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Pulmonary mucormycosis in an ill patient with poorly controlled chronic lymphocytic leukemia was diagnosed with open lung biopsy without excision. He improved on medical management and became ambulatory. At autopsy one year later, no residual mucormycosis was present. Better control of leukemia and more specific antimicrobial therapy are discussed as potentially important factors in patient management.
Rhinocerebral mucormycosis is a fungal diseases that has a 50% mortality. Its occurrence has increased, possibly because of greater use of chemotherapeutic agents that mya compromise the immunologic defenses of the host or alter the normal flora. The earliest signs, ulceration and pain, may appear in the mouth. In the patient described in this report, the autopsy showed that mucormycosis had entered the brain cells.
During a 24-year period, seven patients with leukemia undergoing cytotoxic or immunosuppressive therapy developed pulmonary mucormycosis in our hematology ward. The autopsy incidence in patients with acute leukemia was 2.1%, with no significant rise during the last decade. Most cases occurred in early autumn. Two patients diagnosed premortem were successfully treated with antifungal drugs, whereas five patients diagnosed postmortem died within three weeks following radiographic identification. Persistent fever despite antibiotic coverage was the first clinical presentation, followed mostly by the radiographic appearance of rounded densities, subsequently progressing to hemorrhagic infarction with hemoptysis and/or pleuritic pain. Crescentic cavitation developed when hematologic remission was achieved. Thus, certain radiographic patterns with or without pulmonary infarct syndrome in the proper clinical setting should arouse suspicion of mucormycosis, providing the opportunity for early diagnosis and adequate treatment.
A rare case of rhinocerebral mucormycosis occurred in a 74-year-old diabetic male with gradually progressive right visual loss and total ophthalmoplegia. Computed tomography and magnetic resonance imaging revealed an invasive right orbital apex mass, destroying the medial wall of the orbit and extending into the right cavernous sinus and right middle fossa. Laboratory data demonstrated no signs of inflammation. A carcinomatous lesion originating in the paranasal sinuses and extending into the intracranial space was diagnosed. The mass was totally removed through a subfrontal approach to confirm the histological diagnosis and decompress the optic nerve. The histological diagnosis was mucormycosis. Despite aggressive medical therapy, dissemination resulted in mucor pleuritis and mucor encephalitis or meningitis. He died of septic shock and acute renal failure.
OBJECTIVES: Mucormycosis is an acute and often fatal infection caused by a fungus of the Mucorales order of the Zygomycetes class. In the majority of cases, it is associated with an underlying disorder, such as diabetes mellitus with ketoacidosis, or with immunocompromising factors, but it may appear in healthy people, although rarely. Early diagnosis and treatment are critical to prevent an otherwise fatal outcome. This article presents and discusses the early (alarming) signs and symptoms and the predisposing factors that should be considered to avoid delays in diagnosis. METHODS: We review seven cases of rhinocerebral mucormycosis admitted to our hospitals from 1998 to 2003. RESULTS: All patients had an underlying immunocompromising factor and/or diabetes mellitus. Five patients had palatal necrotic ulcers and/or black eschars. Three patients had unilateral blindness, and two patients required orbital exenteration. Four patients died because of a delayed diagnosis. CONCLUSIONS: Early diagnosis is critical in the prevention of intracranial extension of the infection, which is the cause of death in 80% of cases. Therefore, a high index of clinical suspicion is essential in immunocompromised or diabetic patients with acute sinus infection. Identification of a fungal organism on histopathology is the most specific element for diagnosis. A team approach to management is recommended for early surgical debridement, correction of diabetic ketoacidosis, and systemic antifungal agents. Timely medical-surgical treatment proves extremely important for prognosis.
The defect in host defense that makes the diabetic ketoacidotic (DKA) patient susceptible to mucormycosis has not been identified. Sera from 10 DKA patients and three normal volunteers were tested for their capacity to support the in vitro growth of a common etiologic agent of mucormycosis, Rhizopus oryzae. After equilibration with room air none of the normal or DKA sera, each of which was now extremely alkaline, supported growth of R. oryzae. When the sera were placed in a CO2 atmosphere that permitted simulation of the in vivo clinical pH (normal 7.40 and DKA 7.3-6.6), four of seven DKA sera supported profuse fungal growth. No growth occurred in normal serum. The three DKA sera that did not support fungal growth at pH less than or equal to 7.3 contained less iron (x = 13 micrograms/dl) than the four sera that supported profuse fungal growth (x = 69 micrograms/dl). Increasing the iron content of iron-poor DKA serum that did not support R. oryzae growth allowed profuse growth at acidotic conditions but not at pH greater than or equal to 7.4. Simulated acidotic conditions (pH 7.3-6.6) also decreased the iron-binding capacity of normal serum stepwise from 266 micrograms/dl to 0. Our data indicate that acidosis temporarily disrupts the capacity of transferrin to bind iron and suggest that this alteration abolishes an important host defense mechanism that permits growth of R. oryzae.
