Disseminated
Pulmonary Aspergillosis in a Previously Healthy Adolescent Sarmistha B. Hauger M.D.
Introduction isseminated
pulmonary
t aspergillosis has been well-described in the clinical setting of known immunowith compromised patients and hematologic lymphoreticular
malignancies, leukopenia, or prolonged antibiotic or corticosteroid therapy. In addition, this condition has been described in a few healthy adults and children.l~ The following is a case report of disseminated aspergillosis in a previously healthy adolescent in whom no predisposing condition for immunocompromise could be identified.
Case Report A 14-year-old male presented to the pediatric emergency room with a 10-day history of intermittent fevers to 103°F, myalgia, diffuse abdominal pain, malaise, and bilateral conjunctivitis. Four days before admission, he had been examined in the pediatric emergency room for bronchospasm. He was discharged with a diagnosis of asthma exacerbation and placed on oral bronchodilator therapy. He returned one day prior to ad-
mission with continued complaints of abdominal pain; a chest roentgenogram revealed an infiltrate in the right lung. The patient was sent home on oral erythromycin therapy for a presumptive diagnosis of
Mycoplasma pneumoniae nia. He returned
pneumo-
the
following day with continued complaints and diminished oral intake. On physion
cal exam, he was found to be afebrile, thin, and in no acute distress. Significant physical findings included orthostatis on blood pressure bilateral measurement, palpebral and bulbar conjunctival infection, decreased bilateral breath sounds with rales and wheezing on lung auscultation, and diffuse abdominal pain with voluntary guarding without rebound. There was no evidence of lymphadenopathy, hepatosplenomegaly, skin findings, or focal neurological findings. The patient had a past history of atopy and asthma requiring intermittent bronchodilator therapy; he had no history of systemic corticosteroid or drug use, homosexual encounters, or serious previous infection. His family history was non-
contributory. Laboratory data included a complete blood count (CBC) with a peripheral white blood cell (WBC) count of 3,200/cu mm (59% neutro-
Address correspondence to: Sarmistha B. Hauger M. D., Assistant Professor of Clinical Pediatrics, Division of Pediatric Infectious Disease, Department of Pediatrics, Columbia University, College of Physicians and Surgeons, 622 W. 168th Street, VC 4402, New York, NY 10032. (212) 305-7573
phils, 3% banded neutrophils, 25% lymphocytes, 5% atypical lymphocytes, 8% monocytes), a hematocrit of 43.3%, and a platelet count of
290,000/cu mm. The fell to 1,900/cu mm
count
subsequent
CBC with
an
WBC on a
absolute
Downloaded from cpj.sagepub.com at Purdue University on May 23, 2015
neutrophil count of 1,258/cu mm. Serum analysis revealed the following: SGOT: 62 U/L (nl: 10-50 U/L), SGPT 40 U/L (nl:10-50 U/L) , LDH 356 U/L (nl: 90-200 U/L), CPK 208 U/L (nl:
1-50 U/L), total bilirubin 0.4 mg/dL with direct fraction 0.2 mg/dL, serum amylase 174 IU/L (nl: 5-81 IU/L), lipase 33 IU/L (nl: 14-24 IU/L). Uri-
nalysis was significant only for trace proteinuria, and 25-40 RBC/hpf. The patient was admitted with a presumptive diagnosis of systemic illness secondary to Mycoplasma or viral infection. He was managed with intravenous fluids for hydration and oral tetracycline. A diagnostic evaluation included blood, stool, and urine culture ; nasopharynx, eye, and rectal viral cultures; and Mycoplasma complement-fixation test. During the first week of hospitalization, he had a daily temperature elevation above 101°F. His complaints and physical findings remained unchanged. Tetracycline was discontinued after 10 days. Complete blood count revealed the absolute neutrophil count had fallen to 600/cu mm; a PPD and DT control were both negative. All sputum, blood, stool, and urine bacterial cultures as well as nasopharynx, eye, and rectal viral cultures remained negative. An ophthalmoexamination revealed logic bilateral conjunctivitis with no evidence of uveitis. Ten days after admission, the patient had lost 5.3 kg; his complaints continued. Further diagnostic evaluation included repeat chest roentgeno-
187
gram with
findings
of bilateral in-
filtrates, normal abdominal roentgenogram, abdominal ultrasound, sinus roentgenogram, and intrave-
nic, and his clinical
course
pro-
gressed over four weeks to a dissem-
ulant was equivocal. An ANA test was
inated death.
