Gastrointestinal mucormycosis complicated by arterio‐enteric fistula in a patient with non‐Hodgkin's lymphoma

Gastrointestinal mucormycosis is a rare, often fatal, systemic infection found predominantly in immunocompromised patients. We report a case of gastrointestinal mucormycosis in a 53‐year‐old female with non‐Hodgkin's lymphoma. Following her first course of chemotherapy, bowel obstruction developed as a result of mucormycosis. Despite treatment with antifungal therapy, she required a laparotomy owing to severe haemorrhage caused by mucormycosal invasion of her iliac artery. With continued antifungal treatment and further chemotherapy, she ultimately underwent reversal of her Hartmann's procedure and remains disease‐free.     

Successful treatment of mucormycosis infection after liver transplantation: report of a case and review of the literature

Mucormycosis (zygomycosis) is a rare opportunistic fungal infection mainly affecting patients with diabetes mellitus, immunodeficiency, malignancies and solid organ transplant. We present a 55-year-old female with a mucormycosis infection primarily affecting the paranasal sinuses after liver transplantation. The patient presented with a one-week history of right-sided occipital headache and gradual loss of vision in the right eye just 6 months after liver transplantation. Imaging studies revealed a right-sided sphenoiditis with orbital apex involvement. The patient underwent endoscopic sinus surgery and the histology confirmed the diagnosis of mucormycosis. Aggressive surgical ablation of the infected parts, along with antifungal treatment and adjustment of her immunosuppressive maintenance resulted in a good outcome and long-term survival.     

The role of BAL in the diagnosis of pulmonary mucormycosis

Five patients with pulmonary mucormycosis diagnosed during life are described. All had underlying predisposing conditions: either posttransplant or hematologic malignancies. In all cases, the diagnosis was made using fiberoptic bronchoscopy. In three patients, BAL was diagnostic. In two of these patients, the diagnosis was made by identifying the typical hyphae of mucormycosis in the BAL fluid alone. Transbronchial biopsy was diagnostic in three patients. Treatment was based on IV antifungal chemotherapy together with surgical removal of involved lung tissue whenever feasible. The clinical outcome of these patients was dismal and was determined primarily by the underlying condition.     

Cluster of pulmonary infections caused by Cunninghamella bertholletiae in immunocompromised patients.

Cunninghamella bertholletiae is a rare cause of pulmonary mucormycosis. We describe a cluster of invasive pulmonary infections caused by C. bertholletiae in 4 immunocompromised patients that occurred during a 2-year period at 1 center. Three of the patients were receiving antifungal prophylaxis with itraconazole. Presenting symptoms were fever unresponsive to antibacterial chemotherapy, hemoptysis, and infiltrates on chest radiograms. Three patients were treated with liposomal amphotericin B. Only 1 patient survived.     

Diagnosis and treatment of mucormycosis in patients with hematological malignancies: guidelines from the 3rd European Conference on Infections in Leukemia (ECIL 3)

Mucormycosis is an emerging cause of infectious morbidity and mortality in patients with hematologic malignancies. However, there are no recommendations to guide diagnosis and management. The European Conference on Infections in Leukemia assigned experts in hematology and infectious diseases to develop evidence-based recommendations for the diagnosis and treatment of mucormycosis. The guidelines were developed using the evidence criteria set forth by the American Infectious Diseases Society and the key recommendations are summarized here. In the absence of validated biomarkers, the diagnosis of mucormycosis relies on histology and/or detection of the organism by culture from involved sites with identification of the isolate at the species level (no grading). Antifungal chemotherapy, control of the underlying predisposing condition, and surgery are the cornerstones of management (level A II). Options for first-line chemotherapy of mucormycosis include liposomal amphotericin B and amphotericin B lipid complex (level B II). Posaconazole and combination therapy of liposomal amphotericin B or amphotericin B lipid complex with caspofungin are the options for second line-treatment (level B II). Surgery is recommended for rhinocerebral and skin and soft tissue disease (level A II). Reversal of underlying risk factors (diabetes control, reversal of neutropenia, discontinuation/taper of glucocorticosteroids, reduction of immunosuppressants, discontinuation of deferroxamine) is important in the treatment of mucormycosis (level A II). The duration of antifungal chemotherapy is not defined but guided by the resolution of all associated symptoms and findings (no grading). Maintenance therapy/secondary prophylaxis must be considered in persistently immunocompromised patients (no grading).     

