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Blood, 1 November 2001, Vol. 98, No. 9, pp. 2875-2877
CORRESPONDENCE
To the editor:
Short-course corticosteroid-induced pulmonary and apparent
cerebral aspergillosis in a patient with idiopathic thrombocytopenic
purpura
In a recent report on adults with idiopathic thrombocytopenic
purpura (ITP), Portielje et al1 presented limited data on the morbidity and mortality attributed to the systemic effects of
short-course corticosteroids in the context of initial treatment of
ITP.2 Certain patients may be at high risk for unusual
opportunistic infections. In this letter we present a patient with ITP and no occupational hazard
or apparent underlying disease who, during the course of treatment with
oral methylprednisolone (MP), developed invasive bilateral pulmonary
aspergillosis and multiple intracerebral lesions, presumably due to
aspergillosis. We believe that this is the first reported case of
cerebral aspergillosis after short-course corticosteroid treatment in
an otherwise immunocompetent host with ITP. A 52-year-old man was admitted to our department with asymptomatic
severe thrombocytopenia (18 × 109/L), found on a
routine full blood count (FBC). Clinical examination was unremarkable.
Routine blood chemical values were normal, and tumor markers were
negative. Serological tests for hepatitis B and C viruses,
cytomegalovirus, Epstein-Barr virus, herpes simplex virus, herpes
zoster virus, and human immunodeficiency virus (HIV) were negative. The
patient had no clinical or laboratory evidence of autoimmune or
immunodeficiency syndromes. Findings on chest radiograph and computed
tomography (CT) scans of the chest, abdomen, and pelvis were normal. A
bone marrow smear revealed normal numbers of megakaryocytes in an
otherwise normal bone marrow, while antiplatelet IgG and IgM antibodies
were positive. Treatment was initiated with 1 mg/kg oral MP daily, and
3 days later the patient was discharged after a prompt recovery of the
platelet (PTL) count (70 × 109/L). The patient was
followed up at the outpatient clinic, and tapering of MP was initiated
after 4 weeks of treatment, while corticosteroid-induced type 2 diabetes mellitus developed. Eight weeks later, while on 24 mg MP
daily, the patient was readmitted, afebrile and with a 3-day history of
fatigue and palpitation. The FBC revealed a normal hemoglobin level and
white blood cell and platelet counts. A radiograph of the chest showed
patchy, nodular consolidations in both lungs. MP was tapered to 16 mg every other day (and discontinued on the 14th day of hospital stay),
while cotrimoxazole, ceftriaxone, clarythromycin, and fluconazole were
administered. Repeat virology (including HIV) and immunological laboratory tests again excluded any underlying autoimmune or
immunodeficiency syndromes. Culture specimens of blood, sputum, and
urine were negative for microorganisms. A bone marrow smear was
unremarkable. Microscopical examination of a stained specimen of sputum
showed no acid-fast bacilli. A urine test for legionella antigen was negative. On the fifth day of hospital stay, the patient became febrile
(39°C) and developed a bloodstained productive cough. A chest
radiograph revealed an increase in the bilateral nodular and patchy
consolidations, while a CT scan of the chest on the eighth day of
hospital stay showed bilateral multifocal nodules with cavitation.
Amphotericin 1.5 mg/kg IV and itraconazole 400 mg daily were initiated.
