Acute Rheumatic Fever in Adults

Anthony L. Barnert, MD; Edwin E. Terry, MD; Robert H. Persellin, MD

Acute rheumatic fever (ARF) in 53 adults was characterized by a severe, series, even though the disease mani¬
febrile migratory polyarthritis involving primarily large joints in the lower ex- festations in some resembled those of
tremities, with evidence of an antecedent streptococcal infection. Carditis, the poststreptococcal group. None of
present in only eight (15%) of the adults, was mild and transient. The charac- these 13 had carditis.
teristic abnormality in laboratory findings was an erythrocyte sedimentation
RESULTS
rate (Westergren) greater than 100 mm/hr. Response to high-dose aspirin
therapy was prompt and dramatic in all patients. Mild and evanescent ab- The 53 patients represent approxi¬
normalities of both renal function and hepatic function (not aspirin-medi- mately 0.5% of all patients hospi¬
ated) were detected in 51% and 64%, respectively. A common disorder in talized on the general medical service
San Antonio, ARF has distinctive symptoms. It can be readily diagnosed and during this period. Admissions for
promptly treated. In the adult, it is almost exclusively a syndrome of events ARF were virtually negligible (total,
severe but transient in the joints, and mild and transient in the heart, kid- one case) in the months of September
neys, and liver. and October; otherwise, they were
(JAMA 232:925-928, 1975) equally distributed throughout the
year. The mean age of patients was
29±13 (1 SD) years (median, 24); 25
ACUTE rheumatic fever (ARF) is id erythrocyte sedimentation rate were women. Twelve (23%) had recur¬
considered a disease of decreasing in¬ (ESR) and is very responsive to ade¬ rent ARF.
cidence,' less common in warm cli¬ quate administration of salicylate. The major and minor diagnostic
mates'' and rare in adults. Carditis was infrequent in our pa¬ criteria for our patients are shown in
-

Most "

previous clinical series of patients
with ARF have either dealt with chil¬
dren or have been based on diagnostic
criteria less definitive than the 1965
revision of the Jones criteria.7 The
two reports of ARF in adults in the
past decade"-" included high percent¬
ages of recurrences (86% in one report
and 49% in the other); in both, pre¬
tients, and the overall course was
benign.
METHODS
All patients were seen between
1969 and 1974 at the Bexar County
Hospital, the teaching hospital for
the University of Texas Health Sci¬
ence Center at San Antonio. This in¬
Table 1. All had migratory poly¬
arthritis and their conditions fulfilled
at least two minor criteria; only eight
(15%) had active carditis. Two had
erythema marginatum; there were no
instances of subcutaneous nodules or
chorea in these adults.
The striking feature of this ill¬
ness was the severe migratory poly¬

existing rheumatic heart disease
(RHD) and new carditis were com¬
mon, leading to rates of residual
RHD of 86% and 69%, respectively.
Acute rheumatic fever is not a rare
disease in adults in San Antonio, Tex.
In the past four years we have seen
53 adults with this disorder. The clini¬
cal manifestations of the patients de¬
scribed in this report emphasize that
the illness is primarily that of an
acute, febrile migratory polyarthri¬
tis associated with an extremely rap-
From the Division of Rheumatology, Depart-
ment of Medicine, University of Texas Health
Science Center at San Antonio, San Antonio,
Tex.
Read in part before the Sixth Pan-American
Congress on Rheumatic Diseases, Toronto,
June 17, 1974.
Reprint requests to Division of Rheumatology,
University of Texas, Health Science Center,
7703 Floyd Curl Dr, San Antonio, TX 78284 (Dr.
Persellin).
stitution provides health care primar¬
ily for the medically indigent
residents of the area. The patients
were all admitted with the complaint
of joint pain and swelling of acute on¬
set. During this 4%-year period, no
patient, admitted with symptoms of
carditis without arthritis, was later
found to have ARF. The diagnosis of
ARF was made when Jones' criteria7
were met, including proof of an ante¬
cedent streptococcal infection, and
when other rheumatic disorders were
excluded. The antistreptolysin 0
(ASO) titer was considered elevated
if found to be 250 Todd units or
greater.7 '" " During this time, 13
adults fulfilled the criteria in the ab¬
sence of an antecedent streptococcal
infection (by throat culture or ASO
titer). Lacking this evidence, we did
not include these patients in our
arthritis. The onset of joint symp¬
toms was usually abrupt and associ¬
ated with fever. The inflammatory
reaction at the initial and subsequent
sites would reach maximum severity
within 12 to 24 hours and then gradu¬
ally subside over a period of two to
five days. Without a definite pattern,
new joints would become inflamed as
the symptoms in others were subsid¬
ing. The polyarthritis was extremely
variable in both severity and dura¬
tion: mild inflammation in joints re¬
mitted promptly, sometimes within
12 hours of onset in the untreated in¬
dividual. Once the migratory poly¬
arthritis had started, an average of
two joints would show symptoms
simultaneously, and the total number
of involved joints per patient was 6.7
(range, 2 to 16). Symmetrical arthritis
occurred in 35% of the patients. As

