A previously fit and well child is seen in outpatient clinic by the Paediatricians, as he has now developed tics. As if to emphasise the point the boy suddenly jerks as though ”shocked” and then bursts into tears. His parents are beside themselves with worry. Whilst planning how to manage the child’s neurological symptoms the story comes out that he had a bit of a sore throat a couple of weeks earlier (not an uncommon complaint in 5 year olds). The Paediatrician devises a management plan for the child’s tics but takes a throat swab “just in case” the child has tonsillitis.
Later that day, whilst discussing another patient with the Microbiologist, the Paediatrician happens to mention the boy with tics and a sore throat. “I wonder if he has PANDAS?” the Microbiologist says. “What have giant pandas got to do with it?” asks the Paediatrician. “Not giant pandas, but PANDAS - Paediatric Autoimmune Neuropsychiatric Disorder associated with group A beta-haemolytic Streptococci” explains the Microbiologist. “What are you talking about?!” exclaims the Paediatrician with a weary smile… Ah… let me expand…
Later that day, whilst discussing another patient with the Microbiologist, the Paediatrician happens to mention the boy with tics and a sore throat. “I wonder if he has PANDAS?” the Microbiologist says. “What have giant pandas got to do with it?” asks the Paediatrician. “Not giant pandas, but PANDAS - Paediatric Autoimmune Neuropsychiatric Disorder associated with group A beta-haemolytic Streptococci” explains the Microbiologist. “What are you talking about?!” exclaims the Paediatrician with a weary smile… Ah… let me expand…
What are Giant Pandas?
With only 1,864 in the wild, pandas are the rarest member of the bear family. They have recently been downgraded from endangered to vulnerable. Pandas live mainly in temperate broadleaf and mixed forests high in the mountains of southwest China, where they subsist almost entirely on bamboo. They are excellent tree climbers despite their size; adults can weigh 75-135kg… but I digress…
What is PANDAS?
Paediatric autoimmune neuropsychiatric disorder associated with group A beta-haemolytic streptococci (PANDAS) describes a group of patients who have symptoms of obsessive compulsive disorder (OCD) or tic disorders caused or made worse by infection with the Group A beta-haemolytic Streptococcus (S. pyogenes). PANDAS was originally described in young children; it is rare after age 12 but has been known to affect adolescents and young adults.
Okay, I know how this sounds and believe me I was sceptical when I first came across this back in 2007 but I have to say that the evidence was pretty convincing then and continues to support an association between the symptoms and infection. However, PANDAS is still a controversial topic so it’s worth discussing further.
Researchers first started to look at PANDAS when they noticed an association between OCD and Sydenham’s chorea. Sydenham’s chorea is a movement disorder with writhing serpentine movements, emotional lability and reduced muscle tone; it is one of the major criteria in the Jones criteria for diagnosing rheumatic fever following infection with Group A beta-haemolytic streptococci (GAS). The researchers also noted that some children had OCD or tic disorders following infection which were not Sydenham’s chorea1.
Tics are sudden abnormal jerking movements whereas chorea (from the Latin choreus meaning dance) is rapid and unpredictable movements of the limbs, face and trunk giving the appearance of writhing or fidgeting. Both are not within the control of the individual.
How does PANDAS present?
The diagnostic features of PANDAS include:
What is the controversy about PANDAS?
There are a number of key questions that haven’t yet been fully answered about PANDAS. Does Group A streptococcus cause PANDAS? Is PANDAS an autoimmune disease? Should children with OCD or tic disorders be investigated for GAS infection?
Does GAS infection cause PANDAS?
The hypothesis for how GAS causes PANDAS is that infection triggers an autoimmune response in certain children with the production of autoantibodies which damage or disrupt the central nervous system. This hypothesis is unproven, which is not really surprising as we also do not yet know why Sydenham’s chorea occurs in rheumatic fever and yet this was first described by Thomas Sydenham in 1686 and its association with rheumatic fever documented in 1866. If we haven’t worked out Sydenham’s chorea in over 300 years it’s certainly still early days for PANDAS!
Further evidence for the role of GAS comes from a case control study which took children diagnosed with OCD or tic disorders as cases and compared them to otherwise healthy children as controls. The cases were 2-3 times more likely to have had a GAS infection within 3 months of the onset of their neurological disease. This shows an association but does not confirm causality… further work is clearly needed.
Is PANDAS an autoimmune disease?
Some studies have shown that children with PANDAS have higher than normal levels of anti-neuronal antibodies; antibodies which target nerve cells. On the other hand, other researchers have failed to demonstrate these higher anti-neuronal antibodies. Again further work is required to show whether PANDAS is autoimmune or not.
Should children with OCD or tic disorders be investigated for GAS infection?
