“You just can’t beat on those mind guerrillas
Absolute elsewhere in the stones of your mind”
-John Lennon (Mind Games – 1973)
If you clicked on the link here because of the cute panda pic, sorry for the bait and switch. Today we are going to explore PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders associated with Streptococcal infections). This topic has been a source of controversy among the medical community. The focus of discussion will be to discuss what is known, what is speculated, and how to manage those who may have the condition.
What is PANDAS?
Again, PANDAS is an acronym used to describe a condition affecting children after infection with beta-hemolytic streptococcus (primarily “strep throat”) and manifesting as a sudden onset of obsessive-compulsive disorder symptoms, vocal and/or motor tics, and other behavioral changes. This condition is also sometimes referred to as CANS (childhood acute neuropsychiatric symptoms) or PANS (pediatric acute-onset neuropyschiatric syndrome) depending on some of the inclusion criteria for having the disorder. We will use PANDAS here, if for no other reason that I find them cuter, and the purpose of this blog is not to split hairs over nomenclature.
If you find either of the flanking photos cuter than the panda in the middle, there is a high likelihood the Tin Man was your favorite character in the Wizard of Oz. Don’t sweat it if you are, it’s probably protected under H.R.5. If only I could say the same for women’s athletics.
A Brief History Regarding the Origin of PANDAS
There are many sequelae (consequences) of infection with strep bacteria. Some are preventable with prompt treatment of strep infections, such as rheumatic fever. Others are simply rare and unfortunate consequences that even immediate diagnosis and treatment cannot prevent, such as glomerulonephritis. PANDAS, as we will see, may represent a hybrid of these types of consequences with a certain degree of unavoidable problem but where diagnosis and treatment of strep may assist.
One of the components of acute rheumatic fever is a movement disorder known as Syndenham’s chorea. Many affected with Syndenham’s chorea also demonstrate emotional lability. It is the combination of movement disorder with emotional disturbance from one known consequence of strep infection that led to speculation that other consequences with similar manifestations may exist.
In 2005, a study by Mell, et al conducted a retrospective case-control study and reported that pediatric patients (ages 4-13 years) receiving a diagnosis of OCD, Tourette’s, or a tic disorder were twice as likely to have had a strep throat infection in the three months than a control group. For those children who had multiple strep throat infections in the year prior to diagnosis, the associated increase in risk was 13 fold. While this study shows a potential association, it does not show causality. This study contradicts another study performed around the same time (a prospective case-control study) that concluded there was no difference in risk for OCD or tic disorders from recent strep infections. Despite the many years that have transpired since these studies, there have not been any significant studies reported to truly address a causal relationship between strep and OCD/tic disorders or to properly define the epidemiology of the concern.
For the purposes of the remaining discussion, I am going to work under the assumption that PANDAS as an entity exists. Based on what my own eyes have seen in twenty years, there are a handful of children that truly did appear to fit the description of having PANDAS. Edgar Allen Poe was attributed with saying “Believe nothing you hear, and only one half that you see.” With that in mind, my experience with this handful of children does not provide proof of anything. For more on what assumption is, I refer you to a clip from the movie Under Siege II (language advisory).
While this concludes our Brief History of PANDAS, we will take a second to offer you a reading suggestion: A Brief History of Time by Stephen Hawking (whose neurological condition was not related to strep infection). And for some of you looking for something a little less taxing on your brain and want to learn a bit about the origins of pandas, the mammal, click here.
Jeff Beck performing “Scatterbrain.” A virtuoso who once played with the Yardbirds, a band who churned out great guitarists. Eric Clapton and Jimmy Paige to name a couple of others.
Proposed Mechanism of Disease Progression
To date, it has been postulated that an abnormal immune response to strep bacteria is the root cause of rheumatic fever and Syndenham’s Chorea. To date, this hypothesis has not been proven. Those in the camp that PANDAS is an entity believe that the root cause is similar. Specifically, a person gets exposed to strep and as part of their immune response to the strep bacteria, some of the response (presumably antibodies) ends up interacting with their own nerve tissues causing inflammation and symptoms of disease. Again, this is proposed, not proven.
Signs and Symptoms
The major signs and symptoms reported as associated with PANDAS are obsessive-compulsive and tic related (motor and verbal). Many report issues with focus and hyperactivity (ADHD like symptoms). Others report separation anxiety, other mood changes, changes in motor coordination (such as handwriting issues), or sleeping disturbances including bedwetting. Key again is that these symptoms should start abruptly and be related in temporal proximity to strep infection.
