This medical condition has either been superseded or has become inactive
Specific Conditions |
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Indication for Ig Use |
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Level of Evidence | Evidence of probable benefit – more research needed (Category 2a) |
Description and Diagnostic Criteria |
Paediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) was first described in the early 1990s. PANDAS is characterised by rapid-onset tics associated with obsessive-compulsive disorder (OCD) in the context of recent streptococcal infection. Molecular mimicry between streptococcal antigens and the central nervous system is thought to underlie the cause. Symptomatic therapy is used with variable response. It has been observed that streptococcal infection is not the only trigger of acute neuropsychiatric disorders, but other infectious agents can also trigger acute neuropsychiatric events. For this reason, the term paediatric acute neuropsychiatric disorders (PANS) was added. PANDAS and PANS have remained controversial entities, partly due to the absence of a reliable and available biomarker. The diagnosis remains based upon the clinical syndrome. The hallmark of these diseases is the very rapid acute onset of emotional lability, OCD, tics and a ‘change in behaviour’ that occurs in the days or weeks after an infectious trigger. Swedo et al (1998) define the presentation: I. Abrupt, dramatic onset of obsessive-compulsive disorder or severely restricted food intake II. Concurrent presence of additional neuropsychiatric symptoms, (with similarly severe and acute onset), from at least two of the following seven categories:
Unlike Tourette syndrome and idiopathic OCD (which tend to wax and wane in severity), PANDAS and PANS have a ‘shark tooth’ pattern of disease severity with infection triggered severe episodes, followed by complete remissions. The episodes tend to reoccur, and the ability to achieve complete remissions tends to decline with time, resulting in potential persistent symptoms. PANDAS and PANS are probably rare conditions, and it is important to distinguish the entity from ‘idiopathic’ Tourette syndrome or OCD. The hallmark of the disease remains the infection triggered acute onset of neuropsychiatric change. A trial of antibiotics can be used first but if this is inadequate, and the patient is significantly impaired, a trial of steroid, or intravenous immunoglobulin (IVIg) can be considered. A consensus definition of PANS was proposed in 2015 although the definition has not been tested by independent observers (Chang et al, 2015). Given the rarity and controversy of the entities, it is recommended to seek second opinion from specialists with expertise in the field. |
Justification for Evidence Category |
A single randomised placebo-controlled trial using intravenous immunoglobulin (IVIg) for paediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) showed prolonged and significant improvement in obsessive-compulsive symptoms, anxiety, depression, emotional lability and overall function compared with placebo. Improvements in symptoms were still evident at one-year follow-up. A futher uncontrolled retrospective description of 12 individuals with PANDAS described benefit when using 2g/kg of IVIg in the first course or 1 to 1.5g/kg of IVIg for further doses. The single randomised controlled trial supported the use of IVIg in PANDAS. However there has been no further study to confirm this finding. |
Diagnosis Requirements |
A diagnosis must be made by an Immunologist or a Neurologist. |
Qualifying Criteria for Ig Therapy |
Paediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) or paediatric acute neuropsychiatric disorders (PANS) unresponsive to trial of antibiotic therapy, and significant impairment requiring intervention
This indication is for patients who have not trialled off Ig therapy for PANS/PANDAS in the previous three months. Any patients who have, and have since relapsed, should apply for Ig therapy under the indication: Relapse of paediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) or paediatric acute neuropsychiatric disorders (PANS) symptoms within three months of commencement of trial off Ig therapy
For stable patients on maintenance treatment, review by a neurologist or immunologist is required at least three monthly. Documentation of clinical effectiveness is necessary for continuation of IVIg therapy. Relapse of paediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) or paediatric acute neuropsychiatric disorders (PANS) symptoms within three months of commencement of trial off Ig therapy
This indication is for patients who have had a Relapse of paediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) or paediatric acute neuropsychiatric disorders (PANS) symptoms within three months of commencement of trial off Ig therapy. Any patients who have not trialled off Ig therapy for PANDAS/PANS in the last six months should apply for Ig therapy under the indication: Paediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) or paediatric acute neuropsychiatric disorders (PANS) unresponsive to trial of antibiotic therapy, and significant impairment requiring intervention.
For stable patients on maintenance treatment, review by a neurologist or immunologist is required at least three monthly. Documentation of clinical effectiveness is necessary for continuation of IVIg therapy. |
Review Criteria for Assessing the Effectiveness of Ig Use |
Paediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) or paediatric acute neuropsychiatric disorders (PANS) unresponsive to trial of antibiotic therapy, and significant impairment requiring intervention
Review by a neurologist or imumunologist is required within one month of treatment to determine whether the patient has responded.