In general practice thousands of throat swabs are taken from children to look for GAS. If these throat swabs are positive for GAS then the children should be given antibiotics to get rid of the GAS and prevent rheumatic fever, glomerulonephritis and yes also PANDAS. Investigators found only 1 case of PANDAS amongst 3,000 children with throat swabs positive for GAS. Therefore, in a normal paediatric population PANDAS is rare e.g. if a Paediatrician has 10 children with GAS it is unlikely any will have PANDAS. But if the symptoms of PANDAS are OCD and tic disorders, how many OCD patients actually have GAS? The rate of OCD in children is actually quite high; 1 in 300. Studies have shown that 1 in 10 children with OCD have PANDAS… that’s 10%. So if the same Paediatrician had 10 children with OCD, 1 is likely to have PANDAS.
If 10% of children with OCD could be treated and possibly cured then surely it is worthwhile looking for it in all OCD children.
How should I test my patient?
I think the fact that 10% of OCD children could have PANDAS does make it worthwhile testing every child with OCD for GAS. This is done by taking a throat swab PLUS testing serum for blood markers of recent GAS infection, both anti-streptolysin O titre (ASOT) and anti-DNase B initially and repeated 4 weeks later. Antibiotics are recommended with a positive throat culture or blood tests. Remember 9 out of 10 children with OCD will have negative tests and another cause for the OCD.
Now I’m a great believer in that there is little point doing a test on a patient unless it is going to change your management of that patient, so how is GAS in PANDAS treated?
Should PANDAS be treated with antibiotics?
So does treating GAS improve PANDAS? In prospective studies the neuropsychiatric symptoms improved with antibiotics in 33-50% of children with PANDAS. Not only do the neuropsychiatric symptoms improve but the risk of other post-streptococcal sequelae such as rheumatic fever and glomerulonephritis are also reduced with antibiotics. The Americans (who have the most experience with PANDAS) tend to use oral cephalosporins such as the broad spectrum Cephalexin however narrow spectrum Amoxicillin could also be used.
Immunomodulatory therapy with steroids, immunoglobulin or plasma exchange have been suggested as treatments but these make little difference to the symptoms of PANDAS in most children and there are high rates of adverse effects from these interventions. At present there is no evidence that the benefits of immunomodulatory therapy outweigh the risk from adverse effects.
Children who have had PANDAS do not need to be given prophylactic antibiotics as they would if they had had rheumatic fever. Whilst it is logical to assume that preventing GAS infection will prevent relapses, as it does for rheumatic fever, there is no evidence to support this in PANDAS. This may be due to the fact that the causative role of GAS in PANDAS is not yet certain, therefore it is hard to justify using antibiotic prophylaxis.
So the boy from clinic had GAS detected in his throat and was given 10 days of oral Amoxicillin. At his next clinic appointment his parents were delighted, reporting that his tics had gone away and he was back to his normal self. Did the child have PANDAS? I’ll leave you and the Paediatrician to decide…
NB: I do love this bacterium, Group A beta-haemolytic streptococcus, it’s so versatile, causing so many different diseases, (tonsillitis, cellulitis, septic arthritis, necrotising fasciitis and now PANDAS) it certainly keeps us microbiologists on our toes and it still remains sensitive to penicillin!
References
With only 1,864 in the wild, pandas are the rarest member of the bear family. They have recently been downgraded from endangered to vulnerable. Pandas live mainly in temperate broadleaf and mixed forests high in the mountains of southwest China, where they subsist almost entirely on bamboo. They are excellent tree climbers despite their size; adults can weigh 75-135kg… but I digress…
What is PANDAS?
Paediatric autoimmune neuropsychiatric disorder associated with group A beta-haemolytic streptococci (PANDAS) describes a group of patients who have symptoms of obsessive compulsive disorder (OCD) or tic disorders caused or made worse by infection with the Group A beta-haemolytic Streptococcus (S. pyogenes). PANDAS was originally described in young children; it is rare after age 12 but has been known to affect adolescents and young adults.
Okay, I know how this sounds and believe me I was sceptical when I first came across this back in 2007 but I have to say that the evidence was pretty convincing then and continues to support an association between the symptoms and infection. However, PANDAS is still a controversial topic so it’s worth discussing further.
Researchers first started to look at PANDAS when they noticed an association between OCD and Sydenham’s chorea. Sydenham’s chorea is a movement disorder with writhing serpentine movements, emotional lability and reduced muscle tone; it is one of the major criteria in the Jones criteria for diagnosing rheumatic fever following infection with Group A beta-haemolytic streptococci (GAS). The researchers also noted that some children had OCD or tic disorders following infection which were not Sydenham’s chorea1.
Tics are sudden abnormal jerking movements whereas chorea (from the Latin choreus meaning dance) is rapid and unpredictable movements of the limbs, face and trunk giving the appearance of writhing or fidgeting. Both are not within the control of the individual.
How does PANDAS present?
The diagnostic features of PANDAS include:
- Sudden onset OCD or tic disorder
- Paediatric onset (from 3 years to puberty)
- Association with GAS infection at onset and with future relapses or exacerbations
- Neurological abnormalities during exacerbations e.g. hyper activity, choreiform movements or tics
What is the controversy about PANDAS?
