injection, the patient developed acute-on-chronic renal failure and multiple rounded maculopapular, erythematous, and ulcerated skin lesions. Renal and skin biopsy specimens revealed granulomatous drug-induced responses in both organs, and granulomatous diseases of infectious and oncological sources were ruled out. We performed an electronic search of the PubMed/MEDLINE database with no language or time restrictions using the keywords “intravitreal bevacizumab” or “intravitreal Avastin” combined with “systemic side effects,” “systemic complications,” or “systemic adverse,” or “systemic adverse event.” The search yielded ۱۴۷ articles published over almost two decades. After screening and assessment, we selected and summarized ۴۰ primary studies that mentioned IVB-related systemic complications. Conclusions: IVB-induced systemic complications, such as arteriothrombotic events, venous thrombotic events, and hypertension, are rare but potentially serious. Care should be taken when administering multiple doses of intravitreal IVB to patients with pre-existing kidney dysfunction. Bevacizumab-related toxicity must be considered in cases of sudden deterioration of renal function and / or unexpected granulomatous skin lesions in oncologic or chronically polymedicated patients. Keywords: state of the art reviews case study avastin intravitreal injection chronic renal insufficiency drug side effect drug toxicity