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Prospective Identification and Treatment of Children With Pediatric Autoimmune Neuropsychiatric Disorder Associated With Group A Streptococcal Infection (PANDAS)
Marie Lynd Murphy, MD;
Michael E. Pichichero, MD
Arch Pediatr Adolesc Med. 2002;156:356-361.
ABSTRACT
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Background The current diagnostic criteria for pediatric autoimmune neuropsychiatric
disorder associated with group A streptococcal infection (PANDAS) are pediatric
onset, neuropsychiatric disorder (obsessive-compulsive disorder [OCD]) and/or
tic disorder; abrupt onset and/or episodic course of symptoms; association
with group A ß-hemolytic streptococcal (GABHS) infection; and association
with neurological abnormalities (motoric hyperactivity or adventitious movements,
including choreiform movements or tics).
Objective To assess new-onset PANDAS cases in relation to acute GABHS tonsillopharyngitis.
Design Prospective PANDAS case identification and follow-up.
Results Over a 3-year period (1998-2000), we identified 12 school-aged children
with new-onset PANDAS. Each patient had the abrupt appearance of severe OCD
behaviors, accompanied by mild symptoms and signs of acute GABHS tonsillopharyngitis.
Throat swabs tested positive for GABHS by rapid antigen detection and/or were
culture positive. The GABHS serologic tests, when performed (n = 3), showed
very high antideoxyribonuclease antibody titers. Mean age at presentation
was 7 years (age range, 5-11 years). In children treated with antibiotics
effective in eradicating GABHS infection at the sentinel episode, OCD symptoms
promptly disappeared. Follow-up throat cultures negative for GABHS were obtained
prospectively after the first PANDAS episode. Recurrence of OCD symptoms was
seen in 6 patients; each recurrence was associated with evidence of acute
GABHS infection and responded to antibiotic therapy, supporting the premise
that these patients were not GABHS carriers. The OCD behaviors exhibited included
hand washing and preoccupation with germs, but daytime urinary urgency and
frequency without dysuria, fever, or incontinence were the most notable symptoms
in our series (58% of patients). Symptoms disappeared at night, and urinalysis
and urine cultures were negative.
Conclusion To our knowledge, this is the first prospective study to confirm that
PANDAS is associated with acute GABHS tonsillopharyngitis and responds to
appropriate antibiotic therapy at the sentinel episode.
INTRODUCTION
GROUP A ß-hemolytic streptococcal (GABHS) tonsillopharyngitis occurs
in school-aged children and causes sore throat, fever, headache, and abdominal
pain. Peak seasonal occurrence is in the winter and spring months in temperate
climates. Diagnosis is confirmed by throat culture, and treatment includes
antibiotics. The sore throat illness is self-limited and will usually resolve
in about 5 days, even without antibiotic treatment. Infection with GABHS leads
to the production of serum antibodies, such as antistreptolysin O (ASO) and
antideoxyribonuclease B (anti–DNase B). In certain individuals, infection
and antibody production lead to end-organ damage, as antibodies cross-react
with tissue of the kidney (post-GABHS glomerulonephritis), heart (rheumatic
fever), and brain (Sydenham chorea). Typically, nephritis occurs about 10
days after GABHS throat infection, and rheumatic fever occurs about 18 days
after infection, whereas chorea occurs months later.1
Because the throat culture may no longer be positive, diagnosis of post-GABHS
nonsuppurative sequelae depends on a history of a positive throat culture
in the preceding months or the presence of elevated titers of at least 1 of
the streptococcal antibodies.2
Obsessive-compulsive disorder (OCD) is characterized by obsessions,
the intrusive and unwanted thoughts or images that cause anxiety or distress,
and compulsions, the actions performed to soothe the distress caused by the
obsessions. The disorder is usually diagnosed in adolescence in men and early
adulthood in women, and it has a lifetime prevalence of 2% to 3%. Comorbid
conditions include depression, tics, and anxiety disorders. Typically, there
is a slow, insidious onset over months to years before diagnosis.3 Children with Sydenham chorea also exhibit OCD.4 In one series, 70% of those with Sydenham chorea had
