Evidence-Based Reviews

Is it PANDAS? How to confirm the sore throat/OCD connection

Current Psychiatry. 2005 July;4(7):33-48

References

1. Snider LA, Swedo SE. PANDAS: current status and directions for research. Mol Psychiatry 2004;9(10):900-7.

2. Hosier DM, Craenen JM, Teske DW, Wheller JJ. Resurgence of acute rheumatic fever. Am J Dis Child 1987;141:730-3.

3. Stollerman GH. Rheumatic fever. Lancet 1997;349:935-42.

4. Swedo S, Leonard HL, Schapiro MB, et al. Sydenham’s chorea: Physical and psychological symptoms of St.Vitus’ dance. Pediatrics 1993;91:706-13.

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;155:1122-4.

6. Mercadante MT, Busatto GF, Lombroso PJ, et al. The psychiatric symptoms of rheumatic fever. Am J Psychiatry 2000;157:2036-8.

7. National Institute of Mental Health. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. Available at: http://intramural.nimh.nih.gov/pdn/web.htm. Accessed June 9, 2005.

8. 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(2):264-71.

9. Kim SW, Grant JE, Kim SI, et al. A possible association of recurrent streptococcal infections and acute onset of obsessive-compulsive disorder. J Neuropsychiatry Clin Neurosci 2004;16(3):252-60.

10. Garvey MA, Giedd J, Swedo SE. PANDAS: the search for environmental triggers of pediatric neuropsychiatric disorders. Lessons from rheumatic fever. J Child Neurol 1998;13(9):413-23.

11. March JS. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS): implications for clinical practice. Arch Pediatr Adolesc Med 2004;158:927-9.

12. Zohar AH. The epidemiology of obsessive-compulsive disorder in children and adolescents. Child Adolesc Psychiatr Clin N Am 1999;8:445-59.

13. Murphy ML, Pichichero ME. Prospective identification and treatment of children with pediatric autoimmune neuropsychiatric disorder associated with group A streptococcal infection (PANDAS). Arch Pediatr Adolesc Med 2002;156(4):356-61.

14. Dajani A, Taubert K, Ferrieri P, et al. Treatment of acute streptococcal pharyngitis and prevention of rheumatic fever: a statement for health professionals. Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young, the American Heart Association. Pediatrics 1995;96:758-764.

15. Gray GC, McPhate DC, Leinonen M, et al. Weekly oral azithromycin as prophylaxis for agents causing acute respiratory disease. Clin Infect Dis 1998;26:103-10.

16. Snider LA, Lougee L, Slattery M, et al. Antibiotic prophylaxis with azithromycin or penicillin for childhood-onset neuropsychiatric disorders. Biol Psychiatry 2005;57:788-92.

17. 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(12):1564-71.

18. Pediatric OCD Treatment Study (POTS) Team. Cognitive-behavior therapy, sertraline, and their combination for children and adolescents with obsessive-compulsive disorder: the Pediatric OCD Treatment Study (POTS) randomized controlled trial. JAMA 2004;292(16):1969-76.

19. Leonard HL, Swedo SE. Paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS). Int J Neuropsychopharmacol 2001;4(2):191-8.

20. Snider LA, Swedo SE. Childhood-onset obsessive-compulsive disorder and tic disorders: case report and literature review. J Child Adolesc Psychopharmacol 2003;13(suppl 1):S81-S88.

21. Storch EA, Gerdes AC, Adkins JW, et al. Behavioral treatment of a child with PANDAS. J Am Acad Child Adolesc Psychiatry 2004;43(5):510-11.

22. Nicolson R, Swedo SE, Lenane M, et al. An open trial of plasma exchange in childhood-onset obsessive-compulsive disorder without poststreptococcal exacerbations. J Am Acad Child Adolesc Psychiatry 2000;39(10):1313-5.

23. Perlmutter SJ, Leitman SF, Garvey MA, et al. Therapeutic plasma exchange and intravenous immunoglobulin for obsessive-compulsive disorder and tic disorders in childhood. Lancet 1999;354 (9185):1153-8.

24. Snider LA, Swedo SE. Post-streptococcal autoimmune disorders of the central nervous system. Curr Opin Neurol 2003;16:359-65.

25. Murphy TK, Sajid M, Soto O, et al. Detecting pediatric autoimmune neuropsychiatric disorders associated with streptococcus in children with obsessive-compulsive disorder and tics. Biol Psychiatry 2004;55(1):61-8.

Recurrences. PANDAS has an episodic course, and approximately 50% of patients experience recurrences.¹³ Whether PANDAS remits completely, becomes dormant when neuropsychiatric symptoms are waning, or consistently progresses to a more chronic illness is unclear.

Because young children diagnosed with PANDAS often have repeated, frequent GABHS infections,⁸ give careful attention to:

unexplained abdominal pain accompanied by fever
history of scarlet fever
brief episodes of tics, OCD, or compulsive urination that remitted
illness accompanied by sudden onset of OCD or tic-like behaviors
history of sore throats not severe enough to seek medical attention
dramatic improvement in behavior/neuropsychiatric symptoms following standard antibiotictherapy for unrelated infection.