infection and eventual During this time, the pro-
pyelogram. Serologic testing hepatitis A and B, Epstein-Barr virus, syphilis, brucel-
positive
at 1:160; anti-DNA antibody and LE prep tests were negative. A CH5o assay was normal. An HIV an-
gressive pneumonia was refractory to conventional therapy. The diagnosis of Aspergillus infection was es-
losis, and rickettsial infection
tibody test was negative. The patient’s coagulopathy was corrected with cryoprecipitate and fresh-frozen plasma infusions, and on the 19th day of hospitalization, the patient underwent an openlung biopsy. The pathology report revealed panarteritis and evidence of invasive fungal organisms, with multiple sections of obliterative and necrotizing pneumonitis. No eosinophilic infiltrates or cavitary lesions were seen. The patient was begun on intravenous amphoteri-
tablished
nous
for mycoplasma,
was
negative. Serum immunoglobulin concentrations were IgG 1,260
mg/dL (nl: 700-1,700), IgA 219 mg/dL (nl: 70-350), IgM 135 mg/dL (nl: 50-300), and IgE 474 mg/dL . Serum lymphocyte enumeration was interpreted as generalized lymphocytic depletion, with normal T4/T8 ratio. Total lymphocyte count was 650/cu mm; total T4 count, 195/cu mm. An NBT test normal. The patient’s serum concentration continued to rise; urinalysis continued to reveal hematuria and proteinuria. A bone marrow aspirate demonwas
amylase
strated normal precursors with no evidence of either malignant or infiltrative process. Bone marrow and sputum smears were negative for acid-fast bacilli. Two weeks after admission, the patient’s temperature curve had risen to daily fever up to 103° F; he continued to complain of diffuse
myalgia and chest and abdominal pain. He began to have respiratory distress with nasal flaring; an arterial blood gas a
on room
air revealed
pH of’7.54, p02of 75, pC02 of 25,
and 02 saturation of 95%. A chest roentgenogram revealed worsening infiltrates with possible cavitation on the right side. Chest CT scan revealed bilateral parenchymal nodular pulmonary lesions at the bases and periphery of the lung fields. The patient was empirically started on oral isoniazid 300 mg/day and rifampin 600 mg/day. A gallium scan revealed diffuse uptake in the lungs and abdomen. In
preparation for a diagnostic openlung biopsy, the patient was found to have evidence of prolonged bleed-
188
ing time, disseminated intravascular coagulopathy, and thrombocytopenia. A test for lupus-like anticoag-
cin B. Over the next two
weeks, he
had
progressive multisystem failure, with refractory coagulopathy, seizures, renal failure requiring dialysis, and pulmonary failure requiring mechanical ventilation. An ophthalmologic exam revealed cotton-wool spots in both retinas. Massive pulmonary hemorrhage precipitated recurring cardiac arrests. Despite maximum cardiovascular pressor and ventilatory support, the patient expired on the 32nd day of hospitalization. Lung tissue grew Aspergillus fumigatus. An autopsy revealed disseminated aspergillosis with multiple abscesses in lungs, adrenals, kidneys, heart, thyroid, lymph nodes, and brain. There was evidence of necrotizing vasculitis with thrombosis in the lung and brain. No granuloma formation was identified.