sudden-onset OCD.5
Pediatric autoimmune neuropsychiatric disorder associated with group
A streptococcal infection (PANDAS) is a recently described entity that may
be similar in mechanism to other nonsuppurative post-GABHS disorders. Unlike
typical patients with OCD, children with PANDAS develop sudden-onset OCD or
tic behavior shortly after GABHS infection. The working criteria for a diagnosis
of PANDAS are (1) presence of OCD and/or tic disorder; (2) pediatric onset;
(3) abrupt onset and episodic course; (4) association with GABHS infections;
and (5) association with neurological abnormalities, such as motoric hyperactivity,
choreiform movements, or tics.6-7
To date, most knowledge about PANDAS has been obtained by studying patients
with a known tic disorder or long-standing OCD in research facilities and
referral centers.6, 8-12
The authenticity of PANDAS has been questioned.13-14
We describe 12 patients in a primary care practice identified at the onset
of a first episode of PANDAS and followed prospectively to address questions
about age of onset, sex predominance, seasonal occurrence, relationship to
GABHS infection, and response to antibiotic treatment. We conclude that there
is an association between sudden onset of neuropsychiatric symptoms, especially
OCD, and GABHS tonsillopharyngitis in some previously healthy children.
PARTICIPANTS AND METHODS
This prospective study was conducted at the Elmwood Pediatric Group,
a primary care, pediatric office practice in suburban Rochester, NY. Patients
were identified and followed during a 3-year time period, from 1998 to 2000.
Children presenting with the abrupt, explosive onset of a significant new
behavioral problem, such as OCD, tic disorder, age-inappropriate separation
anxiety, or late age–onset attention-deficit/hyperactivity disorder
(ADHD) were considered for admission to the study group. Children with long-standing
behavioral symptoms presenting for initial care were not included. Once the
explosive onset of behavior was identified, the presence of GABHS infection
was investigated. If GABHS infection was present (positive throat culture
at presentation or recorded in the medical record in recent prior weeks) or
had occurred recently (as documented by an elevated ASO or anti–DNase
B titer) a diagnosis of PANDAS was made, antibiotic treatment was rendered,
and the patient was observed prospectively. Behavioral symptoms were reported
by parents and/or observed in the office. Severity was estimated by the inability
to attend school normally or the degree to which symptoms interfered with
family routines.
No patient had been previously diagnosed with acute rheumatic fever,
Sydenham chorea, Tourette syndrome, or ADHD. One child had transient Bell
palsy after varicella. Another child had acute onset of OCD behavior in 1997,
but she entered our study group during a recurrence of OCD symptoms when it
was first recognized that she had PANDAS. Subsequent medical record review
was used to determine the GABHS history in prior years. As with patients presenting
with rheumatic fever, the presence of GABHS infection was determined by throat
swabs tested by rapid antigen-detection assay (Acceava; Thermo BioStar, Inc,
Boulder, Colo) or throat culture on sheep blood agar plates in the Elmwood
Pediatric Group office laboratory (Clinical Laboratory Improvement Act level
3 certified). The GABHS antibody titers (ASO and anti–DNase B) were
quantitated at commercial laboratories. Analyses of antineuronal antibodies
were performed as previously described15 (courtesy
of John Zabriskie, PhD).
Once identified, patients with PANDAS were followed prospectively to
document improvement of the OCD behavior by parent report and, in some cases,
independent psychiatric evaluation. Improvement in tic behavior was documented
by a physician. Serial titers or follow-up throat cultures documented resolution
of the initial acute GABHS infection. Patients were instructed to return for
evaluation if fever, sore throat, or recurrence of behavioral symptoms occurred.
The time course of onset was again documented, patients were examined, and
rapid antigen-detection assay or throat culture for GABHS was performed. If
there was no evidence of GABHS on initial throat culture, patients were instructed
to return in 3 days for another culture.
