Background: The pediatric autoimmune neurologic disorders associated with streptococcal infections (PANDAS) comprise a group of patients who, after infection with group A β-hemolytic streptococci (GAS), exhibit a spectrum of neuropsychiatric symptoms that include obsessive thoughts, compulsive behaviors, tics, hyperactivity, inattention, and mild choreiform movements. More recently, a group of patients with a symptom complex similar to PANDAS without evidence of streptococcal etiology was given the acronym pediatric acute-onset neuropsychiatric syndrome (PANS). Despite more than several decades of study and increasing numbers of patients being identified with PANDAS and PANS, there are ongoing controversies, which range from disagreements about specific pathogenetic mechanisms to whether these entities actually exist. Objective: The purpose of this report was to examine the current body of evidence that deals with the relationship(s) of immunologic host responses to infection and putative immunologic mechanisms involved in the pathogenesis of these disorders, to evaluate the effectiveness of anti-inflammatory and immunomodulatory therapies with intravenous immunoglobulin (IVIG), and to consider the extent to which allergist/immunologists might be involved in their management. Methods: An extensive literature review was conducted in medical literature data bases by applying terms such as PANDAS, PAN, autoimmune encephalitis, neuroinflammation, and autoimmune obsessive-compulsive disorders. Results: PANDAS and its later iterative form, PANS, continue to challenge clinicians, patients, and their families. Although the precise reason why these disorders develop remains unknown, both are considered to have an autoimmune basis related to the production of antibodies directed at antigens of the putative causative infectious disease agents that are cross-reactive with antigenic epitopes on selected brain nuclei, which lead to the neuroinflammatory sequelae responsible for the neuropsychiatric symptoms of these conditions, a phenomenon referred to as molecular mimicry. Conclusion: The PANDAS/PANS disorders are a continuing burden for growing numbers of patients, health-care providers, and the global health-care systems, and are a particular challenge for the allergist/immunologist who is increasingly being called upon for their management. Because of the importance of immunologic factors in the pathogenesis and treatment of these conditions with anti-inflammatory and immune-modulating treatments, the allergist/immunologist is well poised to offer consultative care.
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