A case of chronic myelogenous leukemia with pulmonary aspergillosis diagnosed by the detection of circulating Aspergillus antigen]

Immunocompromised hosts usually develop invasive mycotic disease. Among many pathogenic fungi. Aspergillus spp, is the most common pathogen of respiratory infection. Early diagnosis of invasive type pulmonary aspergillosis is still difficult, and the treatment is usually difficult. Many investigations have recently suggested that detection of Aspergillus antigen from sera of the patients is useful for early diagnosis to save their lives. We have experienced a case diagnosed by the detection of circulating Aspergillus antigen by Pastorex Aspergillus, who was a 64-year-old female with the blastic crisis chronic myelogenous leukemia. After anti-leukemic chemotherapy, she suffered from pneumoniae with pleural effusions and severe hypoxia, which did not respond to antibiotics. At this point, her serum sample showed positive Aspergillus antigen by Pastorex Aspergillus. She was treated by intensive antifungal chemotherapy, and thereafter improved quickly. Titers of Pastorex Aspergillus were well correlated with her clinical course. The sensitivity of the test requires further improvement, but the specificity of the test is considered to be high enough for clinical use.     

A case of endobronchial mucormycosis with peculiar bronchoscopic findings]

Small cell lung cancer was diagnosed in a 54-year-old man in 1997. He had received 5 cycles of systemic chemotherapy and thoracic irradiation since 1997, and a favorable response had been achieved. In August 2001, pro-GRP was again elevated, and he was readmitted. Bronchoscopic findings revealed a white dendritic endobronchial mass on a cheese-like plug obstructing the left upper bronchus division. Numerous mucor hyphe and cancer cells were detected by transbronchial biopsy, and a fungal culture disclosed mucor. Although no antifungal drug was administered, the bronchial lesion disappeared after removal with biopsy forceps and 2 cycles of systemic anticancer chemotherapy. Endobronchial involvement of mucormycosis is rare and this case is unique because of the peculiar bronchoscopic finding with the endobronchial lesion.     

Successful treatment of mucormycosis endocarditis complicated by pulmonary involvement

Cardiac mucormycosis is an exceedingly rare condition. This case report describes mucormycosis endocarditis in an immunocompromised patient with ulcerative colitis. His condition was further complicated by multiple septic emboli to the lungs. His management included surgical excision of the right atrial endocarditic vegetation and antifungal treatment with high-dose liposomal amphotericin B.     

Paraneoplastic Raynaud’s phenomenon in a breast cancer survivor

A 35-year-old woman with a history of breast cancer, treated 3 years ago with surgery, radiation, and chemotherapy presented with a rapid onset of severe Raynaud’s phenomenon. On physical examination, she had digital ulcers and splinter hemorrhages; there were no signs of an underlying rheumatic condition. Laboratory evaluation revealed anemia, the presence of antinuclear antibody and slight depression in her serum complement C3 level. The remainder of her serologic evaluation, including extractable nuclear antigens, anti-double-stranded DNA antibody, antiphospholipid antibodies, rheumatoid factor, anti-neutrophil cytoplasmic antibodies, cryoglobulins, and cold agglutins, were negative. Within weeks of her presentation, she developed acute renal failure and bilateral lower extremity edema. A computed tomography scan of her abdomen and pelvis showed bulky lymphadenopathy and hydronephrosis; a pelvic lymph node biopsy revealed metastatic breast cancer. She was initially managed with passive rewarming strategies, topical antibiotics, vasodilator and anti-platelet therapy, but had a negligible response. However, once she was started on chemotherapy for her recurrent malignancy, there was a significant improvement in her Raynaud’s symptoms and resolution of her digital ulcers.     

Successful high-titer immunoglobulin therapy for persistent parvovirus B19 infection in a lymphoma patient treated with rituximab-combined chemotherapy

A 40-year-old female diagnosed with follicular lymphoma was treated with rituximab-combined chemotherapy. Although she achieved complete remission, she developed progressive anemia and reticulocytopenia. Bone marrow examination revealed features of pure red cell aplasia and hemophagocytosis. In addition, the appearance of large pronormoblasts suggested that she was infected with parvovirus B19. Excess viral DNA in her bone marrow confirmed that her illness was caused by persistent parvovirus B19 infection. Serum immunoglobulin levels decreased beyond the lower normal limit, which indicated that her humoral immunity was impaired after rituximab-combined chemotherapy. Although she had been infected with parvovirus B19, she was re-infected and failed to control the viral expansion. High-titer immunoglobulin against parvovirus B19 was intravenously administrated and resulted in remarkable reticulocytosis and improvement of anemia. High-titer immunoglobulin, which contained a sufficient amount of neutralizing antibodies against parvovirus B19, likely inactivated most viruses in vivo. We successfully eradicated the virus after 2 courses of high-dose therapy at 0.5 g/kg/day every week followed by 8 courses of maintenance therapy at 0.1 g/kg/day every other week. It is important to consider that parvovirus B19 infection is a possible cause of progressive anemia in B-cell lymphoma patients treated with rituximab-combined chemotherapy. We propose that the use of high-titer immunoglobulin against parvovirus B19 may enable such immunocompromised patients to eradicate the virus before sufficient immune system reconstruction.     

