| Abstract|| |
Streptococcal infections in children rarely lead to neuropsychiatric manifestations referred to as pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. The common sequelae include tics, Tourette's syndrome or obsessive-compulsive disorder. Rare presentations may include separation anxiety disorder, body dysmorphic disorder and attention deficit hyperactivity disorder. We present a case of a 10-year-old child that presented primarily with abrupt onset of separation anxiety without any other neuropsychiatric manifestations such as tics or obsessive-compulsive symptoms. Streptococcal infections may present with varied neuropsychiatric manifestations in the pediatric age group and one needs to be more vigilant in cases that have an abrupt onset and unusual presentation. A high index of suspicion is important to diagnose such cases and provide them with a timely treatment.
Keywords: Pediatric autoimmune neuropsychiatric disorders associated with streptococcal, school refusal, separation anxiety
|How to cite this article:|
Navkhare P, Kalra G. The curious case of the "inseparable child". Indian J Psychiatry 2014;56:292-4
| Introduction|| |
Streptococcal infections in children are common, but usually benign and self-limited. A variety of pediatric behavioral problems may be triggered by streptococcal throat infections. The term pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) was coined by Swedo et al., to describe cases of childhood obsessive-compulsive disorders (OCD) and tic disorders that were triggered by Group A-beta hemolytic streptoccal (GABHS) infection.  In some cases, such infections lead to other behavioral and psychiatric manifestations in children. We present the case of a child who presented solely with separation anxiety and was later diagnosed to have PANDAS.
| Case Report|| |
A 10-year-old male child was brought by his parents with a 1-month history of irritability, restlessness, and increased anxiety on separation from parents. These symptoms were abrupt in onset, with the child suddenly refusing to play with his sister and other children in his neighborhood. He began asking his parents to be around him and cried if they did not listen. He insisted that his parents and siblings did not move away from him even for a minute to the point of not allowing them to go to another room. Within 2 days, the behavior increased to such an extent, that he would cry at the thought of separation from his parents and siblings. At one point, when the parents resisted his behavior, he got very angry and scratched himself on his face leading to abrasions. However, such symptoms were very discrete and were present only for some time during a day (usually from 1 to 5 pm everyday) with no exacerbating or relieving factors. For the rest of the day, though he appeared slightly anxious, he did not have as much separation anxiety.
His parents noticed that the child had difficulty completing any work at home like helping his mother in her chores, which he would do with ease otherwise. His handwriting had deteriorated and he was unable to complete his homework since a month. Over the next 4-5 days, his anxious behavior persisted even though his parents were present around him. He was taken to a psychiatrist where he was prescribed oral escitalopram (5 mg) and clonazepam (0.25 mg bid). However, despite being on these drugs for 15 days there was no improvement after which the child was brought to us.
On detailed probing, there was no recent stressor in the child's life either at home or school. The parents also revealed that the child stopped going to school for 5 days before the onset of these symptoms and that he was having mild grade fever for those 5 days, which receded without medications.
His birth and developmental history was normal. He was good in his studies and there was no past history of school refusal, truancy or failures or bullying at school. Physical examination revealed healed scar marks on his face, which occurred when he scratched himself in a fit of anger on one occasion. His systemic examination was normal. On mental state examination, he was anxious and irritable. Throughout the interview, he was clinging to his parents and did not allow separation from them.
He was advised complete blood counts, erythrocyte sedimentation rate (4 mm/h), liver function tests, renal function tests, 24 h urine copper levels, serum copper levels (9 μg/dl), serum ceruloplasmin levels (10 mg/dl) and anti-streptolysin-O (ASO) titers. Ophthalmological consultation was sought for a slit-lamp examination for Kayser-Fleischer ring. All his investigations were within normal limits, but his ASO titers were elevated (800 IU/ml). A pediatric consultation was then sought for the raised ASO titers. A detailed history by the pediatrician revealed multiple episodes of throat infection in the past 1 year.