Table 2

Differential diagnosis of OCD, tic disorders, and PANDAS

Characteristic	OCD	Tourette’s/tic disorders	PANDAS
Typical age of onset	10 years	7 years	7 years
Gender relatedness	Slightly higher prevalence in boys than girls before age 15; female-to-male ratio increases after puberty	2:1 male-to-female ratio	5:1 male-to-female ratio before age 8; thereafter, boys slightly outnumber girls
Course	Typically unremitting, though some episodic cases reported	Peak severity at age 10; 50% of cases remit by late teens	Episodic or sawtooth course; long-term prognosis unknown
Involvement of basal ganglia	Strong evidence	Strong evidence	Good evidence
GABHS trigger	Reported; cause uncertain	Reported in some cases; cause uncertain	Proposed association
Neurologic findings	Increased findings of NSS, including choreiform movements	Increased findings of NSS, including choreiform movements	Choreiform movements
GABHS: group A beta-hemolytic streptococcal infection
NSS: neurologic soft signs
OCD: obsessive-compulsive disorder
PANDAS: pediatric autoimmune neuropsychiatric disorders associated with streptococcus

WEIGHING TREATMENT OPTIONS

Antibiotics. Antibiotic treatment of GABHS infection has been thoroughly studied among patients with rheumatic fever. American Heart Association guidelines for preventing rheumatic fever after GABHS infection recommend oral penicillin, 250 mg bid.¹⁴ Studies also indicate that using azithromycin, 500 mg once weekly, can protect against GABHS infection but may also increase resistance to macrolide antibiotics.¹⁵

Because antibiotic prophylaxis for GABHS infection is effective for rheumatic fever, some researchers have hypothesized that similar treatment would reduce neuropsychiatric symptoms in PANDAS patients.

In a double-blind, randomized, controlled trial, Snider et al¹⁶ found significant decreases in GABHS infection and neuropsychiatric symptoms in 23 PANDAS patients who took penicillin (250 mg bid) or azithromycin (250 mg bid on one day of the week) for 12 months.

An earlier study using penicillin for PANDAS prophylaxis was inconclusive. Its design limited more-definitive conclusions by allowing a high rate of antibiotic use during the placebo phase.¹⁷

An uncontrolled prospective study by Murphy et al¹³ documented rapid resolution of primary OCD, tic, and anxiety symptoms after appropriate antibiotic treatment in 12 children with PANDAS. Obsessive-compulsive symptoms remitted 5 to 21 days after patients received penicillin, amoxicillin/clavulanate potassium, or a cephalosporin. Symptoms resolved much more quickly than nonPANDAS obsessive-compulsive and tic disorders usually remit with cognitive-behavioral, habit reversal, and/or drug treatment.¹⁸ One-half of patients had at least one OCD recurrence, all documented as GABHS-positive with throat culture or rapid antigen-detection assay.

Recommendation. Obtain a GABHS culture if a child presents with sudden-onset OCD. If positive, treat with a standard course of antibiotics.¹⁹ Caution is strongly recommended when using antibiotics in children, as antibiotic-resistant organisms may develop. Collaborate with the child’s pediatrician to ensure that strep infections are treated consistently.

CASE CONTINUED: USING CBT FOR PANDAS

Giving John antibiotics when he had the sore throat might have been a rational choice to manage acute OCD symptoms. However, the scant literature on antibiotic prophylaxis for PANDAS subtype OCD led us to also consider cognitive-behavioral therapy (CBT).

CBT alone or with a selective serotonin reuptake inhibitor (SSRI) is first-line therapy for pediatric OCD.^18,20 We hypothesized, therefore, that CBT might also be useful in PANDAS and provided John with five CBT sessions within 1 week, without giving an antibiotic or other medication. [See our study²¹ for therapy details.]

At baseline, John’s score on the Children’s Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) was 34, indicating severe OCD symptoms, and his score on the Anxiety/Depression subscale of the Child Behavior Checklist (CBCL) was elevated (t = 66). After five CBT sessions, John’s CY-BOCS score decreased by 75% to 8 and his CBCL Anxiety/Depression score decreased into the average range (t = 50).²¹

Given PANDAS’ fluctuating course, his symptoms could have remitted spontaneously. His symptoms remained in remission 6 months later.

We believe John’s case is the only published description of using CBT alone to treat a patient with PANDAS. Since then, our team has successfully treated several other PANDAS patients using CBT. Based on our experience with trained clinicians, CBT provided an appropriate treatment option for this handful of cases. Controlled trials are needed to establish CBT’s efficacy for treating documented PANDAS.

SSRIs. As stated, CBT alone or with an SSRI is first-line therapy for pediatric OCD, and CBT alone or with an SSRI reduces pediatric OCD symptoms more effectively than antidepressants alone.¹⁸ Because no published reports of SSRI use in PANDAS exist, we recommend treating a child with PANDAS as you would any child presenting with OCD and tics: