Amoxicillin for the Treatment of Pediatric Autoimmune Disorders Associated With Streptococcal Infections

Overview

Bacteria carry substances on their surface called antigens. When antigens come into contact with the right kinds of cells in the body an immune reaction is caused. This reaction is often the symptoms of sickness that a patient feels. In order for the body to fight off the attack of antigens, it creates substances called antibodies. Antibodies counter the action of antigens and make the bacteria harmless. However, the immune system must learn how to make the right antibodies for the right antigens. Sometimes the body creates antibodies that confuse normal tissues as foreign and attack them. This is called an autoimmune reaction and sometimes occurs when the body is exposed to certain bacteria. One bacteria known for causing autoimmune reactions is Group A beta-hemolytic Streptococcus (GABHS). This bacteria often causes throat infections commonly known as "strep throat". Some researchers believe that the autoimmune reaction associated with strep throat infections may cause neuropsychiatric disorders, like obsessive-compulsive disorder and/or tic disorder in children. As a result, each time a child with one of these disorders experiences an infection with GABHS his/her symptoms can reoccur or worsen. Researchers believe that by giving patients a certain antibiotic, they can prevent GABHS infection and thus prevent the return of symptoms. This study is designed to test the effectiveness of the antibiotic Amoxicillin for the treatment of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS). Patients will receive Amoxicillin for six weeks and placebos "inactive sugar pills" for six weeks in order to see if the medication is truly working. Effectiveness of the treatment will be based on the presence or absence of symptoms. If at the end of the study Amoxicillin is proven to be effective treatment for PANDAS patients may be offered the opportunity to continue taking the medication for an additional six months.

An increasing body of evidence suggests that Group A beta-Hemolytic Streptococcal throat infections (GABHS) may trigger the onset of obsessive-compulsive disorder (OCD) and/or tic disorder in certain vulnerable children via an autoimmune process. In this subgroup of children with childhood-onset OCD and tic disorders, preliminary data suggest some children have a rapid response to amoxicillin. After only 24 to 48 hours of treatment, they have a dramatic reduction in OC symptoms and tics. To date, we have observed this phenomenon in at least 5 children, each of whom relapsed when the amoxicillin was stopped. These observations raise a number of questions, including whether or not amoxicillin has a direct central nervous system (CNS) effect or an indirect effect through perturbations of the immune system (e.g., cytokine shifts). The purpose of this study is to determine if amoxicillin is an effective treatment for PANDAS, as well as examining possible mechanisms of this effect. We propose to do this with a 3-month double-blind placebo-controlled crossover trial of amoxicillin treatment with a randomized A-B-A-B design. Outcome measures will be blinded ratings of tic severity, standardized measures of psychopathology, and immunologic assays (such as type I and type II cytokine levels).