Evidence-Based Reviews

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

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

Michael J. Larson, MS

Eric A. Storch, PhD

Tanya K. Murphy, MD

Antibiotics are indicated in only a minority of cases.

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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.

John, age 6, presented for psychiatric evaluation with acute, incapacitating obsessive-compulsive symptoms. For 4 weeks he washed his hands compulsively and had pervasive obsessions about death by choking.

These symptoms had suddenly worsened over 2 days. At first, he washed his hands more than 35 times per day in rituals lasting several minutes each. Then, within 2 weeks, John’s handwashing spontaneously decreased, but his choking fears dramatically increased. He refused all solid foods and continuously sought reassurance from his parents that he would not choke or die.

Approximately 1 week before these symptoms began, John had a sore throat and tested positive via throat culture for group A beta-hemolytic streptococcal infection (GABHS).

Sore throat followed by sudden-onset obsessive-compulsive symptoms or tics in a child such as John suggests a pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS). The association between GABHS infection and these symptoms remains uncertain, as the mechanism by which GABHS infection may cause obsessive-compulsive symptoms and other childhood-onset neuropsychiatric disorders is largely unknown.

Since PANDAS was recognized (Box 1),^1-6 some data have emerged on the disorder’s symptoms, course, and prognosis. However:

diagnostic criteria are not well-defined
few controlled studies have examined treatment response
using antibiotics and immunotherapies to treat or prevent PANDAS symptoms remains controversial because of unproven efficacy and potential adverse effects.

To help you diagnose and treat patients with suspected PANDAS, this article examines the limited evidence for the disorder, discusses diagnostic guidelines, and reviews preliminary indications for behavioral and medical treatments.

Box1

PANDAS and strep infection: The rheumatic fever link

PANDAS stands for pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. It describes childhoodonset OCD or tic cases whose onset or worsening appears to be linked to group A beta-hemolytic streptococcal (GABHS) infection.

GABHS antibodies cross-react with the cellular components of the basal ganglia, particularly in the caudate nucleus.¹ PANDAS was first recognized in 1987 during an unexpected resurgence of rheumatic fever in the United States.² Sydenham chorea is thought to occur when GABHS antibodies undergo molecular mimicry and cross-react with epitopes on neurons in the basal ganglia and other brain areas, causing motor and behavioral disruptions.³ Rheumatic fever patients with Sydenham chorea show a high prevalence (up to 70%) of obsessive-compulsive disorder (OCD).^4,5

Although individuals with Sydenham chorea appear to be at greatest risk for OCD after GABHS infection, rheumatic fever patients without chorea also appear to be at increased OCD risk.⁶

CASE REPORT CONTINUED: PANDAS CLUES

John’s sudden-onset compulsive behaviors and obsessive thoughts exemplify the rapid symptom onset often seen in children with PANDAS. His medical records showed a temporal relationship between his streptococcal infection and symptom exacerbations, which his parents confirmed. On examination, we noted choreiform movements when we asked John to extend his hands in a supinated position.

Because this was John’s first documented presentation of PANDAS-like symptoms, an additional episode would provide more convincing support for classifying his OCD as the PANDAS subtype.

DIAGNOSTIC CRITERIA

National Institute of Mental Health (NIMH) diagnostic guidelines for PANDAS,⁷ initially proposed as working guidelines by Swedo and colleagues,⁸ are listed in Table 1.

Time between GABHS infection and symptom onset varies, but post-streptococcal diseases generally emerge after a few days to several weeks.⁹ Because this latent period makes retrospective assessment difficult,¹⁰ NIMH guidelines require a prospective link between GABHS infection and at least two OCD/tic symptom episodes.^7,8,11 These additional criteria are necessary to avoid misdiagnosing PANDAS in cases when the GABHS infection/OCD connection is spurious.

Table 1

Guidelines for PANDAS diagnosis

Presence of obsessive-compulsive disorder and/or tic disorder
Pediatric symptom onset (age 3 years to puberty)
Episodic course of symptom severity
Prospectively established association between group A beta-hemolytic streptococcal infection (GABHS)—as shown by positive throat culture and/or elevated anti-GABHS antibody titers and at least 2 separate OCD/tic symptom episodes
Association with neurologic abnormalities (motoric hyperactivity or adventitious movements, such as choreiform movements)
PANDAS: pediatric autoimmune neuropsychiatric disorders associated with streptococcus
Source: References 7, 8, and 11

PROSPECTIVE DIAGNOSIS

Neuropsychiatric symptoms. Early PANDAS symptoms are often similar to those of pediatric OCD and tic disorders (Table 2). Notable differences include:

Sudden onset of obsessive-compulsive or tic behaviors shortly after GABHS infection, as opposed to OCD’s typical insidious course.
Prepubertal onset (average age 7, as with Tourette’s syndrome^7,8), compared with average age 10 of childhood OCD.¹²

Other psychiatric symptoms frequently reported in PANDAS patients include separation anxiety, hyperactivity, inattention, and emotional lability.⁴ Some researchers, therefore, suggest the PANDAS syndrome should include primary diagnosis of late-onset attention-deficit/hyperactivity disorder and age-inappropriate separation anxiety disorders.^8,13

Compulsions reported in PANDAS include germ-related behaviors such as hand washing, hoarding, and excessive toilet hygiene rituals. Most studies show consistent gender differences, with more washing behaviors by girls and more checking behaviors, aggression, and tics among boys.¹³