RESULTS
CASE REPORT
A 5-year-old boy suddenly developed frequent daytime urination (Table 1; patient No. 7). The onset was
pinpointed to one evening. He voided, then immediately felt the urge to void
again, producing only drops of urine. This behavior peaked in the morning
when he was trying to catch the school bus. There was no fever, dysuria, or
incontinence. The symptoms did not occur through the night.
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Demographic and Disease Characteristics of 12 Patients With PANDAS*
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This obsession with urine and the compulsive need to repeatedly urinate
increased over 7 days, along with the acute onset of an age-inappropriate
separation anxiety. He cried for hours when his mother left for work and he
was left in the care of his father.
On examination, marked tonsillopharyngeal erythema, an impetiginous
lesion at the corner of the lip, and moderate cervical adenopathy were present
without fever or tonsillar enlargement. A throat culture was positive for
GABHS. A cephalosporin was prescribed, and within 6 days, his compulsive need
to urinate ended, his separation anxiety improved, and he was attending school
normally.
A month later, the patient returned with another abrupt onset of compulsive
urination, separation anxiety before school, and a mild sore throat. On examination,
the posterior pharynx was intensely red, without enlargement of the tonsils,
fever, or adenopathy. Throat culture and rapid antigen-detection assay were
both negative for GABHS. The patient was instructed to have another throat
swab in 72 hours, which was positive for GABHS. He was treated with a cephalosporin,
and, in 5 days, his OCD behaviors and anxiety had normalized. The findings
from the follow-up examination were normal, the throat culture was negative
for GABHS, and symptoms did not recur during 12 months of follow-up.
AGE, SEX, AND SEASONAL PATTERN
Data summarizing age, sex, month of OCD onset, neuropsychiatric symptoms,
and recurrences for the 12 cases of PANDAS in our series are shown in Table 1. Mean age was 7 years (age range,
5 years 4 months, to 10 years 11 months). The sex ratio showed a predominance
of boys (1.4:1), and the months of initial OCD episode were September through
April.
NEUROPSYCHIATRIC SYMPTOMS
All patients had abrupt onset of neuropsychiatric symptoms, and 7 (62%)
of 12 patients could pinpoint the day symptoms started. All patients had obsessive
thought patterns, 75% of which were germ- or illness-related, causing compulsive
hand washing or excessive toilet hygiene rituals. One child compulsively hoarded
items her germs had touched. Seven children (58%; including 4 [80%] of the
5 girls) exhibited a pattern of compulsive daytime urinary urgency, frequency,
and wiping without fever, dysuria, or nighttime symptoms and without evidence
of urinary tract infection by urinalysis or urine culture. Forty-two percent
of patients experienced a new onset of extreme and age-inappropriate separation
anxiety when leaving their mothers. This symptom was manifest especially in
the morning before the school bus arrived, with children physically clinging
to their parents' legs and refusing to part. The oldest child in the series
was able to verbalize his obsessive, irrational fear of dying or being sent
to prison, but the younger children with this compulsive need to be with their
mothers could not verbalize the thoughts leading to this behavior. Four (33%)
of 12 children had clear-cut neurologic abnormalities. Two boys had recurrent
tics, including head tilting, nodding, and eye blinking. One of these patients
showed negative and aggressive behaviors. One boy had transient ADHD-like
symptoms, including fidgeting, memory impairment, and deterioration of handwriting.
No patients had classic chorea, but the 1 patient most severely affected exhibited
choreiform finger movements. All patients were emotionally labile and exhibited
motoric hyperactivity during these episodes.
The first 4 patients were referred for psychiatric evaluation because
the severity of their symptoms interfered with daily activities. Three were
incapacitated and unable to leave the home. In each patient, OCD with or without
anxiety was confirmed by history, but the patients had already improved following
antibiotic treatment by the time of psychiatric evaluation several weeks later.
