Most, if not all, of us have likely had strep throat as children or even as adults caused by that pesky microorganism known as group A streptococcus. Hopefully all of us listened to our physicians and took every last antibiotic as prescribed and then went about our lives just as before, but for some this doesn't seem to be how things work out. Pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS), aside from being a mouth-full, was given its name by Susan Swedo in the 90's while studying other disorders associated with untreated group A infections, and is believed to be the cause behind behavioral cognitive changes seen in some children following strep infections (Zamzow, 2019). Particularly, those thought to be suffering from PANDAS express tics, and obsessive-compulsive behaviors as well as a dampening of motor functions, anxiety, and developmental regression (Hesselmark & Bejerot, 2017).
So what is thought to be happening in these few individuals that are unfortunate enough to develop these symptoms? We aren't entirely sure, which is why some in the medical community still discount the existence of PANDAS all together, but in recent years researchers have come a little closer to an explanation. The culprit, they think, is our own immune system being overzealous resulting in postinfectious autoimmunity resulting in neuroinflammation (Swedo et al., 2017). Surprisingly our good friend the NMDA receptor could have something to do with it! Researchers recently discovered that "rouge antibodies" attack these receptors causing seizures, and in 2018 these antibodies were discovered to attach to a large number of receptors in the basal ganglia which is associated with voluntary motor movement, learning, cognition, and emotion (Zamzow, 2019).
As it currently stands however, there is still a lot to learn about PANDAS before we can know exactly what causes it, or whether it even exits at all as some argue since it is incredibly difficult to link a streptococcal infection, which clears quickly, to symptoms that may not develop until a few months after. For now, patients believed to be suffering PANDAS are treated with immunomodulatory therapy, where a healthy individuals antibodies are infused to deactivate the patients own (Swedo et al. 2019). This treatment also accompanies psychotherapy and antibiotic treatment. But wait... should we be treating patients that no longer have an active infection with antibiotics?! This is definitely an ethical question for concern considering what we already know about the rampant overuse of antibiotics and the "super-bugs" that its brought about. More importantly, immunomodulatory therapies also failed to show any results that bested the placebo they were tested against (Zamzow, 2019). This begs the question of whether these treatments should continue to be administered to individuals considering they have a disorder that some argue doesn't even exist and has no clear etiology.
Original article:
https://www.sciencenews.org/article/strep-throat-infections-brain-ocd-anxiety-mental-illness-kids
Works Cited:
Biomarkers for diagnosis of Pediatric Acute Neuropsychiatric Syndrome (PANS) – Sensitivity and specificity of the Cunningham Panel. Hesselmark, Eva et al. Journal of Neuroimmunology, Volume 312, 31 - 37.
Swedo, S. E., Frankovich, J., & Murphy, T. K. (2017). Overview of Treatment of Pediatric Acute-Onset Neuropsychiatric Syndrome. Journal of child and adolescent psychopharmacology, 27(7), 562–565. doi:10.1089/cap.2017.0042
Zamzow, R. (2019, August 26). How strep throat may spark OCD and anxiety in some kids. Retrieved September 30, 2019, from https://www.sciencenews.org/article/strep-throat-infections-brain-ocd-anxiety-mental-illness-kids.
I had never heard of this before and find it most interesting that there are neurodevelopmental delays seen in a rare population of children months after having strep throat. It's fascinating to make the connection back to strep infections. Given that treatment post infection is treated with an antibiotic and an immunomodulatory therapy but there is no concrete evidence that this PANDAs therapy works is concerning. Since there are people in the medical community who do not even believe this is a real "disease," potentially over treating patients with more antibiotics isn't necessarily the best option in my opinion. Though it can be expensive, an "out of nowhere" onset of some of the symptoms of PANDAs can potentially be better explained by using Exome Sequencing. Exome sequencing is used in rare diseases and isolates all protein coding regions of genes in the genome. This technique can further isolate which genes are being affected (sometimes - it isn't always accurate for some rare diseases that show SNPs that aren't associated with the disease being isolated and WES results are difficult to interpret). Depending on how much the Rare Genomics Institute grows, the database to compare rare diseases with specific genes can better determine diagnosis and most importantly treatment options.
ReplyDeleteGiven that the overuse of antibiotics can cause superbugs and immunomodulatory treatment hasn't shown to be truly effective, I think that research clinicians need to consider beneficence and non-malfeasance in regard to understanding and researching this rare disease more effectively. If the placebo has the same effect as the immunomodulatory therapy, what does that mean regarding treatment for the patient? Is the patient improving from one or the other in equal amounts? If the patient shows improvement with the placebo just as often as improvement with antibiotics and immunomodulatory therapy, what is happening physiologically to "improve" these symptoms? Though I do not discount that PANDAs is a real phenomenon, I think more has to be done in order to provide non-malfeasance care and justice for those who appear to show symptoms after contracting strep. Since strep can be contagious and schools are rampant for passing around germs, the likelihood of contracting PANDAs is rare, but nonetheless potentially present. For bacterial infections to then mutate further after the appearance of improvement I think is a viable explanation not only for PANDAs but perhaps for other bacterial infections that may or may not be causing later onset issues. Overall, more research needs to be performed in understanding the what as well as treatment options for these children who "appeared normal" then after a strep infection showed a psychological change.
