PANS/PANDAS intervention starts with identifying and treating any triggering infections. Symptoms may respond to anti-inflammatory agents and supportive, behavioral, psychopharmacological, and psychotherapeutic interventions.
Soon after the PANDAS and PANS research criteria were developed, concern emerged that antibiotics might be prescribed for children unnecessarily. (The evidence does not support prophylactic antibiotics for PANDAS as it does for rheumatic fever; however, cautious prophylactic treatment with low-dose antibiotics may be considered for children who have multiple GAS-associated neuropsychiatric exacerbations or recurrences of debilitating symptoms, as well as to minimize the risk of long-term sequelae such as brain injury.)
Such concerns slowed acceptance of the validity of the syndromes. However, appropriate recognition, diagnosis, and judicious treatment based on newly developed guidelines for PANS/ PANDAS have grown, and dedicated PANS clinics have opened at Massachusetts General Hospital (Harvard University); Yale Child Study Center; Stanford University; and the Universities of South Florida, Arizona, Minnesota, and Missouri, and Saskatchewan (Canada). Because established PANS clinics and practitioners cannot accommodate even regional referrals, diagnostic and treatment guidelines have been published to assist community clinicians in treating young patients with PANS/PANDAS.8-11
Rapid GAS screens may miss 15% to 20% of GAS infections; therefore, culture should be performed. Two-week interval changes in, not just elevation of, GAS titers (ASO and DNase B) indicate recent GAS infection. Many children without PANS/PANDAS have elevated titers, and some children with PANS/PANDAS and GAS infection do not demonstrate positive titers. GAS can affect the perianal and vaginal areas; if redness, itching, and discharge are present, culture for GAS. Children with PANS/PANDAS can react to others’ GAS infection or carrier state; screen family members and close contacts for GAS.
Sinusitis and M pneumoniae infection are frequent triggers. (See Chang and colleagues8 for complete evaluation recommendations.) Infections should be treated according to standard pediatric practice. Tonsillectomy and adenoidectomy should be performed according to pediatric otolaryngology guidelines. (See Cooperstock and colleagues11 for complete PANS/PANDAS infectious disease recommendations.)
Once underlying infections are identified and treatment has begun, immunomodulatory interventions may be considered, tailored to disease severity and clinical course. Before immunomodulatory treatments are initiated, other inflammatory/immune conditions, such as immunodeficiency and acute encephalitis, should be considered. While the treatment of infections follows standard pediatric practice, current immunomodulatory guidelines derive from pooled expert consensus, limited research, and extrapolation from related inflammatory illnesses.
For mild disease, retrospective clinical data support the use of NSAIDs and brief oral corticosteroid bursts (akin to the treatment of asthma flares). These data suggest that each intervention can decrease the length of the flare and that the sooner the intervention is begun, the shorter the flare. Before corticosteroids are initiated, occult infections such as tuberculosis and fungal diseases should be ruled out. Note that corticosteroids may temporarily exacerbate emotional and behavioral symptoms.
For moderate to severe disease, more prolonged or aggressive corticosteroid treatment, intravenous pooled human immunoglobulin (IVIG) therapy, or both may help. For extreme to life-threatening disease, plasma exchange (plasmapheresis) or intravenous corticosteroids plus IVIG may be indicated. Consultation with a pediatric rheumatologist is recommended if rituximab, cyclophosphamide, or other therapies used to treat inflammatory brain disease are being considered.10
Dr. Thienemann is Clinical Professor of Psychiatry, Stanford University School of Medicine, and Co-Director of the PANS Program, Stanford Children’s Health, Palo Alto, CA. Dr. Frankovich is Clinical Associate Professor, in the Department of Pediatric Rheumatology, and Co-Director of the PANS Program, Stanford University School of Medicine, Palo Alto, CA.
Dr. Thienemann reports no conflicts of interest concerning the subject matter of this article.
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