Discussion This
patient presented with a presumed viral illness characterized by fever, myalgias, conjunctivitis, and pneumonia. He was found to be lymphopenic and neutrope-
Downloaded from cpj.sagepub.com at Purdue University on May 23, 2015
specimens
from
pathology
of
lung tissue when he critically ill for over two
had been weeks. At postmortem examination, he had evidence of multiple abscess formation in virtually every organ. Aspergillus infection is acquired of spores, after which inhalation by several distinct clinical syndromes may arise in humans. These include
saprophytic bronchopulmonary aspergillosis (colonization), aspergilloma (mycetoma), hypersensitivity-induced aspergilloses, and invasive aspergillosis. Neutrophils and macrophages appear to be most important in the body’s defense against Aspergillus infections. Diseases and drugs that depress either the number and or the function of these cells predispose the patient to invasive disease.5 Several cases of invasive pulmonary aspergillosis have been described as occuring in patients following infection with influenza virus; many of these patients were lymphopenic. Influenza is also known to cause transient anergy and a decrease in circulating T cells.6 This patient had evidence of both neutrophil and lymphocyte compromise during his hospitalization. He became profoundly
neutropenic, although an NBT test normal. Quantitative and qualitative T-cell dysfunction was docu-
was
as he had a decrease in absolute counts and percentages as well as documented intradermal skin test anergy. The pathology specimens were characteristic of invasive aspergillosis commonly seen in immunocompromised patients in that massive tissue and vascular invasion with infarction
mented,
was
predominant
and
no
granu-
loma formation could be demonstrated.’ However, no infection or condition could be identified as a cause for either his neutropenia or his lymphopenia. Given his initial presentation, the presumption is that he had a viral infection which led to immunocompromise and invasive aspergillosis. Previous reports of disseminated aspergillosis in normal hosts have been associated with the use of prolonged broad-spectrum antibiotics.’ This patient had received
only 12 days of therapy with either erythromycin or tetracycline. It is doubtful that this length of antibiotic therapy would predispose him to disseminated aspergillosis. A provocative question in this patient’s history is his long-standing history of asthma and a markedly elevated IgE level. Aspergillus sp. have a considerable potential to act as potent allergens in the human respiratory tract. Three different syndromes have been deextrinsic scribed, including asthma, extrinsic allergic alveolitis, and allergic bronchopulmonary aspergillosis. Extrinsic asthma is related to the inhalation of aspergillus spores, resulting in the release of mediators from mast cells, which are fixed with aspergillus-directed IgE antibodies. Fever and pulmonary infiltrates are not usually associated with this entity. The other two
hypersensitivity syndromes
are
both associated with fever, pulmonary infiltrates, elevated levels of precipitating IgG and IgE antibodies, and an actual superficial infection with the fungus, along with the
potential for sequelae of irreversible lung-tissue damage.77 Another mode of acquisition of Aspergillus infection is via use of contaminated materials. Aspergillus has been identified in street marijuana, commercial cigarettes, and pipe tobaccos. In addition, several
cases of invasive and pulmonary aspergillosis have been described in immunocompromised patients who
have smoked contaminated marijuana.8°9 This patient denied any
smoking history. A major obstacle in the management of this illness is the difficulty in establishing the diagnosis. The organism is infrequently cultured from the respiratory tract.3 Even when the organism is demonstrated in pathological specimens, it is successfully cultured only in about 40% of cases. Serologic diagnosis has yielded varying results, since immunoprecipitation, immuno-
Acknowledgment The author would like to thank Dr. Anne Gershon for her thoughtful comments and review of this paper.
~Er~NCEs 1.
2.
3.
prognosis of invasive asper-
gillosis is dismal. This is due in part to the difficulty in making the diagnosis. Estimated mortality rate is approximately 91 %; even among patients who receive amphotericin B, survival rate is only 22%.3 More data suggest that combination therapy with amphotericin B and 5-flucytosine may lower mortality in neutropenic patients, although relapse is common.10,11 Itraconazole, a member of the azole family of antifungal agents, recent
promising as therapy in Aspergillus infections. This agent has good bioavailability when administered orally and has few toxic
4.
5.
6.
7.
Downloaded from cpj.sagepub.com at Purdue University on May 23, 2015
209:1191-1195. Roselle GA, Kauffman CA. Invasive pulmonary aspergillosis in a nonSci. 1978;276:357-361. Hillerdal G, Benson L, Lindgren A, et al. Fatal disseminated aspergillosis in a previously well young woman. Scand J
Infect Dis. 1984;16: 217-222. Bodey GP, Vartivarian S. Aspergillosis. EurJ Clin Microbiol Infect Dis. 1989 :413437. Lewis M, Kallenbach J, Ruff P, et al. Invasive pulmonary aspergillosis complicating influenza A pneumonia in the previously healthy patient. Chest.