Skin lesion in a patient after hematopoietic stem cell transplant

We present a case of a 61‐year‐old Caucasian woman who was hospitalized with fever on day 176 after a matched unrelated stem cell transplant for acute myelogenous leukemia. She developed hemorrhagic bullae on the skin of her right thigh, and both blood cultures and skin biopsy confirmed Fusarium proliferatum. Despite antifungal therapy, her condition worsened and she died while on comfort‐only measures.     

Mucormycosis: its contemporary face and management strategies

Several countries have seen rising frequencies of mucormycosis among patients with haematological disorders, malignancies, or diabetes mellitus, and among transplant recipients. Growing numbers of immunocompromised hosts, widespread use of antifungal agents inactive against mucormycosis, or other unidentified factors, could be contributing to this situation. The predominant clinical manifestations of mucormycosis vary from host to host. Additionally, risk factors specific to different subgroups have been identified, such as leukaemia, allogeneic haemopoietic stem-cell transplant, voriconazole prophylaxis, diabetes, and malnutrition. We summarise the current state of knowledge of characteristics and risk factors and discuss topical developments in therapeutic methods and strategies in the management of mucormycosis.     

Porphyria cutanea tarda in a patient with acute leukemia

A 20-year-old woman with acute nonlymphocytic leukemia in remission was treated postremission with intermittent courses of intensive chemotherapy. She required blood and platelet transfusions following therapy, and oral contraceptives were used to suppress her menses while she was thrombocytopenic. One and one-half years after treatment began, she developed blisters on her hands, hypertrichosis, and dark urine. The diagnosis of porphyria cutanea tarda was made. This report discusses the possible precipitating cause(s) and the subsequent treatment of both her porphyria and her leukemia.     

Une opacité pulmonaire excavée chez un diabétique

Mucormycosis or zygomycosis is a group of infections caused by filamentous fungi of the mucorales order belonging to the zygomycetes family. They generally appear in patients with uncontrolled diabetes or immunodepression, especially neutropenic immunodepression. Incidence has increased with progress in immunosuppressive therapy and chemotherapy and the absence of the use of antifungal prophylactic agents effective against mucors.We report the case of a diabetic patient presenting with an excavated opacity in the right lung which failed to improve after receiving non-specific antibiotic treatment. Direct examination of the bronchial washing specimen led to the diagnosis of pulmonary mucormycosis. Prognosis depends mainly on early diagnosis, enabling appropriate treatment with amphotericin B. Mortality remains high, around 80%; diagnosis is commonly established post-mortem.     

Minor outbreak of Tuberculosis infection in a junior high school--infection from a preventable case

A second-year junior high school student (14 years old) was diagnosed as pulmonary tuberculosis. She was a member of the volleyball club in the school. She complained a high fever of 39 degrees at first on September 13, 2001. She visited a local physician and was administered medicine for a cold. On September 18, she was seen again for cough and fever, and informed the physician that her father was under treatment for pulmonary tuberculosis since June 2000. As a result, she was examined by chest X-ray, and was diagnosed as pulmonary tuberculosis with moderately positive smear and she was referred to hospital "N" where she was admitted on the next day. Three days after admission, a smear specimen of her sputum was heavily positive for tuberculosis bacilli. She had not been given any preventive chemotherapy when her father was diagnosed with TB because the results of her tuberculin skin test performed two months after her father's onset did not meet the criteria for preventive chemotherapy. Restriction fragment length polymorphism (RFLP) was carried out with 2 strains of tuberculosis bacillus isolated from her and her father, and the RFLP pattern of both strains was same. Thus, it can be concluded that the patient was infected from her father and developed pulmonary tuberculosis. A contact survey was subsequently carried out on October 4, 2001 for 107 students and 20 teachers at the school. None of the subjects examined showed any abnormalities on their chest X-ray. A tuberculin skin test survey of 105 students and one teacher was also carried out on November 12, 2001, about 2 months after the final contact. The diameter of skin reactions revealed a monomodal distribution pattern in subjects. The results of the present tuberculin skin test were verified with respect to the degree of contact and last tuberculin test in routine health examination at the school. Four students who had close contact with the patient evidently and showed a strong positive skin reaction of more than 30 mm in diameter in the present tuberculin skin test, accompanied by enhanced reaction of more than 20 mm compared with the last tuberculin skin test, were administered preventive chemotherapy.     

