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Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) Syndrome: A 10-Year Retrospective Cohort Study in an Italian Centre of Pediatric Rheumatology

La Bella S, Attanasi M, Di Ludovico A, Scorrano G, Mainieri F, Ciarelli F, Lauriola F, Silvestrini L, Girlando V, Chiarelli F, et al. Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) Syndrome: A 10-Year Retrospective Cohort Study in an Italian Centre of Pediatric Rheumatology. Microorganisms. 2024; 12(1):8. https://doi.org/10.3390/microorganisms12010008

PANDAS syndrome, a rare condition in prepubertal children, presents with sudden tic disorders and/or OCD following a documented GAS infection. Current classification criteria lack specificity, resulting in misdiagnosis. In our study, 61 patients were screened by the Pediatric Rheumatology unit for suspected PANDAS, but only 19 met the criteria. Tic disorders, especially in the eyes and head/neck, were predominant, with common vocal tics and less documented OCD. Treatment with antibiotics often led to clinical improvement. Larger, controlled studies are essential to understanding PANDAS characteristics and therapeutic responses comprehensively.

The Intricate Dance of Infections and Autoimmunity: An Interesting Paradox

Rao, A.P., Patro, D. The Intricate Dance of Infections and Autoimmunity: An Interesting Paradox. Indian J Pediatr (2023). https://doi.org/10.1007/s12098-023-04928-8

Besides genetic susceptibility, infections due to viruses, bacteria and protozoa have been implicated in the development of autoimmune diseases (AD). AD can be triggered in a genetically susceptible individual by infections that disrupt immunological tolerance towards self-antigens. Pathogens can initiate autoimmunity by way of molecular mimicry, bystander activation, epitope spreading or persistent infection with polyclonal activation. This review covers two main topics: (i) the mechanisms by which an infectious agent can trigger or worsen autoimmunity; and (ii) the correlation between specific infectious agents and AD in humans with special emphasis on multisystem inflammatory syndrome in children (MIS-C).

Caregiver Burden, Stress, and Relationship Cohesion Among Self-Identified Caregivers of Children with PANS
Tona JT, Ash J, Brown E, Campagna C, Kostek K, Lawton E, Rieth A, Tomita M. Caregiver Burden, Stress, and Relationship Cohesion Among Self-Identified Caregivers of Children with Pediatric Acute-Onset Neuropsychiatric Syndrome. J Child Adolesc Psychopharmacol. 2023 Nov;33(9):378-386. doi: 10.1089/cap.2023.0030. PMID: 37966363; PMCID: PMC10771873.
  • Among the 216 respondents, 79.6% exceeded the CBI threshold, indicating a need for respite in adult care receiver populations. On the CSAQ, 72.9% expressed high distress, 80.5% reported feeling overwhelmed, and 58.1% reported crying spells, meeting cutoffs for support/respite used in adult care receiver populations.
  • The majority of caregivers (85.5%) reported not having the desired degree of cohesion with their child on the IOS. Parents of children with more severe PNSS symptoms performed significantly worse on all measures (CBI: H = 57.83; CSAQ: F = 29.26; IOS: H = 38.04; p < 0.001 for all).

Common Comment Themes

  1. Severe caregiver and/or family emotional distress and trauma.
  2. Caregivers wondering what happened to their child.
  3. Lack of awareness and support among health and education professionals.
  4. Relationship strain with family, friends, and significant others.
  5. Financial and/or legal struggles due to their child’s diagnosis.

“Conclusion: There is strong need for support and respite for children with PANS and their families. Long-term effects including posttraumatic stress symptoms among family members should be studied.”

An updated review of pediatric autoimmune neuropsychiatric disorders associated with Streptococcus/pediatric acute-onset neuropsychiatric syndrome, also known as idiopathic autoimmune encephalitis: What the allergist should know
Hardin H, Shao W, Bernstein JA. An updated review of pediatric autoimmune neuropsychiatric disorders associated with Streptococcus/pediatric acute-onset neuropsychiatric syndrome, also known as idiopathic autoimmune encephalitis: What the allergist should know. Ann Allergy Asthma Immunol. 2023 Nov;131(5):567-575. doi: 10.1016/j.anai.2023.08.022. Epub 2023 Aug 25. PMID: 37634580.

