Pandas -- pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection

Timothy C. Hain, MD

Also see: autoimmune brain disease.

Last edited: June 7, 2018 . This page is in the process of being revised.

The PANDAS syndrome (what a cute name !) stands for pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection. It really says it all. This diagnosis is a new one used to explain psychiatric symptoms in children. It may have some utility as a place to assign causality for a child developing a psychiatric syndrome, as opposed to the more usual attribution of symptoms to stress or bad genes. PANDAS is characterized by an abrupt onset of anxiety and OCD (obcessive-compulsive disorder) with a recently docummented streptococcal infection, generally in children aged 3 to about 12. (Swedo et al, 2015). This can include tics or chorea -- and thus PANDAS may be the same illness as Sydenham chorea, which emphasises chorea after a strep infection. We swap one eponym for another.

The PANDAS syndrome is somewhat controversial. Recently evidence suggests that the "AS" part of PANDAS may be wrong, and the acronym PANDAS has been replaced by PANS, because the link to streptococcal infection appears weak.

The very existence of PANDAS has also been questioned. Orlovska et al (2017) examined Danish children (1067743 in total). They stated "Individuals with a positive streptococcal test result had an increased risk of any mental disorder (n = 15408; IRR, 1.18; 95% CI, 1.15-1.21; P < .001), particularly of OCD (n = 556; IRR, 1.51; 95% CI, 1.28-1.77; P < .001) and tic disorders (n = 993; IRR, 1.35; 95% CI, 1.21-1.50; P < .001), compared with individuals without a streptococcal test. Furthermore, the risk of any mental disorder and OCD was more elevated after a streptococcal throat infection than after a nonstreptococcal infection. Nonetheless, individuals with a nonstreptococcal throat infection also had an increased risk of any mental disorder (n = 11315; IRR, 1.08; 95% CI, 1.06-1.11; P < .001), OCD (n = 316; IRR, 1.28; 95% CI, 1.07-1.53; P = .006), and tic disorders (n = 662; IRR, 1.25; 95% CI, 1.12-1.41; P < .001). " This appears to suggest a slightly increased risk of OCD in streptococcal infections (1.51) vs. non-streptococcal (1.28). In other words, throat infections are associated with OCD, and streptococcal ones slightly more than others. This does not appear to be a very strong assocation, and as noted above, the streptococcal part of the acronym may be inaccurate.

Chairello et al (2017), stated " After almost 20 years, PANDAS has not been accepted as distinct disorder and new criteria for paediatric acute-onset neuropsychiatric syndrome (PANS) have been replaced it, highlighting the fact that several agents rather than only Streptococcus might be involved."

Windfuhr (2016) stated that "Conclusion: Establishing the diagnosis of PANDAS is complicated because of underlying comorbidities in the field of neurology-psychiatry and the lack of a reliable biomarker. The positive outcome after TE as reported in case studies may be influenced by the postoperative medication and is not supported by the results of large-scale studies. In the light of the considerable postoperative morbidity rate, it appears wise to indicate TE for PANDAS only in supervised clinical studies."

Mechanism of PANDAS (or PANS)

For those who believe PANDAS really exists, the theory is that there are antibodies developed against brain dopamine receptors. Orefici et al (2016) state "Anti-neuronal autoantibodies against the brain in SC and PANDAS react with brain antigens including dopamine receptors (Cox, et al., 2013; Brimberg, et al., 2012), lysoganglioside (Kirvan, Swedo, Heuser, & Cunningham, 2003; Kirvan, Swedo, Snider, & Cunningham, 2006a), and tubulin (Kirvan, Cox, Swedo, & Cunningham, 2007), as well as the activation of the calcium calmodulin-dependent protein kinase II (CaM KII) in human neuronal cells (Kirvan, Swedo, Heuser, & Cunningham, 2003). Human anti-brain antibodies expressed in Tg mice targeted dopaminergic neurons and signaled the dopamine D2 receptor (D2R) (Cox, et al., 2013). Evidence strongly suggests that human anti-brain autoantibodies induced by Streptococcus pyogenes infections target the dopamine receptors (Cox, et al., 2013; Brimberg, et al., 2012) and that animal models immunized with the S. pyogenes antigen develop obsessive behaviors and movement problems, along with antibodies that react with the dopamine receptors and signal the CaMKII, similar to antibodies found in humans with SC and PANDAS (Brimberg, et al., 2012; Lotan, et al., 2014a). " This sounds pretty good, but one wonders if this molecular biology has clinical significance.

Diagnosis of PANDAS

Recent papers on PANDAS question whether or not there is a diagnostic test for PANDAS (see above).

Diagnosis of PANDAS is through culture of the nose, throat and skin, testing for ASO and anti DNAase B (helpful when titers are rising, as they persist life-long). The Cunningham panel involves 4 autoantibodies against human neuronal cell lines plus activation of calmodulun kinase. The specificity of this test is difficult to determine. Thus it can be seen, that the diagnosis of PANDAS is somewhat of a voluntary choice by the clinician -- as there seems to be nothing truly specific. To be the devils advocate -- suppose someone who has no issues at all, suddenly develops anxiety and becomes more OCD. They had a sinus infection a few weeks ago. Is this PANDAS ?


And how are people treated differently, with or without the label of PANDAS ? Treatment of PANDAS involves mainly watchful waiting, and aggressive treatment of strep infections. This doesn't really seem much different than just being careful to treat infections -- in other words, ignore the "evidence based medicine" people who say that one should just let people fight off their infections all by themselves, without the aid of antibiotics.

Sigra et al (2018) did a systemic review of articles on PANDAS. They stated "We determined that rigorously conducted research regarding treatments for PANDAS is scarce, and published studies have a high risk of bias. Further research is needed in which promising treatment strategies for PANDAS and other variants of OCD with proposed autoimmune etiology are rigorously investigated." So in other words, there is no definitive treatment. There are a myriad of articles suggesting that various approaches succeeded in this or that case. For example, antibiotics, IGG, Steroids, plasmapheresis (Nave et al, 2018). Williams et al (2016) reported in regards to IVIG that "the double-blind comparison failed to demonstrate superiority of IVIG over placebo. "

Burchi and Pallanti (2018) examined antibiotic treatment. They stated "Conclusions: Whereas the use of eradicating antibiotic therapy during active infections in PANDAS/PANS is well established, there is still a need for studies that improve the quality of evidence supporting use of antibiotics in this population independent of ongoing infections. " Or in other words, it doesn't help to treat with antibiotics after the infection is done.

Farhood et al (2016), concluded "There is a paucity of high-level studies regarding this rare disorder and no hard treatment recommendations can be made. Tonsillectomy should only be performed in those who are surgical candidates based on current published guidelines. Antibiotics are an option but provide uncertain benefit. CBT remains a low-risk option. ". In other words, treat them like everybody else and ignore the PANDAS idea.

Drug treatment (i.e. symptom treatment) includes SSRIs for OCD, CBT, and treatment of tics with alpha-2 adrenergic agonists rather than neuroleptic agents. Drugs for ADHD are also sometimes useful. (Chang et al, 2015). Again, this is what one would do with or without the "diagnosis" of PANDAS.