Clinical Disease Manifestations Presentation and First Evaluation
Patients with HPS typically present in a very nonspecific way with a relatively short
febrile prodrome lasting 3-5 days. In addition to fever and myalgias, early symptoms
include headache, chills, dizziness, non-productive cough, nausea, vomiting, and other
gastrointestinal symptoms. Malaise, diarrhea, and lightheadedness are reported by
approximately half of all patients, with less frequent reports of arthralgias, back pain,
and abdominal pain. Patients may report shortness of breath, (respiratory rate usually 26
- 30 times per minute). Typical findings on initial presentation include fever, tachypnea
and tachycardia. The physical examination is usually otherwise normal.
HPS Clinical Presentation
Most Frequent |
Frequent |
Other |
fever |
headaches |
shortness of breath |
chills |
nausea, vomiting |
dizziness |
myalgias |
abdominal pain |
arthralgia |
|
diarrhea |
back or chest pain |
|
cough |
sweats |
|
malaise |
|
The diagnosis is seldom made at this stage, as cough and tachypnea generally do not
develop until approximately day seven. Once the cardiopulmonary phase begins,
however, the disease progresses rapidly, necessitating hospitalization and
often ventilation within 24 hours.
Signs that make a diagnosis of HPS unlikely include rashes, conjunctival or
other hemorrhages, throat or conjunctival erythema, petechiae, and peripheral or
periorbital edema.
Clinical Assessment
If a hantavirus infection is suspected, a CBC and blood chemistry should be repeated
every 8 to 12 hours.
A fall in the serum albumin and a rise in the hematocrit may indicate a fluid shift
from the patient's circulation into the lungs. The white blood cell count tends to be
raised with a marked left shift. The percentage of white blood cells precursors may be as
high as 50% and atypical lymphocytes are frequently present, usually at the time of onset
of pulmonary edema.
In about 80% of individuals with HPS, the platelet count is below 150,000 units. A
dramatic fall in the platelet count may herald a transition from the prodrome to the
pulmonary edema phase of the illness.
The most severe cases of HPS develop disseminated intravenous coagulation (DIC), but,
unlike the hantavirus-related hemorrhagic fevers (HFRS) seen in Asia, this is uncommon.
Coagulation Abnormalities in HPS
A Fatal Case
|
Day 1 |
Day 3 |
PT |
13.5 (NL) |
29.8 (up) |
PTT |
32.8 (NL) |
>240 (up) |
Fibrinogen |
|
144 (down) |
Fibrin Split Products |
|
>4000 (up) |
Proteinuria, and mild elevations of transaminases, CPK, amylase, and creatinine have
also been reported.
When metabolic acidosis, prolongation of PT and PPT times and rising serum lactate
levels develop, the prognosis is poor. Marked renal insufficiency has mainly been noted
among cases from the southeastern United States although some degree of renal
insufficiency, assessed by elevated serum creatinine levels, has been noted in 15% of all
patients.
The combination of atypical lymphocytes, a significant bandemia, and thrombocytopenia
in the setting of pulmonary edema is strongly suggestive of a hantavirus infection.
Disease Development
Within 24 hours of initial evaluation, most patients develop some degree of hypotension
and progressive evidence of pulmonary edema and hypoxia, usually requiring mechanical
ventilation. The patients with fatal infections appear to have severe myocardial
depression which can progress to sinus bradycardia with subsequent electromechanical
dissociation, ventricular tachycardia or fibrillation.
Hemodynamic compromise occurs a median of 5 days after symptom onset--usually
dramatically within the first day of hospitalization. In contrast to HFRS, overt
hemorrhage occurs rarely in HPS, although hemorrhage is occasionally seen in association
with disseminated intravascular coagulation. In contrast to septic shock, HPS patients
have a low cardiac output with a raised systemic vascular resistance. Poor prognostic
indicators include a plasma lactate of greater than 4.0 mmol/L or a cardiac index of less
than 2.2 L/min/m2 Whilst pulmonary edema and pleural effusions are
common, multiorgan dysfunction syndrome is rarely seen. However, HPS patients sometimes
have mildly impaired renal function. Survivors frequently become polyuric during
convalescence and improve almost as rapidly as they decompensated.
Differential Diagnosis
The prodromal phase of HPS is indistinguishable clinically from numerous other viral
infections. Often the only guide to the etiology of the patient's illness is the blood
picture, which may show circulating immunoblasts, which appear as large atypical
lymphocytes, and thrombocytopenia. However, unlike other viral infections, HPS patients
usually have concurrent left-shifted neutrophilia with circulating myelocytes.
