524 Notes Eur. J. Clin. Microbiol. Infect. Dis. Case Report. In October 1992, a 26-year-old Catheter-Related Cutaneous female intravenous drug addict diagnosed as HIV positive in 1986 was admitted to our institute. She Aspergillosis Complicated by presented with fever, weight loss, oropharyngeal Fungemia and Fatal Pulmonary candidiasis, anemia, marked thrombocytopenia, high serum lactate dehydrogenase levels and a Infection in an HIV-Positive pelvic mass with a diameter of 13 x 10 cm. The di- Patient with Acute agnosis of ALL was made on the basis of morpho- logical and immunophenotypic features of bone Lymphocytic Leukemia marrow needle aspirate and bilateral lilac poste- rior crest biopsy. At the time of diagnosis, micro- biological, virological and clinical findings were C. Girmenia, R. Gastaldi, P. Martino* negative for the presence of C1-CDC opportunis- tic infections (8), and the absolute CD4+ lympho- cyte count was 145/mm 3. There was no detectable HIV p24 serum antigenemia. A central venous A case of intravenous catheter-related cutaneous catheter (Groshong catheter placed through a aspergillosis and Aspergitlus fumigatus fungemia subcutaneous tunnel) was inserted before initia- in an HIV-positive patient with Burkitt-cell acute tion of an aggressive chemotherapy (from 27 Oc- lymphocytic leukemia is reported. The patient tober to I February) according to the BFM-NHL developed pulmonary aspergillosis with a rapidly 83 protocol (9). During chemotherapy, steroids, fatal outcome despite recovery from neutropenia parenteral nutrition, oral methadone and an- and improvement of the underlying malignancy. timicrobiat prophylaxis with fluconazole, The unusual severity and rapid spread of the infec- trimethoprim-sulfamethoxazole and acyclovir tion, despite normal neutrophil count and prompt were also administered. The patient experienced antifungal therapy, suggest that HIV-related three febrile episodes of unidentified origin immunocompromise might play a role in the impair- during the post-chemotherapy neutropenic peri- ment of host defenees against Aspergillus infec- ods, all of which responded to empiric broad- tion. Thus catheter-related cutaneous aspergillosis spectrum antibacterial treatment. could lead to a severe deep-seated infection in HIV- positive patients. On 22 February, the patient developed fever with an indurated erythema (without skin necrosis) at the catheter exit site. A chest radiograph per- formed two days later showed a nodular pulmo- Invasive aspergiltosis, once rather infrequent in nary lesion at the upper right lung field. Multiple AIDS patients, has recently emerged as a consid- blood cultures taken from the catheter grew erable clinical problem. Use of corticosteroids, Aspergillus furnigatus, whereas four peripheral neutropenia, hematological malignancy, pneu- blood cultures were negative. Leukocyte count monia due to other pathogens, marijuana smok- was 3,660/mm 3 with 3,140 neutrophils and 180 ing or the use of broad-spectrum antibiotics are lymphocytes. The absolute CD4+ cell count was predisposing factors (1-6). The role of cytome- 24/mm 3, with no HIV p24 antigenemia. Treat- galovirus infection as cofactor in invasive asper- ment with itraconazole (200 mg/day) was started gillosis is the subject of debate (1-3). but, due to persistence of fever and positive blood On the other hand, data from clinical and in vitro cultures, the catheter was removed. Aspergillus studies suggest that HIVorelated immunosup- fumigatus was isolated from the catheter tip as pression may by itself predispose to invasive well as from a purulent secretion from the cathe" aspergillosis (6-7). We report a case of primary ter exit site. Following removal of the catheter, cutaneous infection caused by Aspergitlus fumi- fever disappeared, blood cultures became negative gatus and fungemia associated with a central and cutaneous infection progressively improved. venous catheter followed by a fatal pulmonary in- A bone marrow needle aspirate and bilateral iliaC fection in an HIV-positive patient with Burkitt- posterior crest biopsy showed complete remis- celt acute lymphocytic leukemia (ALL). sion of the underlying malignancy and echo- graphic examination showed a greater than 80 % reduction in the size of the pelvic mass. Section of Haematology, Department of Human Bio- pathology, University La Sapienza, Via Benevento 6, 00161 On 19 March, two small cavitary lesions (pseudo- Rome, Italy. mycetomas) were seen in the upper right lung Vol. 14, 1995 Notes 525 field on chest radiograph and CT scan. Thus, itra- In immunosuppressed patients with aspergillosis, Conazole administration was replaced by in- the respiratory tract is the almost exclusive site of travenous amphotericin B (1 mg/kg/day). On the entry. Skin and