Five cases of mucormycosis are reported, 2 of them suffered from immunosuppression, the other 3 did not. We conclude that a combination of CT and bacteriological findings is useful for the diagnosis of mucormycosis differentially from other diseases. Therapy consisted of paranasal debridement and administration of amphotericin B.
Opportunistic fungal infections occur with increasing frequency during chemotherapy induced granulocytopenia. A 27-year-old woman developed mucormycosis in the ileocecal region with fatal dissemination to the liver while receiving consolidation therapy for acute T-lymphoblastic leukemia. The infection occurred during a period of decreased colonization resistance in the intestinal tract. Early symptoms were high fever unresponsive to broad spectrum antibiotics, severe pain in the right lower abdominal quadrant and diarrhoea. This was followed by an infiltrate in the right abdomen, ileus, and icterus. Diagnosis was established in the living patient by thin needle aspiration from affected liver tissue. Giemsa's stain and fungal cultures revealed Mucor indicus. The fatal outcome of disseminated mucormycosis justifies a high index of suspicion and a maximal (invasive) diagnostic effort as localised infections might be cured by resection and amphotericin B.
A case of invasive pulmonary mucormycosis complicated by fatal, massive haemoptysis in a patient with acute myeloid leukaemia is reported. This patient represents the twelfth reported case of fatal haemoptysis due to mucormycosis. The other 11 cases are reviewed and the aetiology of cavity formation and massive haemoptysis is discussed. The development of the air crescent sign on chest radiograph is an important clinical indicator of potentially fatal haemoptysis and should lead to appropriate antifungal and surgical therapy.
We describe two cases of disseminated mucormycosis following allogeneic bone marrow transplantation (BMT). Both patients were suffering from chronic graft-ver-sus-host disease (GVHD) and treated with prolonged administration of corticosteroid. In both cases, the initial symptoms were high fever and left flank pain. Involved organs were the spleen, right kidney and the right lung in one case, and the spleen and the brain in the other. The diagnosis was confirmed by pathology after splenectomy. One patient, in whom the immunosuppressants could be discontinued, was treated with prolonged conventional and liposomal amphotericin B and 5-fluorocytosine. The other, in whom the immunosuppressants could not be discontinued due to extensive GVHD, was unresponsive to amphotericin B, and eventually died from the fungal infection. Although mucormycosis, especially the disseminated form thereof is infrequent, it should be considered in high-risk patients because early diagnosis and timely therapy combining antifungal drug or surgery and reduction of immunosuppression appear to improve the prognosis.
Rhinocerebral mucormycosis is a rare and fatal deep fungus infection occurring in debilitated patients. Its reports have been recently increased because of the increase of such conditions as uncontrolled diabetics, leukemia, and cancer. A 60-year-old male suffering from continuous headache and fever was diagnosed as meningitis, and repeated culture of cerebrospinal fluid was negative. Antibiotic therapy was ineffective. CT scan revealed brain abscess in the right frontal lobe and bone defect over the right posterior ethmoidal sinuses. Both maxillary and ethmoidal sinuses were operated on 38 years ago. The patient was suspected to have rhinologic brain abscess. We intended to remove the source of infection in the right posterior ethmoidal sinuses beneath the base of the skull and to repair the defect of dura mater. The operation was tried on the 6th hospital day. There was a cyst in the posterior ethmoidal sinuses and an intact denuded dura mater over the cyst. The causative organism was not detected by smear test, bacteriological and fungal culture. He relapsed into lethargy, and died on the 21st hospital day due to the vast cerebral infarction. Autopsy revealed rhinocerebral mucormycosis. The literature on this disease was also reviewed and discussed.
The term mucormycosis encompasses a distinctive group of infections caused by fungi belonging to genera within the taxonomic order Mucorales, usually Rhizopus, Absidia, Mortierella, and Mucor. These fungi are widespread in nature, subsisting on decaying vegetation and diverse organic materials. Although the fungi and spores of Mucorales show minimal intrinsic pathogenicity toward normal persons, they can initiate aggressive and fulminant infections under certain clinical conditions. Ketoacidotic diabetics are predisposed to rhinocerebral mucormycosis, whereas patients with leukemia or lymphoma are susceptible to pulmonary or disseminated infections. These infections, which often result in devastating long-term sequelae for surviving patients, pose difficult diagnostic and therapeutic challenges.
Brain and bone scan findings in two patients suffering from rhinocerebral mucormycosis following kidney transplantation are presented. Two patients who had had kidney transplants and were sustained for over a month on immunosuppressive drugs developed a rare type of opportunistic infection--mucormycosis. They were examined in various stages of their disease. Special attention was paid to the scintillagraphic findings.
Mucormycosis is a rare often fatal opportunistic condition. It mainly occurs in immunocompromised subjects but rarely in AIDS patients. An eighteen-year-old HIV+ man from Zaire died rapidly from disseminated mucormycosis with pulmonary, cardiac, renal, hepatic, splenic and gastric involvement. Fungi were observed in all these organs with a particular vascular trophism. Rhizopus orizae was identified on cultures. Rapid microscopic diagnosis, in the localized stage, could improve the poor prognosis of this infection.
