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Renal invasive aspergilloma: Unusual infection in AIDS
Journal of Infection (1996) 33, 6 1 - 6 3
CASE REPORT
Renal Invasive Aspergilloma: Unusual Infection in AIDS I. Fiteni*, M a J. Crusells, J. Cuesta and S. Letona Division of Infectious Diseases, Department of Internal Medicine. Hospital Clinico Universitario of Zaragoza, Spain Accepted for publication 13 March 1 9 9 6
Invasive aspergillosis is a devastating i@ction that mainly affects immunocompromised hosts. Nevertheless it is not a common infection in AIDS p~vbably due to specific immune aspects. Even more rare in this group of patients is infection limited to the kidney without dissemination as occurred in our case reported here. He had heroin addiction, AIDS in advanced stage C3, neutropenia and received antifungal prophyllaxis as predisposing factors to aspergillosis. Despite correct therapy with Amphotericine B and drainage of one of the abscesses, he died due to antibiotic side-effects and persistence of not-drained contralateral abscess. Our experience supports the fact that we should have a high index of suspicion for funsal aetiology in kidney infection in AIDS patients with predisposing factors discussed in the text, in order to make earls diagnosis and to establish prompt aggressive antifungal therapy supported by drainage of fungus collections, or even nephrectom9 if required.
Introduction Isolated renal involvement by aspergillus is a very unusual disease which mostly develops in patients with a severe immunity disorder. 1'2 Nevertheless it is seldom diagnosed in AIDS, despite the underlying immune defect) In fact only two cases of such infection have been described in AIDS population to the best of our knowledge. 3'4 We report a new case of isolated renal aspergillosis in a patient with AIDS and its therapeutic challenge.
a 3 cm hypodense mass which destroyed p a r e n c h y m a and progressed to posterior left pararenal space with inflammation of perinephric fat. With suspicion of infectious pyelonephritis and perinephritis, empirical treatment was started with cefotaxime (8 g/day) and netilmicine (300 mg/day). The fever disappeared but pain remained. A new CT scan a week after showed an enlargement of the mass and a new one in the right kidney (Figure 1). In view of this progression, percutaneous needle aspiration was performed under US control. 10 cc of chocolate-coloured pus was drained from left renal mass. Right mass was not drained due to
Case Report The patient was a 29-year-old male intravenous drug user, known to have positive HIV serology for 4 years and diagnosed of AIDS after oesophagic candidiasis. Ten days before admission he began with right upper abdominal pain referred to the back and temperature of 39°C. On admission, abdominal examination revealed hepatomegaly spanning 4 cm as well as splenomegaly with tenderness over both costovertebral angles. Laboratory data revealed an haematocrit of 39%, haemoglobin of 13 g/d, white blood cells of 3.1 x 109/1 with 0.4 x 109/I lymphocytes with an absolute CD4 lymphocyte count of 70. Urinalysis was normal. Blood, faeces and urine cultures were repeatedly negative. Serology for different pathogens was negative. CT scan with endovenous contrast disclosed an enlarged left kidney with Address correspondence to: Isabel Fiteni. C/ Cesareo Alterta 22, 8 °, 50008 Zaragoza, Spain. O163-4453/96/040061 +03 $12.00/0
Figure 1. Abdominal CT scan showing a hypodense cystic mass in left kidney with posterior extension to left psoas muscle and a 4 cm mass in the right kidney displacing excretory system. © 1996 The British Society for the Study of Infection
62
I. Fiteni et al.
Figure 2. CT scan after left kidney drainage: disappearance of left abscess and persistence of the right one.
technical problems. After this procedure the pain almost disappeared. Culture of this substance yielded Aspergillus fumigatis with intermediate susceptibility to imidazoles and sensitive only to Amphotericin which was started with 1 m g / k g / d a y for 22 days. After a total dose of 1400 mg, response was satisfactory but the patient developed pancytopenia secondary to medication that precluded its further use. Maintenance therapy was then continued with fluconazol, despite its weak effectiveness. A new CT scan showed at this m o m e n t complete normalization of left kidney but persistence of a smaller right mass (Figure 2). TWo weeks after amphotericine interruption, fever reappeared with mental disability a n d several generalized seizures worsening his situation. He did not respond to antitoxoplasma therapy. Cerebral CT scan showed several round masses suggesting aspergillus broad dissemination. The patient died and necropsia was denied.