1985;87:691-693. Pennington JE. Aspergillus lung disease. Med 1980;64:475-490. Clin North Am.
8.
Kurup VP, Resnick A, Kagen SL, et al. Allergenic fungi and actinomycetes in smoking materials and their health implications. Mycopatholgia. 1983;82:61-64.
9.
Sutton S, Lum BL, Torti FM. Possible risk of invasive pulmonary aspergillosis
appears
effects. It has been found to be active in vitro against several species of Aspergillus; an in vivo animal model has revealed it to have greater activity than ketoconazole. 12 Recent reports of the use of itraconazole for the treatment of invasive Aspergillus infection in immunocompromised hosts have noted favorable results.13 Further studies will be needed to determine its potential as an alternative therapy for aspergillosis.
aspergillosis in nonimmunocompromised, nonneutropenic hosts. Rev Infect Dis. 1986;8:357. Vedder JS, Schorr WF. Primary disseminated pulmonary aspergillosis with metastatic nodules.JAMA. 1969;
immunosuppressed patient. Am, j Med
promising.3 The
GH, Griffin FM. Invasive pulmo-
nary
digusion, and counterimmunoelec-
trophoresis have had poor results. A newer ELISA test may be more
Karam
with marijuana use during chemotherapy for small cell lung cancer. Drug Intell
Clin Pharm. 1986;20:289-291. SD, Tobias JS, Hannigan M. Combined amphotericin B flucytosine
10.
Codish
11.
therapy in aspergillus pneumonia. JAMA. 1979;241:2418-2419. Denning DW, Stevens DA. Antifungal and
12.
13.
surgical
treatment
of invasive
as-
pergillosis : review of 2,121 published cases. Rev Infect Dis. 1990;12:1147-1201. Green M, Wald ER, Tzakis A, et al. Aspergillosis of the CNS in a pediatric liver transplant recipient: case report and review. Rev Infect Dis. 1991;13:653-657. Denning DW, Tucker RM, Hanson LH, et al. Treatment of invasive aspergillosis itraconazole. with Am J Med. 1989;86:791-800.
189
Pulmonary Aspergillosis in a Previously Healthy Adolescent Sarmistha B. Hauger M.D.
Introduction isseminated
pulmonary
t aspergillosis has been well-described in the clinical setting of known immunowith compromised patients and hematologic lymphoreticular
malignancies, leukopenia, or prolonged antibiotic or corticosteroid therapy. In addition, this condition has been described in a few healthy adults and children.l~ The following is a case report of disseminated aspergillosis in a previously healthy adolescent in whom no predisposing condition for immunocompromise could be identified.
Case Report A 14-year-old male presented to the pediatric emergency room with a 10-day history of intermittent fevers to 103°F, myalgia, diffuse abdominal pain, malaise, and bilateral conjunctivitis. Four days before admission, he had been examined in the pediatric emergency room for bronchospasm. He was discharged with a diagnosis of asthma exacerbation and placed on oral bronchodilator therapy. He returned one day prior to ad-
mission with continued complaints of abdominal pain; a chest roentgenogram revealed an infiltrate in the right lung. The patient was sent home on oral erythromycin therapy for a presumptive diagnosis of
Mycoplasma pneumoniae nia. He returned
pneumo-
the
following day with continued complaints and diminished oral intake. On physion
cal exam, he was found to be afebrile, thin, and in no acute distress. Significant physical findings included orthostatis on blood pressure bilateral measurement, palpebral and bulbar conjunctival infection, decreased bilateral breath sounds with rales and wheezing on lung auscultation, and diffuse abdominal pain with voluntary guarding without rebound. There was no evidence of lymphadenopathy, hepatosplenomegaly, skin findings, or focal neurological findings. The patient had a past history of atopy and asthma requiring intermittent bronchodilator therapy; he had no history of systemic corticosteroid or drug use, homosexual encounters, or serious previous infection. His family history was non-
contributory. Laboratory data included a complete blood count (CBC) with a peripheral white blood cell (WBC) count of 3,200/cu mm (59% neutro-
Address correspondence to: Sarmistha B. Hauger M. D., Assistant Professor of Clinical Pediatrics, Division of Pediatric Infectious Disease, Department of Pediatrics, Columbia University, College of Physicians and Surgeons, 622 W. 168th Street, VC 4402, New York, NY 10032. (212) 305-7573
phils, 3% banded neutrophils, 25% lymphocytes, 5% atypical lymphocytes, 8% monocytes), a hematocrit of 43.3%, and a platelet count of
290,000/cu mm. The fell to 1,900/cu mm
count
subsequent
CBC with
an
WBC on a
absolute
