EXPERIENCE AND REASON 631
Subclinical
Hepatic
Changes
in Varicella
Infection
Varicella is a common viral disease of children
which frequently occurs in epidemics. The diagnosis
is generally obvious from clinical criteria. The
dis-ease is usually self-limited and benign, but the
complications of pneumonia and encephalitis are
well recognized.’ Recently, chicken pox has been
implicated in 10% to 18% of cases of Reye’s
syn-drome, and varicella hepatitis is being increasingly
recognized.24 However, the incidence of subclinical
liver involvement in children or adults with
van-cella is not known.4’5
In this study we have obtained historical,
physi-cal, and biochemical data on patients with varicella
infections during the active phase of their disease.
Patients were questioned about previous hepatic
disease, the use of salicylates or phenothiazine class
drugs, the onset and sequence of their symptoms,
and signs of neurologic or hepatic involvement.
Physical examination was keyed to the clinical
di-agnosis of chicken pox according to the criteria of
Krugman and Ward’ and to any evidence of hepatic,
pneumonic, or neurologic involvement. The
bio-chemical measurements selected were those rou-tinely required for the diagnosis of varicella
hepa-titis or Reye’s syndrome-determinations of SGOT,
serum ammonia, and glucose levels and of
pro-thrombin activity. When possible, creatine
phos-phokinase (CPK) levels were determined to
evalu-ate myocardial or skeletal muscular involvement.
In addition, a salicylate level was obtained if there
was a history of ingestion within the previous 24
hours.
MATERIALS AND METHODS
Thirty-nine patients with overt varicella
infec-tions, aged 8 months to 25 years, were studied
between January and April 1978. In addition, data
were obtained on 1 1 afebrile noninfected children
seen concurrently in the outpatient department. AU
patients but one were outpatients. Patients were
seen after presenting to the emergency room or
outpatient department, or after referral by a local
pediatrician or the Providence School Department.
Patients were studied and examined by one of the
investigators while they evidenced active cutaneous lesions, with no attempt made to select the duration
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of disease for entry to the study. When possible, 10
ml of nonfasting blood was obtained from an
ante-cubital or another free-flowing vein. Samples for
ammonia and glucose determinations were
trans-ported on ice; hemolyzed specimens were discarded.
All ammonia determinations were performed within
one hour of drawing, and all determinations were
complete within 24 hours.
SGOT level was determined by a kinetic
spectro-photometric procedure utilizing Spin Chem reagent
(Smith Kline Instruments, mc, Sunnyvale, CA).
With one exception blood studies were performed
using standard laboratory techniques: in
determi-nations of ammonia concentration, in which the
isothermal distillation occurred at pH 10, a
modifi-cation of the method of Seligson and Hirahara6 was
used. Normal values from this laboratory for
chil-dren are reported in the text.
The study was approved by the Human
Investi-gation Committee, and patients were examined only
after informed consent was obtained.
RESULTS
Thirty-nine patients with chicken pox and
with-out clinical evidence of Reye’s syndrome were
stud-ied. Determinations of all ammonias (normal <100
mg/100 ml), CPK (normal <135 lU/liter), glucose
(>40 mg%), and prothrombin activity (>50% of
control) were within normal limits. SGOT (normal
<31 lU/liter) elevations were noted in 77% of
pa-tients (Table). SGOT levels were arbitrarily divided
into three classes: normal (0-31 lU/liter), mildly
elevated (32-50 lU/liter), and markedly elevated
(>50 lU/liter). Twenty-three percent were normal,
49% mildly elevated, and 28% markedly elevated.
x2
and regression analyses disclosed no correlationbetween SGOT levels and duration of rash, physical
findings, age of patient, or history of vomiting or
salicylate ingestion. The eight salicylate levels
ranged from 0%-7.7 mg/100 ml which is far below
accepted toxic levels. No patient had received a
phenothiazine class drug.
SGOT level determinations were obtained from
11 afebrile, noninfected children, all of whom had
values within normal limits (mean = 22.6 lU/liter,
SD = 4.0).
