1. General introduction 19 1. hypopigmentation, and telangiectasia are frequently observed after treatment.51 Although uncommon with intralesional corticiosteroid delivery, there is also a risk of systemic adverse events such as immunosuppression, adrenal insufficiency, and Cushing's syndrome, particularly with long-term use of high doses. Other intralesional treatment options are cryotherapy, and chemotherapeutics such as 5-Fluorouracil and bleomycin.52 A meta-analysis showed that bleomycin treatment was associated with a lower risk of keloid recurrence compared to 5-Fluorouracil monotherapy or combination therapy with 5-Fluorouracil and triamcinolone.53 Intralesional bleomycin treatment Bleomycin is an antibiotic with chemotherapeutic properties, derived from Streptomyces verticillus bacteria.54 This antineoplastic agent inhibits collagen synthesis via a decrease in TGF-β and causes DNA damage and cell apoptosis.55 Moreover, it inhibits endothelial cell migration and hereby also exhibits anti-angiogenic activities.56 Bleomycin has been used for intravenous treatment of head and neck tumors, and offlabel as intradermal treatment for several dermatological indications, including recalcitrant warts, hemangioma and non-melanoma skin cancer.57 Its topical use is limited due to the large molecular mass (1415 Da) and high hydrophilicity.58 However, it has been used successfully as intradermal treatment for keloids using conventional needles. Treatment with intralesional bleomycin potentially may lead to low recurrence rates in keloids due to its antimitotic and anti-angiogenic effects.59 Clinical application of NFI-assisted treatment with bleomycin in keloids Bleomycin can be degraded by the enzyme bleomycin hydrolase. Since there is a low expression of this enzyme in the lungs, high dosages of bleomycin can result in lung fibrosis.60,61 In patients treated for dermatological indications, lung toxicity has not been reported, probably because of the use of low dosages (usually 2–4 U). However, potentially harmful aerosols can form when bleomycin is administered with NFIs.62
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