Discussion Different species of Aspergillus can cause h u m a n disease, but the most commonly involved is A. furnigatus. ~'2's Although the exposure to this fungus is worldwide, the development of the disease requires predisposing host conditions. It is actually a saprofite and only becomes a pathogen for m a n in certain conditions. Those situations include most of the weakening illnesses such as diabetes, alcoholism, tuberculosis, granulomatous diseases but it is mainly reported in patients with severe immunodepression situations such as organ transplant, steroid therapy, haematologic malignancies, chemotherapy or
broad spectrum antibiotics. 1-s Nevertheless the low incidence of this infection in patients with AIDS is surprising. This can be due to the selective T-cell involvement in AIDS with relative preservation of neutrophil and macrophage phagocytic function, principle agents with antifungal action whose defect m a y allow the development of aspergillosis usually with disseminated forms. In that way it has also been reported in AIDS with severe neutropenia and probably facilitated by drugs such as antiviral agents, steroids or broad-spectrum antibiotics) '4'7 The commonest form of aspergillosis is pulm o n a r y disease. 4 Renal aspergillomas are extremely unusual. 1-3 According to a literature review by Bibler 8 from 1962 to 1986, and by ourselves up until 1993, 23 cases of renal aspergillosis have been published. Renal parenchymal invasion is described in only three; the rest of the cases are located somewhere along the excretory system with obstructive clinical forms produced by fungus balls. To date only two cases of renal aspergillomas in patients with AIDS as invasive forms are reported, both were fatal despite treatment. 3'4 To the best of our knowledge, this is the third case of invasive renal aspergillosis in AIDS. Our patient was an intravenous drug abuser and was known to have stage C 3 HIV infection for 2 years. As predisposing factors he had severe neutropenia, low CD4 count, previous antibiotic prophyllaxis for PCP and antifungal therapy, in addition to HIV disease. Only the aspirate of the collection yielded the diagnosis after several studies and empirical treatments. Renal aspergillosis remains a therapeutic challenge, especially for its underlying immunosuppression background. Conventional treatment consists of IV amphotericin B at a dose between 0.5 and 0.6 mg/kg/day, that is a total course from 940 to 2500 mg. 3 Despite correct therapy, the mortality rate is still high in invasive forms. 3's's'9 Another drawback is bone m a r r o w toxicity which is frequent and cumulative dose-dependent. Good results have been lately reported with azoles such as itraconazole 7'9'mwith better outcome in pulmonary disease t h a n for other sites such as the kidney, 1° where drugs excreted in the urine m a y be more effective. 3's Nevertheless, high variability in serum itraconazole concentration among patients with AIDS has been reported and, together with the low susceptibility in our patient, was a drawback for its use. Our results support previous experience that emphasize the need of surgical drainage2'3; drained kidney showed normalization on CT scan but aspergilloma remained, despite thorough medical treatment for 22 days and maintenance therapy with fluconazole. Medical treatment alone was demonstrated to be unsatisfactory and this fatal case highlights the importance of drainage reinforced by indefnite secondary prophyllaxis after complete treatment
Renal Invasive Aspergilloma in these immunocompromised patients. Although it is extremely unusual, we must have a high index of suspicion and consider the possibility of invasive aspergillosis in patients with AIDS and predisposing factors as discussed above, ~in order to establish promptly the proper treatment and perform special techniques such as drainage or nephrectomy, if necessary.
4 5 6 7
References 1 Davies SP, Webb WJS, Patou G, Murray WK, Denning DW. Renal aspergiloma: a case illustrating the problems of medical therapy. Nephrol Dial Transplant 1987; 2: 568-572. 2 Chmel H, Grieco MH. Cerebral mucormycosis and renal aspergillosis in heroin addicts without endocarditis. Am J Med Sci 1973; 266: 225-231. 3 Kalpern M, Szabo S, Hochberg E et al. Renal aspergiloma: an unusual
8 9 10
63
cause of infection in a patient with the acquired inmunodeficiency syndrome. Am /Med 1992; 4: 437-440. Klapholz A, Salomon N, Perlman DC, Talavera W., Aspergillosis in the Acquired Immunodeficiency Syndrome. Chest 1991; 100: 1614-1618. Bennett JE. Species of Aspergillns. In: Mandell GL, Douglas RG, Bennett JE, Eds. Principles and practice of infectious diseases. New York: Churchill Livingstone Inc., 1990: 2072-2076. Melchior M, Mebust WK, Valk WL. Ureteral colic from a fungus ball: unusual presentation of systemic aspergillosis. J UroI 1972: 108: 698-699. Denning DW, Follansbee SE, Scolaro M, Norris S, Edelstein H, Stevens DA. Pulmonary aspergillosis in the acquired inmunodeficiency syndrome. N Engl J Med 1991', 324: 654-662. Bibler MR, Gianis JT. Acute ureteral colic from an obstructing renal aspergiloma. Rev hTfect Dis 1987; 9: 790-794. Denning DW, Tucker RM, Hanson LH, Stevens DA. Treatment of invasive aspergfllosis with itraconazole. Am J Med 1989; 86: 791-800. Hostetler JS, Denning DW, Stevens DA. US Experience with Itraconazole in Aspergillus, Cryptococcus and Histoplasma Infections in the Inmunocompromised Host. Chemotherapkl 1992; 38: 12-22.