DISCUSSION
Vancella involvement of the liver has rarely been
described. Four cases of clinical hepatitis with liver
tenderness, jaundice, and abnormal liver function
were observed in 20 adults with varicella
pneu-1 Specific pathologic changes have been
noted at autopsy in fatal cases, and the virus has
been cultured from the liver.7’8 These facts, along
with well-described instances of hepatitis by other
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TABLE. SGOT Level vs Laboratory and Clinical Findings
632 PEDIATRICS Vol. 65 No. 3 March 1980
SGOT* (lU/liter) NH.t (g/100 ml) Glucose (mg/100 ml) PTA (% control) CPKt (lU/li-ter)
Age (yr) Sex History
of Vomit-ing (%) History of Salicylate Ingestion (%) Dura-tion of Rash (days) SGOT (0-31)
n 9 3 5 6 4 9
Mean 28.0 39.3 101.6 62.0 8.8 7 2 2.2
SD 3.7 4.5 27.3 17.5 6.8 2 22% 67% 1.1
SEM 1.3 2.6 12.2 8.7 2.3 0.4
Range 19-31 35-44 75-147 67-100 40-77 3-23 0-4
SGOT (32-50)
n 19 9 15 11 5 19
Mean 40.3 50.6 82.9 54.4 8.1 8 9 2.8
SD 4.6 20.4 9.7 16.5 5.8 11 d 5% 47% 1.4
SEM 1.1 6.8 2.5 7.4 1.4 0.3
Range 33-49 21-85 70-101 84-100 31-67 8mo-25yr 0-7
SGOT (> 50)
n 11 3 7 7 3 11
Mean 156.3 45.0 83.3 54.0 8.5 3 9 3.8
SD 216.6 2.6 8.0 29.0 4.9 8 27% 55% 1.0
SEM 65.3 1.5 3.0 16.8 1.5 0.3
Range 55-794 43-48 76-97 62-100 26-84 2-17 0-7
* Normal SGOT level is 0-31 lU/liter.
t Normal ammonia level is <100 &g/100 ml.
:1:
Normal CPK level is <135 lU/liter.viruses of the herpes family, would suggest the
potential for subclinical hepatic involvement.
Re-cently, two patients with varicella hepatitis and persistent vomiting were reported.4
Stanton and Joos9 found the SGOT levels to be
normal in children with various infections and
re-solving rheumatic fever. This suggests that our
patients’ elevations with varicella infection are not
simply a response to a nonspecific febrile ifiness.
However, further studies of a large population of
febrile patients are warranted.
We were unable to obtain sufficient follow-up
data to delineate the time course for normalization
of transaminase levels. However, it obviously does
occur since the prior occurrence of chicken pox does
not appear to be associated with any future liver
disorder.
The assignment of the elevated SGOT level as
being hepatic in origin appears warranted. The level
of CPK, which should be elevated if the enzyme
source were cardiac or ‘#{176}was normal in all
12 children studied, eight of whom had elevated
SGOT levels. No patient had clinical evidence of
myositis, carditis, or hemolysis.
We conclude that mild transient hepatic enzyme
elevation, as measured by SGOT levels in
conjunc-tion with normal prothrombin time and ammonia
and glucose levels, appears to be common in
chil-dren with routine cases of chicken pox. Of the six
patients who reported vomiting, in five it occurred
only once at about the time of the onset of the rash.
One patient, however, developed nearly intractable
vomiting on the third day of her illness, with no
change in sensorium. She was admitted for
obser-vation, had an SGOT level of 794 lU/liter and a
normal blood ammonia reading. The vomiting
ceased shortly after admission, and she was
dis-charged on the second day. Her SGOT level was
normal six weeks after discharge. Finally, no
con-stellation of findings on physical examination or
single historical finding correlated with SGOT levels except, as noted above with a single patient,
persistent vomiting.
Our data, when combined with other reports,
suggest that post-vaicella Reye’s syndrome is prob.
ably not merely severe varicella hepatitis. Reye’s
syndrome occurs with SGOT levels no higher than
those in four of our patients (>2#{189}times normal),
none of whom had neurologic changes or changes
in prothrombin activity or in level of glucose or
ammonia. This argues in favor of the view that the
degree of hepatocyte damage is not the only factor.
In addition, autopsy findings in patients dying from
disseminated varicella infection are entirely
differ-ent from those found in Reye’s syndrome.9 It
ap-pears that elevated levels of transaminase with
varicella are common and that marked elevations
of SGOT are probably not rare, whereas Reye’s
syndrome depends on a separate pathogenic
mech-anism.
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EXPERIENCE AND REASON 633 ACKNOWLEDGMENTS
We wish to thank James Driscoll, PhD, Department of
Biochemistry, Rhode Island Hospital, for technical
as-sistance and Ms Donna Perry for secretarial assistance.
