Am J Psychiatry 157:12, December 2000
The Psychiatric Symptoms of Rheumatic Fever
Marcos T. Mercadante, M.D., Ph.D.
Geraldo F. Busatto, M.D., Ph.D.
Paul J. Lombroso, M.D.
Lísia Prado, B.S.
Maria C. Rosário-Campos, M.D., M.Sc.
Raquel do Valle, M.Sc.
Maria J. Marques-Dias, M.D., Ph.D.
Maria H. Kiss, M.D., Ph.D.
James F. Leckman, M.D.
Euripedes C. Miguel, M.D., Ph.D.
Objective: This study examined the frequency and age at on-
set of psychiatric disorders among children with rheumatic fe-
ver, Sydenham’s chorea, or both and a comparison group.
Method: Twenty children with rheumatic fever, 22 with Syden-
ham’s chorea, and 20 comparison children were assessed by
means of a semistructured interview and rating scales for tic
disorders and obsessive-compulsive disorder.
Results: Obsessive-compulsive symptoms were more frequent
in both the Sydenham’s chorea and rheumatic fever groups
than in the comparison group. The Sydenham’s chorea group
had a higher frequency of major depressive disorder, tic disor-
ders, and attention deficit hyperactivity disorder (ADHD) than
both the comparison and rheumatic fever groups. ADHD symp-
toms were associated with a higher risk of developing Syden-
Conclusions: Both the rheumatic fever and Sydenham’s cho-
rea groups were associated with a higher risk of developing
neuropsychiatric disorders than the comparison group. ADHD
appears to be a risk factor for Sydenham’s chorea in children
with rheumatic fever.
(Am J Psychiatry 2000; 157:2036–2038)
Rheumatic fever is an autoimmune disorder that oc-
curs after infection by specific strains of β-hemolytic strep-
tococci. Sydenham’s chorea, the late central nervous system
expression of rheumatic fever, has been associated with
higher rates of psychiatric disorders, such as obsessive-
compulsive disorder (OCD), tic disorders, major depressive
disorder, and attention deficit hyperactivity disorder
(ADHD), than those found in comparison patients (1–3).
In the present study, we systematically assessed the pres-
ence and the age at onset of neuropsychiatric symptoms in
patients with rheumatic fever, with and without Syden-
ham’s chorea, and a matched comparison group to deter-
mine the frequency and onset of psychiatric disorders.
All consecutively admitted patients with acute rheumatic fever
and Sydenham’s chorea from two academic hospitals in São
Paulo, Brazil, were assessed over an 18-month period (4). The ex-
clusion criteria were age less than 5 years or more than 16 years or
the presence of other neurological disorders. A comparison group
of children was matched for age and gender with the rheumatic
fever group and included children who were either seen in the
outpatient clinic or hospitalized for nonautoimmune medical
disorders. Written informed consent was obtained from all pa-
tients and their parents.
Rheumatic fever diagnoses were made according to the modi-
fied Jones criteria (5) by a pediatrician (M.H.K.). A child neurolo-
gist (M.J.M-D.) performed a complete neurological evaluation to
rule out other forms of chorea in the patients with Sydenham’s
chorea. None of the children in either group had previously been
referred for a psychiatric evaluation. A child psychiatrist (M.T.M.)
interviewed all probands and their parents. Best-estimate psychi-
atric diagnoses were made according to the DSM-IV criteria after
administration of the Schedule for Affective Disorders and
Schizophrenia for School-Age Children—Epidemiologic Version
(6), which includes questions regarding age at onset of psychiatric
symptoms. Although an effort was made to maintain blindness in
this study, it proved impossible regarding subjects in the group
with Sydenham’s chorea because of their overt symptom profiles.
The Yale-Brown Obsessive Compulsive Scale (7) and the Yale
Global Tic Severity Scale (8) were used to determine symptom se-
verity. In order to differentiate choreiform movements from tics,
we emphasized the presence of vocal tics in making a diagnosis of
tic disorders. When motor tics could not be distinguished from
choreic movements, a diagnosis of tic disorders was not made.
Comparisons of categorical variables among groups were per-
formed by means of Pearson’s chi-square analysis and Fisher’s
exact test for two-by-two tables. Comparisons of continuous
variables were carried out by means of ANOVA (Student’s t test
for the comparison of two groups). The ages at onset were com-
pared by means of paired-samples t tests. Significance values of
p<0.05 were used in all analyses. Stepwise backward logistic re-
gressions were also performed to establish the risk for the devel-
opment of Sydenham’s chorea, given the presence of other co-
There were no significant between-group differences in
demographic characteristics when the data were stratified
by referral source. The mean ages of the rheumatic fever,
Sydenham’s chorea, and comparison groups were 10.7
years (SD=2.7), 10.6 years (SD=2.8), and 10.7 years (SD=
2.7), respectively (age: F=0.02, df=2, 59, n.s.; sex: χ2=3.18,
The rates of psychiatric disorders are shown in Table 1.