CASE REPORT
Renal Invasive Aspergilloma: Unusual Infection in AIDS I. Fiteni*, M a J. Crusells, J. Cuesta and S. Letona Division of Infectious Diseases, Department of Internal Medicine. Hospital Clinico Universitario of Zaragoza, Spain Accepted for publication 13 March 1 9 9 6
Invasive aspergillosis is a devastating i@ction that mainly affects immunocompromised hosts. Nevertheless it is not a common infection in AIDS p~vbably due to specific immune aspects. Even more rare in this group of patients is infection limited to the kidney without dissemination as occurred in our case reported here. He had heroin addiction, AIDS in advanced stage C3, neutropenia and received antifungal prophyllaxis as predisposing factors to aspergillosis. Despite correct therapy with Amphotericine B and drainage of one of the abscesses, he died due to antibiotic side-effects and persistence of not-drained contralateral abscess. Our experience supports the fact that we should have a high index of suspicion for funsal aetiology in kidney infection in AIDS patients with predisposing factors discussed in the text, in order to make earls diagnosis and to establish prompt aggressive antifungal therapy supported by drainage of fungus collections, or even nephrectom9 if required.
Introduction Isolated renal involvement by aspergillus is a very unusual disease which mostly develops in patients with a severe immunity disorder. 1'2 Nevertheless it is seldom diagnosed in AIDS, despite the underlying immune defect) In fact only two cases of such infection have been described in AIDS population to the best of our knowledge. 3'4 We report a new case of isolated renal aspergillosis in a patient with AIDS and its therapeutic challenge.
a 3 cm hypodense mass which destroyed p a r e n c h y m a and progressed to posterior left pararenal space with inflammation of perinephric fat. With suspicion of infectious pyelonephritis and perinephritis, empirical treatment was started with cefotaxime (8 g/day) and netilmicine (300 mg/day). The fever disappeared but pain remained. A new CT scan a week after showed an enlargement of the mass and a new one in the right kidney (Figure 1). In view of this progression, percutaneous needle aspiration was performed under US control. 10 cc of chocolate-coloured pus was drained from left renal mass. Right mass was not drained due to
Case Report The patient was a 29-year-old male intravenous drug user, known to have positive HIV serology for 4 years and diagnosed of AIDS after oesophagic candidiasis. Ten days before admission he began with right upper abdominal pain referred to the back and temperature of 39°C. On admission, abdominal examination revealed hepatomegaly spanning 4 cm as well as splenomegaly with tenderness over both costovertebral angles. Laboratory data revealed an haematocrit of 39%, haemoglobin of 13 g/d, white blood cells of 3.1 x 109/1 with 0.4 x 109/I lymphocytes with an absolute CD4 lymphocyte count of 70. Urinalysis was normal. Blood, faeces and urine cultures were repeatedly negative. Serology for different pathogens was negative. CT scan with endovenous contrast disclosed an enlarged left kidney with Address correspondence to: Isabel Fiteni. C/ Cesareo Alterta 22, 8 °, 50008 Zaragoza, Spain. O163-4453/96/040061 +03 $12.00/0
Figure 1. Abdominal CT scan showing a hypodense cystic mass in left kidney with posterior extension to left psoas muscle and a 4 cm mass in the right kidney displacing excretory system. © 1996 The British Society for the Study of Infection
62
I. Fiteni et al.
Figure 2. CT scan after left kidney drainage: disappearance of left abscess and persistence of the right one.
technical problems. After this procedure the pain almost disappeared. Culture of this substance yielded Aspergillus fumigatis with intermediate susceptibility to imidazoles and sensitive only to Amphotericin which was started with 1 m g / k g / d a y for 22 days. After a total dose of 1400 mg, response was satisfactory but the patient developed pancytopenia secondary to medication that precluded its further use. Maintenance therapy was then continued with fluconazol, despite its weak effectiveness. A new CT scan showed at this m o m e n t complete normalization of left kidney but persistence of a smaller right mass (Figure 2). TWo weeks after amphotericine interruption, fever reappeared with mental disability a n d several generalized seizures worsening his situation. He did not respond to antitoxoplasma therapy. Cerebral CT scan showed several round masses suggesting aspergillus broad dissemination. The patient died and necropsia was denied.