Subsequent patients with similar symptoms and severity were followed through
the pediatric office without referral to psychiatric care. The severity of
the illness was determined by parental report. All patients met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition16 criteria for severe OCD because they were unable
to attend or function at school or child care. The Children's Yale-Brown Obsessive-Compulsive
Scale17 criteria of time spent, interference,
distress, resistance, and control over obsessions would place these children
in the category of severe to extreme severity.
ASSOCIATION BETWEEN OCD SYMPTOMS AND GABHS INFECTIONS
Evidence of a clear-cut, temporal relationship between the abrupt onset
and/or exacerbation of OCD symptoms and acute GABHS tonsillopharyngitis infection
was established by prospective throat swab testing in most patients. Antistreptococcal
antibody titers were obtained in a subset for whom the throat cultures were
not concurrently positive with behavior changes. A notable feature of the
tonsillopharyngitis episodes was the lack of severity. Few children had fevers,
and their sore throats were mild. The tonsillopharynx was moderately to intensely
red, but exudate was scant or absent and cervical adenopathy was minimal.
None of these children displayed the typical features of classical severe
GABHS tonsillopharyngitis, although 1 patient had scarlet fever rash.
There was a latent period between GABHS infection at a remote time and
GABHS infection triggering PANDAS. The Elmwood Pediatric Group practice had
cared for most patients since birth and all for at least a year before the
onset of PANDAS. Eleven (92%) of 12 patients had a documented GABHS illness
(range, 1-7 illnesses) prior to the GABHS illness that triggered OCD; 1 had
no documented prior GABHS illness but had febrile lobar pneumonia associated
with a sore throat. Eight (67%) of 12 patients had 4 or fewer episodes of
GABHS infection before they developed PANDAS; the 4 patients who had no recurrences
of OCD were all in this group. Four (33%) of 12 patients had 5 or more episodes
of GABHS infection; the patients with the most OCD recurrences, and the most
severe OCD, were in this group.
SENTINEL EPISODE OF OCD
When new-onset OCD symptoms occurred, evidence of GABHS infection in
recent weeks was sought to establish the diagnosis of PANDAS. Ten (83%) of
12 patients had a throat culture or rapid antigen-detection assay negative
for GABHS within 3 months before the new GABHS infection associated with OCD,
which suggests that they were not carriers; 7 of these patients had a negative
rapid antigen-detection assay or throat culture within 1 month before the
new infection. Documented GABHS infection from throat swabs during a clinical
episode of pharyngitis (in 1 case, scarlet fever) occurred at presentation
in 6 of 12 patients or within 1 month in 4 of 12 patients prior to the initial
episode of OCD, for a total of 10 (83%) of 12 patients. Of the remaining 2
patients, 1 had clinical pharyngitis with a negative rapid antigen-detection
assay 11 days before the new GABHS infection but a documented elevated anti–DNase
B titer (>1360) at onset of OCD. One patient (with 7 previous episodes of
GABHS) had documented GABHS 3 months before and underwent a tonsillectomy
without antibiotic treatment 1 month prior to the onset of OCD. She was included
in the study when we first recognized PANDAS at a recurrence of the GABHS
infection. Nine (75%) of 12 patients had a documented follow-up throat culture
negative for GABHS within 1 month of treatment. Of the remaining 3, 1 had
a decrease in anti–DNase B titer over 6 months (>1360 to 960). The remaining
2 had clinical improvement but no throat culture obtained at the end of treatment.
RESPONSE TO ANTIBIOTIC TREATMENT AT THE SENTINEL PANDAS EPISODE
All patients were treated with 10 days of an antibiotic effective for
eradication of GABHS infection. It is the practice of the Elmwood Pediatric
Group to prescribe penicillins or cephalosporins when GABHS infection occurs.
Five of our patients received penicillin (or amoxicillin because of taste
preference); 1 patient received amoxicillin/clavulanate potassium, and 6 received
a cephalosporin. In each sentinel episode in our series, initiation of antibiotic
therapy appeared to lead to prompt improvement in OCD symptoms. In the 4 patients
with no subsequent recurrences, behavior was normal in 5 to 21 days. The mean
time to resolution of symptoms was similar in patients treated with penicillin
or amoxicillin (14 days) compared with those treated with a cephalosporin;
however, 2 patients treated with a cephalosporin showed the fastest symptom
resolution (5 and 6 days).
