Pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections or P.A.N.D.A.S, is a neuroimmune disorder, most commonly affecting children between the ages of 3 and 12. The condition occurs through a process of molecular mimicry which triggers an autoimmune response. Onset is abrupt and symptoms consist of a variety of psychiatric and neurological abnormalities including: obsessive-compulsive like behaviors, tics, depression, anxiety, and more. Because P.A.N.D.A.S is a clinical diagnosis, no official lab tests can be used to solidify its presence. Still, blood tests such as the Cunningham Panel™ and strep throat cultures can aid doctors in the diagnosis. Treatment of P.A.N.D.A.S typically consists of a single course of antibiotics, however, IVIG and steroids may be used if symptoms are not alleviated by the antibiotics alone.
Pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections, more commonly known as P.A.N.D.A.S, is a rare neurological autoimmune disease. Autoimmune diseases occur when the body’s natural defense system (immune system) attacks the body’s healthy tissues, causing inflammation. In P.A.N.D.A.S, because the streptococcal organisms survive in their host through “molecular mimicry,” a form of disguising themselves to look almost identical to that of the child’s heart, joint, or brain tissues, the bacteria can remain undetected in its host for extensive time periods.  When the body’s immune system recognizes these organisms, however, the antibodies released, known as cross-antibodies, not only attack the strep, but also the child’s healthy tissues that were mimicked through the molecular mimicry. This attack of the brain is specifically targeted at the basal ganglia, a group of subcortical nuclei found within the cerebral hemispheres, and causes inflammation to the region.  This inflammation results in various psychiatric and neurological symptoms.
P.A.N.D.A.S is characterized by a sudden onset of psychological symptoms following a strep throat infection. The most common of these symptoms include tics, anxiety, food restriction, panic attacks, emotional/developmental regression, and OCD-like behaviors. A study done by the Human Phenotype Ontology (HPO), shows that 80-99% of P.A.N.D.A.S patients suffer from tics and another 30-79% show symptoms typically associated with ADHD and depression.  Because these symptoms present similarly to those of more common psychiatric disorders, misdiagnosis among affected children is extremely high. In fact, many children with P.A.N.D.A.S are given an initial diagnosis of OCD or anxiety and put on Selective Serotonin Reuptake Inhibitors (SSRIs), the most commonly prescribed form of antidepressants. They are very effective in increasing serotonin levels for those suffering from anxiety disorders, depression, or any other illness that cause serotonin deficiencies. However, for P.A.N.D.A.S children, the issue stems not from a deficiency itself, but from the body’s immune response (which is likely to be a trigger of such deficiencies). When these drugs fail to alleviate the child’s symptoms, the validity of the initial diagnosis is called into question. Still, even after a correct diagnosis of P.A.N.D.A.S has been received and treatment has been administered, symptoms often relapse and remit over time, especially when contact with group A streptococcus (GAS) occurs.
Diagnosis and Treatment
P.A.N.D.A.S is a clinical diagnosis, meaning that no lab tests are needed to make the diagnosis. Still, many doctors use the Cunningham Panel™ by Moleculera Labs. The Cunningham Panel™ is a blood test used to measure the levels of autoantibodies associated with psychiatric/neurological symptoms. The panel contains 5 tests (Dopamine D1 receptor, Dopamine D2L receptor, Lysoganglioside GM1, Tubulin, and CaM Kinase II).  If any one of these titers are high, it is an indication that P.A.N.D.A.S is present, but typically cannot provide a definitive diagnosis.
Health care providers must also follow diagnostic criteria including:
- Previous/recurring strep infection (confirmed by lab tests or throat culture)
- Presence of tics or obsessive compulsive symptoms
- Abrupt pediatric onset and episodic course of symptoms
- Positive throat culture for GAS or history with scarlet fever
- Neurological abnormalities i.e. hyperactivity, jerky movements, etc. 
Once the P.A.N.D.A.S has been diagnosed, the underlying strep infection must be treated. Then, Physicians take a throat culture to establish whether or not the initial infection is still present. If the culture is positive, antibiotics including azithromycin, amoxicillin, cephalosporins, and penicillin are recommended.  If the course of antibiotics fails to alleviate symptoms, some doctors recommend intravenous immunoglobulin (IVIG), a common treatment for many autoimmune diseases. The IVIG treatment interacts with the body’s immune cells and has proven to be effective in children with P.A.N.D.A.S. In fact, a longitudinal study from 2018 determined that 88% of IVIG patients did not experience any obsessive compulsive symptoms within a span of 4.8 years. . Still, some P.A.N.D.A.S. may not experience remission with antibiotics or IVIG, in which case steroids may be considered. However, this form of treatment is controversial as many report worsening tics or other rebound effects. Additionally, steroids can only be used for a short period of time because long-term use can be detrimental to the child’s health. Fortunately for the many children who do not find relief through any of the previously mentioned treatments, tonsillectomies are currently being researched as a possible solution. A tonsillectomy is the surgical removal of the tonsils. Though it is not yet widely accepted as a viable treatment option by many medical professions, anecdotal evidence and unpublished research findings prove the operation’s success in eradicating strep infections and therefore alleviating P.A.N.D.A.S symptoms.
Lily Kangas, Youth Medical Journal 2021
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