Bevacizumab
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Necrotising enterocolitis and off label use: case report A six-week-old girl developed necrotising enterocolitis (NEC) during off label treatment with bevacizumab for retinopathy due to incontinentia pigmenti. The girl was diagnosed with incontinentia pigmenti (IP) at the age of 3 weeks. At the age of 6 weeks, she was referred to hospital for further treatment. Due to the retinal findings and impending tractional retinal detachment with consecutive amaurosis, an off-label treatment with intravitreal bevacizumab [Avastin] 625µg was given in the left eye. Subsequently, a retinal examination showed aggravating neovascularization of the right eye which required pan-retinal laser photocoagulation 9 days after bevacizumab treatment of the left eye. Unfortunately, the application of bevacizumab could not prevent retinal detachment, which happened 8 days after the bevacizumab application. Six hours post intravitreal bevacizumab treatment, she presented with abdominal distension and bloody stools as signs of an acute necrotising enterocolitis. Examination of the cardiovascular system revealed no abnormalities but X-ray confirmed a distinct pneumatosis intestinalis with no signs for free abdominal air leaks corresponding to Bell stage IIa. The girl was treated with piperacillin, gentamicin and metronidazole. Eight days after the bevacizumab treatment, she developed an acute abdomen with silent murmurs, visible dilated bowel loops and abdominal distension; the abdominal X-ray revealed free abdominal air corresponding to Bell stage IIIb. Her blood tests were unremarkable except a slightly altered coagulation and an elevated C-reactive protein. In an immediate explorative laparoscopy, a pancolitis and a single focal perforation near the base of the appendix were seen. Therefore, the appendix as well as the perforated part of the coecum were removed. A pathological examination revealed the typical picture of NEC. Postoperative enteral feeding was completed uneventfully. One year after the event, she showed normal feeding and an adequate weight gain. To investigate a possible adverse drug effect, serum VEGF levels before and after bevacizumab application were compared using ELISA. A drastic decrease of serum VEGF concentrations was noted just hours after intravitreal application of bevacizumab. Author comment: "As NEC has not been reported in IP and is rarely seen in full-term infants and the onset of symptoms was time-related to intravitreal anti-VEGF application, we hypothesized a possible link between the single intravitreal application of bevacizumab and the development of the NEC/pancolitis as a systemic adverse event of intravitreal application of bevacizumab." Kunzmann S, et al. Necrotizing enterocolitis after intravitreal bevacizumab in an infant with Incontinentia Pigmenti-a case report. BMC Pediatrics 19: No. 1, 15 Oct 2019. Available from: URL: http://doi.org/10.1186/s12887-019-1732-z 803435090 Germany
0114-9954/19/1780-0001/$14.95 Adis © 2019 Springer Nature Switzerland AG. All rights reserved
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