Ulcerations within striae distensae associated with bevacizumab therapy
Authors: Sara A. Farber, Sara Samimi, Misha Rosenbach
Journal: Journal of the American Academy of Dermatology (2014)

To the Editor: We present the case of a 29-year-old woman with glioblastoma multiforme (GBM) who developed ulcers localized to corticosteroid-induced striae. GBM in the setting of severe headaches and nausea was diagnosed. After complete resection of the mass, she was started on a course of dexamethasone to which daily temozolomide 75 mg/m2 and every other week bevacizumab 10 mg/kg were added 4 months later. She also underwent localized radiation therapy. Soon after starting this combination regimen, she noted small tender ulcers on her abdomen and arms. Physical examination revealed scattered saucer-shaped ulcerations confined to the striae on her abdomen and arms (Fig 1). Because bevacizumab-induced ulceration was suspected and given her degree of discomfort, bevacizumab was discontinued. The patient remained on temozolomide and dexamethasone. The ulcers significantly improved within 1 month with local wound care consisting of white petrolatum and nonstick dressings. GBM is the most aggressive primary brain tumor in adults. Standard treatment for GBM after surgical resection includes radiotherapy in conjunction with temozolomide, followed by adjuvant temozolomide alone. Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), received FDA approval in 2009 for the treatment of recurrent GBM.1Cohen M.H. Shen Y.L. Keegan P. Pazdur R. FDA drug approval summary: bevacizumab (Avastin) as treatment of recurrent glioblastoma multiforme.Oncologist. 2009; 14: 1131-1138Crossref PubMed Scopus (483) Google Scholar Delayed healing of surgical wounds is a well-known adverse effect of bevacizumab, in addition to other cutaneous adverse effects including painful hand-foot syndrome, exfoliative dermatitis, skin discoloration, and xerosis.2Scappaticci F.A. Fehrenbacher L. Cartwright T. Hainsworth J.D. Heim W. Berlin J. et al.Surgical wound healing complications in metastatic colorectal cancer patients treated with bevacizumab.J Surg Oncol. 2005; 91: 173-180Crossref PubMed Scopus (496) Google Scholar, 3Fourcade S. Gandy-Marqueste C. Tasei A.M. Richard M.A. Grob J.J. Localized skin necrosis of steroid-induced striae distensae–an unusual complication of bevacizumab and irinotecan therapy.Arch Dermatol. 2011; 147: 1227-1228Crossref PubMed Scopus (15) Google Scholar There have been several reports3Fourcade S. Gandy-Marqueste C. Tasei A.M. Richard M.A. Grob J.J. Localized skin necrosis of steroid-induced striae distensae–an unusual complication of bevacizumab and irinotecan therapy.Arch Dermatol. 2011; 147: 1227-1228Crossref PubMed Scopus (15) Google Scholar, 4Dosal J. Handler M.Z. Ricotti C.A. Vega J. Tosti A. Kerdel F.A. Ulceration of abdominal striae distensae (stretch marks) in a cancer patient.Arch Dermatol. 2012; 148: 385-390Crossref PubMed Scopus (11) Google Scholar, 5Peters K.B. Coyle T.E. Vredenburgh J.J. Desjardins A. Friedman H.S. Reardon D.A. Ulceration of striae distensae in high-grade glioma patients on concurrent systemic corticosteroid and bevacizumab therapy.J Neurooncol. 2011; 101: 155-159Crossref PubMed Scopus (18) Google Scholar of ulcer formation within corticosteroid-induced striae in patients receiving bevacizumab for advanced GBM. Striae often develop in the setting of chronic corticosteroid use secondary to epidermal atrophy and dermal changes from decreased collagen synthesis. While the exact mechanism of ulceration is unknown, we hypothesize that bevacizumab contributes by impairing striae healing through VEGF inhibition, rendering them persistently weakened and susceptible to ulceration from trauma. Additionally, bevacizumab may increase thrombotic events via endothelial cell disruption, leading to the formation of vascular microthrombi and regions of skin necrosis within striae.4Dosal J. Handler M.Z. Ricotti C.A. Vega J. Tosti A. Kerdel F.A. Ulceration of abdominal striae distensae (stretch marks) in a cancer patient.Arch Dermatol. 2012; 148: 385-390Crossref PubMed Scopus (11) Google Scholar Striae are vascular in nature, making them more susceptible to these effects. Once an ulcer forms, bevacizumab inhibits healing through similar mechanisms.3Fourcade S. Gandy-Marqueste C. Tasei A.M. Richard M.A. Grob J.J. Localized skin necrosis of steroid-induced striae distensae–an unusual complication of bevacizumab and irinotecan therapy.Arch Dermatol. 2011; 147: 1227-1228Crossref PubMed Scopus (15) Google Scholar, 4Dosal J. Handler M.Z. Ricotti C.A. Vega J. Tosti A. Kerdel F.A. Ulceration of abdominal striae distensae (stretch marks) in a cancer patient.Arch Dermatol. 2012; 148: 385-390Crossref PubMed Scopus (11) Google Scholar, 5Peters K.B. Coyle T.E. Vredenburgh J.J. Desjardins A. Friedman H.S. Reardon D.A. Ulceration of striae distensae in high-grade glioma patients on concurrent systemic corticosteroid and bevacizumab therapy.J Neurooncol. 2011; 101: 155-159Crossref PubMed Scopus (18) Google Scholar Proper identification and management is crucial once a patient presents with ulcerated striae. When possible, cessation of bevacizumab may lead to resolution of these areas. However, there are situations when its withdrawal is not feasible. In such cases, dermatologists must be aware of the implications of this regimen and how to prevent further ulcer formation in susceptible patients. In patients started on bevacizumab in the setting of preexisting striae, the striae should be kept moisturized and protected from trauma.5Peters K.B. Coyle T.E. Vredenburgh J.J. Desjardins A. Friedman H.S. Reardon D.A. Ulceration of striae distensae in high-grade glioma patients on concurrent systemic corticosteroid and bevacizumab therapy.J Neurooncol. 2011; 101: 155-159Crossref PubMed Scopus (18) Google Scholar Striae must be closely monitored for ulceration and when identified, early wound care is key. Several management techniques have been reported and include the use of silicone based or colloid dressings with the addition of silver foam or dressings if signs of infection are apparent.5Peters K.B. Coyle T.E. Vredenburgh J.J. Desjardins A. Friedman H.S. Reardon D.A. Ulceration of striae distensae in high-grade glioma patients on concurrent systemic corticosteroid and bevacizumab therapy.J Neurooncol. 2011; 101: 155-159Crossref PubMed Scopus (18) Google Scholar This case reinforces that ulcers localized to striae are a rare but possible side effect of combined therapy with dexamethasone and bevacizumab, and highlights the importance of early recognition and proper management in these patients.