RECURRENCE OF PANDAS
Six (50%) of 12 patients had at least 1 distinct recurrence of OCD.
Two patients had 1 recurrence, 2 had 2, 1 had 4, and 1 had 6, for a total
of 16 recurrent episodes in these 6 patients. The 2 patients with the most
recurrences both experienced more than 6 episodes of GABHS prior to the GABHS
infection that triggered PANDAS. Both patients developed a waxing and waning
course. In every instance, the recurrence of PANDAS behavior was associated
with a GABHS infection. Fourteen (87%) of the 16 recurrent OCD episodes were
preceded by a documented throat culture negative for GABHS 1 to 3 months prior
to illness, suggesting that the patients were not chronic GABHS carriers.
All recurrent cases had a documented throat culture or rapid antigen-detection
assay positive for GABHS. All patients were treated with antibiotics (usually
a cephalosporin), all had prompt improvement of their OCD symptoms, and all
had a documented throat culture negative for GABHS after treatment. In no
instance did a new recurrence of OCD occur in the absence of a new GABHS infection,
nor did a GABHS infection occur without OCD symptoms recurring. In the patients
with 1 or 2 recurrences, they occurred 1 to 6 months later. In each patient
with multiple recurrences, the recurrences spanned the entire 3-year study
period. Some parents identified a recurrence of behavioral symptoms even before
the culture was positive for GABHS. They were instructed to return in 72 hours,
and throat cultures were then positive. The OCD symptoms were similar to prior
symptoms at recurrence.
SEROLOGIC TESTING
Serologic tests for acute GABHS were conducted on 3 children. Titers
for anti–DNase B were elevated above the laboratory reporting range
(>1360) for 2 patients at the onset of the neuropsychiatric episodes. Two
patients also had elevated ASO titers (2- to 3-times the normal level) at
the time of the PANDAS diagnosis. One patient was tested for antineuronal
antibodies9 and they were detected.
COMMENT
The identification and prospective observation of 12 children with PANDAS
provided an opportunity to address several important questions about the disorder.
AGE, SEX, AND SEASONAL OCCURRENCE
The children with PANDAS had an age of onset (5-12 years old) and seasonal
occurrence (September-April) similar to the peak age and seasonal occurrence
of GABHS tonsillopharyngitis,1 which is not
surprising because PANDAS is associated with GABHS infection. In our practice,
the peak of GABHS infection occurs between September and April.18
Boys were more commonly identified with PANDAS. Tics, GABHS, and OCD are more
common in men.1 The age of onset of classic
OCD is much different than in our patient group; OCD usually has its onset
in late adolescence or early adulthood.3 Previous
studies of PANDAS have defined the disorder as prepubertal, with a predominance
of boys affected.7
NATURE OF OCD SYMPTOMS
The nature of the OCD symptoms in our series is similar to other reports
of OCD. Germ-related behaviors included repeated hand washing, hoarding of
items germs had touched, and excessive toilet hygiene rituals. In most studies,
women show more washing behaviors, and men show more checking behaviors, aggressive
behaviors, and comorbid tics.3 The specific
complaint of compulsive urinary frequency was more common in this series then
in general reports of obsessive-compulsive behavior.
NEUROPSYCHIATRIC SYMPTOMS ONSET AND GABHS INFECTION
At the sentinel episode of neuropsychiatric symptoms, onset was sudden
and dramatic and, in every case, was associated with concurrent GABHS tonsillopharyngitis
or a GABHS throat infection in the previous 4 weeks. A positive throat culture
or rapid antigen-detection assay demonstrated the association. Streptococcal
serologic tests (ASO and/or anti–DNase B) were conducted for 3 children
and followed sequentially. However, as Swedo et al6
and others12-13 have pointed out,
positive antistreptococcal titers obtained at the time of neuropsychiatric
symptom exacerbation are not sufficient to prove that a child has PANDAS because
titers may remain elevated for several months following an acute infection.
