This is from Up to Date, which many medical personnel use. A friend sent it to me. More references than one would perhaps like to controversy.
PANDAS: Pediatric autoimmune neuropsychiatric disorder associated with group A streptococci
Michael E Pichichero, MD Section Editors
Sheldon L Kaplan, MD
Douglas R Nordli, Jr, MD
Thomas JA Lehman, MD Deputy Editor
Mary M Torchia, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jun 2012. | This topic last updated: Jun 24, 2012.
INTRODUCTION — Pediatric autoimmune neuropsychiatric disorder associated with group A streptococci (PANDAS) is a term used to describe a subset of children whose symptoms of obsessive compulsive disorder (OCD) or tic disorders are exacerbated by group A streptococcal (GAS) infection . The hypothesized association between PANDAS and GAS is controversial, as is the limitation of the diagnosis exclusively within the pediatric age group. (See 'Areas of controversy' below.)
An overview of PANDAS will be presented below. Other aspects of GAS infection in children, including diagnosis, treatment, prevention, and complications, are discussed separately. (See "Approach to diagnosis of acute infectious pharyngitis in children and adolescents" and "Complications of streptococcal tonsillopharyngitis" and "Treatment and prevention of streptococcal tonsillopharyngitis".)
BACKGROUND — Most of the knowledge about PANDAS has been obtained by studying patients with a known tic disorder or long-standing OCD in research facilities and referral centers [1-4]. Investigators at these centers noted an association between Sydenham chorea and OCD [5-7]. Sydenham chorea is a movement disorder characterized by chorea, emotional lability, and hypotonia. It is one of the major clinical manifestations of acute rheumatic fever (ARF). The investigators also identified a subset of children with OCD or tic disorders following GAS infection who did not meet criteria for Sydenham chorea [4,8,9]. This subset is described by the acronym PANDAS . (See "Sydenham chorea" and "Clinical manifestations and diagnosis of acute rheumatic fever".)
The diagnostic criteria for PANDAS, which are discussed in greater detail below, include the following [1,10]:
Obsessive-compulsive disorder (OCD) and/or tic disorder (Tourette disorder, chronic motor or vocal tic disorder)
Pediatric onset (between three years and onset of puberty)
Abrupt onset and episodic course of symptoms
Temporal relation between group A streptococcal (GAS) infection and onset and/or exacerbation
Neurologic abnormalities, such as motoric hyperactivity, choreiform movements, or tics during exacerbations
Whether PANDAS is a distinct form of more typical cases of OCD or tic disorder remains controversial; the proposed pathogenesis is also controversial [11-13]. These issues are important because they affect evaluation and management. They are discussed in greater detail below.
Areas of agreement — Although PANDAS is a controversial diagnosis, there is general agreement on the following points:
GAS is one of several factors that can exacerbate OCD or tic disorder in a subset of patients [1,9,14-17]
Children with signs and symptoms compatible with GAS infections should be evaluated for GAS infection [10,12] (see "Approach to diagnosis of acute infectious pharyngitis in children and adolescents", section on 'Diagnostic approach')
Children with GAS infection and OCD/tic disorder require standard treatments for these problems (regardless of whether GAS and OCD/tic disorder are causally associated) [10,12] (see 'Management' below)
Routine administration of immunomodulatory therapy (eg, glucocorticoids, plasma exchange, intravenous immunoglobulin [iVIG]) is not indicated for children who meet PANDAS criteria [10,12,18]
Routine administration of prophylactic antibiotics is not indicated for children who meet PANDAS criteria [10,12]
Areas of controversy — Controversies surrounding PANDAS include:
Whether PANDAS is sufficiently different from OCD/tic disorder to be considered a separate entity [14,17,19] (see 'Clinical features' below)
The nature of the association between GAS and PANDAS (eg, causal versus incidental) and whether it is important to single out GAS among the many other precipitants of OCD/tic disorders [13,14,17,20-23] (see 'Association with GAS' below)
Whether PANDAS is an autoimmune disorder [19,20] (see 'Pathogenesis' below)
Whether evidence of GAS infection should be sought in children with OCD/tic disorders [11,12,24] (see 'Diagnostic process' below)
PATHOGENESIS — The proposed model for pathogenesis of PANDAS suggests that group A streptococcal (GAS) infection in a susceptible host causes an abnormal immune response with resultant central nervous system manifestations. If this hypothesis is correct, there might be a role for prophylactic antibiotics and/or immune modulating therapies in the prevention and treatment of PANDAS. However, the hypothesis is as yet unproven.