At this time, there is no “test” for PANDAS. Diagnosis is based on a several criteria, and these are not formally rigidly defined at that. The criteria are: OCD and/or tic disorder consistent with DSM-V definitions, onset between age 3 and puberty, abrupt onset of symptoms with episodic course, temporal relation between strep infection and onset, and the presence of neurologic abnormalities.
Strep infection diagnosis is best if a positive throat culture or rapid antigen test is performed at the time of the abrupt onset of symptoms. There are antibody tests that can be performed though the results of these do not necessarily permit timing the actual infection with strep and may remain positive for months. This creates an issue because strep infection is so common at that age group. Attributing anything based on these blood tests therefore runs a significant risk of over-diagnosis.
Demonstration of rapid resolutions of symptoms with treatment for acute strep infection is also considered when addressing for PANDAS. Again, consideration and having a formal diagnostic methodology are not one and the same.
A Quick Summary
So far we have given you a name for a condition that is still disputed along with symptoms attributed to this condition and some loosely defined diagnostic criteria. For many conditions, this would not suffice for much. Before moving onto discussing treatment for such a condition, I would like to distill everything so far down to this: it doesn’t matter if PANDAS exists or not, as those affected with the symptoms need assistance regardless of the speculated cause. With that in mind, we are next going to take a look at how those with PANDAS are best treated and the rationale underlying their therapies.
Treatment for PANDAS encompasses several different modalities that address the speculated underlying infectious cause, the resulting speculated abnormal immune response, and the symptoms themselves. A great review addressing treatments for PANDAS can be found here. Read on for the significantly distilled version. The current recommendations that are discussed come from the consensus guidelines for treating PANDAS as published in the Journal of Child and Adolescent Psychopharmacology in 2017. Links to the full reports can be found on Stanford University’s website.
Antibiotics to treat strep infection is the easy part of this equation. Formal studies (of which there have been over 100) have not demonstrated that antibiotics are effective to treat PANDAS. So why did I say they are the easy part of the equation? Easy, because even if not related to the symptoms, strep throat should be treated in the age group discussed due to risk of rheumatic fever and heart disease. Most strep bacteria are easy to kill – amoxicillin or cephalexin are commonly used for such. Consideration for azithromycin is often undertaken in those treating PANDAS, as it has improved coverage if the bacteria were to be intracellular rather than extracellular.
Antibiotic prophylaxis to prevent future exacerbations is a strategy that has had minimal investigation to date, but are used by some, especially if having repeated exacerbations of PANDAS symptoms triggered by recurrent strep infections. The goal here is prophylaxis from future infection with strep NOT to be treating a chronic strep infection.
For a more detailed look at antibiotic therapy for those with PANDAS, click here.
Cognitive Behavior Therapy
Cognitive Behavior Therapy (CBT) is a modality of treatment that is aimed at treating the OCD symptoms associated with PANDAS. This form of therapy is widely used and accepted a treatment for a wide range of psychiatric problems. To read more about this type of therapy in general and the conditions it assist with, click here.
Current recommendations are to start CBT as early as possible to assist those with PANDAS. Studies treating OCD in general for children have demonstrated that this technique is among the most effective interventions. There is no significant downside to such therapy, and hence why it is recommended as part of the first line in treatment.
A cover of Jimi Hendrix’s Manic Depression with Zakk Wylde on guitar. Experience Hendrix has come around Long Island a couple of times, should we have such opportunities again, strongly recommend this one.
Psychotropic medications are often used as part of the treatment for PANDAS. The theory underlying these choices is that they are commonly used successfully for children with OCD and tic disorders and that PANDAS would simply represent a subset of these patients. Controlled studies for such treatments with those diagnosed with PANDAS is currently limited.
Current recommendations are to trial a serotonin re-uptake inhibitor (SSRI) if a medication option is necessary. These are very well tolerated overall with little potential for toxicity. In addition, they are not addictive. The authors of the recommendations discussed using benzodiazapines to help manage some of the anxiety components. These medication have more significant side effects and addictive potential and are rarely, if ever, used at this time in clinical practice for children on a routine basis. For those children with significant tics, trials on guanfacine are indicated. This medication is quite well tolerated and used commonly for tic disorders as well as ADHD in children. For those that take the time to read the whole article, there are a lot of references to anti-psychotics and a couple of other neurologic agents. These would be reserved for patients that have not responded to the common modalities of therapy due to their side effect profiles.