After entering the study, cultures negative for GABHS were documented before
the next positive GABHS culture associated with recurrence of PANDAS behavior
changes.
The number of prior episodes of GABHS infection was the only factor
that appeared to predict a more severe, relapsing course of PANDAS. The patients
who did not have recurrences had fewer episodes of GABHS prior to PANDAS onset,
and those with the most severe and relapsing course had the most episodes
of GABHS before the onset of PANDAS. Those with the most recurrences developed
more significant behavioral symptoms, which then began to wax and wane. Their
OCD symptoms became more chronic and persistent. This result is consistent
with the increased incidence and severity of OCD seen with recurrences of
Sydenham chorea.19
The association of GABHS infection with symptom exacerbation was determined
prospectively for all episodes. Data from rheumatic fever studies demonstrate
that a GABHS infection can precede chorea symptoms by several months,2 although the lag between subsequent infections and
symptom exacerbation is much shorter, often only a few days to a week apart,
suggesting an immunological memory response. Our finding of a new acute GABHS
throat infection that triggers PANDAS preceded by a GABHS infection at least
6 months earlier is consistent with the same immune response pattern. Possibly,
in the early stage of GABHS infection, an antibody is stimulated that may
precipitate behavioral effects even days before the quantity of GABHS is sufficient
to be detected by rapid antigen-detection assay or throat culture.
RESPONSE TO ANTIBIOTIC TREATMENT
Surprisingly, with antibiotic treatment appropriate for GABHS infection,
our patients exhibited dramatic, rapid resolution of their sentinel OCD, anxiety,
and tic symptoms. Resolution of symptoms occurred an average of 14 days after
treatment began. This is in marked contrast to typical OCD, which evolves
slowly and requires extensive treatment with cognitive behavioral therapy
and/or medication to alleviate symptoms over months to years.3
Compulsive wiping and washing rituals disappeared first, and the obsessive
thought patterns presumed to lead to the separation anxiety cleared more slowly
(usually within several weeks) but completely. The rapid, apparent response
to treatment suggests to us the possibility of a GABHS-associated toxin that
is a mediator of PANDAS. We speculate about this possibility because such
a response would not seem as likely if the process were autoimmune antibody–mediated.
These observations did not occur in the context of a double-blind, randomized,
controlled trial, so further examination of these potentially important findings
is clearly needed.
AUTHENTICITY OF GABHS DIAGNOSIS
By definition, because these children displayed symptoms and signs of
GABHS tonsillopharyngitis, albeit milder then the classic case, they were
not carriers. The negative cultures before and after onset of OCD and before
and after recurrences of OCD episodes further argue against the notion that
these children were carriers. Third, GABHS carriers do not show antibody increases
in response to streptococcal antigens. Although more than 60% of patients
with rheumatic fever show significantly elevated ASO titers, those with chorea
are less likely to exhibit elevated ASO titers, and multiple antibody tests,
including anti–DNase B, may be needed to document bona fide GABHS infection.2 When obtained, serologic test results showed the children
had very elevated anti–DNase B and/or elevated ASO titers. However,
we were struck by the absence of a strong inflammatory response (symptoms
and signs) elicited by the GABHS strain infecting our patients. This is similar
to the experience documented by Veasy et al20
during recent acute rheumatic fever outbreaks.
Characterization of these strains of GABHS that are prone to the induction
of PANDAS in the susceptible host will be of interest. The factors that confer
susceptibility to the development of PANDAS, the possible association D8/17
B-lymphocyte antigen as a marker trait,21 the
immune response associated with the development of the clinical symptoms,
and identification of the anatomical structures involved in the expression
of the clinical symptoms of PANDAS need to be explored. Might these children
be rendered less susceptible by prevention of GABHS infection through antibiotic
prophylaxis? Would immunization against GABHS, when it becomes available,
be of benefit, or would it induce autoimmune antibodies?