The model for PANDAS pathogenesis is based upon the clinical similarities between Sydenham chorea and PANDAS . The pathogenesis of Sydenham chorea and acute rheumatic fever (ARF) are incompletely understood. However, preceding GAS pharyngitis and an abnormal immune response (in which antibodies directed against GAS antigens cross-react with host antigens in brain and other tissues) are widely accepted as important components. (See "Epidemiology and pathogenesis of acute rheumatic fever", section on 'Molecular mimicry'.)
Association with GAS — The association between neuropsychiatric symptoms and GAS infection was evaluated in a case-control study from a large health maintenance organization . The investigators identified 144 patients with obsessive-compulsive disorder (OCD), Tourette syndrome, or a tic disorder (in a population of about 75,000 children) and matched them with one to five control subjects. The following findings were noted:
Cases were more likely than controls to have had a GAS infection in the three months before onset of neurologic disease (odds ratio [OR] 2.22, 95% CI 1.05-4.69)
Cases were more likely than controls to have had multiple GAS infections during the 12 months before onset of neurologic disease (OR 3.1, 95% CI 1.77-8.96)
Prospective studies have confirmed that GAS is associated with the onset or exacerbation of OCD or tic disorder in at least some patients [14,15]. However, the high background rates of GAS infection, GAS carriage, and OCD/tic disorders in prepubertal children make it difficult to establish causality [10,12,13]. (See 'Differential diagnosis' below.)
Autoimmunity — The role of autoimmunity in PANDAS is controversial.
Support for a role of autoimmunity is provided by reports of response to treatment with immune-modifying therapies, such as glucocorticoids, intravenous immunoglobulin (IVIG), and plasma exchange [4,25,26]. The response to plasma exchange appears to be specific to children with OCD/tic disorders and preceding GAS infection; in an open trial, plasma provided no benefit for children with OCD whose symptom exacerbation did not follow GAS infection .
An autoimmune mechanism for PANDAS also is supported by animal studies, as well as studies demonstrating increased antineuronal antibodies in patients with PANDAS compared with patients with OCD/tic disorders but no evidence of GAS infection and patients with GAS infection but without OCD/tic disorder [26,28-30]. However, other studies have been unable to distinguish patients with PANDAS or Tourette syndrome from control patients on the basis of autoantibody profiles [31-34]. The inconsistent findings may be related to methodologic differences [35,36].
Additional observations that conflict with the hypothesis that PANDAS is caused by antineuronal antibodies include:
The failure of immunologic markers to correlate with clinical exacerbations in PANDAS patients in a longitudinal case-control study 
The failure of microinfusion of PANDAS serum into rodent striatum to produce changes in behavior 
EPIDEMIOLOGY — The incidence and prevalence of PANDAS are not known, although it is rare. In our prospective study , only 10 cases were identified among 30,000 throat cultures positive for GAS; since then, the annual incidence has ranged between 0 per 10,000 cultures to 10 per 30,000 cultures, depending upon the strain of GAS and host genetics (unpublished data) . Despite its rarity, some investigators suggest that it may account for ≥10 percent of childhood-onset OCD and tic disorders [40,41].
In the original series of 50 patients, the mean age of onset was 6.3 years for children with tics and 7.4 years for children with OCD . PANDAS was more common among boys and children with a family history of rheumatic fever.
Working diagnostic criteria — PANDAS is characterized by five working criteria [1,4,10]:
Obsessive-compulsive disorder (OCD) and/or tic disorder (Tourette, chronic motor, or vocal tic disorder that meets the DSM-IV diagnostic criteria). (See "Hyperkinetic movement disorders in children", section on 'Tic disorders'.)
Pediatric onset (between three years and onset of puberty).
Abrupt onset and episodic course of symptoms. (See 'Clinical course' below.)