BACKGROUND AND OBJECTIVES: In recent years pulmonary mucormycosis has been reported in patients with leukemia and lymphoma and bone marrow transplant recipients. It carries an extremely poor prognosis. We report our experience of clinical findings, diagnostic procedures, treatment and outcome of mucormycosis diagnosed in neutropenic patients affected by hematologic neoplasms admitted to our Department. DESIGN AND METHODS: From November 1987 to July 1999 we observed 13 cases of Mucor. Their median age was 61 years (range 20-75), and they were predominantly in the aplastic post-chemotherapy period (12/13), affected by acute myeloid leukemia (11 cases ) or non-Hodgkin's lymphoma (2 cases). Six patients (all with leukemia) were receiving inductionEth consolidation therapy, 7 had progressive hematologic disease. At the onset of infection all patients were neutropenic (N < 0.5x10(9)/L). No patients had diabetes mellitus. Two patients had been receiving steroid therapy for 5 and 7 days. RESULTS: The lung was involved in all cases (13/13); disseminated disease was present in 8/13 patients. All cultures (blood, sputum, nasal swabs and bronchoalveolar lavage) were negative. In 3 patients a histologic diagnosis was made in vivo: in 1 patient by percutaneous pulmonary biopsy, in 1 patient by pulmonary lobectomy, and in the last patient by percutaneous pulmonary biopsy confirmed by excision of a cerebellar abscess. In the remaining 10 cases diagnosis was made post-mortem. Five patients were not treated, 2 because of poor clinical condition and 3 because fungal infection was not suspected. Amphotericin B (1 mg/kg/day) was given empirically to 6 patients and 2 responded to treatment. The remaining 2 patients with neurologic symptoms at the onset of infection were treated with liposomal amphotericin, Ambisome, one with 3 and one with 5 mg/kg/day; of these two patients the first died in 4 days; the second, with both pulmonary and cerebellar localizations, was treated successfully with 5 mg/kg/day for 4 weeks and then with 3 mg/kg/day, and excision of a brain abscess at neutrophil recovery (total dose of Ambisome: 12,000 mg). The 3 surviving leukemic patients were able to complete subsequent consolidation therapy using amphotericin B or liposomal amphotericin as secondary prophylaxis during aplasia. INTERPRETATION AND CONCLUSIONS: In neutropenic hematologic patients Mucor is rarely suspected. In our patients infection was often characterized by disseminated disease and a rapidly fatal course; only early aggressive amphotericin B (or Ambisome) treatment together with neutrophil recovery appeared to improve the outcome. Diagnosis is very important for programming antifungal therapy and secondary prophylaxis with amphotericin B, because Mucor is usually resistant to itraconazole.
We report a case of mucormycosis in a 48 year-old diabetic woman. She presented with nasosinusal ulcer accompanied by panophthalmitis in the left eye and central retinal artery occlusion in the right eye. Left eye enucleation was performed and the diagnosis of mucormycosis was made on histopathologic examination displaying fungal micro-organisms in the optic nerve and in the retina. The patient died of stress ulcer hemorrhage. Mucormycoses are rare and severe diseases affecting immunocompromised hosts, especially diabetic patients during ketoacidosis. The treatment includes surgical debridement and amphotericin B but prognosis remains severe.
Mucormycosis is an infection caused by fungi in the Mucorales order, of which the most relevant family is Mucoraceae, which includes the Rhizopus, Mucor and Absidia genera. It is a severe infection which involves diabetic patients with ketoacidotic decompensation and immunosuppressed patients. We report here five cases (four with rhino-cerebral forms) attended at our hospital in the last ten years. Three patients had diabetes, one was infected with the human immunodeficiency virus, and the other was on a programme of peritoneal dialysis due to renal failure. The most relevant clinical manifestation was the presence of the necrotic lesion in three of the four patients with rhinocerebral involvement (two in the palate, one in the nasal mucosa). Two patients died as a result of the direct infection a few days after diagnosis. In summary, mucormycosis is an infection with a low prevalence but still maintaining a high mortality rate. An early diagnosis is essential and thereby a high index of clinical suspicion is required in patients with predisposing factors.
Mucormycosis is an opportunistic fungal infection usually observed in diabetic or neutropenic patients. Prognosis is serious with a high rate of mortality. Intravenous amphotericin B is the gold standard treatment. The main side effect is renal failure. Liposomal amphotericin B (AmBisome(R)) is not nephrotoxic and can be proposed as an alternative treatment although its cost is high. We report a case of mucormycosis in a diabetic woman who developed renal failure after intravenous amphotericin B treatment. AmBisome(R) could not be used for long-term treatment due to its high case. The patient was given nebulized amphotericin B and achieved recovery. This kind of treatment may provide a useful alternative to intravenous amphotericin B.