He was started on oral cefixime (100 mg bid) with oral acetaminophen (40 mg/kg) for 10 days. On follow-up after 10 days, parents reported complete remission of his symptoms within 5 days of starting medications.
| Discussion|| |
In a small percentage of children suffering from streptococcal infections, neurological and/or psychiatric sequelae can occur. The index case discussed here had a number of throat infections in the past 1 year and his current episode was also preceded by a short duration of febrile period, following which he presented with abrupt onset separation anxiety in the absence of any other neuropsychiatric sequelae such as tics, Tourette's syndrome, or OCD.
The patient was given several differential diagnoses. Since anxiety disorders are the most common psychiatric illness in children and adolescents,  various anxiety disorders were considered as the primary differential diagnoses. Separation anxiety disorder was ruled out because the child's anxious behavior did not subside even when he was near his parents; he continued to cling to them. Social phobia was less likely as the child was anxious even in known social circumstances, that is, within his own family, whereas in social phobia, a patient is usually anxious in unknown circumstances fearing scrutiny by others. Generalized anxiety disorder (GAD) was ruled out since the symptoms of generalized anxiety need to be present for more than 6 months for a diagnosis of GAD to be made. Wilson's disease was suspected but was ruled out after all relevant investigations were normal. Since there was history of fever for 5 days prior to the onset of these symptoms and since the symptoms appeared only for a part of the day (1 pm to 5 pm everyday) an infectious etiology was suspected. Since there was a history of multiple throat infections in the past, he was specifically investigated for ASO titers which showed higher levels. Although measurement of both ASO and anti-DNAse-B titers are more accurate than either alone,  in our case, the parents couldn't afford to do both and hence only did ASO titers, which were found to be high.
Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections is a rare sequela of streptococcal infection in children that manifests as acute onset of OCD, tics or Tourette syndrome. , Other psychiatric comorbidities of PANDAS include emotional lability and oppositional behaviors.  Although these are the common sequelae, Pavone et al.,  point towards other variations in psychiatric manifestations of PANDAS such as body dysmorphic disorder and attention deficit hyperactivity disorder. Bernstein et al. reported that PANDAS children are significantly more likely to present with separation anxiety and deterioration in handwriting.  Our case had both these symptoms, but separation anxiety was the main presenting complaint as it was overwhelming for the parents.
O'Rourke,  discusses three short case-histories of varied presentations of PANDAS and acknowledges that such presentations startle parents, school nurses, physicians and the children equally. A majority of children with streptococcal infections are not at risk for developing PANDAS, but for those who do suffer may leave the treating psychiatrist confused about the possible etiology of the behavioral changes. This is what happened in our case. The child did not respond to a trial of an antidepressant and a benzodiazepine. Although, the trial was too short (only 15 days), there was no change in his symptoms (especially anxiety levels) at all. The specific nature of his symptoms and raised ASO titers led us to suspect PANDAS as the probable diagnosis.
The pathogenesis of neuropsychiatric manifestations in PANDAS is complex. Some children form higher levels of antibodies during a streptococcal infection. Subsequently, these antibodies mis-identify and attack healthy brain cells through a process called molecular mimicry causing inflammation of certain brain structures. , This cross reaction of the antibodies against GABHS and neuronal tissue supposedly leads to behavioral abnormalities including obsessive-compulsive symptoms and Tourette's syndrome.  However, what causes some cases to develop OCD and others to develop tics and other neuropsychiatric symptoms is still unknown. A course of antibiotics such as penicillin, amoxicillin, and cephalosporins may help to resolve the symptoms of PANDAS.  The index case described here responded to a course of cephalosporin.
This case highlights the importance of considering the differential diagnosis of autoimmune neuropsychiatric manifestation of streptococcal infection in a child who develops sudden onset behavioral change including symptoms of separation anxiety or school refusal.
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Dr. Gurvinder Kalra
Northern Area Mental Health Services, The Northern Hospital, 185, Cooper Street, Epping, Victoria
Source of Support: None, Conflict of Interest: None