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 shown in Fig 1, involvement of large
Table 1.—Manifestations of Acute Rheumatic Fever (ARF) in 53 Adults
joints was common. Lower-extremity
No. Positive/ joints were frequently the initial site
_No. Studied (%) of arthritis (85%) and were ultimately
Major criteria involved in all. The hands were rela¬
Migratory polyarthritis_53/53 [100]
tively spared. Seldom would a joint
Carditis_ _8/53 (15] showing symptoms early in the course
Erythema marginatum_2/53 [4]
Subcutaneous nodules_0/53 (0)
of the disease become inflamed again.
Chorea 0/53 (0) ~
Symptoms of the febrile, migratory
Minor criteria polyarthritis were present for an
Fever (>38.0 C [100.4 F])_48/53 (91) average of ten days before hospital-
Erythrocyte sedimentation rate (>20
mm/hr)_53/53 (1001 ization, and subsided after treatment
First-degree heart block_15/53 (28) in each case.
Prior ARF or rheumatic heart disease_12/53 (23) fluid from inflamed joints
Antecedent streptococcal infection
Synovial
Throat culture*_14/40 (35) was evaluated in 25 patients, most
often from knee and ankle joints, at
Antistreptolysin
O _51/52 (98)
'Studied at time of admission.
varying stages of the rapidly evolv¬
ing synovitis. The average white
blood cell count of synovial fluid was
16,000/cu mm, ranging from 600 to
80,000/cu mm; 21 patients (84%) had
counts greater than 5,000/cu mm.
These observations reflected the vari¬
able intensity of inflammatory
changes evident clinically. Polymor-
phonuclear leukocytes predominated
(mean, 90%±9%; range, 73% to 100%).
The fluids were uniformly sterile and
free from crystals, with glucose con¬
centrations equivalent to those in
simultaneously drawn plasma sam¬
ples. Thus, the synovial fluids were
helpful in excluding other arthritides,
especially traumatic, septic, and crys¬
tal-induced disorders.
The manifestations of heart in¬
volvement in eight patients with car¬
ditis (Table 2) were mild and in seven
were completely transient, resolving

Fig 1 —Frequency of joints inflamed and site of initial joint involvement in 53 adults with by the time of hospital discharge
acute rheumatic fever. (within ten days in most). The one pa¬
tient with a persistent new murmur
has had a stable condition, with a
Table 2.—Manifestations of Carditis in Adults With Acute Rheumatic Fever mild course, for 34 months of follow-
up. No additional evidence of heart
Cardiac Findings disease has been detected as yet in
Age, yr/
Sex Persistent Transient any of the patients.
17/M Mitral insufficiency Middiastollc murmur, pericarditis, Fever, as defined in Table 1, was
cardiomegaly, S3,* first-degree found in 91% of patients at the time
heart block
25/M Aortic insufficiency (old) Cardiomegaly, first-degree heart block
of hospital admission. The admission
19/M Aortic Insufficiency, first-degree ESR (Westergren) was markedly ab¬
heart block normal in all patients, averaging 110
22/M Aortic insufficiency, pericarditis, mm/hr (range, 46 to 155), with a time
first-degree heart block course depicted in Fig 2. After one
19/M Pericarditis
15/F Mitral insufficiency and middiastolic week, the mean ESR was 70 mm/hr,
murmur, S, and by four weeks it was 39 mm/hr.
51/F Mitral insufficiency, S3, first- First-degree heart block was seen in
degree heart block five of the eight patients with carditis
54/F Aortic insufficiency, S3 and in ten of the remaining 45 with¬
*S3 indicates third heart sound. out carditis; it was transient in all. In