subcutaneous tissue are only same day, cytomegalovirus viremia was detected rarely involved as either the primary or secondary by shell vial culture. Despite antifungal treat- focus of invasive aspergillosis. However, primary ment, the cavitary lesions increased in size and cutaneous aspergillosis may occur at the site of Small new lesions appeared on a chest radiograph the intravenous catheter, which could be the por- of both lung fields. Sputum culture yielded Asper- tal of entry of a deep-seated infection with a poor gillus fumigatus. On 1 April, the patient reported outcome in severely immunocompromised bilateral chest pain. Subcutaneous emphysema of patients, particularly those with neutropenia (16). the neck with crepitus was observed. A CT scan In the present case, the exit site of the central showed bilateral pneumothorax and a small venous catheter was presumably the primary pneumomediastinum with emphysema of the soft source of the infection. Despite the patient's re- tissues of the neck. Pneumothorax and pneumo- covery from neutropenia, the cutaneous infection mediastinum spontaneously resolved, while sub- was complicated by fungemia and fatal pulmo- Cutaneous emphysema resolved on insertion of nary infection with pneumomediastinum and skin needles. However, the patient's general con- pneumothorax, a well-known late complication dition progressively deteriorated, with respira- of pulmonary aspergillosis (17). tory failure and development of new pulmonary Our patient developed an unusually severe and lesions, The patient was then discharged to un- rapidly spreading pulmonary aspergillosis, dergo a treatment regimen at home, where she despite normal neutrophil count and prompt anti- died a few days later. fungal therapy. It seems reasonable to assume that HIV-related immunocompromise with a low Discussion. Despite the severe CD4+ cell deple- CD4+ lymphocyte count played an important tion seen in patients with AIDS, invasive aspergil- role in the impairment of the host defences losis is very uncommon unless other well-known against the Aspergillus infection, adding to the risk factors for the development of this disease immunocompromise due to the underlying malig- are also present. In particular, neutropenia, nancy, previous neutropenia and steroid therapy. corticosteroids and broad-spectrum antibiotic We conclude that primary cutaneous aspergillosis therapy have traditionally been recognized as risk occurring at the exit site of intravenous catheters factors for the development of invasive aspergil- could be a serious complication in HIV-positive Iosis (1-6). Denning et al. (1) cited infection with patients with hematological malignancies, as it cytomegalovirus as a risk factor for aspergillosis, can lead to a fatal, deep-seated infection. The in- but this association was not considered relevant fection requires early diagnosis, early catheter re- by other authors, as the effects of cytome- moval and prompt treatment with amphotericin galovirus in promoting fungal infection have been B, even in non-neutropenic patients. documented only in animal models (2, 3). Inter- estingly, cytomegalovirus viremia was docu- mented at the time of the' fungal infection in our Acknowledgement patient, however, no definite conclusion can be drawn from this finding. Data from clinical and The study was supported by the Progetto Finalizzato ACRO CNR Italy. Applicazioni Cliniche nella Ricerca laboratory investigations suggest that the immu- Oncologica (Unit P. Martino) No. 92.02219.39. nosuppression caused by HIV infection itself Could have a role in the increased predisposition to the fungal disease and/or the severity of the in- References fection. Lortholary et al. (6) reported that ap- proximately 50 % of the patients in their study 1. Denning DW, Follansbee SE, Scolaro M, Norris S, did not exhibit any classic risk factors and that al- Edelstein H, Stevens DA: Pulmonary aspergillosis in the acquired immunodeficiency syndrome. New England most all patients had a CD4+ cell count of less Journal of Medicine 1991, 324: 654-662. !han 50/ram 3. Lymphopenia related to other viral 2. Schaffner A: Pulmonary aspergillosis in AIDS. New Eng- !nfections has been reported to predispose to land Journal of Medicine 1991, 325: 355-356. mvasive infection with Aspergillus (10, 11). De- 3. Stevens DA, Denning DW: Pulmonary aspergillosis in fective in vitro functions of the monocyte/macro- AIDS. New England Journal of Medicine 1991,325: 356- 357. Phage system and neutrophils of HIV-positive 4. Minamoto GY, Barlam TF, Vender Els NJ: tnvasive asper- Patients would predispose to invasive aspergillo- gillosis in patients with AIDS. Clinical Infectious Diseases sis (7, 12-15). 1992, 14: 66-74. 526 Notes Eur. J. Clin. Microbiol. Infect. Dis. 5. Pursell