Anti-inflammatories are frequently prescribed for PANDAS treatment. These come in two varieties, steroids and non-steroids (NSAID). As examples of one in each category that most would recognize – prednisone is a steroid, ibuprofen is an NSAID. The theory for use of these types of medications for PANDAS is that they should diminish the inflammatory response that is caused by the abnormal immune response to strep infection in affected individuals. There is anecdotal evidence for their use (ie: “Johnny said this leaf cured his asthma”), but clinical trials have failed to show consistent benefit from their use.
Current recommendations for use of anti-inflammatories are a bit convoluted and beyond the scope of discussion here. If interested, you can find the entire article here. The brief version is that they are part of a second line of therapy for those that did not respond to initial treatment with antibiotics and CBT therapy after a few weeks. Depending on the severity of symptoms, duration of symptoms, and prior attempts to treat with anti-inflammatories, the form of treatment varies. In all cases, the duration of treatment described is at most on the scope of weeks.
Plasma therapies include plasma exchanges with a donor as well as infusions with antibodies such as IVIG therapy. The theory here is that the donor plasma or infused antibodies will outcompete the problematic antibodies made by affected individual and reduce the inflammation/damage caused by them. At risk of sounding like a broken record, there are some studies that demonstrated benefit from such therapies, but at this time the overall data is inconclusive to recommend the use of these therapies as a regular part of treatment.
Current recommendations for plasma therapies are that they are to be used for those with moderate to severe disease burden who have not responded to other treatments including antibiotics, therapy, and anti-inflammatories.
Tonsil and Adenoid Removal
Historically, tonsil and adenoid removal was commonplace for those who had frequent strep infections. This has become less the case over the years in part because it didn’t have the expected impact in case reduction, and in part because of the risks of the surgery itself. To date there are no controlled studies looking at the benefit of these procedures in those with PANDAS. Remember, the definition of a minor surgery is surgery on someone else…..
The Black Crowes performing Traffic’s Medicated Goo in London. The Black Crowes are back together. Add that to the list on canceled concerts last summer.
A Word of Caution
There are physicians out there that are now making a living as PANDAS specialists. I cannot speak to anyone in particular, but will offer you this warning, and it applies to many that treat poorly defined or currently intractable chronic illnesses – BE CAREFUL!
If a physician is ordering twenty pages of labs on your 5 year old with new onset of tics, it is almost never warranted based on any guideline as part of a workup. This is called throwing crap against the wall to see what sticks. If they are telling you that the labs must be ordered from some specialty lab because the major labs don’t know what they are doing, you are dealing with a charlatan.
If a physician is prescribing forty supplements to your child, you can rest assured you are also dealing with a charlatan. Bonus points here if they are willing to sell them to you from their office. This is a conflict of interest. If it was just convenience, every doctor would have a pharmacy in their office.
If a physician is telling you that your child needs IV antibiotics to treat strep, it is not founded in any data anywhere for this condition. If they are saying it is needed for multiple years, run. They only thing you will accomplish is either an allergic reaction or a child with profuse diarrhea from c. dificile colitis.
I can go on an on with these types of folks. They prey on the desperate with disregard for the outcomes. I know I am dealing with them when I see the fifth child seek their care, receive the same extreme workup with differing results, yet the same expensive chronic treatments. No thought process, no discretion, just pocket lining. There is a sucker born every minute per PT Barnum. Don’t be that sucker.
In summary, there are children who suffer with OCD, as well as tic disorders and other emotional concerns. Some of these children may have these symptoms brought on by strep infections. In those cases, the condition is referred to as PANDAS, as it is presumed to be due to an inappropriate immune response to strep bacteria that leads to inflammation and ultimately symptoms. Formal diagnosis using specified criteria does not truly exist for the condition at this time though there are some recommended guidelines in place. At the end of the day, all I see in these cases is a child who is in need of help. My recommendation for these children stems from my Flying Spaghetti Monster version of the Serenity Prayer:
“Grant me the serenity to accept the things I cannot change,
courage to change the things I can,
and wisdom to know the difference.”
I cannot change what caused the concern in these children – they already have symptoms. I can help with some of the symptoms for which many options were outlined above. What I am always cognizant of however is not inflicting further damage in trying to assist those in need.
Have a great week all! Stay safe!
Post authored by Jason Halegoua PhD, MD, MBA, FAAP. Jason is the founder of Peds First Pediatrics in 2009, and has been a practicing general pediatrician since completing residency at Schneider Children’s Hospital in 2004. In addition to earning his medical degree from the Medical College of Pennsylvania, Jason earned a PhD in Molecular Pathobiology for his work contributing to the understanding of the genetic regulation of immune responses to murine leukemia viruses from Hahnemann University in Philadelphia and an MBA in Finance from Hofstra University.