On the 10th day of hospital stay, a bronchoscopy was performed and
aspergillus fumigatus was isolated from bronchoalveolar lavage fluid
samples. The patient showed no clinical or radiological improvement
over the following days and was switched to liposomal amphotericin 5 mg/kg, while itraconazole was increased to 800 mg daily. The patient
showed a slow but stable improvement and, on the 27th day of hospital
stay, became afebrile. On the 30th day of hospital stay, the patient
developed a brief Jacksonian-type seizure. Magnetic resonance imaging
(MRI) of the brain disclosed multiple (19 in total) ring-shaped brain
abscesses. T1- and T2-weighted images showed low-intensity
lesions containing high-intensity areas and high-intensity lesions,
respectively (Figure 1). Cerebrospinal fluid (CSF) revealed a glucose level of 64 mg/dl (serum glucose 160 mg/dl), 2 cells/mm3, 15 RBC/mm3, and 55-mg/dl
protein. Microscopic examination (gram staining, acid-fast bacilli,
fungi) and CSF cultures were sterile. Serum and CSF enzyme-linked
immunosorbent assay antigen test for IgA, IgM, and IgG toxoplasma
gondii antibodies and CSF latex agglutination tests for aspergillus and
cryptococcus neoformans antigens were negative. The good condition of
the patient and the small size of the intracerebral lesions (the
largest, 19 mm in diameter) discouraged neurosurgeons from performing a
stereotactic biopsy. Although central nervous system (CNS)
toxoplasmosis was most unlikely, a 2-week trial of sulfadiazine and
pyramethamine was initiated, and follow-up CT scans of the brain failed
to show improvement in the lesions, ruling out CNS toxoplasmosis. We
persisted with antifungal treatment, and the pulmonary lesions
gradually improved while the brain lesions remained unchanged in number
and size. On the 60th day of hospital stay, the patient was discharged
with itraconazole 400 mg daily, in good condition and with marked
improvement of pulmonary lesions but stable cerebral lesions. Over the
next months, follow-up CT scans showed a slow improvement of the
intracerebral lesions, while a 12-month follow-up MRI scan disclosed
complete resolution of these lesions (Figure
2). The presenting features and the
clinical course yielded an apparent diagnosis of cerebral aspergillosis.
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| Figure 1.
Axial contrast-enhanced T1-weighted MRI image of the
brain at diagnosis.
Multiple intraparenchymal lesions are detected, some with surrounding
vasogenic edema. Characteristic ring-enhancing lesions are shown at the
right inferior frontal gyrus and the corticomedullary junction of the
left superior frontal gyrus.
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| Figure 2.
Axial contrast-enhanced T1-weighted MRI image of the
brain 12 months after diagnosis.
Complete disappearance of intracerebral lesions after treatment with
oral itraconazole.
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It is thought that vascular spread of aspergillosis is not a feature in
immunocompetent patients. Immunosupression of a degree sufficient to
permit the development of systemic disease in this patient was probably
the result of the combination of two cofactors that compromised
phagocytosis by macrophages and neutrophils: treatment with
corticosteroids and hyperglycemia (a side effect often encountered in
clinical practice). Although pneumonia due to aspergillosis in
presumably immunocompetent hosts has received increased recognition
over the years,3-4 this rare case of successfully treated
cerebral aspergillosis suggests that short-course treatment with
corticosteroids can exert deleterious systemic effects in certain
patients with no evidence of autoimmune or immunodeficiency syndromes.
John Apostolidis, Marina Tsandekidi, Demitris Kousiafes, Maria Pagoni, Chrisanthi Mitsouli, Themis Karmiris, Maria Bakiri, Demitris Karakasis, Nikolaos Harhalakis, and Emmanuel Nikiforakis
Correspondence: John Apostolidis, Department of
Hematology and Lymphoma, Evangelismos Hospital, 43-45 Ipsilandou st,
Athens 106 76, Greece; e-mail: japostol{at}otenet.gr
References
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Portielje JEA, Westendorp RGJ, Kluin-Nelemans HC, Brand A.
Morbidity and mortality in adults with idiopathic thrombocytopenic purpura.
Blood.
2001;97:2549-2554[Abstract/Free Full Text].
2.
George JN, Woolf SH, Raskob GE, et al.
Idiopathic thrombocytopenic purpura: a practical guideline developed by explicit methods for the American Society of Hematology.
Blood.
1996;88:3-40[Free Full Text].
3.
Karman GH, Griffin FM.
Invasive pulmonary aspergillosis in nonimmunocompromised, nonneutropenic hosts.
Rev Infect Dis.
1986;8:357-363[Medline]
[Order article via Infotrieve].
4.
Clancy CJ, Nguyen MN.
Acute community-aquired pneumonia due to Aspergillus in presumably immunocompetent hosts: clues for recognition of a rare but fatal disease.
Chest.
1998;114:629-634[Abstract/Free Full Text].
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