Appeal type: Medical Necessity
Decision: Insurer Denial Overturned

Summary Reviewer  
 
The patient is a 12-year-old male who has been diagnosed with autoimmune 
encephalitis/encephalopathy and pediatric autoimmune neuropsychiatric disorder associated 
with streptococcus (PANDAS) following the acute onset of mental health symptoms in 2020. 
The patients parent has requested reimbursement for GammaGard (IVIG) provided from 
9/05/20 through 12/28/20.  The physician reviewer found that the treatment of PANDAS 
involves approaching both the physical and psychiatric symptoms. Treatment must reduce the 
OCDs, the tics or other behaviors that could interfere with day-to-day living and school. The 
treatment of the streptococcal infection is performed with antibiotics. The psychiatric 
symptoms can begin to improve upon the start of the antibiotic treatment. The OCD and other 
psychiatric symptoms are generally treated with the cognitive behavioral therapy and/or 
selective serotonin reuptake inhibitors. Some severe cases of PANDAS may not respond to 
drugs and behavioral therapy. IVIG has been described in multiple case reports and case series. 
The 2018 study by Pavone and colleagues included a cohort of 34 children diagnosed with 
severe PANDAS. In this cohort, 29 out of 34 of children treated with IVIG showed a reduction or 
disappearance of the symptomatology, while in five cases (15%), despite three IVIG courses, 
there was only temporary improvement of clinical symptoms, with their reappearance within 
one to six months. Limitations of the study included the absence of case controls and long-term 
follow-up. The 2020 study by Pavone and colleagues included a cohort of 55 children diagnosed 
with moderate-to-severe PANDAS who were treated with IVIG. The study found a noticeable 
improvement in symptoms for at least one year for 47 of the 55 patients (85%). While 12 of the 
patients (21.8%) went from having extreme symptoms to having no symptoms, 22 of the 
patients (40%) went from having extreme symptoms to having mild symptoms.  In 11 patients 
(20%), only one treatment of IVIG was required, while 36 patients (65.5%) required a second 
course of treatment. A multi-site open label study by Melamed and colleagues consisted of 21 
subjects (7 per site) with moderate-to-severe PANS. The mean age was 10.86 years. Results 
demonstrated statistically significant reductions in symptoms from baseline to end of 
treatment in all six assessments measured. Furthermore, the National Institute of Mental 
Health NIMH states on their website, Plasma exchange or immunoglobulin (IVIG) may be a 
consideration for acutely and severely affected children with PANDAS. Research suggests that 
both active treatments can improve global functioning, depression, emotional ups and downs, 
and obsessive-compulsive symptoms...the treatments should be reserved for severely ill 
patients and administered by a qualified team of health care professionals. Additionally, first-
line therapeutic agents used to treat autoimmune encephalitis include IVIG. This patient has 
been diagnosed with PANS/PANDAS and autoimmune encephalitis/encephalopathy and has not 
responded to other treatments, including psychotropic medications and steroids. Records 
report that he has had a positive response to IVIG. There is sufficient evidence in the medical 
literature and in the clinical response of the patient to support the use of IVIG. Therefore,  GammaGard (IVIG) provided from 9/05/20 through 12/28/20 was medically necessary for the 
treatment of this patient.