FINAL DIAGNOSIS: DISSEMINATED SCEDOSPORIUM PROLIFICANS (INFLATUM) INFECTION
Antemortem and postmortem blood cultures, as well as postmortem cerebrospinal fluid and splenic cultures yielded Scedosporium prolificans.
During the past two decades opportunistic fungal infections have emerged as important causes of morbidity and mortality in patients with severe underlying illness and compromised host defense. Collectively Aspergillus and Candida account for the majority of these infections, but recent epidemiologic trends indicate a shift towards infections caused by previously uncommon opportunistic fungi (1). These previously uncommon hyaline filamentous fungi (such as Fusarium species, Acremonium species, Paecilomyces species, Pseudallescheria boydii, and Scedosporium prolificans) are increasingly encountered in life threatening invasive infections that are often refractory to therapy.
Infection with Scedosporium prolificans was first described in 1984 in an immunocompetent 6-year old boy from Minnesota who developed osteomyelitis after he punctured his foot on a rusty nail (2). Consequently, the clinical spectrum of this infection was thought to be limited to local invasion of musculoskeletal tissue following penetrating trauma or surgery.
Subsequently, numerous reports appeared in the literature detailing cases of transitory colonization (3, 5), localized infection (4, 6), or more commonly (as in our case) generalized infection emerging in immunocompromised hosts (4, 7, 8, 9, 10). Localized infections described included pulmonary infections in patients with long standing bronchiectasis (4), meningoencephalitis following intrathecal treatment for acute myelocytic leukemia (6), maxillary sinusitis after maxillary surgery (14) and other localized infections in trauma and surgery patients (16).
Immunocompromised hosts included transplant patients (3), AIDS patients with neutropenia (5, 8), cystic fibrosis patients (12), trauma and surgery patients (14), intravenous drug abusers or more commonly (as in our patient) leukemic patients treated with chemotherapy who developed profound neutropenia (6,7,9,10,11, 12).
In most cases the implicated portal of entry is the skin, in others the aerodigestive tract. Nosocomial airborne outbreaks were also described (1, 13) with disseminated fatal cases in patients with hematologic malignancies. In this patient the most probable portal of entry was the skin, possibly during gardening activities, since no fungal lesions were detected in the lungs or gastrointestinal tract.
Morphologically, in tissue sections, the organism is similar to Aspergillus species, with the typical acutely branched septate hyphae. However, the presence of characteristic conidia (spore forming cells) should suggest the possibility of Scedosporium. Scedosporium prolificans has a distinctive swelling at the base of the sporeforming (conidiogenous) cell, which distinguishes the organism from its more familiar "relative" Scedosporium apiospermum, which is the sexual (anamorph) form of Pseudallescheria boydii (2). Of note, hyphal forms of Scedosporium inflatum and Pseudallescheria boydii are indistinguishable in tissue and require culture for definitive identification. In fact, definitive identification of hyphal forms based exclusively upon microscopic morphology in tissue (particularly in the immunocompromised host) is hazardous.
Scedosporium prolificans is quite susceptible to phagocytosis. (15) As a result, it has very low pathogenicity in immunocompetent individuals. In contrast, Scedosporium prolificans has marked resistance to currently available antifungal agents. Consequently, disseminated infection in immunocompromised hosts is generally fatal - as illustrated by this case.
Contributed by Octavia Graur, MD, PhD, Larry Nichols, MD and Jeanette C Dunn, MD