Both the Sydenham’s chorea and rheumatic fever groups
had higher rates of obsessive-compulsive symptoms, tic
disorders, ADHD, and major depressive disorder than the
Am J Psychiatry 157:12, December 2000
comparison subjects (Table 1). Compared to the rheu-
matic fever group, the Sydenham’s chorea group showed
no difference in the rate of obsessive-compulsive symp-
toms, but the group with Sydenham’s chorea was at
greater risk for ADHD, tic disorders, and major depressive
disorder. The onsets of major depressive disorder, obses-
sive-compulsive symptoms, and tic disorders were con-
temporaneous or subsequent to the onset of rheumatic
fever in 89% (8 of 9), 42% (5 of 12), and 55% (11 of 20) of
the cases, respectively. But in 90% (9 of 10) of the cases
of ADHD, age at onset was significantly earlier than for
rheumatic fever (rheumatic fever or Sydenham’s chorea:
mean=10.6 years, SD=2.7, versus ADHD: mean=6.7 years,
SD=2.2) (t=5.40, df=9, p<0.01, Student’s t test).
The presence or absence of ADHD symptoms was a pre-
dictor for the risk of developing Sydenham’s chorea in this
study group. Specifically, if a child with rheumatic fever
had an antecedent history of ADHD, combined type, he or
she had a markedly higher risk of developing Sydenham’s
chorea (95%) than did rheumatic fever patients without
such a history (36%) (symptoms of inattention: B=1.40,
Wald’s χ2=2.32, df=1, p=0.13; symptoms of hyperactivity or
impulsive behavior: B=2.20, Wald’s χ2=3.71, df=1, p=0.05).
Similar to earlier reports, this study found major depres-
sive disorder, tic disorders, and ADHD to be more frequent
in patients with Sydenham’s chorea than in patients with
rheumatic fever (1, 2). Although the frequency for obses-
sive-compulsive symptoms was higher in the rheumatic
fever and Sydenham’s chorea groups than in the compari-
son group, we found obsessive-compulsive symptoms to
be present equally in both the rheumatic fever and Syden-
ham’s chorea groups. On the basis of the results of earlier
studies (1, 2), this finding was unexpected. This difference
may be explained by the small group sizes, the cross-sec-
tional design, and the differences in assessment methods,
including the fact that the individual responsible for the
best-estimate diagnoses was aware of the subjects’ initial
group assignments. The present study also differed from
previous investigations by its ascertainment of patients in
the acute phase of their illness (4) and in their first episode
of rheumatic fever or Sydenham’s chorea. Subsequently,
we monitored each of the children with rheumatic fever
and diagnosed with either obsessive-compulsive symp-
toms or OCD. Thus far, over the ensuing 12–24 months,
none of these children has developed Sydenham’s chorea.
In this study, a systematic comparison of age at onset for
different neuropsychiatric disorders allowed us to deter-
mine the temporal relationship among the different syn-
dromes. For a number of individuals, there was a simulta-
neous beginning of the rheumatic or choreic symptoms,
the tic disorders, and the psychiatric symptoms of major
depressive disorder and OCD. This finding is consistent
with an autoimmune process being associated with both
movement and neuropsychiatric disorders (i.e., mental
disorders due to a general medical condition) (DSM-IV)
(1, 2, 9). However, a substantial number of individuals re-
ported the onset of ADHD, tic disorders, and obsessive-
compulsive symptoms before the occurrence of rheu-
matic fever. Although, the significance of these findings is
unclear, they suggest that in some cases, ADHD, tic disor-
ders, and obsessive-compulsive symptoms may reflect a
vulnerability to developing rheumatic fever and Syden-
ham’s chorea. Future longitudinal studies are necessary to
evaluate whether these psychiatric symptoms represent
the early expression of an autoimmune process triggered
by streptococcus infections (9) or evidence of an increased
central nervous system vulnerability to rheumatic fever
and Sydenham’s chorea due to some other cause.
Presented in part at the Congress of the International Association
for Child and Adolescent Psychiatry and Allied Professions, Stock-
holm, August 2–7, 1998. Received Nov. 23, 1998; revisions received
Dec. 15, 1999, and June 1, 2000; accepted July 5, 2000. From the
Departments of Psychiatry and Pediatrics, Medical School, University
of São Paulo, São Paulo, Brazil; and the Child Study Center, School
ofMedicine, Yale University. Address reprint requests to Dr.
Mercadante, Child Study Center, Yale University, 230 South Front-
age Rd., P.O. Box 207900, New Haven, CT 06520-7900; mtmerc@
TABLE 1. Frequency of Psychiatric Diagnoses Among Children With Rheumatic Fever or Sydenham’s Chorea and Compari-
Children With Rheumatic
Fever or Sydenham’s
ADHD (combined type) 1023.8b
Any tic disorder2047.6a
Major depressive disorder921.4b
Generalized anxiety3 7.1
aSignificantly different from comparison children (p<0.01, Fisher’s exact test, two-tailed).
bSignificantly different from comparison children (p<0.05, Fisher’s exact test, two-tailed).
cSignificantly different from children with rheumatic fever (p<0.01, Fisher’s exact test, two-tailed).
BRIEF REPORTS Download full-text
Supported in part by grants from the Fundação de Amparo à Pes-
quisa do Estado de São Paulo (5012-7, 5013-3, 11991-0, and 7525-0)
and the Conselho Nacional de Desenvolvimento Científico e Tec-
nológico (521369) to Drs. Miguel and Mercadante and from NIMH
(MH-01527 and MH-49351) to Drs. Lombroso and Leckman.
The authors thank Drs. José Alberto del Porto, Orlando Barreto,
Vanda Bastos, Eunice Mitiko Ocuda, and Silvana Brasilia Sachetti for
reviewing this manuscript.
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