Temporal relation between group A streptococcal (GAS) infection and onset and/or exacerbation. The time frame for the temporal relation was not specified in the original description . Antibody levels to streptolysin O and DNase B remain elevated for several months after an acute infection, complicating the applicability and interpretation of elevated titers . (See 'Laboratory features' below.)
Neurologic abnormalities, such as motoric hyperactivity, choreiform movements (elicited through stressed postures, but not present at rest), or tics during exacerbations. Frank chorea (rapid, irregular, and nonstereotypic jerks that are continuous while the patient is awake but improve with sleep) suggests Sydenham chorea. (See "Sydenham chorea".)
Some experts have questioned whether the above criteria are useful in distinguishing patients with PANDAS from patients with more typical cases of OCD or tic disorder [11,12,19]. However, observational studies suggest that clinical and laboratory features can distinguish PANDAS from OCD or tic disorder without PANDAS:
In a prospective study, 12 children with PANDAS were identified in a primary care practice over a three-year period . All had positive throat cultures at the time of onset of neuropsychiatric symptoms and improvement of neuropsychiatric symptoms with antibiotic therapy. Symptoms resolved completely in four patients within 5 to 21 days after onset, and none of these patients had a recurrence. Recurrent symptoms developed in the remaining children, and each recurrence was associated with a new episode of culture-proven GAS tonsillopharyngitis and amelioration of symptoms with antibiotic therapy.
In another study of 109 prepubertal children with tics, OCD, or both, dramatic onset of symptoms, remissions in neuropsychiatric symptoms, a clinical course marked by definite remissions, and remission of neuropsychiatric symptoms during antibiotic therapy were more likely among the 48 children with who met criteria for PANDAS (including positive GAS culture or rising antibody titers at the onset or exacerbation of neuropsychiatric symptoms) than those who did not .
Clinical course — The clinical course of PANDAS is characterized by a "sawtooth" pattern with periods of symptom quiescence, followed by exacerbations with abrupt onset and gradual resolution (over weeks to months) [1,4,10,15]. Abrupt onset of OCD/tic disorder symptoms also has been noted in patients without PANDAS [13,44]. Neuropsychiatric exacerbations in children with PANDAS begin at the time of GAS infection or within one to two weeks after GAS infection [1,10,15].
Children with PANDAS and tics occasionally have simultaneous onset of frequent, severe, and varied motor and vocal tics, prompting emergency treatment . This is in contrast to the typical onset of isolated, intermittent, simple motor or vocal tic that has a much more gradual onset and is milder [10,45].
Similarly, children with PANDAS and OCD are described as having an "explosion" of OCD symptoms, reaching clinically significant impairment in 24 to 48 hours . This is in contrast to the typical undulating waxing and waning pattern of OCD symptoms in patients without PANDAS [46,47].
Because fever and other stressors of illness are known to exacerbate OCD and tic disorders, to meet criteria for PANDAS, the exacerbations should have an association with GAS infection, documented by culture or serology to qualify as a possible case .
Laboratory features — Diagnosis of PANDAS requires a temporal relation between GAS infection and the onset and/or exacerbation of neuropsychiatric abnormalities [1,10].
GAS infection is confirmed by:
Positive throat or skin culture or rapid antigen detection test for GAS at the beginning of a PANDAS exacerbation, or
Clinically significant rise in antistreptococcal antibody between the onset of symptoms and four to six weeks later. It is important to obtain anti-DNase B as well as anti-streptolysin O titers since anti-DNase B titers are elevated in approximately 80 percent of PANDAS cases, whereas ASO titers are significantly elevated in 20 to 50 percent of cases .
Some authorities suggest repeat cultures and/or serology when children with suspected recurrent episodes of PANDAS are well to exclude streptococcal carriers [1,10,48].
DIAGNOSTIC PROCESS — PANDAS is a clinical diagnosis. It may be suspected in children with an abrupt onset of neuropsychiatric symptoms, recent group A streptococcal (GAS) infection, and remission of neuropsychiatric symptoms with antibiotic therapy. The obsessive-compulsive disorder (OCD)/tic disorder and acute GAS infection should be treated as outlined below. Patients with suspected PANDAS should be monitored for recurrence of neuropsychiatric symptoms and/or GAS infection because approximately 50 percent have second episodes . (See 'Management' below.)
