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Ecthyma Gangrenosum is a manifestation of Pseudomonas Aeruginosa infection, usually occurring in immunocompromised patients, which can be associated with Pseudomonas Aeruginosa bacteremia with potentially lethal outcome. The clinical appearance is of an inflammatory cutaneous lesion with a central necrotic spot; the lesion then rapidly progresses to a gangrenous ulcer with a gray-black eschar extending in the deep soft tissues. Treatment of Ecthyma Gangrenosum includes both aggressive systemic antibiotic therapy and surgical procedures. A 2-year-old girl affected by B-cell precursor acute lymphoblastic leukemia was admitted to our hospital for suspected sepsis; the diagnosis was later confirmed by blood cultures positive for Pseudomonas Aeruginosa. In the days following the diagnosis, the patient developed a necrotic lesion of the right gluteal area consistent with Ecthyma Gangrenosum. Aggressive surgical debridement was then performed, followed by negative-pressure wound therapy and reconstruction with dermal substitute and autologous skin graft, which were successful. Ecthyma Gangrenosum is a potentially lethal condition affecting especially immunocompromised patients; aggressive medical treatment with combination antibiotic therapy is warranted and multiple surgical procedures, including extensive surgical debridement and diverting colostomy, are needed. Various reconstructive techniques have been reported in the literature, although no gold-standard can be established to date. Since Ecthyma Gangrenosum lesions are characterized by the presence of both high inflammatory activity due Pseudomonas infection and extensive tissue loss, the association of negative-pressure therapy and dermal substitutes implant seem to have a rationale in the surgical treatment of Ecthyma Gangrenosum and should therefore be considered.