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 the 12 patients with prior episodes of
ARF, there was only one case of car¬
ditis, and in this patient no residual
heart disease developed.
Of considerable interest was the
finding of transient laboratory abnor¬
malities suggesting renal and hepatic
dysfunction. A total of 24 patients
had abnormal findings on urinalysis
initially:
Urinalysis (N 47)
=

Normal 49%
Trace or protein ( 1 + ) 28%
> 2+Protein
or casts 23%
Renal function
1 transient azotemia
1 poststreptococcal glomerulonephritis
(demonstrated by biopsy)
1 active, chronic glomerulonephritis
(demonstrated by biopsy)
Infection
3 Urinary tract infections (none with
streptococci)
Three patients had urinary tract in¬
fections, none with streptococci. Al¬ Fig 2.—Changes in erythrocyte sedimentation rate in 53 adults with acute rheumatic
fever. Shown are ±1 standard error of the mean for numbers of patients included
though slight proteinuria was de¬ in parentheses.
means

tected frequently (in 13 [28%] of

patients), protein concentrations
equal to or in excess of 100 mg/100 ml
were noted in 11 patients (23%); 23
(49%) showed normal results. The pro¬
teinuria was transient in all cases but
one. Furthermore, five patients had
either microhematuria or cellular
casts. Transient azotemia (serum cre-
atinine level, 2.6 mg/100 ml) was seen
in one patient. Another patient, a 14-
year-old male, was admitted to the
hospital with an acute, febrile, migra¬
tory polyarthritis of four days' dura¬
Even though the time of onset of the
Table 3.—Hepatic Abnormalities in
glomerulonephritis occurring af¬ Adults With ARF
ter ARF suggested an intercurrent
streptococcal infection, this could not Highest
be proved. There was also one case of _No.
Normal
(%)_Level
14/39 (36)
active, chronic glomerulonephritis, ÎSGOT* 19/32(59) 450 mlU/mlf
confirmed by biopsy. ÎAKP 7/19(37) 210mlU/ml
Mild and evanescent abnormalities Tbilirubln7/18(39) 2.7 mg/100 ml
in liver function tests (Table 3) were HB Ag 0/10 (0)_„._
seen in more than half the patients *SGOT indicates serum glutamic oxalo-
acetic transaminase; AKP, alkaline phospha-
studied (25/39). The serum glutamic tase; HB Ag, hepatitis B-associated antigen;
oxaloacetic transaminase (SGOT) lev¬ Î elevated value; I decreased value.
, ,

tion. There was no history of an ante¬
cedent streptococcal infection, but the
ASO titer was 333 units. He had had
ARF at age 8 years, with similar
manifestations. His ESR was 120
mm/hr. Results of the urinalysis were
normal. The fever and arthritis
promptly subsided with aspirin ther¬
el was elevated in 19 of 32 patients
(59%). The elevated values were noted
before initiation of salicylate ther¬
apy, and returned to normal within
one week (with continued salicylate
therapy) in all patients. Elevations in
serum glutamic pyruvic transaminase
levels were similar and showed a sim¬
fmlU indicates international milliunits.
in 4, and high in 11. One patient
showed serial levels (in tests done
twice weekly) of 70,155, 197, 230, and
330 mg/100 ml. The C3 level did not
correlate with the presence of carditis
or renal involvement.