We suggest that children who present with abrupt onset of OCD/tic disorder be evaluated for GAS infection.
Diagnosis of PANDAS requires prospective evaluation with documentation of an episode of neuropsychiatric symptoms associated with evidence of GAS infection. Evidence of GAS is provided by [1,10,48]:
A positive throat or skin culture or rapid antigen detection test for GAS, or
A rise in antistreptococcal antibody (ASO and/or anti-DNase titers (twofold or greater)
Demonstration of negative throat culture or declining antistreptococcal antibody titers during remission of neuropsychiatric symptoms is helpful in distinguishing GAS carriers .
The diagnostic process described above is that which is outlined by investigators at the National Institutes of Mental Health (NIMH) [1,10]. They maintain that the risk of acute rheumatic fever mandates the detection and appropriate treatment of GAS infections, including mildly symptomatic infections and infections in which neuropsychiatric manifestations are the only symptoms. (See "Treatment and prevention of acute rheumatic fever".)
However, this process is not endorsed by all experts [11,12]. Until a causal relationship between PANDAS and GAS infection is established, the American Heart Association (AHA) Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee does not recommend routine laboratory testing for GAS to diagnose PANDAS in children with OCD/tic disorders .
The evaluation of children with pharyngitis in the absence of neuropsychiatric manifestations is discussed separately. (See "Evaluation of sore throat in children" and "Approach to diagnosis of acute infectious pharyngitis in children and adolescents", section on 'Diagnostic approach'.)
DIFFERENTIAL DIAGNOSIS — The major considerations in the differential diagnosis of PANDAS are obsessive-compulsive disorder (OCD)/tic disorder in a child with coincident or intercurrent episodes of group A streptococcal (GAS) or a child with GAS carriage and Sydenham chorea [1,10,12,49].
Tic disorder or OCD — Both neuropsychiatric symptoms and GAS are common in prepubertal children. OCD occurs in 1 to 2 percent of school-age children and transient motor tics in as many as 25 percent [50-52]. GAS accounts for 15 to 30 percent of all cases of pharyngitis in children between the ages of 5 and 15 years. Prospective surveillance identified GAS carriage in 2.5 percent of well children and 4.4 percent of children with URI (including a sore throat) . (See "Approach to diagnosis of acute infectious pharyngitis in children and adolescents", section on 'Group A streptococcus' and "Antibiotic failure in the treatment of streptococcal tonsillopharyngitis", section on 'Streptococcal carriage'.)
Strict adherence to the diagnostic process described above should help to distinguish between PANDAS and coincidental simultaneous occurrence of these problems . Documenting negative throat culture and/or stable antistreptococcal antibody titers during remission helps to exclude GAS carriage. (See 'Diagnostic process' above.)
Sydenham chorea — Sydenham chorea is a movement disorder characterized by chorea, emotional lability, and hypotonia. Neuropsychiatric manifestations that may be present in Sydenham chorea also may occur in PANDAS patients (eg, OCD, separation anxiety, hyperactivity, adventitious movements) [6,49,54]. (See "Sydenham chorea".)
NATURAL HISTORY — The natural history of PANDAS was described in a prospective case-control study of 40 children with PANDAS and 40 children with obsessive-compulsive disorder (OCD)/tic disorders but no evidence of group A streptococcal (GAS) infection . Throat cultures were obtained once per month, and streptococcal antibody titers were measured at least once every three months, for two years; testing for GAS also was performed during exacerbations. Case subjects were treated with standard therapies for their neuropsychiatric symptoms and received prompt antibiotic therapy for GAS infections. Prophylactic antibiotics and immune modulating therapy were not administered. Laboratory personnel were blinded to the status of the patient (case versus control and exacerbation versus routine monitoring), and clinical raters were blinded to the laboratory results.
The following observations were made:
Forty neuropsychiatric exacerbations (clinically significant worsening for ≥5 days unrelated to a change in medication) occurred in 21 case patients (0.56 exacerbations per person year), and 25 neuropsychiatric exacerbations occurred in 14 control subjects (0.28 exacerbations per person year). These rates were lower than expected.