The possibility that pathogens other than GABHS can induce neuropsychological
symptoms6 was not confirmed in our study. Our
findings do not support the postulate that GABHS needs to be the initial autoimmunity-inciting
event, but that subsequent symptom exacerbations can be triggered by viruses,
other bacteria, or noninfectious immunological responses.6
Previous PANDAS studies included children with long-standing Tourette syndrome.6 Our study and application of the PANDAS diagnostic
criteria to an unselected private practice population suggest tics are not
as common as previously reported, although several boys in our series had
tics.
Comorbid symptoms (emotional lability, separation anxiety, and oppositional
and age-inappropriate behaviors) were also episodic and temporally related
to PANDAS in our patients. Some of these symptoms were present in all our
patients, so we consider them manifestations of the PANDAS phenomenon. We
concur with Swedo et al6 that perhaps the PANDAS
syndrome should be expanded to include primary diagnosis of late-onset ADHD
and age-inappropriate separation anxiety disorders, as well as OCD and tic
disorders. In any case, the abrupt onset of OCD at an early age is quite distinct
from the usual pattern of OCD characterized by gradual onset presenting in
adolescence or early adulthood.3 The present
study also identifies urinary frequency and urgency and associated toilet
hygiene rituals as another OCD behavior common in patients with PANDAS.
The design of our study does not allow a determination of the incidence
of children with neuropsychiatric disorders who have PANDAS. However, if physicians
look for this disorder, the average community-based practitioner may see 1
to 3 new cases per year. This is far more common than rheumatic fever or poststreptococcal
glomerulonephritis. Physicians caring for children should be aware of PANDAS
because our study strongly suggests that appropriate antibiotic treatment
directed at GABHS eradication at the sentinel episode of PANDAS may be of
benefit. Further studies to examine the best method of eradicating GABHS from
the oropharynx and presumed circulating autoantibodies should be undertaken.
| What This Study Adds
The possible association between streptococcal infections and the sudden
onset of neuropsychiatric disorders such as OCD and tic disorder has been
described in the psychiatric literature and in patients with long-standing
Tourette syndrome seen in research centers. This is the first prospective
study in a primary care setting to confirm an association between sudden onset
of a first episode of OCD, anxiety, ADHD, or tic disorder and streptococcal
throat infections. It is also the first study to document the disappearance
of neuropsychiatric symptoms during antibiotic treatment for streptococcal
sore throat, the recurrence of behavioral symptoms with streptococcal sore
throat, and the subsequent disappearance of symptoms with appropriate antibiotic
treatment.
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AUTHOR INFORMATION
Accepted for publication January 3, 2002.
Corresponding author and reprints: Michael E. Pichichero, MD, Elmwood
Pediatric Group, University of Rochester Medical Center, 601 Elmwood Ave,
Box 672, Rochester, NY 14642 (e-mail: michael_pichichero{at}urmc.rochester.edu).
From the Elmwood Pediatric Group, University of Rochester Medical Center,
Rochester, NY.
REFERENCES
| |
1. Kaplan EL. Group A streptococcal infections. In: Feigen R, Cherry JD, eds. Textbook of Pediatric
Infectious Diseases. 3rd ed. Philadelphia, Pa: WB Saunders Co; 1992:1296-1303.
2. Lennon DR. Acute rheumatic fever. In: Feigen R, Cherry JD, eds. Textbook of Pediatric
Infectious Diseases. 3rd ed. Philadelphia, Pa: WB Saunders Co; 1992:387-396.
3. Zohar AH. The epidemiology of obsessive-compulsive disorder in children and adolescents. Child Adolesc Psychiatr Clin N Am. 1999;8:445-459.
ISI
| PUBMED
4. Swedo SE, Rapoport JL, Cheslow DL, et al. High prevalence of obsessive-compulsive symptoms in patients with Sydenham's
chorea. Am J Psychiatry. 1989;146:246-249.