Downloaded from cpj.sagepub.com at Purdue University on May 23, 2015
neutrophil count of 1,258/cu mm. Serum analysis revealed the following: SGOT: 62 U/L (nl: 10-50 U/L), SGPT 40 U/L (nl:10-50 U/L) , LDH 356 U/L (nl: 90-200 U/L), CPK 208 U/L (nl:
1-50 U/L), total bilirubin 0.4 mg/dL with direct fraction 0.2 mg/dL, serum amylase 174 IU/L (nl: 5-81 IU/L), lipase 33 IU/L (nl: 14-24 IU/L). Uri-
nalysis was significant only for trace proteinuria, and 25-40 RBC/hpf. The patient was admitted with a presumptive diagnosis of systemic illness secondary to Mycoplasma or viral infection. He was managed with intravenous fluids for hydration and oral tetracycline. A diagnostic evaluation included blood, stool, and urine culture ; nasopharynx, eye, and rectal viral cultures; and Mycoplasma complement-fixation test. During the first week of hospitalization, he had a daily temperature elevation above 101°F. His complaints and physical findings remained unchanged. Tetracycline was discontinued after 10 days. Complete blood count revealed the absolute neutrophil count had fallen to 600/cu mm; a PPD and DT control were both negative. All sputum, blood, stool, and urine bacterial cultures as well as nasopharynx, eye, and rectal viral cultures remained negative. An ophthalmoexamination revealed logic bilateral conjunctivitis with no evidence of uveitis. Ten days after admission, the patient had lost 5.3 kg; his complaints continued. Further diagnostic evaluation included repeat chest roentgeno-
187
gram with
findings
of bilateral in-
filtrates, normal abdominal roentgenogram, abdominal ultrasound, sinus roentgenogram, and intrave-
nic, and his clinical
course
pro-
gressed over four weeks to a dissem-
ulant was equivocal. An ANA test was
inated death.
infection and eventual During this time, the pro-
pyelogram. Serologic testing hepatitis A and B, Epstein-Barr virus, syphilis, brucel-
positive
at 1:160; anti-DNA antibody and LE prep tests were negative. A CH5o assay was normal. An HIV an-
gressive pneumonia was refractory to conventional therapy. The diagnosis of Aspergillus infection was es-
losis, and rickettsial infection
tibody test was negative. The patient’s coagulopathy was corrected with cryoprecipitate and fresh-frozen plasma infusions, and on the 19th day of hospitalization, the patient underwent an openlung biopsy. The pathology report revealed panarteritis and evidence of invasive fungal organisms, with multiple sections of obliterative and necrotizing pneumonitis. No eosinophilic infiltrates or cavitary lesions were seen. The patient was begun on intravenous amphoteri-
tablished
nous
for mycoplasma,
was
negative. Serum immunoglobulin concentrations were IgG 1,260
mg/dL (nl: 700-1,700), IgA 219 mg/dL (nl: 70-350), IgM 135 mg/dL (nl: 50-300), and IgE 474 mg/dL . Serum lymphocyte enumeration was interpreted as generalized lymphocytic depletion, with normal T4/T8 ratio. Total lymphocyte count was 650/cu mm; total T4 count, 195/cu mm. An NBT test normal. The patient’s serum concentration continued to rise; urinalysis continued to reveal hematuria and proteinuria. A bone marrow aspirate demonwas
amylase
strated normal precursors with no evidence of either malignant or infiltrative process. Bone marrow and sputum smears were negative for acid-fast bacilli. Two weeks after admission, the patient’s temperature curve had risen to daily fever up to 103° F; he continued to complain of diffuse
myalgia and chest and abdominal pain. He began to have respiratory distress with nasal flaring; an arterial blood gas a
on room
air revealed
pH of’7.54, p02of 75, pC02 of 25,
and 02 saturation of 95%. A chest roentgenogram revealed worsening infiltrates with possible cavitation on the right side. Chest CT scan revealed bilateral parenchymal nodular pulmonary lesions at the bases and periphery of the lung fields. The patient was empirically started on oral isoniazid 300 mg/day and rifampin 600 mg/day. A gallium scan revealed diffuse uptake in the lungs and abdomen. In
preparation for a diagnostic openlung biopsy, the patient was found to have evidence of prolonged bleed-
188
ing time, disseminated intravascular coagulopathy, and thrombocytopenia. A test for lupus-like anticoag-
cin B. Over the next two
weeks, he
had
