History and exam
Key diagnostic factors
common
presence of risk factors
Key risk factors for PANS are a pre-pubescent onset; a family history of psychiatric disorder, autoimmunity, or developmental disorder; and immune dysfunction.
acute-onset (<72 hours) obsessive-compulsive disorder (OCD)
To meet clinical criteria for PANS children must present with abrupt and dramatic onset (culmination within 72 hours) of new OCD or severely restricted food intake along with concurrent neuropsychiatric symptoms, with similarly severe and acute onset, from at least 2 of the following 7 categories:[1][2][20]
Anxiety
Emotional lability and/or depression
Irritability, aggression, and/or severely oppositional behaviours
Behavioural (developmental) regression
Deterioration in school performance
Sensory or motor abnormalities
Somatic signs and symptoms including sleep disturbance, enuresis, or urinary frequency.
The obsessive-compulsive symptoms must meet Diagnostic and statistical manual of mental disorders, 5th edition, text revision (DSM-5-TR) criteria for OCD.[1][57] In addition, the criteria for PANS requires that symptoms are not better explained by a known neurological or medical disorder, such as Sydenham chorea, systemic lupus erythematosus, Tourette disorder, or others.[1]
Children with PANS may present with severe impulsivity and compulsive behaviours posing danger to self, others, or properties.[3][58] They are often acutely conscious of, and even embarrassed or frightened by, their unwanted intrusive thoughts and obsessions. They need reassurance that they do not have to reveal their content before acknowledging the OCD thoughts.
acute-onset (<72 hours) severely restricted food intake
To meet clinical criteria for PANS, children must present with abrupt and dramatic onset (culmination within 72 hours) of new obsessive-compulsive disorder or severely restricted food intake along with concurrent neuropsychiatric symptoms, with similarly severe and acute onset, from at least 2 of the following 7 categories:[1][2][20]
Anxiety
Emotional lability and/or depression
Irritability, aggression, and/or severely oppositional behaviours
Behavioural (developmental) regression
Deterioration in school performance
Sensory or motor abnormalities
Somatic signs and symptoms including sleep disturbance, enuresis, or urinary frequency.
In addition, the criteria for PANS requires that symptoms are not better explained by a known neurological or medical disorder, such as Sydenham chorea, systemic lupus erythematosus, Tourette disorder, or others.[1]
acute-onset (<72 hours) concurrent neuropsychiatric symptoms
To meet clinical criteria for PANS children must present with concurrent neuropsychiatric symptoms to acute-onset new obsessive-compulsive disorder (OCD) or severely restricted food intake from at least 2 of the following 7 categories:[1]
Anxiety
Emotional lability and/or depression
Irritability, aggression, and/or severely oppositional behaviours
Behavioural (developmental) regression
Deterioration in school performance
Sensory or motor abnormalities
Somatic signs and symptoms including sleep disturbance, enuresis, or urinary frequency.
Children with PANS:[20]
May appear hypervigilant, highly anxious, and in the 'fight or flight' mode during an acute episode.
Often cannot recall details of their symptoms or their impact on functioning.
Present with mood-incongruent involuntary and often uncontrollable episodes of crying or laughing (emotional lability is a distinctive symptom of PANS). Depression is common, particularly during the later stages of the illness; the child may present with a flat or depressed affect.[3][7]
Commonly present with agitation, irritability, aggression, and temper tantrums/rage episodes.[3][58]
Often have their speech affected; changes are various and may include 'baby talk' secondary to developmental regression, a lack of speech, selective mutism, or new-onset stuttering.
May experience auditory or visual hallucinations, as well as violent imagery, and suicidal or homicidal ideation.[59]
In addition, the criteria for PANS requires that symptoms are not better explained by a known neurological or medical disorder, such as Sydenham chorea, systemic lupus erythematosus, Tourette disorder, or others.[1]
relapsing-remitting course
Symptoms may improve, and even return to their usual baseline, and then relapse as seen in acute rheumatic fever and Sydenham's chorea. Relapses last on average 4 months; similar to the relapse duration in acute rheumatic fever and Sydenham's chorea.[23]
Other diagnostic factors
common
current or past group A streptococcus (GAS) infection
GAS infection (e.g., streptococcal pharyngitis, impetigo, peri-anal streptococcal infection) may precede or be present at onset and relapses.[4][3][7][9][21][35][48] However, note that these infections may also be missed as neuropsychiatric symptoms may have started weeks after resolution of infection.
