Meiqian Ma

Pediatric acute-onset neuropsychiatric syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS), represent an overlapping group of disorders which is characterized by acute-onset obsessive compulsive disorders, eating restriction, tics, cognitive and behavioral deterioration which typically follows a relapsing-remitting course but some patients have a primary or secondary persistent progress. This condition is likely caused by heterogeneous inflammatory mechanisms (autoantibodies, complement activation, pro-inflammatory cytokine production) involving the basal ganglia as evidenced by imaging studies (patients vs. controls), sleep studies that found movements and/or atonia during REM sleep, and neurological soft signs that go along with basal ganglia dysfunction. The condition causes significant psychiatric and behavioral symptoms, caregiver burden and sleep abnormalities. Autoantibodies resulting from molecular mimicry of infectious agents (namely group A Streptococcus) and neuronal autoantigens that map to the basal ganglia play also a subtle role. This narrative review aims to describe the key immunological features documented thus far and that likely play a role in the pathogenesis and clinical manifestations of this disorder.

Pediatric acute-onset neuropsychiatric syndrome (PANS) is characterized by abrupt-onset obsessive-compulsive symptoms plus other abrupt-onset neuropsychiatric symptoms (sleep disruption, urinary changes, cognitive function loss, behavior deterioration, emotional lability, and irritability) causing significant patient, family, or caregiver distress.^1-3 Pediatric acute-onset neuropsychiatric syndrome follows a relapsing-remitting course of flares (abrupt psychiatric symptom deteriorations) between periods of relative symptom quiescence.^4,5 Classification of a pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) requires a temporal association with group A streptococcal (GAS) infection.⁶ The more general term, PANS, describes similar symptoms as PANDAS but is agnostic to the preceding infection⁷ (eAppendix 1 in Supplement 1). Provisional management recommendations for PANS include (1) clearing an infection if present, (2) anti-inflammatory treatments, and (3) standard psychiatric care.^8-13 Anti-inflammatory treatments include intravenous immunoglobulin, corticosteroids, and nonsteroidal anti-inflammatory drugs, but randomized placebo-controlled trials are lacking.^4,5,13,14

Pediatric acute-onset neuropsychiatric syndrome (PANS), pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections, Sydenham chorea, and other postinfectious psychiatric deteriorations are thought to be caused by inflammatory/autoimmune mechanisms, likely involving the basal ganglia based on imaging studies. Patients have a relapsing-remitting course and some develop severe refractory psychiatric disease. We found that 55/193 (28%) of consecutive patients meeting PANS criteria developed chronic arthritis and 25/121 (21%) of those with related psychiatric deteriorations developed chronic arthritis. Here we describe 7 of these patients in detail and one sibling. Many of our patients often have “dry” arthritis (no effusions found on physical exam) but subtle effusions detected by imaging and features of spondyloarthritis, enthesitis, and synovitis. Joint capsule thickening, not previously reported in children, is a common finding in the presented cases and in psoriatic arthritis in adults. Due to the severity of psychiatric symptoms in some cases, which often overshadow joint symptoms, and concomitant sensory dysregulation (making the physical exam unreliable in the absence of effusions), we rely on imaging to improve sensitivity and specificity of the arthritis classification. We also report the immunomodulatory treatments of these 7 patients (initially nonsteroidal anti-inflammatory drugs and disease-modifying antirheumatic drugs with escalation to biologic medications) and note any coincidental changes to their arthritis and psychiatric symptoms while on immunomodulation. Patients with overlapping psychiatric syndromes and arthritis may have a unifying cause and pose unique challenges; a multi-disciplinary team can utilize imaging to tailor and coordinate treatment for this patient population.