Nick and Alex,
ReplyDeleteAfter discussing this topic with you in class I began to complete my own research on PANDAS. From my search I learned that PANDAS, now commonly known as a broader iteration as PANS (paediatric acute-onset neuropsychiatry syndrome) has no definite proof of the causes (Wilbur et al, 2018). This disorder is classified by a check list of criteria that was developed in 1998 including the symptoms of OCD and/or tick disorder and association with A beta-hemolytic streptococcus infection (Wilber et al, 2018). The criteria was updated for PANS in 2012 to include the abrupt onset of obsessive compulsive disorder and concurrent presence of neuropsychiatric symptoms including anxiety, depression and sensory or motor difficulties (Wilber et al, 2018). Treatments vary from psychiatric interventions to immunotherapy and antibiotics (Wilber et al, 2018).
However, studies within the last twenty years comparing children diagnosed with PANDAS and non-PANDAS subjects showed that there is no evidence of the existence of phenomenological features that are specific to PANDAS (Orefici et al, 2016). These studies include one written by Kurlan et al in 2008 with data concluding that patients with PANDA and patients with OCD or chronic tic disorders were comparable (Kurlan et al, 2008). Another study completed in 2012 by Murphy et al sowed that there were no clinical difference between subjects diagnosed with PANDAS and the control non-PANDAS subjects (Murphey et al, 2008).
It seems to me after completing this research that the causes of PANDAS are unclear. Due to this, the treatments vary and it is because of this fact that I find some of the treatments to be unethical. Antibiotics, one of the more common treatments for PANDA, can have negative side effects on individuals. This can include the decrease and disruption of the diversity of the microbiome of the gut. A lack of diversity of the gut microbiome leads to a host of diseases including IBD due to the increase in inflammation. The microbiome can also affect the immune system by causing the failure of the immune system to regulate responses (Langdon, Crook & Dantas, 2016). I do not think that treatment with antibiotics should continue due to the ethical principles of non-maleficence. While treating with antibiotics can aid in managing PANDAS symptoms, they can also cause harm in the patient’s future. I think that in order to determine an effective treatment, the underlying causes of PANDA need to be identified so that treatments can be personalized to the individual.
References:
Kurlan R., Johnson D., Kaplan E. L., Tourette Syndrome Study Group. Streptococcal infection and exacerbations of childhood tics and obsessive-compulsive symptoms: a prospective blinded cohort study. Pediatrics. 2008;121(6):1188–1197.
Langdon, A., Crook, N., & Dantas, G. (2016). The effects of antibiotics on the microbiome throughout development and alternative approaches for therapeutic modulation. Genome medicine, 8(1), 39.
Murphy T. K., Storch E. A., Lewin A. B., Edge P. J., Goodman W. K. Clinical factors associated with Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections. Journal of Pediatrics. The Journal of Pediatrics. 2012;160(2):314–319.
Orefici, G., Cardona, F., Cox, C. J., & Cunningham, M. W. (2016). Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). In Streptococcus pyogenes: Basic Biology to Clinical Manifestations [Internet]. University of Oklahoma Health Sciences Center.
Wilbur, C., Bitnun, A., Kronenberg, S., Laxer, R. M., Levy, D. M., Logan, W. J., ... & Yeh, E. A. (2018). PANDAS/PANS in childhood: Controversies and evidence. Paediatrics & child health, 24(2), 85-91.
This post really intrigued me as it was a condition I had never heard of before. The first question that came to my mind was why are there doctors who do not believe this condition exists, what is their alternative diagnosis? Upon further research I found that some doctors believe that an illness such as strep-throat can exacerbate underlying mental illness that presents as OCD or tics versus causing the problem itself (Quandt, 2017). There is no diagnostic test for PANDAS so the diagnosis is based on symptomology and exclusion of other conditions.
ReplyDeleteThe second point that caught my attention was the prolonged use of antibiotics in an attempt to treat PANDAS. There is definitely an ethical question to be raised here. If antibiotic resistance and superbugs are a serious health risk we are facing in todays day and age, why are doctors using antibiotics as a treatment when it has not proven to be effective thus far? I did a bit of research and found there are other treatment methods being tested for the treatment of PANDAS. One is the use of Intravenous Immunoglobulin (IVIG) which is an immuno modulatory therapy that should help re-regulate the immune system. In the PANDAS group IVIG was administered to, 45% of patients experienced marked reduction in symptoms. In a group of patients diagnosed with tics but not PANDAS, none of the patients showed any improvement in symptoms (Kovacevic, Grant, Swedo, 2015). At this point I believe doctors should be moving away from the use of antibiotics in PANDAS patients and use other methods such as IVIG that do not have the potential to create superbugs. This condition needs more research for scientists to truly understand the mechanisms behind the disease and develop better treatments.
References:
Kovacevic, M., Grant, P., & Swedo, S. E. (2015). Use of intravenous immunoglobulin in the treatment of twelve youths with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. Journal of child and adolescent psychopharmacology, 25(1), 65-69.
Quandt, K. PANDAS: A Rare Disease? Or No Disease at All? March 3, 2017. Retrieved October 9, 2019 from https://undark.org/article/doctors-divide-on-pandas.