FREE FULL TEXT
5. Asbahr FR, Negrao AB, Gentil V, et al. Obsessive-compulsive and related symptoms in children and adolescents
with rheumatic fever with and without chorea: a prospective 6-month study. Am J Psychiatry. 1998;155:1122-1124.
FREE FULL TEXT
6. Swedo SE, Leonard HL, Garvey M, et al. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal
infections: clinical description of the first 50 cases. Am J Psychiatry. 1998;155:264-271.
FREE FULL TEXT
7. Leonard HL, Swedo SE, Garvey M, et al. Postinfectious and other forms of obsessive-compulsive disorder. Child Adolesc Psychiatr Clin N Am. 1999;8:497-511.
ISI
| PUBMED
8. Perlmutter SJ, Garvey MA, Castellanos X, et al. A case of pediatric autoimmune neuropsychiatric disorders associated
with streptococcal infections. Am J Psychiatry. 1998;155:1592-1598.
FREE FULL TEXT
9. Kiessling LS, Marcotte AC, Culpepper L. Antineuronal antibodies in movement disorders. Pediatrics. 1993;92:39-43.
FREE FULL TEXT
10. Garvey MA, Perlmutter SJ, Allen AJ, et al. A pilot study of penicillin prophylaxis for neuropsychiatric exacerbations
triggered by streptococcal infections. Biol Psychiatry. 1999;45:1564-1571.
FULL TEXT
|
ISI
| PUBMED
11. Garvey MA, Giedd J, Swedo SE. PANDAS: the search for environmental triggers of pediatric neuropsychiatric
disorder; lessons from rheumatic fever. J Child Neurol. 1998;13:413-423.
FREE FULL TEXT
12. Swedo SE, Leonard HL, Kiessling LS. Speculations on antineuronal antibody-mediated neuropsychiatric disorders
of childhood. Pediatrics. 1994;93:323-326.
FREE FULL TEXT
13. Shulman S. Pediatric autoimmune neuropsychiatric disorders associated with streptococci
(PANDAS). Pediatr Infect Dis J. 1999;18:281-282.
FULL TEXT
|
ISI
| PUBMED
14. Kaplan EL. PANDAS? PAND? Or both? Or neither? Assessing a (possible?) temporal
or pathogenetic relationship with the Group A "streptococcal diseases complex." Contemp Pediatr. August 2000:81-96.
15. Swedo SE, Leonard HL, Mittleman BB, et al. Identification of children with pediatric autoimmune neuropsychiatric
disorders associated with streptococcal infections by a marker associated
with rheumatic fever. Am J Psychiatry. 1997;154:110-112.
ABSTRACT
16. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth
Edition. Washington, DC: American Psychiatric Association; 1994.
17. Goodman WK, Price LH, Rasmussen SA, et al. Yale-Brown Obsessive Compulsive Scale, II: validity. Arch Gen Psychiatry. 1989;46:1012-1016.
FREE FULL TEXT
18. Pichichero ME, Green JL, Francis AB, et al. Recurrent group A streptococcal tonsillopharyngitis. Pediatr Infect Dis J. 1998;17:809-815.
FULL TEXT
|
ISI
| PUBMED
19. Asbahr FR, Ramos RT, Negrao AB, Gentil V. Case series: increased vulnerability to obsessive-compulsive symptoms
with repeated episodes of Sydenham chorea. J Am Acad Child Adolesc Psychiatry. 1999;38:1522-1525.
FULL TEXT
|
ISI
| PUBMED
20. Veasy LG, Tani LY, Hill HR. Persistence of acute rheumatic fever in the intermountain area of the
United States. J Pediatr. 1994;124:9-16.
FULL TEXT
|
ISI
| PUBMED
21. Murphy TK, Goodman WK, Fudge MW, et al. B-lymphocyte antigen D8/17: a peripheral marker for childhood-onset
obsessive-compulsive disorder and Tourette's syndrome? Am J Psychiatry. 1997;154:402-407.
ABSTRACT
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