PANDAS Treatment: Why Early Treatment Matters
An exacerbation can relapse and remit; they tend to increase in duration and intensity with each episode. Untreated PANDAS/PANS can cause permanent debilitation, and in some cases, can become encephalitic. Repeat strep infections can cause serious problems, so it is vital to eradicate strep. Subsequent episodes can be caused by environmental and infectious triggers different from the original infection. Treated early and in a timely fashion, PANDAS/PANS can remit entirely.
PANDAS/PANS Consortium Guidelines Parts 1, 2 & 3 for Parents and Doctors
2020 American Academy of Neurology Guidelines for Parent and Doctor
The type of infection dictates the type of antibiotic needed. If no improvement occurs over time, it may indicate a different antibiotic is needed or that a different or additional infection is present.
- Penicillin: This is a great first choice because it is a well-studied prophylactic antibiotic for illnesses like rheumatic fever and Sydenham’s chorea.
- Augmentin (Amoxicillin/Clavulanate Blend): This is used by many consortium doctors.
- Cephalosporins (Cephalexin, Cefdinir): These have been excellent for arresting most strains of strep.
- Azithromycin: Azithromycin is a front-line, broad-based antibiotic that protects against many forms of bacteria. A study of azithromycin helps treat youth with acute onset OCD can be found here: https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.109.191959
It has been recommended by physicians that the PANDAS child remains on prophylactic antibiotics in accordance with the rheumatic fever (RF) guidelines established by the American Academy of Pediatrics (AAP) Journal. The RF guideline by the AAP dictates that prophylaxis should last for five years after the last attack, or until age 21 (whichever is longer). According to the World Health Organization, the duration of prophylaxis for RF is five years after the last attack, or until 18 years old (whichever is longer).
Children who have had Sydenham’s chorea, rheumatic fever or PANDAS have a risk of developing a more severe symptom relapse upon reinfection with strep. Prophylaxis prevents reinfection.
Long-term prophylactic antibiotic use for PANDAS has been shown in the study Antibiotic Prophylaxis with Azithromycin or Penicillin for Childhood-Onset Neuropsychiatric Disorders to “…play a role in the management of children in the PANDAS subgroup, as well as provide support for the assertion that GAS plays an etiologic role in some children with tics and/or obsessive-compulsive disorder.” In that same study, it also states that “There was a 61% overall reduction in neuropsychiatric symptom exacerbations during the year of antibiotic prophylaxis and a 94% reduction in GAS-triggered neuropsychiatric symptom exacerbations.”
IVIG is an intravenous pooled blood product comprised of immunoglobulins used to treat immune deficiencies, encephalitis and other medical conditions. The Immune Deficiency Foundation has more information on IVIG here.
PANDAS/PANS children can have a difficult time getting coverage for IVIG. This is why we advocate state by state for healthcare coverage for this newly recognized disease.
In 2021, a phase 3 clinical trial of IVIG is being conducted by the University of Arizona.
New IVIG clinical research has recently been published as well.
Why Try IVIG?
Drs. Perlmutter and Swedo first introduced the use of IVIG in the 1999 Lancet article, “Therapeutic plasma exchange and intravenous immunoglobulin for obsessive-compulsive disorder and tic disorders in childhood,” where all of the children benefited from its use.
IVIG is endorsed for treating PANDAS by a consortium of physicians and researchers, as PANDAS is an autoimmune irregularity that causes encephalitic-like inflammation. The PANDAS Physicians Network gives recommended dosing and is outlined in the aforementioned JCAP Guidelines.
Healing is gradual over several months. Any form of infection will exacerbate symptoms in a child while healing, so manage exposures and illnesses carefully.
About 20% of PANDAS children are found to be immune deficient (primary immunodeficiency [PID] or common variable immunodeficiency [CVID]), according to the PANS Consortium initial research. Consultation with an immunologist is important, and IVIG follow-up may be different in these cases. Learn more about immune deficiency here.
How Does IVIG Work?
The exact mechanisms of IVIG are not thoroughly understood. IVIG has been shown to be helpful with the harmful inflammation caused by autoimmune illnesses, but the exact causative actions are not yet clear. Donor antibodies may “retrain” the abnormal antibodies in the patient, or the large amounts administered may simply overwhelm the harmful antibodies—thereby removing them from the PANDAS patient.
2016 NIMH and 2021 Independent IVIG Studies
NIMH IVIG study shows a 60% mean reduction in symptoms for PANDAS patients. An October 2016 paper submitted to the Journal of the American Academy of Child & Adolescent Psychiatry describes the outcome of the NIMH double-blind placebo-controlled study of IVIG for treatment of symptoms in children who met the criteria of PANDAS. Read more about it on the PANDAS Physicians Network.
In 21 patients with moderate to severe PANS, results demonstrated significant reductions in symptoms from baseline to end of treatment. Read the full 2021 paper here.
Plasmapheresis (apheresis) or plasma exchange (PEX) is a process during which the harmful auto-antibodies are removed from the blood system. This procedure is done in a hospital setting. You can read more about the procedure here.
Not many providers offer plasmapheresis for PANDAS and PANS, but those who do have cited seeing symptoms improve even while the procedure is still occurring. When a child is presenting with severe symptoms that would be considered life-threatening, plasmapheresis may be the preferred method of treatment due to the quick response rate. In some cases, PEX has had to be repeated (as with IVIG). Again, prophylactic antibiotics should be maintained.