progressive multisystem failure, with refractory coagulopathy, seizures, renal failure requiring dialysis, and pulmonary failure requiring mechanical ventilation. An ophthalmologic exam revealed cotton-wool spots in both retinas. Massive pulmonary hemorrhage precipitated recurring cardiac arrests. Despite maximum cardiovascular pressor and ventilatory support, the patient expired on the 32nd day of hospitalization. Lung tissue grew Aspergillus fumigatus. An autopsy revealed disseminated aspergillosis with multiple abscesses in lungs, adrenals, kidneys, heart, thyroid, lymph nodes, and brain. There was evidence of necrotizing vasculitis with thrombosis in the lung and brain. No granuloma formation was identified.
Discussion This
patient presented with a presumed viral illness characterized by fever, myalgias, conjunctivitis, and pneumonia. He was found to be lymphopenic and neutrope-
Downloaded from cpj.sagepub.com at Purdue University on May 23, 2015
specimens
from
pathology
of
lung tissue when he critically ill for over two
had been weeks. At postmortem examination, he had evidence of multiple abscess formation in virtually every organ. Aspergillus infection is acquired of spores, after which inhalation by several distinct clinical syndromes may arise in humans. These include
saprophytic bronchopulmonary aspergillosis (colonization), aspergilloma (mycetoma), hypersensitivity-induced aspergilloses, and invasive aspergillosis. Neutrophils and macrophages appear to be most important in the body’s defense against Aspergillus infections. Diseases and drugs that depress either the number and or the function of these cells predispose the patient to invasive disease.5 Several cases of invasive pulmonary aspergillosis have been described as occuring in patients following infection with influenza virus; many of these patients were lymphopenic. Influenza is also known to cause transient anergy and a decrease in circulating T cells.6 This patient had evidence of both neutrophil and lymphocyte compromise during his hospitalization. He became profoundly
neutropenic, although an NBT test normal. Quantitative and qualitative T-cell dysfunction was docu-
was
as he had a decrease in absolute counts and percentages as well as documented intradermal skin test anergy. The pathology specimens were characteristic of invasive aspergillosis commonly seen in immunocompromised patients in that massive tissue and vascular invasion with infarction
mented,
was
predominant
and
no
granu-
loma formation could be demonstrated.’ However, no infection or condition could be identified as a cause for either his neutropenia or his lymphopenia. Given his initial presentation, the presumption is that he had a viral infection which led to immunocompromise and invasive aspergillosis. Previous reports of disseminated aspergillosis in normal hosts have been associated with the use of prolonged broad-spectrum antibiotics.’ This patient had received
only 12 days of therapy with either erythromycin or tetracycline. It is doubtful that this length of antibiotic therapy would predispose him to disseminated aspergillosis. A provocative question in this patient’s history is his long-standing history of asthma and a markedly elevated IgE level. Aspergillus sp. have a considerable potential to act as potent allergens in the human respiratory tract. Three different syndromes have been deextrinsic scribed, including asthma, extrinsic allergic alveolitis, and allergic bronchopulmonary aspergillosis. Extrinsic asthma is related to the inhalation of aspergillus spores, resulting in the release of mediators from mast cells, which are fixed with aspergillus-directed IgE antibodies. Fever and pulmonary infiltrates are not usually associated with this entity. The other two
hypersensitivity syndromes
are
both associated with fever, pulmonary infiltrates, elevated levels of precipitating IgG and IgE antibodies, and an actual superficial infection with the fungus, along with the
potential for sequelae of irreversible lung-tissue damage.77 Another mode of acquisition of Aspergillus infection is via use of contaminated materials. Aspergillus has been identified in street marijuana, commercial cigarettes, and pipe tobaccos. In addition, several
cases of invasive and pulmonary aspergillosis have been described in immunocompromised patients who
have smoked contaminated marijuana.8°9 This patient denied any
smoking history. A major obstacle in the management of this illness is the difficulty in establishing the diagnosis. The organism is infrequently cultured from the respiratory tract.3 Even when the organism is demonstrated in pathological specimens, it is successfully cultured only in about 40% of cases. Serologic diagnosis has yielded varying results, since immunoprecipitation, immuno-
Acknowledgment The author would like to thank Dr. Anne Gershon for her thoughtful comments and review of this paper.