Only five neuropsychiatric exacerbations occurred within four weeks of GAS infection; all of these occurred in PANDAS patients. This was greater than the number expected by chance (1.6). However, in a subsequent similarly designed study by the same group, no neuropsychiatric exacerbations occurred within two months of newly diagnosed GAS infection in 31 PANDAS patients who were followed for 25 months .
The majority of exacerbations in PANDAS patients (87.5 percent) had no relation to GAS infection.
Definite or probable GAS infection was more frequent among cases than controls (0.43 versus 0.13 infections per person-year, relative risk 2.76, 95% CI 1.4-5.3).
These observations and those from other studies suggest that a subgroup of patients with tics/OCD may be vulnerable to GAS as a precipitant of neuropsychiatric symptoms, but the majority of exacerbations have other triggers [14,17,22]. In addition, PANDAS has a relatively benign clinical course when neuropsychiatric exacerbations and GAS infection are treated with standard therapies. (See 'Management' below.)
MANAGEMENT — The management of children with PANDAS centers on providing standard therapies for group A streptococcal (GAS) infection and obsessive-compulsive disorder (OCD)/tic disorder [10,12].
Antibiotic therapy — Antibiotic therapy is indicated for the treatment of acute streptococcal infection as diagnosed by a positive throat or skin culture or rapid antigen detection test .
GAS infection — We recommend that children with positive culture or rapid antigen detection test for GAS be treated with antistreptococcal therapy (whether or not they have neuropsychiatric symptoms). Antimicrobial therapy is administered to reduce the severity and duration of signs and symptoms, including suppurative complications, reduce the incidence of nonsuppurative complications (eg, acute rheumatic fever), and reduce the risk of transmission. Treatment of GAS pharyngitis is discussed separately. (See "Treatment and prevention of streptococcal tonsillopharyngitis".)
PANDAS subgroup — There are no randomized controlled trials of antibiotic treatment of children suspected of having PANDAS syndrome. In a prospective study that identified 12 children with abrupt onset of neuropsychiatric symptoms and evidence of recent GAS infection, antistreptococcal (penicillin or cephalosporin) therapy was associated with prompt symptom resolution in all cases . Antistreptococcal therapy also was associated with prompt resolution of symptoms in the six patients who developed recurrent symptoms associated with GAS infection. The mean time to resolution of symptoms was shorter among children treated with cephalosporin than with penicillin (14 versus 5 to 6 days).
Whether prompt antimicrobial treatment of GAS infection prevents the development of neuropsychiatric symptoms is not known [21,22].
We suggest that children with suspected PANDAS (ie, abrupt onset of neuropsychiatric symptoms and evidence of recent GAS infection) be treated with antimicrobial therapy, even if the episode of GAS was already treated (given the failure rates for penicillin and amoxicillin therapy). (See "Treatment and prevention of streptococcal tonsillopharyngitis", section on 'Selection'.)
The author of this topic review suggests therapy with a cephalosporin rather than a penicillin. Several alternative regimens are listed below:
Cefadroxil (30 mg/kg per day in one dose for 10 days)
Cephalexin (30 mg/kg per day in two divided doses for 10 days)
Cefuroxime (30 mg/kg per day in two divided doses for 10 days)
Cefpodoxime (10 mg/kg per day in two divided doses for five days)
Cefdinir (14 mg/kg per day in two divided doses for five days)
Neuropsychiatric therapy — Children with OCD and/or tic disorders should receive standard neuropsychiatric treatment for these disorders (whether or not the children have evidence of recent GAS infection) [10,12]. Treatment of neuropsychiatric symptoms should not be delayed pending confirmation of PANDAS (eg, documenting rise in antistreptococcal antibodies or while monitoring for a second episode).
The neuropsychiatric manifestations of children in the PANDAS subgroup respond to treatment with standard pharmacologic and behavior therapies . OCD symptoms generally respond to a combination of pharmacotherapy (typically a selective serotonin reuptake inhibitor) and cognitive behavior therapy. Motor and vocal tics can be treated with a variety of medications. (See "Tourette syndrome", section on 'Management'.)
