In the Journal of Child and Adolescent Psychopharmacology’s July 2017 issue, a group of respected individuals representing diverse expertise published “guidelines” to support clinical management of pediatric acute-onset neuropsychiatric syndrome (PANS) and its subclass PANDAS (those associated with streptococcal infection). PANS represents an enigmatic clinical syndrome that includes abrupt onset of obsessive-compulsive disorder (OCD) or eating restriction in combination with anxiety, attention deficit, hyperkinesia, emotional lability, irritability, aggressive or oppositional behavior, or academic decline. Neurologic findings also may be present; these are most often motor or vocal tics, but choreiform movements of the finger (repetitive motions that are rapid, jerky, and involuntary), deteriorating penmanship, sleep disruptions, or urinary frequency also may be present. The clinical course most often is relapsing and remitting with overall improvement over months or years.
These events are often, but not universally, associated with infections, both for the initial clinical presentation as well as the subsequent exacerbations. A spectrum of inciting infections, most often upper respiratory tract disease including rhinitis, sinusitis, and pharyngitis, are reported as precipitating events. Group A streptococcal (GAS) infection has been most commonly identified. The evidence for GAS includes retrospective studies of increases in antistreptolysin O (ASO), anti-DNAse B (ADB), or anticarbohydrate-specific antibody titers associated with OCD or tic exacerbations; epidemiologic studies linking GAS infections in the prior 3 months with OCD and tic disorders; and animal studies demonstrating neuropsychiatric changes after GAS immunizations. Other infectious agents, specifically Mycoplasma pneumoniae, influenza viruses, Lyme borreliosis, and sinus infections, also are suspected triggers for PANS. Definitive proof, however, of a causal relationship between infection and PANS or PANDAS remains lacking.
The PANS/PANDAS consortium made specific recommendations for the management of patients with this clinically diagnosed syndrome (J Child Adolesc Psychopharmacol. 2017 Apr 7. doi: 10.1089/cap.2016.0151 ).
Specific recommendations include:
1. Searching for a coexisting infectious etiology with history, exam, and appropriate laboratory testing (including ASO and ADB antibodies), and, when present, treating accordingly. Even in the absence of definitive evidence of GAS infection, they recommend an initial course of antimicrobial therapy such as that given to patients with rheumatic fever.
2. For children with PANDAS (PANS with either culture or serologic evidence of GAS), consider instituting long-term streptococcal prophylaxis. The data on its value is mixed; however, most studies find more than 40% (and as many as 75%) of exacerbations are associated with GAS, and at least one study reports a reduction in neuropsychiatric exacerbations in children on penicillin or azithromycin prophylaxis for a 1-year period. Such decisions should be individualized: In children with strong evidence of exacerbations linked to GAS, there was thought to be greater likelihood of benefit, while, in those with no evidence for prior GAS infection, the potential for benefit was thought to be insufficient to justify prophylaxis. Furthermore, the optimal duration of prophylaxis is unknown. The guidelines recommend up to 2 years, but individualization is appropriate since severe cases may warrant prolonged prophylaxis.
3. In children who present with PANDAS and a positive throat culture for GAS, follow-up should be the same as that given for rheumatic fever, with reculture at 2-7 days and retreatment if there is persistence of GAS.
4. Vigilance for GAS infection in family members is appropriate, including obtaining throat cultures from persons with pharyngitis and treating them promptly when results are positive.
5. When GAS infection is not identified, the clinician should search for alternative infectious agents, such as Mycoplasma pneumoniae (using polymerase chain reaction on throat or nasopharyngeal swab), influenza virus, or alternative infections such as sinusitis, and treat accordingly.
6. Children with PANS and PANDAS should be immunized according to Advisory Committee of Immunization Practices recommendations, which includes annual influenza immunization. The committee reported that symptom flares after immunization were uncommon, brief, and manageable with NSAIDs.
7. The committee suggested that optimization of serum vitamin D levels among children with PANS and PANDAS could be of benefit, despite limited evidence. The committee members recommended treating children with PANS/PANDAS with vitamin D3 as needed to maintain serum 25-hydroxy vitamin D levels above 30 ng/mL. No benefit for adenotonsillectomy was identified. The committee recommended that tonsillectomy and/or adenoidectomy should limited to those with traditional indications (sleep apnea, failure to thrive, and abnormally large tonsils, etc.). The committee also found no evidence to suggest that probiotics modulate this condition.
These guidelines come with an important caveat. They represent a practical clinical approach for the management of infection in the context of PANS or PANDAS and rely heavily on the clinical experience of the members of the PANS/PANDAS Consortium . They provide criteria for the retrospective diagnosis of GAS infection and recommend treatment of GAS in all patients with newly diagnosed PANS. The suggested guidelines are supported by limited data and recognize that further prospective study of the mechanistic link between infection and PANS, clarification of the risk factors for development of PANS, and definitive study of the risks and benefits of antimicrobial prophylaxis are needed.
The consortium also has published two accompanying guidelines that address psychiatric (J Child Adolesc Psychopharmacol. 2017. doi: 10.1089/cap.2016.0145 ) and immunomodulatory management (J Child Adolesc Psychopharmacol. 2017. doi: 10.1089/cap.2016.0148 ) in the same issue of the Journal of Child and Adolescent Psychopharmacology.
Proposed criteria for documenting GAS infection in PANS pediatric patients
These are the criteria proposed by the consortium for documentation of active or prior GAS infection in children with PANS:
Source: J Child Adolesc Psychopharmacol. 2017. doi: 10.1089/cap.2016.0151 .
Dr. Pelton is chief of pediatric infectious disease and coordinator of the maternal-child HIV program at Boston Medical Center. Dr. Pelton said he had no relevant financial disclosures. Email him at pdnews@frontlinemedcom.com .