Discussion Different species of Aspergillus can cause h u m a n disease, but the most commonly involved is A. furnigatus. ~'2's Although the exposure to this fungus is worldwide, the development of the disease requires predisposing host conditions. It is actually a saprofite and only becomes a pathogen for m a n in certain conditions. Those situations include most of the weakening illnesses such as diabetes, alcoholism, tuberculosis, granulomatous diseases but it is mainly reported in patients with severe immunodepression situations such as organ transplant, steroid therapy, haematologic malignancies, chemotherapy or
broad spectrum antibiotics. 1-s Nevertheless the low incidence of this infection in patients with AIDS is surprising. This can be due to the selective T-cell involvement in AIDS with relative preservation of neutrophil and macrophage phagocytic function, principle agents with antifungal action whose defect m a y allow the development of aspergillosis usually with disseminated forms. In that way it has also been reported in AIDS with severe neutropenia and probably facilitated by drugs such as antiviral agents, steroids or broad-spectrum antibiotics) '4'7 The commonest form of aspergillosis is pulm o n a r y disease. 4 Renal aspergillomas are extremely unusual. 1-3 According to a literature review by Bibler 8 from 1962 to 1986, and by ourselves up until 1993, 23 cases of renal aspergillosis have been published. Renal parenchymal invasion is described in only three; the rest of the cases are located somewhere along the excretory system with obstructive clinical forms produced by fungus balls. To date only two cases of renal aspergillomas in patients with AIDS as invasive forms are reported, both were fatal despite treatment. 3'4 To the best of our knowledge, this is the third case of invasive renal aspergillosis in AIDS. Our patient was an intravenous drug abuser and was known to have stage C 3 HIV infection for 2 years. As predisposing factors he had severe neutropenia, low CD4 count, previous antibiotic prophyllaxis for PCP and antifungal therapy, in addition to HIV disease. Only the aspirate of the collection yielded the diagnosis after several studies and empirical treatments. Renal aspergillosis remains a therapeutic challenge, especially for its underlying immunosuppression background. Conventional treatment consists of IV amphotericin B at a dose between 0.5 and 0.6 mg/kg/day, that is a total course from 940 to 2500 mg. 3 Despite correct therapy, the mortality rate is still high in invasive forms. 3's's'9 Another drawback is bone m a r r o w toxicity which is frequent and cumulative dose-dependent. Good results have been lately reported with azoles such as itraconazole 7'9'mwith better outcome in pulmonary disease t h a n for other sites such as the kidney, 1° where drugs excreted in the urine m a y be more effective. 3's Nevertheless, high variability in serum itraconazole concentration among patients with AIDS has been reported and, together with the low susceptibility in our patient, was a drawback for its use. Our results support previous experience that emphasize the need of surgical drainage2'3; drained kidney showed normalization on CT scan but aspergilloma remained, despite thorough medical treatment for 22 days and maintenance therapy with fluconazole. Medical treatment alone was demonstrated to be unsatisfactory and this fatal case highlights the importance of drainage reinforced by indefnite secondary prophyllaxis after complete treatment
Renal Invasive Aspergilloma in these immunocompromised patients. Although it is extremely unusual, we must have a high index of suspicion and consider the possibility of invasive aspergillosis in patients with AIDS and predisposing factors as discussed above, ~in order to establish promptly the proper treatment and perform special techniques such as drainage or nephrectomy, if necessary.
4 5 6 7
References 1 Davies SP, Webb WJS, Patou G, Murray WK, Denning DW. Renal aspergiloma: a case illustrating the problems of medical therapy. Nephrol Dial Transplant 1987; 2: 568-572. 2 Chmel H, Grieco MH. Cerebral mucormycosis and renal aspergillosis in heroin addicts without endocarditis. Am J Med Sci 1973; 266: 225-231. 3 Kalpern M, Szabo S, Hochberg E et al. Renal aspergiloma: an unusual
8 9 10
63
cause of infection in a patient with the acquired inmunodeficiency syndrome. Am /Med 1992; 4: 437-440. Klapholz A, Salomon N, Perlman DC, Talavera W., Aspergillosis in the Acquired Immunodeficiency Syndrome. Chest 1991; 100: 1614-1618. Bennett JE. Species of Aspergillns. In: Mandell GL, Douglas RG, Bennett JE, Eds. Principles and practice of infectious diseases. New York: Churchill Livingstone Inc., 1990: 2072-2076. Melchior M, Mebust WK, Valk WL. Ureteral colic from a fungus ball: unusual presentation of systemic aspergillosis. J UroI 1972: 108: 698-699. Denning DW, Follansbee SE, Scolaro M, Norris S, Edelstein H, Stevens DA. Pulmonary aspergillosis in the acquired inmunodeficiency syndrome. N Engl J Med 1991', 324: 654-662. Bibler MR, Gianis JT. Acute ureteral colic from an obstructing renal aspergiloma. Rev hTfect Dis 1987; 9: 790-794. Denning DW, Tucker RM, Hanson LH, Stevens DA. Treatment of invasive aspergfllosis with itraconazole. Am J Med 1989; 86: 791-800. Hostetler JS, Denning DW, Stevens DA. US Experience with Itraconazole in Aspergillus, Cryptococcus and Histoplasma Infections in the Inmunocompromised Host. Chemotherapkl 1992; 38: 12-22.