Neither PANS nor Sydenham's chorea diagnoses require evidence of GAS infection. However, from the experience of the authors of this topic, the majority of cases of PANS that are evaluated using PANS guidelines are ultimately classified as post-GAS PANS.[20][33]
To meet the diagnostic criteria for paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS), initial symptom onset and occurrence of subsequent exacerbations must be temporally associated with confirmed GAS infection.[2][20]
The diagnostic criteria for PANDAS were developed for use in clinical research. In clinical practice, proving a temporal association between symptom onset and exacerbations with GAS infections is often difficult as GAS infections are prevalent in school aged children and may go undetected due to the asymptomatic nature of rheumatogenic GAS organisms.[19] In addition, the GAS infection may have been cleared at the time of presentation of symptoms; this is similar to Sydenham's chorea, where the chorea may lag behind the inciting GAS infection by 6 months or longer. By then, the GAS infection has been cleared from the throat (thus cultures are negative) and the rise in antibody titres has already occurred, so it is no longer possible to establish a causal relationship between GAS and the neuropsychiatric symptoms.[1]
motor signs associated with basal ganglia dysfunction
These may include positive glabellar tap, hung-up reflexes, overflow dystonia, wormian tongue movements, weak grip with subtle milkmaid grip, choreiform movements of fingers, and overflow dystonia. These signs typically improve in remission.
One diffusion-weighted study showed that these signs are associated with more widespread microstructural changes.[37]
Suspect Sydenham's chorea in patients presenting with frank chorea.[70]
sinusitis, otitis media, and other sinopulmonary infections
Infection may precede or be present at onset of initial episode and relapses. Psychiatric symptoms may be overwhelming and the child may not spontaneously mention these symptoms.
Specifically inquire about headaches and facial pressure worse with inverting head; check for tenderness over sinuses including ethmoid sinuses (pinch bridge of nose).[33][62]
systemic inflammation/immune dysregulation
Concurrent evidence of immune dysregulation, autoimmunity, and inflammatory diseases is common, especially in older children who have a history of numerous relapses and chronic symptoms.
Signs of systemic inflammation/immune dysregulation include iron deficiency anaemia, enthesitis, arthritis, inflammatory back pain, and presence of other concurrent autoimmune diseases - the most common are enthesitis related arthritis, coeliac disease, thyroiditis, psoriasis, inflammatory bowel disease, and spondyloarthritis.[3][48]
enuresis
Patients may present with urinary complaints including enuresis.
frequent urination
Patients may present with urinary complaints including increased urinary frequency.
sleep disturbances
Patients may present with new-onset sleep disturbance, especially those who are severely ill.
dehydration
Children with severely restricted food and fluid intake (usually because of fears of contamination, choking, vomiting) present with dehydration.[51]
uncommon
palatal petechiae
Palatal petechiae are a sign of recent group A streptococcus (GAS) or other infection or inflammatory process and have been observed in about 20% of new-onset PANS.
This sign may represent small vessel vasculitis/vasculopathy with or without GAS pharyngitis. Palatal petechiae are 95% specific for streptococcal pharyngitis but other organisms may also cause it.[33][62]
low body mass index (BMI)
Children with restricted food and fluid intake (usually because of fears of contamination, choking, vomiting) present with significant weight loss (>10% of body weight).[51]
vital sign instability
Children with severely restricted food and fluid intake (usually because of fears of contamination, choking, vomiting, etc.) present with vital sign instability.[51]
Risk factors
strong
pre-pubescent onset
The signs and symptoms of PANS are typically first seen in childhood, from age 3 years to the beginning of puberty.[1][2][20]
The average age of onset of PANS ranges from 6.5 years to 8.5 years.[3][7][21]
In the study describing the first 50 patients with PANDAS, the mean age of onset was 6.3 years for children with tics and 7.4 years for children with obsessive-compulsive disorder.[6]
family history of psychiatric disorder
Psychiatric illnesses are highly prevalent in patients with PANS. Between 72% and 78% of patients have a first-degree relative who has a history of psychiatric illness.[3][48] Two additional studies that considered first-, second-, and third-degree relatives found slightly lower rates (51% and 64%).[4][21]
A study looking at family clustering of immune-mediated diseases in children with abrupt-onset obsessive-compulsive disorder (OCD) found that 16% of first-degree relatives of patients with PANS had been diagnosed with OCD compared with only 1% of first-degree relatives in the healthy control group.[49]
family history of autoimmunity
Family history of autoimmune disease or inflammatory disorder is common in people with PANS, with 67% to 80% of first-degree relatives having at least one autoimmune disease.[3][48]
One study found that 76% of relatives of children with PANS had at least one autoimmune disease.[4] Another study looking at family clustering of immune-mediated diseases in children with abrupt-onset obsessive-compulsive disorder found that 14% of first-degree relatives of patients with PANS had immune-mediated comorbidities compared with only 3% of first-degree relatives in the healthy control group.[49]
history of developmental disorder
One study found that 60% of males and 40% of females with PANS/PANDAS had a developmental disorder such as attention deficit hyperactivity disorder, sensory disorder, learning disability, autism spectrum, handwriting problem, or speech delay.[50] In another study, developmental abnormalities were noted in 18% of patients with PANS.[4]
immune dysfunction
Since patients with PANS have a high rate of developing arthritis and often have autoantibodies (i.e., antinuclear antibodies, histone antibodies, and thyroid antibodies), low complement levels, and low levels of immunoglobulins, it is thought that they may have underlying immune dysfunction, or that the infection that triggers PANS is thought to cause immune dysfunction.[4][50][51][52][53]
weak
male sex
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