~Er~NCEs 1.
2.
3.
prognosis of invasive asper-
gillosis is dismal. This is due in part to the difficulty in making the diagnosis. Estimated mortality rate is approximately 91 %; even among patients who receive amphotericin B, survival rate is only 22%.3 More data suggest that combination therapy with amphotericin B and 5-flucytosine may lower mortality in neutropenic patients, although relapse is common.10,11 Itraconazole, a member of the azole family of antifungal agents, recent
promising as therapy in Aspergillus infections. This agent has good bioavailability when administered orally and has few toxic
4.
5.
6.
7.
Downloaded from cpj.sagepub.com at Purdue University on May 23, 2015
209:1191-1195. Roselle GA, Kauffman CA. Invasive pulmonary aspergillosis in a nonSci. 1978;276:357-361. Hillerdal G, Benson L, Lindgren A, et al. Fatal disseminated aspergillosis in a previously well young woman. Scand J
Infect Dis. 1984;16: 217-222. Bodey GP, Vartivarian S. Aspergillosis. EurJ Clin Microbiol Infect Dis. 1989 :413437. Lewis M, Kallenbach J, Ruff P, et al. Invasive pulmonary aspergillosis complicating influenza A pneumonia in the previously healthy patient. Chest.
1985;87:691-693. Pennington JE. Aspergillus lung disease. Med 1980;64:475-490. Clin North Am.
8.
Kurup VP, Resnick A, Kagen SL, et al. Allergenic fungi and actinomycetes in smoking materials and their health implications. Mycopatholgia. 1983;82:61-64.
9.
Sutton S, Lum BL, Torti FM. Possible risk of invasive pulmonary aspergillosis
appears
effects. It has been found to be active in vitro against several species of Aspergillus; an in vivo animal model has revealed it to have greater activity than ketoconazole. 12 Recent reports of the use of itraconazole for the treatment of invasive Aspergillus infection in immunocompromised hosts have noted favorable results.13 Further studies will be needed to determine its potential as an alternative therapy for aspergillosis.
aspergillosis in nonimmunocompromised, nonneutropenic hosts. Rev Infect Dis. 1986;8:357. Vedder JS, Schorr WF. Primary disseminated pulmonary aspergillosis with metastatic nodules.JAMA. 1969;
immunosuppressed patient. Am, j Med
promising.3 The
GH, Griffin FM. Invasive pulmo-
nary
digusion, and counterimmunoelec-
trophoresis have had poor results. A newer ELISA test may be more
Karam
with marijuana use during chemotherapy for small cell lung cancer. Drug Intell
Clin Pharm. 1986;20:289-291. SD, Tobias JS, Hannigan M. Combined amphotericin B flucytosine
10.
Codish
11.
therapy in aspergillus pneumonia. JAMA. 1979;241:2418-2419. Denning DW, Stevens DA. Antifungal and
12.
13.
surgical
treatment
of invasive
as-
pergillosis : review of 2,121 published cases. Rev Infect Dis. 1990;12:1147-1201. Green M, Wald ER, Tzakis A, et al. Aspergillosis of the CNS in a pediatric liver transplant recipient: case report and review. Rev Infect Dis. 1991;13:653-657. Denning DW, Tucker RM, Hanson LH, et al. Treatment of invasive aspergillosis itraconazole. with Am J Med. 1989;86:791-800.
189
