Jennifer Frankovich MD MS, clinical professor at Stanford University/Lucile Packard Children’s Hospital, discusses the co-occurrence of systemic inflammatory and autoimmune diseases – including the overlap between pediatric acute-onset neuropsychiatric syndrome (PANS) and autism. She outlines the presentation of classic rheumatologic diseases noting the prevalence of mental health symptoms and provides clinical criteria for PANS. Frankovich discusses PANS as a relapsing/remitting condition and explores the clinical management options, citing recent studies on steroid use. She concludes by reemphasizing the association of psychiatric symptoms with autoimmune and rheumatologic diseases and states the importance of post-flare rehabilitation before opening the floor to questions.

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In this presentation

3:20 – Inflammatory diseases with comorbid psychiatric symptoms
20:20 – PANS clinical criteria
34:54 – PANS model
22:15 – Prevalence of PANS comorbid traits
23:48 – Non-specific inflammatory signs
29:00 – Clinical Management of PANS
33:30 – Study: Impact of steroid treatments on PANS episode duration
37:15 – Study: Monocyte subsets associated with PANS clinical states
44:16 – Q & A session


Classic rheumatologic conditions such as Lupus (4:30), Behçet’s syndrome (5:43), Sjögren’s syndrome (9:30), Scleroderma (9:53), Spondyloarthritis (10:31), Inflammatory bowel disease (11:30), Psoriasis/Psoriatic Arthritis (12:03), CNS Vasculitis (13:05), and Sydenham Chorea (SC) (13:20) are associated with psychiatric symptoms such as OCD, anxiety, depression and/or other behavior changes. PANS (20:20) also presents with acute onset of OCD or eating disorders. These psychological comorbidities – specifically OCD – overlap with common symptoms of autism spectrum disorder making inflammatory diseases difficult to diagnose in children on the spectrum. Psychiatric symptoms in individuals with autism can distract from rheumatologic symptoms due to subtle/masked physical manifestations and/or communication difficulties. The onset of certain diseases – especially PANS – can also exacerbate psychological symptoms of ASD and often lead to autoimmune disease diagnosis (2:35).

There is a historic association of pediatric streptococcal throat infections with mental disorders – particularly OCD and tic disorders (18:00). This is especially true in cases of SC and PANS/PANDAS where patients generally present with symptoms 1 – 8 months after exposure to a Group A Streptococcal infection (13:20). Studies have also shown increased volume of basal ganglia during the first episode(s) of CS and PANS (18:42) demonstrating onset of encephalitis. PANS cases present with an acute onset of OCD or eating restrictions and at least 2 of seven comorbid symptoms (20:20). Patients display a very abrupt deterioration in performance, behavior, and mental stability – parents have described it as a personality shift overnight.

Clinical management of PANS (29:00) varies based on each patient. Treatments are generally approached in three stages:

  1.   Find and treat active infections (i.e. strep, sinusitis, etc.)
  2.   Treat post-infectious inflammation and autoimmunity (if present)
  3.   Note that inflammation can cause tissue injury making post-flare rehabilitation highly important (40:00)
  4.   Treat psychiatric symptoms

Post-infectious inflammation is often treated with steroids (NSAIDS, IVIG, etc.). 5 day oral steroid bursts have proven helpful if administered at the beginning of an episode and IVIG trials are taking shape currently (32:00). PANS is understood as a relapsing/remitting disease (21:35) and most patients will return to baseline within a few months after the initial episode. Later, likely following some sort of infection, they will have a relapse episode lasting around 3 months. If flares are caught quickly and treated properly, over time episode length can shrink. However, without treatment, after 4 or 5 flares the symptoms become more chronic (33:30). Episodes generally decrease with age but it is suspected that patients maintain the predisposition to episodes throughout their lifetime and a number of patients develop autoimmune diseases over time (27:30).

Frankovich concludes (38:42) by emphasizing the strong association of post-infectious inflammatory disorders and autoimmune diseases with psychiatric symptoms. She notes that psychiatric symptoms can precede full presentation of inflammatory conditions and urges clinicians and parents to use PANS evaluation guidelines when a child with ASD suddenly develops new psychiatric traits. During the Q&A Frankovich comments on differences between regressive autism and PANS, treatment options, limitations to diagnosis and clinician assistance, international programs and more.

For treatment recommendations and steroid regimens see appendix B of the treatment guidelines found at (publications tab).

About the speaker:

Dr. Jennifer Frankovich is a Clinical Professor in the Department of Pediatrics, Division of Allergy, Immunology Rheumatology (AIR) at Stanford University/Lucile Packard Children’s Hospital (LPCH). Her clinical expertise is in systemic inflammatory and autoimmune diseases that co-occur with psychiatric symptoms. She completed her training in pediatrics, pediatric rheumatology, and clinical epidemiology at Stanford University/LPCH. In addition to generating clinical data to better understand the PANS illness, she is collaborating with ten basic science labs who aim to understand the immunological underpinnings of the illness.

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