REFERENCES
PAUL A. PITEL, MD
KENNETH L. MCCORMICK, MD
EILEEN FITZGERALD, MD
JAY M. OisoN, MD
Rhode Island Hospital and
Brown University
Providence, Rhode Island
1. Krugman 5, Ward R (eds): Infectious Diseases of Children,
ed 4. St Louis, CV Mosby Co, 1973, p 412
2. Huttenlocker PR: Reye’s syndrome: Relation of outcome to therapy. J Pediatr 80:845, 1972
3. Vaughan VC, McKay JR (eds): Nelson Textbook of Pedi-atrics, ed 10. Philadelphia, WB Saunders Co, 1975, p 671
4. Landay SG: Varicella hepatitis and Reye’s syndrome: An
interrelationship? Pediatrics 60:746, 1977
5. Hoeprich PD (ed): Infectious Diseases. New York, Harper
and Row Publishers, Inc, 1977, p 750
6. Seligson D, Hirahara K: The measurement of ammonia in
whole blood, erythrocytes, and plasma. J Lab Clin Med 49:
962, 1957
7. Eschar J, Teit L, Waron M, et al: Hepatic lesion in chicken
pox. Gastroenterology 64:462, 1973
8. Cheatham WJ, Weller TH, Dolan TF, et al: Varicella: Report
of two fatal cases with necropsy, virus isolation and serologic studies. Am J Pathol 32:1015, 1956
9. Stanton RE, J005 HA: Glutamic-oxalocete transaminase of
serum in infancy and childhood. Pediatrics 24:352, 1959
10. Seaman WE, Ishak KG, Plotz PH: Aspirin-induced
hepato-toxicity in patients with systemic lupus erythematosis. Ann Intern Med 80:1, 1974
Familial
Asplenia,
Other
Malformations,
and
Sudden
Death
Sometimes the sudden, unexpected death of an
infant is shown by necropsy to be associated with
a clinical entity more clearly defined than sudden
infant death syndrome. This is a report of two
unrelated families, each with two affected members.
In one, asplenia occurred with and without
gastroin-testinal malformations. In the other, cardiovascular
malformations occurred in one member and
lye-mark syndrome’ in the other. Each asplenic infant
died suddenly.
CASE REPORTS
Case 1
I. H., a 7-month-old girl was in good health until fever,
cough, and irritability appeared three days before death.
On postmortem examination, no spleen was detected.
There were no other malformations. The respiratory sys-tern showed congestion of the entire airway. The pulmo-nary arteries were filled with large mononuclear cells and
fibrin that appeared as compact thrombi propagating
from congested larger arteries into small branches. The septa were widened, and their cellularity was increased.
There were a few air spaces with amorphous eosinophiic
material. The brain also showed multiple microthrombi
composed of large mononuclear cells and fibrin.
Postmor-tern bacteriologic culture showed only a rare colony of
Enterobacter. Studies for virus infection showed no
growth.
Case 2
A 1-year-old girl, C. K., died after 24 hours of fever.
Four months previously, she had been treated for a
serious sickness involving shock and hematologic
evi-dence of disseminated intravascular clotting, but with no
growth in a blood culture. At 2 weeks of age, surgery had
been performed on this infant to correct a herniation of
the stomach through the foramen of Bochdalek into the
right hemithorax.
Postmortem examination showed the large intestine to
be imperfectly rotated with the sigmoid largely toward
the midline but stifi on the left. The stomach was in the
right upper quadrant. The liver lay across the upper
abdomen with the right and left lobes approximately the
same size. The gallbladder arose from the right lobe. A
spleen could not be identified. The left diaphragm was
intact. The heart, great vessels, and coronary arteries were entirely unremarkable.
There was no consanguinity in this family, but the
greatgrandmothers of the two cases were sisters.
Case 3
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The first child in the family was a girl, N. G., who
became cyanotic shortly after birth. Catheterization and
angiographic studies showed transposition of the great
arteries plus the presence of subpulmonary stenosis of a
mild degree. A normal spleen and splenic artery were
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1980;65;631
Pediatrics
Paul A. Pitel, Kenneth L. McCormick, Eileen Fitzgerald and Jay M. Orson
Subclinical Hepatic Changes in Varicella Infection
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1980;65;631
Pediatrics
Paul A. Pitel, Kenneth L. McCormick, Eileen Fitzgerald and Jay M. Orson
Subclinical Hepatic Changes in Varicella Infection
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