The American Society for Apheresis lists plasma exchange as an accepted first-line therapy, either alone or with other treatment for a PANDAS exacerbation. The 2019 Guidelines from the Journal of Clinical Apheresis can be found here.
The full ASFA guidelines, as established in the 2013 Journal of Clinical Apheresis, appeared in their “Special Issue” that is published every three years. The guidelines can be found at “Guidelines on the Use of Therapeutic Apheresis in Clinical Practice—Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Sixth Special Issue.”
Merck Manual on Therapeutic Apheresis also lists plasma exchange as first-line therapy at http://bit.ly/1JcvSth.
- CBT/ERP: CBT (cognitive behavioral therapy) or ERP (exposure and response prevention) may be beneficial for a recovering PANDAS child. Medical interventions, such as antibiotics, IVIG, etc., are needed to lay a foundation for therapy to be introduced. Some information on CBT as it pertains to PANDAS and PANS can be found in Dr. Eric Storch’s presentation CBT for PANDAS and PANS (2012).
- Steroids: Steroids likely reduce the inflammation occurring in the child’s brain and have been shown to reduce the severity of symptoms in patients with Sydenham’s chorea. Active infections need to be addressed with the use of steroids. But some children with PANDAS/PANS can experience a worsening of tics or aggression with the use of steroids. It is important to discuss with your provider the pros and cons of using steroids.
- Tonsillectomy: A tonsillectomy may be considered by an experienced ENT. Some research has shown marked improvement post-tonsillectomy, including full cessation of symptoms in some patients.
- Omega 3s: Some children are advised to take an omega-3 supplement because of its known positive effect on brain function. It is also known to reduce inflammation, reduce hyperactivity and increase focus in children with ADHD.
- NSAIDs: Ibuprofen is classified as a nonsteroidal anti-inflammatory drug (NSAID). Some children have a temporary easing of symptoms with ibuprofen. If a child does not show any improvement with ibuprofen, this does not dismiss a possible PANDAS or PANS diagnosis. Ibuprofen should only be given under the direction of a physician.
Probiotics: Probiotics help maintain healthy gut bacteria, which can be compromised with antibiotic use. Probiotics should be taken a minimum of two hours apart from an antibiotic.
Parents want to know if their child will outgrow PANDAS and PANS. There is currently no long-term prospective study of PANDAS/PANS children. The prognosis is not known over a lifetime. However, we are seeing positive outcomes for the majority of children. Efforts are underway in 2021–22 to develop a national biorepository and RedCap patient registry.
Positive Outcomes with Treatment: The PANS Consortium has been meeting to discuss case outcomes since 2013, and the majority of children improve and return to school and normal social activities with immune modulation treatments. The Guidelines set forth in the JCAP (described in the Diagnosis and Treatment sections) have improved and healed the lives of several thousands of children worldwide to date.
Positive Outcomes with Maturity: Susceptibility to group A strep lessens for most children by puberty. Pediatric immune system malfunctions (e.g., dysgammaglobulinemia, neutropenia, severe allergies, etc.) are often outgrown as children mature into young adulthood.
Possible Genetic Predisposition: Ongoing human genetic studies in several U.S. research centers indicate that PANDAS/PANS likely affects a genetically sensitive group of children. The mutated genes seem to regulate immune function. PANDAS children and some young adults do have an aberrant reaction to strep bacteria and often (but not well-tracked by researchers yet) other environmental irritants. With PANS as well, it is important to keep all infections and allergic reactions at bay. Many children stay on a prophylactic dose of antibiotics well into adulthood to prevent strep infections, together with ongoing check-ins with a thoughtful immunologist, pediatrician or the like.
Anecdotal Reports of Approximately 100 Youth (2018 to present) Indicate that Some Teens and Young Adults Relapse: There is unofficial reporting amongst the consortium of re-exacerbations into young adulthood (16 to 25 years of age) for a 2007 pediatric cohort (PANS/PANDAS). These re-exacerbations have occurred with various infections or extreme allergic reactions (food poisoning, septic wounds, pneumonia, mononucleosis, etc.). Symptoms have calmed for some with typical immunomodulation treatments and can be stopped. Other young adults have had severe relapses that significantly impair their quality of life. Research is underway in 2021 to understand these relapses and their outcome.
Takeaways from cases that are in a stable state and functioning normally:
1) Identify and prevent any active infections while in a stable health state.
2) Know the child’s immune system and keep healthy dietary habits.
3) Know the child’s family history of autoimmune illness.
4) Often mild lingering anxiety or OCD may continue, and ongoing psychological supports are helpful for both patient and family.
5) In the case of strep, tell doctors of a family history of rheumatic fever or similar strep history.
Genetic research is being conducted at every PANS research center around the world, and we are hopeful that within a decade this will help explain the propensity to autoimmune overreaction.
Knowledge is power! Stay informed and advocate with the parent community.
Learn More About PANDAS
PANDAS and PANS is a clinical diagnosis based on the collection of signs, symptoms, medical history and laboratory findings that cannot be explained by any other neurological or medical disorders. PANDAS has five distinct criteria for diagnosis.
PANDAS Signs and Symptoms
Learn more about the signs and symptoms associated with PANDAS and PANS, as well as the scales in which they fall for aligning with the diagnosis of this disorder.
Frequently Asked Questions
As awareness and research of PANDAS continue to grow, parents, providers, caretakers and supporters tend to ask the following questions frequently.
Help us continue to support the children and adults living with PANDAS/PANS.