For stable patients on maintenance treatment, review by a neurologist or immunologist is required at least three monthly. Documentation of clinical effectiveness is necessary for continuation of IVIg therapy. Clinical effectiveness of Ig therapy can be assessed by: On review of the initial authorisation period
On review of a continuing authorisation period
Relapse of paediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) or paediatric acute neuropsychiatric disorders (PANS) symptoms within three months of commencement of trial off Ig therapy
Review by a neurologist or immunologist is required within one month of treatment to determine whether the patient has responded.
For stable patients on maintenance treatment, review by a neurologist or immunologist is required at least three monthly. Documentation of clinical effectiveness is necessary for continuation of IVIg therapy. Clinical effectiveness of Ig therapy can be assessed by: On review of the initial authorisation period
On review of a continuing authorisation period
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Dose |
Paediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) or paediatric acute neuropsychiatric disorders (PANS) unresponsive to trial of antibiotic therapy, and significant impairment requiring intervention
The aim should be to use the lowest dose possible that achieves the appropriate clinical outcome for each patient.
Refer to the current product information sheet for further information on dose, administration and contraindications. Relapse of paediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) or paediatric acute neuropsychiatric disorders (PANS) symptoms within three months of commencement of trial off Ig therapy
The aim should be to use the lowest dose possible that achieves the appropriate clinical outcome for each patient.
Refer to the current product information sheet for further information on dose, administration and contraindications. |
Bibliography |
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Bonita, R & Beaglehole, R 1988, ‘Recovery of motor function after stroke’, Stroke , vol. 19, no. 12, pp. 1497-1500. https://www.ahajournals.org/doi/abs/10.1161/str.19.12.3201508 Chang, K, Frankovich, J, Cooperstock, M, et al 2015, ‘Clinical Evaluation of youth with pediatric acute-onset neuropsychiatric syndrome (PANS): Recommendations from the 2013 PANS Consensus Conference’, Journal of Child and Adolescent Psychopharmacology, vol. 25, no. 1, pp. 3-13. https://www.ncbi.nlm.nih.gov/pubmed/25325534 Kovacevic, M, Grant, P & Swedo, SE 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, vol. 25, no. 1, pp. 65-69. https://www.ncbi.nlm.nih.gov/pubmed/25658609 Ontario Regional Blood Coordinating Network 2016, Ontario Intravenous Immune Globulin (IVIG) Utilization Management Guidelines, Version 3.0. [online]. Available from: http://transfusionontario.org/en/. Perlmutter, SJ, Leitman, SF, Garvey, MA, et al 1999, ‘Therapeutic plasma exchange and intravenous immunoglobulin for obsessive-compulsive disorder and tic disorders in childhood’, Lancet, vol. 354, no. 9185, pp. 1153–8. https://www.ncbi.nlm.nih.gov/pubmed/10513708 Rankin, J, 1957, ‘Cerebral vascular accidents in patients over 60’, Scottish medical journal, vol. 2, pp. 200-15. Singer, HS, 1999, ‘PANDAS and immunomodulatory therapy’, Lancet, vol. 354, no. 9185, pp. 1137–8. https://www.ncbi.nlm.nih.gov/pubmed/10513701 Stroke Engine Canada, 'The Modified Rankin Scale'. Available from Modified Rankin Scale (MRS) – Strokengine Swedo, SE, Leonard, HL, Garvey, M, et al 1998, ‘Pediatric autoimmune aeuropsychiatric disorders associated with streptococcal Infections: clinical description of the first 50 cases’, American Journal of Psychiatry, vol. 155, no. 2, pp. 264-271. https://www.ncbi.nlm.nih.gov/pubmed/9464208 UK Department of Health, 2011, ‘Clinical Guidelines for Immunoglobulin Use: Second Edition Update’. Available from: https://www.gov.uk/government/publications/clinical-guidelines-for-immunoglobulin-use-second-edition-update UK Department of Health 2011, ‘Clinical Guidelines for Immunoglobulin Use: Second Edition Update: Summary Poster’. Available from: http://igd.mdsas.com/clinical-info/ Van Swieten, JC, Koudstaal, PJ, Visser, MC, et al 1988, ‘Interobserver agreement for the assessment of handicap in stroke patients’, Stroke, vol. 19, no. 5, pp. 604-607. https://pdfs.semanticscholar.org/fba2/da6e4888b08ee79441937169c53f16aec218.pdf |