Immune modulating therapy — Immune modulating therapies include glucocorticoids, plasma exchange, and intravenous immunoglobulin (IVIG). If PANDAS is an autoimmune disorder (and this remains controversial), immunomodulatory treatments might be beneficial.
We recommend not treating children who meet criteria for PANDAS with immune modulating therapies outside of the research setting . Immune modulating therapy may be an alternative for severely ill patients who have not responded to standard therapies. In such cases, consultation with a specialist in the treatment of neuropsychiatric and/or autoimmune disorders is recommended.
The potential benefits of treatment with plasma exchange or IVIG compared with placebo were evaluated in a randomized controlled trial in 29 children who met PANDAS criteria and were severely affected . Symptom severity was rated at baseline, and at 1 and 12 months after treatment. Significant improvement in symptoms from baseline was noted in the treatment groups at one month; improvements were maintained at one year, although psychotropic medications were decreased or discontinued in only 7 of 13 patients who required them at baseline. Adverse effects, which occurred in approximately two-thirds of patients in the treatment groups, included nausea, vomiting, headache, and dizziness.
Limitations of the trial included the lack of a control for plasma exchange, open treatment of controls after the one-month follow-up (making it impossible to exclude the possibility of spontaneous improvement in the control group at the 12-month follow-up), lack of correlation between therapeutic response and rate of antibody removal, and poorly understood mechanism of therapeutic benefit [19,25].
A subsequent open trial of plasma exchange in children with OCD who did not meet PANDAS criteria failed to demonstrate a benefit . This finding suggests that the effects of plasma exchange in children with OCD may be limited to those with preceding GAS infection, lending support to the autoimmune hypothesis. (See 'Autoimmunity' above.)
Referral indications — Referral to a specialist (neurologist, psychiatrist, mental health provider) for treatment of OCD/tic disorder may be indicated for children who meet criteria for PANDAS. (See 'Neuropsychiatric therapy' above.)
Referral to a rheumatologist/immunologist also may be warranted for patients with severe symptoms that are unresponsive to standard therapies.
PROGNOSIS — The long-term outcome of children who meet criteria for PANDAS is not known. Cases of carditis (as occurs in patients with Sydenham chorea) have not been reported . Unrecognized PANDAS and untreated PANDAS may result in an increased risk of progression to lifelong obsessive-compulsive disorder (OCD) and tic disorders .
PREVENTION — If the proposed pathogenetic model for PANDAS described above is correct, it might be possible to prevent PANDAS by preventing group A streptococcal (GAS) infection. Whether the prompt treatment of GAS infection prevents the development of neuropsychiatric symptoms is not known [21,22]. Recognition of the sentinel PANDAS episode and its prompt treatment may impact the likelihood of a recurrence and prevent kindling (eg, repeated stimulation of autoantibodies that target brain tissue, which eventually results in permanent destruction of the brain cells and permanent disability in the form of obsessive-compulsive [OCD] or tic disorder). (See 'PANDAS subgroup' above.)
GAS infection — Measures to prevent GAS infection include early recognition and prompt initiation of antistreptococcal therapy and taking steps to decrease transmission. School-age children with sore throat or unexplained fever should be evaluated for GAS infection and treated with antibiotics if throat culture or rapid antigen detection test is positive. (See "Approach to diagnosis of acute infectious pharyngitis in children and adolescents" and "Treatment and prevention of streptococcal tonsillopharyngitis".)
To prevent transmission of GAS infection, children with GAS pharyngitis or skin infection should stay home from school or child care until they have received 24 hours of appropriate antimicrobial therapy . They should avoid close contact with other children during this time.
Prophylactic therapy — Prophylactic antibiotics prevent recurrences of acute rheumatic fever and Sydenham chorea . (See "Treatment and prevention of acute rheumatic fever" and "Sydenham chorea".)
If, as hypothesized, the pathogenesis of PANDAS is similar to that of acute rheumatic fever and Sydenham chorea, then prophylactic antibiotics might be expected to prevent recurrences of PANDAS as well. However, the pathogenesis of PANDAS has not been established, and the role of prophylactic antibiotics is unknown. Potential adverse effects of prophylactic antibiotic therapy include diarrhea, pseudomembranous colitis, candida infections, and increased rates of antibiotic resistance .
