Search

Epidermal growth factor receptor (EGFR) and MEK inhibitors (EGFRi/MEKi) are beneficial for the treatment of solid cancers but are frequently associated with severe therapy-limiting acneiform skin toxicities. The underlying molecular mechanisms are poorly understood. Using gene expression profiling we identified IL-36[gamma] and IL-8 as candidate drivers of EGFRi/MEKi skin toxicity. We provide molecular and translational evidence that EGFRi/MEKi in concert with the skin commensal bacterium Cutibacterium acnes act synergistically to induce IL-36[gamma] in keratinocytes and subsequently IL-8, leading to cutaneous neutrophilia. IL-36[gamma] expression was the combined result of C. acnes-induced NF-[kappa]B activation and EGFRi/MEKi-mediated expression of the transcription factor Kruppel-like factor 4 (KLF4), due to the presence of both NF-[kappa]B and KLF4 binding sites in the human IL-36[gamma] gene promoter. EGFRi/MEKi increased KLF4 expression by blockade of the EGFR/MEK/ERK pathway. These results provide an insight into understanding the pathological mechanism of the acneiform skin toxicities induced by EGFRi/MEKi and identify IL-36[gamma] and the transcription factor KLF4 as potential therapeutic targets., Introduction Agents targeting the epidermal growth factor receptor-mediated (EGFR-mediated) signaling pathway are increasingly used for the treatment of advanced lung, pancreatic, colorectal, and head and neck cancers, which benefit from [...]

Actinomycosis is a rare chronic granulomatous infection caused by Gram-positive, non-acid-fast, anaerobic to microaerophilic bacteria.We report a case of cervicofacial actinomycosis in an 86-year-old woman undergoing immunosuppressive therapy with azathioprine and prednisone for rheumatoid arthritis. She underwent a dental treatment several months earlier. The diagnosis of culture-negative actinomycosis was based on histolopathology findings and the isolation of companion bacteria. The patient was treated with amoxicillin-clavulanic acid for 3 months, which produced complete clearance of her cervicofacial actinomycosis.Our case points out the pitfalls of diagnostic procedures in actinomycosis and the ability of this rare disease to mimic other medical conditions.

Purpose: The purpose of this learning activity is to provide information about the etiology and treatment of atrophie blanche., Target Audience: This continuing education activity is intended for physicians and nurses with an interest in skin and wound care., Objectives: After participating in this educational activity, the participant should be better able to:1. Discuss the pathophysiology of atrophie blanche.2. Explore treatment options for livedoid vasculopathy., Abstract: Atrophie blanche (AB) is a porcelain-white scar that may be seen at the base of a healed ulcer or in association with livedoid vasculopathy (LV). The term AB originally had been used synonymously with LV, whereas LV is a noninflammatory thrombotic condition presenting as either a primary or secondary event (often associated with coagulation).