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Eur Reeplr J
1992, 6, 362-364
CASE REPORT
Cytomegalovirus (CMV) pneumonitis in AIDS patients:
the result of intensive CMV replication?
P. Aukrust*, I.N. Farstad**, S.S. Fr0land*, E. Holter***
Cytomegalovirus (CMV) pneumonitis in AIDS patients: the result of intensive CMV
replication? P. Aukrust, /.N. Farstad, S.S. Fr;/and, E. Holter.
ABSTRACf: We report a case of fatal pulmonary disease In a patient Infected
with human Immunodeficiency virus (IUV), where cytomegalovirus (CMV) was the
only causative agent ldentlfled In the lungs at autopsy. The most prominent
histopathological features were numerous lnteralveolar cells containing CMV
Inclusion bodies combined with scanty signs of Inflammation.
We propose that the lung damage caused by CMV In acquired Immune
deftclency syndrome (AIDS) patients Is a direct consequence of cytopathogenic
effects of the virus related to the extent of active virus replication.
Eur Respir J., 1992, 5, 362-364.
• Section of Clinical Immunology and
Infectious Diseases, Medical Dept A. • •
Institute of Pathology and • • • K.aptein W.
Wilhelmsen og frues Institute of Bacteriology, University of Oslo, The National
Hospital, Oslo, Norway.
Correspondence: P. Aukrust
Section of Clinical Immunology and Infectious Diseases
Medical Dept A
The National Hospital
0027 Oslo 1, Norway.
Keywords: Acquired immune deficiency
syndrome; cytomegalovirus; pneumonitis.
Accepted after revision October 30 1991.
Cytomegalovirus (CMV) is a major opportunistic
pathogen in patients with acquired immune deficiency
syndrome (AIDS) [1]. The importance of CMV as a
cause of pulmonary disease in AIDS is controversial.
CMV is frequently isolated from bronchoalveolar lavage
(BAL) fluid in patients infected with human immunodeficiency virus (HIV), and CMV inclusion bodies are
also, if somewhat less often, detected in lung tissue at
autopsy of AIDS patients [2-6]. The clinical relevance
of these findings is, however, often unclear, because
CMV is frequently associated with other pathogens in
the lungs [2-6]. In most reports of patients with AIDS
and pneumonitis, the presence of CMV in BAL fluid
apparently did not influence the clinical outcome [7].
In the present paper, a case of fatal pulmonary
disease in an HIV infected patient is described, where
CMV was the only causative agent identified at autopsy.
Case report
The patient was a 36 yr old homosexual man with
documented HIV infection since 1986. For several
years he had suffered from episodes of bronchitis.
Because of multidermal Varicella zoster virus
infection, treatment with zidovudine was started in
September 1988.
In December 1989, the patient was admitted to
hospital because of dyspnoea on exertion during the
preceding two weeks. Chest X-ray examination
revealed a sparse, localized infiltrate at the base of the
left lung. Haemophi/us influenzae was isolated from the
BAL fluid, and the isolate was susceptible to all
antibiotics used later. BAL virus culture was also
positive for CMV, but intranuclear inclusions were not
detected on cytological examination. Because of
suspected bacterial pneumonia, treatment was started
with amoxycillin, and the patient was discharged after
three days. The clinical manifestations persisted, and
two weeks later the therapy was changed to
ciprofloxacin. However, the patient's condition did not
iniprove, and he was readmitted to the hospital in
February 1990 with fever (39.5°C), dyspnoea and
productive cough. Radiographic examination of the
chest showed bilateral, diffuse, interstitial pulmonary
infiltrates. BAL fluid cultures for bacteria, mycobacteria and fungi, and staining for Pneumocystis carinii and
acid-fast bacteria were all negative. CMV was cultured
from BAL fluid and throat washings, but no intranuclear inclusions were detected.
The white blood cell count was 2.3xl09·J·1• The
CD4+ T-cell number was 490xl<N·1 in October 1989,
50xl<J6·t1 in January 1990 and 16xl<N·1 in February
1990.
Bacterial pneumonia with chest X-rays showing
diffuse bilateral infiltrates may be seen in HIV infected
patients [8], and after bronchoscopic examination intravenous administration of cefuroxime (1.5 g t.i.d.) was
therefore initiated, but the patient's condition continued
to deteriorate. Ophthalmological examination two
weeks after admission showed retinal haemorrhages and
white exudates suggestive of CMV retinitis, and
foscarnet (65 mg·kg·1 t.i.d.) was given. Two days later
a severe respiratory distress developed. Arterial blood
gas examination performed while the patient breathed
room air showed pH 7.27, oxygen tension 5.0 kPa with
CMV PNEUMONITIS IN AIDS PATIENTS
saturation 50%, carbon dioxide tension 9.1 kPa and base
excess 3.0. Since prognosis for survival was judged as
very poor, mechanical ventilation was not started, and
the patient was treated with nasal 0 2• Because of
suspected adrenal insufficiency (hypotension and
hyponatraemia), hydrocortisone was administered.
