Flagellate Erythema Secondary to Bleomycin for Non-Seminomatous Testis Tumor

The development of flagellate erythema secondary to bleomycin treatment is a rare adverse effect. The prevalence varies between 8 to 22% of patients and it is becoming rarer. Flagellate erythema presents as a scaly erythematous papule. A lower amount of bleomycin hydrolase in regions with reduced production, such as skin and lungs, decreases bleomycin degradation, which allows its accumulation in tissues, triggering an inflammatory process, especially in patients with lower basal enzyme function. We report a clinical case of a severe presentation of flagellate erythema secondary to a patient ongoing bleomycin, etoposide and platinum (BEP) based chemotherapy of non-seminomatous testis cancer.

A case of bleomycin-induced flagellate dermatitis: A case report

The article description and significance to dermatologists: bleomycin flagellate dermatitis is a rare cutaneous manifestation, believed to be due to the lack of bleomycin hydrolase enzyme in the skin, which inactivates bleomycin, resulting in its accumulation. This is thought to be a dose-dependent reaction, and doses over 200 U and higher may increase risk. This case describes a male developing a pruritic, erythematous linear flagellated dermatitis to the lower back after his third cycle of bleomycin, etoposide and cisplatin for a stage 3 seminoma. Pruritis resolved and erythema improved with the treatment of bilastine and desoximetasone cream. It is important to recognize this condition because untreated pruritis may lead to increased impairment of the skin barrier in already immunocompromised patient populations. This may also give further evidence to having ongoing and continuing collaboration between Dermatology and Medical Oncology for any patients presenting with a new rash undergoing chemotherapy treatments.

Bleomycin hydrolase regulates the release of chemokines important for inflammation and wound healing by keratinocytes

Bleomycin hydrolase (BLMH) is a well-conserved cysteine protease widely expressed in several mammalian tissues. In skin, which contains high levels of BLMH, this protease is involved in the degradation of citrullinated filaggrin monomers into free amino acids important for skin hydration. Interestingly, the expression and activity of BLMH is reduced in patients with atopic dermatitis (AD) and psoriasis, and BLMH knockout mice acquire tail dermatitis. Apart from its already known function, we have discovered a novel role of BLMH in the regulation of inflammatory chemokines and wound healing. We show that lowered BLMH levels in keratinocytes result in increased release of the pro-inflammatory chemokines CXCL8 and GROα, which are upregulated in skin from AD patients compared to healthy individuals. Conditioned media from keratinocytes expressing low levels of BLMH increased chemotaxis by neutrophils and caused a delayed wound healing in the presence of low-level TNFα. This defective wound healing was improved by blocking the shared receptor of CXCL8 and GROα, namely CXCR2, using a specific receptor antagonist. Collectively, our results present a novel function of BLMH in regulating the secretion of chemokines involved in inflammation and wound healing in human keratinocytes.