Vol. 17, No. 28
THE JOHNS HOPKINS MICROBIOLOGY NEWSLETTER
Monday, July 20, 1998
A. Provided by Carmela Groves, R.N., M.S., Chief, Division of Outbreak Investigation, Maryland Department of Health and Mental Hygiene.
No information reported for this week.
B. The Johns Hopkins Hospital. Information provided by Dr. May Arroyo, Department of Pathology.
Patient History: A 49 year old Caucasian female with a history of postpartum hepatitis associated with pancytopenia of unknown etiology (1978) responsive to steroids and splenectomy, and infiltrating breast ductal carcinoma status post mastectomy, radiation, and chemotherapy (1994), presented to an outside hospital with a one week history of jaundice, fever, and malaise. The patient was found to have an absolute neutrophil count of 175, markedly elevated liver enzymes, anemia, and thrombocytopenia. Hepatitis A, B, and C serologies were negative. A liver biopsy revealed non-specific hepatitis, and a bone marrow biopsy showed replacement by a non-specific lymphoid infiltrate. She was transferred to The Johns Hopkins Hospital where she developed progressive pancytopenia, ascites, diarrhea, and encephalopathy. Blood cultures were repeatedly negative. High dose steroids were initiated. The patient became more somnolent and a head CT revealed signs of herniation. The patient expired three weeks after the onset of her initial symptoms. Consent for an autopsy was obtained which revealed disseminated angioinvasive zygomycosis involving the sphenoid sinuses, cribiform plate, bilateral orbitofrontal cortices, visceral pleura, lungs, and upper gastrointestinal organs. The liver showed fulminant hepatitis of an unknown etiology.
Organism: The morphology of the fungus was most consistent with a Mucoracea. The fungi in this order are characterized on tissue sections by broad, non-septate hyphae with right angle branching (1). Culture and speciation identified the organism as Absidia corymbifera. The Absidia genus contains two members, A. ramosa and A. corymbifera, but only the latter is pathogenic to man (1). Among the mucormycotic infections, Rhizopus, Mucor, and Absidia are the most common isolates, in decreasing order of frequency. These are ubiquitous organisms which cause disease in diabetics, immunocompromised patients, and patients on desferoxamine therapy (1). This predisposition suggests selective growth of the organism in hyperglycemic, acidotic environments with elevated iron availability.
Clinical Manifestations: The diseases commonly associated with the Mucorales include: 1) rhinocerebral disease: This generally presents as headaches, facial pain, fever, sinusitis, or retroorbital pain. In patients with diabetic ketoacidosis, the infection can rapidly progress to cerebral involvement manifesting as stupor, mood disturbances, and confusion, and is often fatal. 2) pulmonary disease: Generally seen in neutropenic patients, the symptoms include chest pain, productive cough, fever, and dyspnea. Due to the angio-tropic nature of these organisms, thrombi and infarcts generally occur. 3) gastrointestinal disease: This is most commonly encountered in malnourished children, although it may also be seen in uremic patients, or patients on steroid therapy. Any segment of the gastrointestinal tract may be affected, and may be associated with erosive ulcers, thrombosis, or gangrene. Symptoms include hematochezia, abdominal pain, diarrhea, and hematemesis. 4) cutaneous disease: Occurs in association with trauma, elastoplast bandages, and burns, as well as diabetes and immunosuppresion. The lesions may present as cellulitis, ulcers, or gangrene. 5) disseminated disease: Risk factors predisposing to the development of disseminated disease include neutropenia, diabetic ketoacidosis, desferoxamine therapy, and immunosuppresion. Case reports of absydiomycosis are rare and include a brain abscess in an IV drug user, cutaneous infections in two neutropenic patients, and a renal abscess in an IV drug user with AIDS(1,2,3).
Laboratory Diagnosis: Tissue biopsies or scrapings from lesions should be sent to pathology for the detection of broad, irregular, ribbon-like, non-septate hyphae with right angle branching on hematoxylin-eosin, methenamine silver stain, or a KOH wet mount. In culture, Absidia is a fast growing filamentous fungus which forms delicate, fine sporangiophores, with conical apophysis, a hemispherical columella, and a pear-shaped sporangium (1).
Treatment: Surgical debridement of all devitalized tissue and IV amphotericin B (0.8 - 1 mg/kd/day) remains the most important option in the management of Mucormycosis. In addition, the underlying disorder, such as diabetic ketoacidosis or therapy-related immunosuppression, should be corrected.
References:
1. Richardson, M.D., and Shankland, G.S. 1995. Rhizopus, Rhizomucor, Absidia, and other agents of systemic and subcutaneous zygomycoses, pp.809-824. In Murray, P.R, et al. (eds.), Manual of Clinical Microbiology, ASM Press, Washington, D.C.
2. Rinaldi, M.G. Zygomycosis. Infectious Disease Clinic of North America 3:19-40;1989.
3. Sugar, A.M. Mucormycosis. Clinical Infectious Diseases 14(suppl. 1):S126-9;1992.
Note: During this patient's hospitalization at this institution, two other cases of Mucormycosis were identified in the intensive care units, suggesting the possibility of a nosocomial outbreak. Identification of the filamentous fungi from two of the cases, however, revealed that they were separate organisms. The patient described above was infected with Absidia. The second case had an invasive cutaneous lesion in the forehead caused by Rhizopus.