apy. After ten days' hospitalization
he was discharged. Two days later,
the abrupt onset of facial edema, 5-kg
(10 lb) weight gain, and hypertension
prompted readmission. He had pro¬
teinuria (1.0 gm/24 hr) and hematuria
with hypocomplementemia and mild
azotemia. A renal biopsy specimen
showed acute glomerulonephritis
with subepithelial electron-dense
deposits diagnostic of acute post¬
streptococcal glomerulonephritis.
ilar time course. Alkaline phosphatase
level was mildly elevated in 7 of 19
patients (37%), often with a mild
conjugated hyperbilirubinemia (39%)
simulating obstruction. Additional
studies, including intravenous cho-
langiogram in three patients and
tests for hepatitis B-associated anti¬
gen in ten, demonstrated no
causation.
Level of serum complement (C3)
was initially low in 4 patients, normal
A striking feature of this illness in
our patients was the nearly uniform
response to aspirin. When adminis¬
tered in a dosage great enough to
produce a plasma salicylate level of
greater than 20 mg/100 ml, aspirin
caused complete subsidence of the se¬
vere synovitis within two days in 91%
other of patients and within four days in
98%. In 89% of febrile patients, the
temperature was persistently normal
(no reading greater than 37.0 C

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 48 hours of treat¬
[98.6 F]) within
ment; all were afebrile within four
days. Drug treatment was gradually
withdrawn over a 4- to 12-week pe-
riod. Antistreptococcal therapy was
'
given to all patients.
COMMENT
Acute rheumatic fever in adults is a
common disorder in our patient popu¬
lation. We have diagnosed this dis¬
ease in patients whose conditions met
the revised Jones' criteria,7 patients
in whom an antecedent streptococcal
infection could be confirmed. Not in¬
cluded were 13 additional subjects
whose conditions fulfilled these cri¬
teria but did not show evidence of
streptococcal infection, and patients
in whom other rheumatic disorders
could be diagnosed. In our hospital,
septic arthritis (especially gonococ-
cal), Reiter syndrome, acute rheuma¬
toid arthritis, systemic lupus er-
ythematosus, and serum-sickness-like
reactions were most often included in
the original differential diagnosis.
The diagnosis of ARF was not changed
in follow-up of any of the 53 patients
described. Persistent joint complaints
have developed in only one patient;
the relationship between chronic joint
pain and his ARF is unclear.
Clinically, the most striking mani¬
festation of ARF in the adult was the
severe migratory polyarthritis. Most
often, the arthritis involved the large
joints, usually in the lower extrem¬
ities. The abrupt onset, the migratory
chracteristics, and the very dramatic
response to adequate aspirin therapy
were typical clinical manifestations.
Although other rheumatic disorders
might show these symptoms, with
consideration of an antecedent
streptococcal infection, extremely
rapid ESR, and the absence of other
specific laboratory findings (such as
results from culture and tests for an¬
tinuclear antibody), the correct diag¬
nosis can be made.
The diagnosis most difficult to ex¬
clude completely is that of "postviral"
arthritis. While many of the known
viral syndromes can produce arthral-
gias or mild arthritis (noninflamma¬
tory synovial fluids found predomi¬
nantly in the hands),12 their
associated findings (such as rash in
rubella or parotitis in mumps) are
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characteristic and there is seldom evi¬
dence of a streptococcal infection
with striking elevation of the ESR
and dramatic response to aspirin. It
is, however, conceivable that a num¬
ber of infectious agents other than
the Streptococcus might produce a
syndrome similar to ARF. A coinci¬
dental streptococcal infection might
then account for the high ASO titer
seen.
We found carditis in only 15% of
patients; this figure is much less than
that reported in other series of adults
with ARF.8-91314 Importantly, the
manifestations of heart involvement
we found were mild and transient,
observations previously reported in
lesser frequency.1518 In our series,
only one new case of RHD occurred; it
should be noted, however, that follow-
up in our patients has been limited.
Renal abnormalities in ARF have
been noted,19-20 and our observations
emphasize this association. In almost
all patients, the abnormalities were
evanescent. The finding of abnormal
SGOT concentrations in ARF has also
been reported.21 Several publications
have suggested that aspirin might
be the cause of hepatocellular dam¬
age2225—the abnormalities developed
after one week of aspirin treatment
and were persistent. In our patients,
hepatocellular abnormalities were de¬
tected before aspirin administration
and all abnormal results on liver
function tests returned to normal
during salicylate therapy. If, indeed,
the illness in our patients was
rheumatic fever and not an as yet un¬
identified viral syndrome, it is likely
that mildly abnormal results on liver
function tests can occur early in this
disorder.
This study was supported in part by a grant
from the South Central Texas Chapter of The
Arthritis Foundation.
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