In the author’s experience, prophylactic antibiotics are an option to aid in the diagnosis of PANDAS and prevent symptom recurrences. The clinical course during prophylaxis may help provide insight into the disease for the patient/family and clinician: remission of neuropsychiatric symptoms helps to establish the diagnosis of PANDAS, whereas recurrence of neuropsychiatric symptoms during prophylaxis excludes the diagnosis. However, other experts recommend against the use of prophylactic antibiotics for children with PANDAS [10,11].
The prophylactic regimen is the same as that for acute rheumatic fever (amoxicillin 250 twice per day orally, or [for penicillin allergic children] a macrolide [eg, azithromycin 5 mg/kg orally once per day, maximum dose 250 mg]). Antibiotic prophylaxis is generally continued for one winter season, coinciding with the peak seasonal occurrence of GAS (about six months). Prophylaxis is discontinued if neuropsychiatric symptoms do not improve or the child has a recurrence of neuropsychiatric symptoms.
In the only placebo-controlled trial, an equal number of GAS infections occurred in the penicillin and placebo groups; failure to achieve adequate prophylaxis against GAS prohibited drawing conclusions regarding efficacy of PANDAS prevention . A subsequent study compared rates of streptococcal infections and neuropsychiatric symptom exacerbation before and during 12 months of prophylaxis with penicillin or azithromycin . Prophylaxis was associated with fewer episodes of GAS infection and fewer neuropsychiatric exacerbations compared with baseline. However, the lack of a placebo group, and other design problems (eg, small numbers, inadequate blinding, nonstandardized definition of exacerbation, failure to exclude GAS carriage), make these results difficult to inconclusive .
SUMMARY AND RECOMMENDATIONS
PANDAS (pediatric autoimmune neuropsychiatric disorder associated with group A streptococci) is a term used to describe a subset of children whose symptoms of obsessive-compulsive disorder (OCD) or tic disorders are exacerbated by group A streptococcal (GAS) infection. The hypothesized association between PANDAS and GAS is controversial. (See 'Background' above.)
PANDAS is characterized by five working criteria (see 'Clinical features' above):
OCD and/or tic disorder
Pediatric onset (between three years and onset of puberty)
Abrupt onset and episodic course of symptoms
Temporal relation between GAS infection and onset and/or exacerbation
Neurologic abnormalities or tics during exacerbations
We suggest that children who present with abrupt onset of OCD/tic disorder be evaluated for GAS infection (Grade 2C). (See 'Diagnostic process' above.)
Diagnosis of PANDAS requires prospective evaluation with documentation of an episode of neuropsychiatric symptoms associated with evidence of GAS infection (positive throat or skin culture, rapid antigen detection test, or rising antistreptococcal antibody titers). (See 'Diagnostic process' above.)
We recommend that children with positive culture or rapid antigen detection test for GAS be treated with antistreptococcal therapy (Grade 1A). (See 'GAS infection' above and "Treatment and prevention of streptococcal tonsillopharyngitis".)
We suggest that children with abrupt onset OCD and/or tic disorders and evidence of GAS infection (ie, those with possible PANDAS) be treated with antistreptococcal therapy (Grade 2C). They should receive standard neuropsychiatric treatment for OCD/tic disorder if the symptoms do not remit after antibiotic therapy. (See 'PANDAS subgroup' above and 'Neuropsychiatric therapy' above.)
We recommend not treating children who meet criteria for PANDAS with immune-modulating therapies outside of the research setting (Grade 1B). (See 'Immune modulating therapy' above.)
Prophylactic antibiotics are an option to aid in the diagnosis of PANDAS and prevent symptom recurrences. The clinical course during prophylaxis may provide insight into the disease for the patient/family and clinician: remission of neuropsychiatric symptoms helps to establish the diagnosis of PANDAS, whereas recurrence of neuropsychiatric symptoms during prophylaxis excludes the diagnosis. (See 'Prophylactic therapy' above.)
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