Disseminated fusarial infection in the immunocompromised host

A report of the species Fusarium proliferatum causing systemic infection in a child with acute lymphoblastic leukemia is presented, with a review of the clinical and laboratory features relating to outcome in disseminated fusarial infections. Thirteen cases of disseminated infection due to Fusarium species have been reported, all but one of which were fatal. Hematologic malignancy is the commonest underlying illness. The frequent occurrence of multiple skin lesions, orbitofacial involvement, and fungemia is in contrast to the otherwise similar disseminated aspergillosis or mucormycosis. Fungemia in disseminated fusariosis may reflect a capacity for invasion of intravascular catheters by Fusarium species. Fusarium isolates from disseminated infections are variably sensitive to amphotericin B, ketoconazole, and miconazole and uniformly resistant to 5-fluorocytosine. The correlation between antifungal susceptibility status and clinical outcome is poor, reflecting problems in susceptibility testing, marginally effective chemotherapy, and serious impairment of host defenses. Attention to early diagnosis and the care of indwelling prosthetic devices may enhance survival until more effective chemotherapy is available.     

Diabetic ketoacidosis and rhino-orbital mucormycosis

Mucormycosis often develops in immunocompromised patients, particularly in patients with diabetic ketoacidosis. Unless early diagnosis and treatment is established mucormycosis leads rapidly to death. A 38-year-old woman was admitted to the hospital with a severe diabetic ketoacidosis. Her clinical status improved in 4 days as a result of aggressive medical treatment. She has complained left cheek pain on the 10th day and had a swelling of her left cheek, facial edema, a black eschar on the palate and nasal cavity in association with visual disturbance and total ophthalmology in a short time. CT scan revealed left orbital cellulitis and pansinusitis. Excessive surgical treatment was performed and liposomal amphotericin-B, 4 mg/(kg day) was applied. Extensive fungal invasion of the orbit and the sinuses was demonstrated in the pathological species and Rhizomucor species were yielded with culture. Repeated superficial debridement was also performed. After 10 weeks, she was discharged with suggestion of insulin treatment and liposomal amphotericin-B with progressively decreasing doses. At the 13th month following the presentation, the patient was free of disease as confirmed by serial imaging and under good glycaemic control with insulin treatment. Although mucormycosis is a fatal infection, early diagnosis and aggressive treatment may decrease mortality.     

A case of pulmonary mucormycosis diagnosed through video-assisted thoracoscopic surgery--report of a case]

We report a case of pulmonary mucormycosis successfully treated by medical methods only. The patient was a 51-year-old man with diabetes mellitus who presented with general fatigue and appetite loss. His chest radiograph and CT scan showed multiple thin-walled cavities in the left upper lobe. Because we could arrive at a clear diagnosis, video-assisted thoracoscopic surgery was performed. Lung biopsy of the left upper lobe revealed pulmonary mucormycosis. Our diagnosis was pulmonary mucormycosis with diabetes mellitus and alcohol addiction. The patient was treated with antifungal drugs--mainly amphotericin-B--while the diabetes mellitus was well controlled, and his diet and nutritional state was improved, resulting in the disappearance of symptoms, improvement of the radiological findings, and the absence of any relapse of the disease of at least 3 years.     

Rhinocerebral mucormycosis in four diabetics

Mucormycosis is caused by a zygomycetes fungus in a vascular location. This fungus is a saprophytic organism which can become pathogenic in specific conditions, particularly in patients with diabetes mellitus. A rhinocerebral localization is common, leading to often fatal devastating sinusitis. Positive diagnosis requires histological proof with characteristic hyphal tissue invasion. Frozen section is essential for diagnosis and management of rhinocerebral mucormycosis. MATERIAL AND METHODS: We report four cases of rhinocerebral mucormycosis in diabetic patients, two men and two women, mean age 51 years. RESULTS: Histological examination showed characteristic hyphae in a vascular localization. Treatment was systemic antifungal therapy with amphotericin B and debridement of necrotic tissue. Three patients recovered completely. One died. CONCLUSION: Rhinocerebral mucormycosis is a rare fungal infection with very poor prognosis. The aim of this study was to report the clinical and pathological features of rhinocerebral mucormycosis and to evaluate the contribution of frozen section for diagnosis and management.