There are a number of key questions that haven’t yet been fully answered about PANDAS. Does Group A streptococcus cause PANDAS? Is PANDAS an autoimmune disease? Should children with OCD or tic disorders be investigated for GAS infection?
Does GAS infection cause PANDAS?
The hypothesis for how GAS causes PANDAS is that infection triggers an autoimmune response in certain children with the production of autoantibodies which damage or disrupt the central nervous system. This hypothesis is unproven, which is not really surprising as we also do not yet know why Sydenham’s chorea occurs in rheumatic fever and yet this was first described by Thomas Sydenham in 1686 and its association with rheumatic fever documented in 1866. If we haven’t worked out Sydenham’s chorea in over 300 years it’s certainly still early days for PANDAS!
Further evidence for the role of GAS comes from a case control study which took children diagnosed with OCD or tic disorders as cases and compared them to otherwise healthy children as controls. The cases were 2-3 times more likely to have had a GAS infection within 3 months of the onset of their neurological disease. This shows an association but does not confirm causality… further work is clearly needed.
Is PANDAS an autoimmune disease?
Some studies have shown that children with PANDAS have higher than normal levels of anti-neuronal antibodies; antibodies which target nerve cells. On the other hand, other researchers have failed to demonstrate these higher anti-neuronal antibodies. Again further work is required to show whether PANDAS is autoimmune or not.
Should children with OCD or tic disorders be investigated for GAS infection?
In general practice thousands of throat swabs are taken from children to look for GAS. If these throat swabs are positive for GAS then the children should be given antibiotics to get rid of the GAS and prevent rheumatic fever, glomerulonephritis and yes also PANDAS. Investigators found only 1 case of PANDAS amongst 3,000 children with throat swabs positive for GAS. Therefore, in a normal paediatric population PANDAS is rare e.g. if a Paediatrician has 10 children with GAS it is unlikely any will have PANDAS. But if the symptoms of PANDAS are OCD and tic disorders, how many OCD patients actually have GAS? The rate of OCD in children is actually quite high; 1 in 300. Studies have shown that 1 in 10 children with OCD have PANDAS… that’s 10%. So if the same Paediatrician had 10 children with OCD, 1 is likely to have PANDAS.
If 10% of children with OCD could be treated and possibly cured then surely it is worthwhile looking for it in all OCD children.
How should I test my patient?
I think the fact that 10% of OCD children could have PANDAS does make it worthwhile testing every child with OCD for GAS. This is done by taking a throat swab PLUS testing serum for blood markers of recent GAS infection, both anti-streptolysin O titre (ASOT) and anti-DNase B initially and repeated 4 weeks later. Antibiotics are recommended with a positive throat culture or blood tests. Remember 9 out of 10 children with OCD will have negative tests and another cause for the OCD.
Now I’m a great believer in that there is little point doing a test on a patient unless it is going to change your management of that patient, so how is GAS in PANDAS treated?
Should PANDAS be treated with antibiotics?
So does treating GAS improve PANDAS? In prospective studies the neuropsychiatric symptoms improved with antibiotics in 33-50% of children with PANDAS. Not only do the neuropsychiatric symptoms improve but the risk of other post-streptococcal sequelae such as rheumatic fever and glomerulonephritis are also reduced with antibiotics. The Americans (who have the most experience with PANDAS) tend to use oral cephalosporins such as the broad spectrum Cephalexin however narrow spectrum Amoxicillin could also be used.
Immunomodulatory therapy with steroids, immunoglobulin or plasma exchange have been suggested as treatments but these make little difference to the symptoms of PANDAS in most children and there are high rates of adverse effects from these interventions. At present there is no evidence that the benefits of immunomodulatory therapy outweigh the risk from adverse effects.
Children who have had PANDAS do not need to be given prophylactic antibiotics as they would if they had had rheumatic fever. Whilst it is logical to assume that preventing GAS infection will prevent relapses, as it does for rheumatic fever, there is no evidence to support this in PANDAS. This may be due to the fact that the causative role of GAS in PANDAS is not yet certain, therefore it is hard to justify using antibiotic prophylaxis.
So the boy from clinic had GAS detected in his throat and was given 10 days of oral Amoxicillin. At his next clinic appointment his parents were delighted, reporting that his tics had gone away and he was back to his normal self. Did the child have PANDAS? I’ll leave you and the Paediatrician to decide…
NB: I do love this bacterium, Group A beta-haemolytic streptococcus, it’s so versatile, causing so many different diseases, (tonsillitis, cellulitis, septic arthritis, necrotising fasciitis and now PANDAS) it certainly keeps us microbiologists on our toes and it still remains sensitive to penicillin!
References
- High prevalence of obsessive-compulsive symptoms in patients with Sydenham's chorea. Swedo S, Rapoport J, Cheslow D et al. American Journal of Psychiatry 1989 146; 2: 246-9
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