After transient improvement, progressive respiratory
failure ensued, leading to coma and death.
Autopsy findings
There was bilateral pleural exudation and both lungs
were rather solid and air depleted. The lower lobes
showed patchy, dark infiltrates. Microscopy revealed
in most part of the lungs a striking picture with
numerous enlarged bi- and multinucleated cells containing intranuclear CMV inclusion bodies in alveolar
spaces, epitheHum and interstitium (fig. 1). Occasional
alveoli contained up to ten such cells. Alveolar septa
were slightly thickened with a sparse inflammatory infiltrate containing few granulocytes, and there was
marked proliferation of pneumocytes. No infected
endothelial cells or other halLmarks of vasculitis were
seen. Scattered areas of the lower lobes revealed signs
of partly organized pneumonia with fibrous obliteration
of alveoli but relatively few CMV infected cells.
Fig. 1. - Lung tissue with thickened alveolar sepia containing
proliferating pneumocytes (black curved arrows) and numerous CMV·
infected cells (black straight arrows). CMV: cytomegalovirus.
(Haematoxylin and eosin; bar equals 10 J.lm).
Adrenals were slightly enlarged with haemorrhages
and necrotic areas. Microscopy disclosed CMV-infected
cells in diseased parts.
Lung and spleen autopsy cultures were positive for
CMV, while no other pathogenic microbes were
isolated.
The ultimate cause of death was assumed to be CMV
pneumonitis.
Methods
BAL fluid, throat washings, urine, peripheral blood
and autopsy specimens were cultured in human embryo
363
fibroblast cells and observed for typical cytopathic
effects diagnostic for CMV.
Discussion
It has been clajmed that CMV in the lungs of AIDS
patients is a passive bystander, and not a pathogen [5].
Nevertheless, it is evident that CMV may also cause
severe symptomatic pulmonary disease in HIV-infected
patients, as shown in this and other reports [3, 4, 7, 9].
The diagnosis of CMV pneumonitis was, in our
opinion, well-documented in this patient, who died of
respiratory failure. There was histological evidence of
florid CMV infection in the lungs, CMV was cultured
from lung specimens, and no other pathogen was found
in lung tissue. Although remnants of previous probable
bacterial pneumonia were detected at autopsy, there was
no sign of ongoing bacterial pneumonia.
The CMV inclusion bodies were most often seen in
alveolar luminal cells probably representing desquamated alveolar lining epithelium. It is possible that
some of these virus-infected cells represent macrophages
and/or fibroblasts, but this is difficult to ascertain from
light microscopy. Others [10] have found, using in situ
hybridization with CMV probes, that the virus infects
pneumocytes, interstitial cells and occasional bronchial
epithelial cells. However, in our case alveolar epithelial
cells seemed the primary cell type to be infected.
There are only a few documented reports of CMV
as the sole causative agent of symptomatic pulmonary
disease in AIDS patients [3, 4, 6, 9]. This is in marked
contrast to the high frequency of serious CMV
pneumonitis in recipients of solid organs and allogeneic
bone marrow aJlografts [11].
[n transplant recipients with CMV pneumonitis,
histological examination usually shows necrotizing
inflammation with relatively few CMV-infected cells
[12]. In the present case, however, the most prominent
histopathological features were numerous cells in the
alveoli contaming CMV inclusion bodies combined with
scanty signs of inflammation.
Different histopathological pictures have been reported
in association with pulmonary CMV infection in AIDS
patients [4, 6, 7). The usual presence of concomitant
pulmonary infections or neoplaslic disease has made it
difficult to assess whether the histological changes in
these cases were due specifically to CMV. However,
the strong correlation between high density of CMV
inclusion bodies and severe, symptomatic pneumonitis,
as seen in our patient, has been reported by others,
regardless of coexisting pulmonary disease [4, 6].
The difference in histopathological features between
AIDS patients and transplant recipients may well reflect
different pathogenetic mechanisms. It has been
suggested that CMV pneumonitis in allogeneic transplant recipients is caused by immune mechanisms
mediated by a T-ceU response to virally induced anti·
gens expressed in the lungs, and severe necrotizing
pneumonitis may occur in spite of suppression of virus
replication during ganciclovir therapy (13, 14]. AIDS
364
P. AUKRUST BT AL.
patients with profound immune deficiency may be
unable to mount the immune response necessary to
cause CMV pneumonitis by this mechanism. In AIDS
patients the lung damage may be due directly to
cytopathogenic effects of CMV, related to the extent of
active virus replication. Animal studies support this
hypothesis described for CMV pathogenesis in AIDS
patients [13], which is assumed to be a late event in a
stage of profound immune deficiency, as demonstrated
in the present case.
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