Cutaneous Eschar in a Growth-Restricted Extremely Premature Infant

A 15-day-old boy born at 24 + 2 weeks with severe fetal growth restriction (375 g) is transferred to our neonatal intensive care unit (NICU) for evaluation and management of a cutaneous abdominal lesion. His early course is notable for respiratory failure, hypotension, a large patent ductus arteriosus, and a grade III intraventricular hemorrhage. He is on prophylactic fluconazole and receives 48 hours of ampicillin and gentamicin, with negative initial blood culture. On day of life (DOL) 10 and 11, an erythematous, ulcerative lesion develops underneath a transparent adhesive dressing without known trauma. Over the next 5 to 6 days, the lesion grows, appearing to involve the dermis and acquiring the appearance of an “eschar” (Figure 1A). Leukocytosis and thrombocytopenia are noted, blood culture is drawn, and vancomycin and ceftazidime are initiated. Within 24 hours, this culture becomes positive for Staphylococcus epidermidis; therefore, he is treated with intravenous immunoglobulin and piperacillin-tazobactam. The lesion darkens and progresses more rapidly, extending to involve the entire the left abdomen from the edge of the rib cage to the groin (Figure 1A and 1B). Transfer of care is requested on DOL 16 to address the need for surgical debridement and possible skin grafting.Upon admission to our NICU, further extension of the necrotizing process is noted (Figure 1C and 1D) along with clinical deterioration, with worsening respiratory failure, worsening hemodynamic instability, disseminated intravascular coagulopathy, and acute renal failure. The Pediatric Infectious Disease and Pediatric Surgery departments are consulted. Fluconazole is increased to treatment dosing, piperacillin-tazobactam is discontinued, and meropenem and clindamycin are added. Given concern for necrotizing fasciitis, it is determined that tissue debridement is indicated. Following a detailed discussion with the patient’s mother regarding the gravity of his condition and his poor prognosis, debridement is performed on DOL 17.Debridement of the necrotic abdominal tissue involves the full thickness of the patient’s abdominal wall spanning an area of 8 × 9 cm, from just the inferior of the diaphragm to the pubis (Figure 2A). Necrotic areas also include the inferior aspect of the spleen, the left lower lobe of the liver, and segments of the small bowel, transverse colon, and greater curvature of the stomach. The necrotic tissues are resected back to the healthy tissue, which, in some areas, appear somewhat dusky, in order to preserve as much healthy tissue possible. A silastic covering of the abdomen is placed owing to the extensive resection of the patient’s abdominal wall (Figure 2B). Portions of the necrotic abdominal wall and jejunum are sent for culture and histopathological evaluation.Within 24 hours, cultures of tissue specimens became positive for a fungal organism. Colonies on blood agar media had a wooly appearance with both lateral and vertical growth (Figure 3A) and, on Sabouraud dextrose agar colonies, contained black dots (Figure 3B).1,2 On microscopic evaluation, broad hyaline aseptate hyphae were noted, with growth branching at 90° angles2 (Figure 4A), with fungal organisms in mucosal and submucosal tissue as well as muscularis propria, and diffuse necrosis (Figure 4B through D).2 These findings are characteristic of Rhizopus arrhizus.Mucormycosis, or infection owing to fungus of the order Mucorales (most commonly Rhizopus), is the second most common invasive mold infecting immunocompromised hosts.1,3 Although infrequent in the United States, mucormycotic infections may be increasing in premature neonates.3 Mucor infections in neonates most often present in the gastrointestinal tract (51%) or the skin (36%), although dissemination occurs in more than one-half of cases, contributing to a higher mortality rate (64%) compared with children (56%).4 The presence of local skin trauma, adhesive dressings, or monitor leads may increase risk. In preterm infants, the stratum corneum is a dysfunctional barrier as it is typically only 2 to 3 layers thick compared with 20 layers in term infants.5 After inoculation, the fungal agent penetrates the stratum corneum and invades the vascular structures of the skin, causing thrombosis and infarction of the blood vessels and resulting in tissue necrosis.5–7Early diagnosis and treatment of mucormycosis can decrease the risk of mortality. Optimal treatment is achieved, particularly in premature extremely patients, by a combination of amphotericin B (or either of its lipid formulations) and aggressive surgical excision and debridement of necrotic areas rather than either antifungal or wound debridement alone.1,8,9 However, in cases of gastrointestinal mucormycosis, surgery does not improve outcomes.4The appearance of this extremely premature patient’s cutaneous lesion associated with an adhesive dressing, along with tissue culture results and histopathology, formed the basis for the diagnosis. Once the presence of fungus was identified on DOL 18, therapy with amphotericin B was initiated. Adjunctive therapy with posaconazole was added on DOL 19 given ongoing progression of the lesion into the groin. Despite these measures, over the next 3 days, the necrotic margins progressed further, and fungal growth was visible below the silastic dressing. Given the patient’s ongoing clinical deterioration, multiple meetings took place with his family, and they agreed to discontinue life-sustaining treatment on DOL 21.Clinicians should consider mucormycosis in patients with rapidly expanding cutaneous and/or soft tissue lesions, particularly those who subsequently develop a necrotic eschar, following invasive procedures or where adhesive dressings have been present.Early initiation of amphotericin B-based therapy and operative debridement provide the best chance of survival for infants, although mortality remains high.