Conclusion: Owing to the complexity and variability in ways patients with IAE may present to the allergist/immunologist office, an interdisciplinary approach is imperative to provide patients with the best medical care. Still, more research is needed to further elucidate the mechanism(s) and optimal treatment algorithm for IAE to facilitate broader recognition and acceptance of this condition by the medical community.

Factors Associated with Symptom Persistence in PANS: Part II—Presenting Features, Medical Comorbidities, and IVIG Treatment History
Denise Calaprice-Whitty, Angela Tang, and Janice Tona.Factors Associated with Symptom Persistence in PANS: Part II—Presenting Features, Medical Comorbidities, and IVIG Treatment History.Journal of Child and Adolescent Psychopharmacology.Nov 2023.365-377.http://doi.org/10.1089/cap.2023.0023
  • Significant relationships were identified among the 646 subjects, linking greater symptom persistence to higher rates of medical comorbidities.
  • Specific comorbidities associated with greater symptom persistence included rashes, headaches, chronic sinusitis, frequent diarrhea, and immune deficiencies.
  • Developmental diagnoses and respondent-perceived developmental lags were more prevalent in subjects with greater symptom persistence.
  • Subjects with greater symptom persistence reported PANS exacerbations associated with infections in close contacts, vaccinations, environmental triggers, and exacerbations of comorbidities.
  • PANS recurrences were more likely to be triggered by Epstein Barr Virus, mycoplasma, and sinus infections in subjects with greater symptom persistence.
  • More persistent PANS was linked to significantly higher frequencies of certain symptoms, including sleep disturbance, urinary incontinence, muscle pain, brain fog, sensory defensiveness, irritability, and aggression-related symptoms.
  • The effectiveness of intravenous immunoglobulin in combating symptoms was found to be less in cases of more persistent PANS.
  • Subjects with greater symptom persistence experienced more difficulty attending school.

“Conclusions: Our results suggest high symptom persistence in PANS to be associated with more pervasive medical and neuropsychiatric symptoms. Differences in symptom persistence are associated with both intrinsic (e.g., immune competence) and extrinsic (e.g., infections, treatment) factors. Because extrinsic factors are potentially modifiable, it is critical that providers be aware of current guidelines on PANS evaluation and treatment.”

Factors Associated with Symptom Persistence in PANS: Part I—Access to Care
Calaprice-Whitty D, Tang A, Tona J. Factors Associated with Symptom Persistence in PANS: Part I-Access to Care. J Child Adolesc Psychopharmacol. 2023 Nov;33(9):356-364. doi: 10.1089/cap.2023.0022. Epub 2023 Oct 30. PMID: 37902790.
  • Greater symptom persistence correlated with longer intervals between symptom onset and treatment (F = 4.43, p = 0.002).
  • Subjects with the least symptom persistence (>75% symptom-free days) were diagnosed by the first practitioner seen in 34% of cases, compared to 13% in those with the most persistent symptoms (symptoms every day) (L-R χ2 = 36.55, p < 0.0001).
  • Lack of access to expertise did not impede diagnosis and treatment for 52% of subjects with the least persistent symptoms, contrasting with 22% in those with the most persistent symptoms (L-R χ2 = 22.47, p < 0.0001).
  • Affordability did not impact diagnosis and treatment for 76% of subjects with the least persistent symptoms, whereas it affected 42% of those with the most persistent symptoms (L-R χ2 = 27.83, p < 0.0001).
  • Subjects whose PANS symptoms resolved with antibiotic treatment had less symptom persistence than others (χ2 = 23.27, p = 0.0001).
  • More persistently symptomatic subjects were more likely to discontinue intravenous immunoglobulin (IVIG) treatment due to access-to-care reasons.

“Conclusions: Unimpeded access to care for PANS is associated with more symptom-free days over reporting periods averaging approximately 4 years. Difficulty reaching expert providers, missed opportunities for diagnoses, and financial limitations may worsen outcomes. Practitioners, particularly primary providers, should adhere to published diagnostic and treatment guidelines promptly upon presentation.”