In the cardiopulmonary stage of the disease, the patients have a diffuse pulmonary
edema. The most frequent cause for such a picture is silent myocardial infarction so it is
important to obtain an ECG and echocardiogram early to aid in the assessment. Intensivists
at the University of New Mexico, where many of the patients have been managed, have found
that a echocardiogram also helps to distinguish these patients from patients with ARDS as
cardiac function is depressed to a much greater degree in the HPS patients and cardiac
output does not respond to fluid challenge as it tends to with ARDS.
Infections in the immunocompetent which might present with a non-specific prodrome
leading to acute cardiopulmonary deterioration as in HPS include leptospirosis,
Legionnaire's disease, mycoplasma, Q fever, chlamydia, and in regions where the organisms
are present, septicemic plague, tularemia, coccidioidomycosis and histoplasmosis.
Non-infectious conditions such as Goodpasture's syndrome should also be considered. Lack
of coryza aids the clinical distinction between HPS and Influenza A infection.
It must be remembered that HPS is relatively uncommon and in the immunocompromised PCP,
CMV, cryptococcus, aspergillus and graft vs. host disease are far more likely to be the
cause of diffuse pulmonary infiltrates than a hantaviral infection.
Atypical Presentations
Atypical clinical presentations with prominent renal insufficiency have also been
reported; therefore, HPS and infection due to Seoul virus, one of the Old World
hantaviruses that cause HFRS, should be considered for patients with unexplained febrile
nephropathies and appropriate laboratory findings. Asymptomatic illness is rare. However,
an increasing number of acutely infected patients who develop either no cardiopulmonary
disease or extremely mild pulmonary disease with minimal hypotension have been identified;
one such patient was managed successfully as an outpatient.
Radiologic Findings
HPS has a characteristic radiological evolution, beginning with minimal changes of
interstitial pulmonary edema, progressing to alveolar edema with severe bilateral
involvement. Pleural effusions are common and are often large enough to be evident
radiographically. Heart size is usually normal. Cardiac silhouette size on chest
radiographs is usually normal.
a) b)
|
|
|
Severe HPS. |
Evolution of HPS, (1). |
Evolution of HPS, (2). |
|
|
Evolution of HPS, (3). |
Large Effusion Associated With HPS. |
To view large versions of these images, click directly on the
image buttons.
Images courtesy D. Loren Ketai, M.D.
Approximately one-third of patients show evidence of pulmonary edema in the initial
radiograph. Forty-eight hours after the initial radiograph, virtually all patients
demonstrate interstitial edema and two-thirds have developed extensive bibasilar or
perihilar airspace disease.
This radiograph shows the interstitial changes of early HPS. At the lung bases are
Kerley B lines, short linear opacities which are perpendicular to the pleural surfaces.
The longer linear opacities radiating from the lung hilum are known as Kerley A lines.
Together these findings are classically seen in heart failure, but are also seen in HPS.
Peribronchial cuffing is also seen well on this film. The bronchi viewed end on are
surrounded by a "cuff" of edema. This makes the bronchi appear as prominent
circular opacities, appearing as "ring-like" shapes next to pulmonary blood
vessels.
|
|
Marked interstitial edema with hilar
indistinctness, Kerley B lines, in HPS. |
Detail showing Kerley B lines. |
To view large versions of these images, click directly on the
image buttons.
Images courtesy D. Loren Ketai, M.D.
The lack of peripheral distribution of the initial airspace disease, the prominence of
interstitial edema and the presence of pleural effusions early in the disease process help
distinguish HPS from ARDS. There is, however, overlap in the radiographic appearance of
the two diseases. Atypical pneumonias such as that caused by mycoplasm pneumonia can
produce radiographic findings similar to early HPS, although the clinical illness tends
to be much less severe.
|
|
Mycoplasm pneumonia can show prominent
interstitial opacities, including Kerley B lines. |
Detail of mycoplasm pneumonia. |
Hyperacute hypersensitivity reactions, mitral stenosis, acute myocardial
infarctions, all can cause interstitial edema with a normal heart size, and are also in
the radiologic differential diagnosis of early HPS.
|
Mitral stenosis can also cause
interstitial edema with a normal-sized cardiac silhouette. |
To view large versions of these images, click directly on the
image buttons.
Images courtesy D. Loren Ketai, M.D.
|