Transforming a devastating chronic illness into a treatable disorder By Gail Szakacs, MD and Nancy O’Hara, MD
PANDAS P
ediatric Autoimmune Neuropsychiatric Disorders associated with Streptococcal Infections, or PANDAS, is a common and devastating autoimmune disorder in children.
PANDAS highlights the link between chronic and recurrent infection and neuropsychiatric and behavioral problems, and the depth and scope of those problems is much more far-reaching than previously thought. PANDAS consequences can include far-reaching movement, behavioral, and cognitive issue. While OCD and tics are still common, other issues like anxiety, bedtime fears, enuresis, ag- gression, and deficits in learning, attention, and social interaction are among the many manifestations that result from PANDAS. Although we focus on the pediatric population as part of the
PANDAS syndrome in this review, immune-mediated OCD/Tics/ Neuropsychiatric Disorders can also affect adolescent and adult populations and should always be considered when specific signs and symptoms emerge. As noted by Dr Sue Swedo at the NIH in the late 1990s, PAN-
DAS involves antibodies from a streptococcal infection reacting with brain tissue (specifically the basal ganglia) and triggers move- ment and behavioral problems. Rheumatic Fever is an older known disorder that illustrates this same disease process, in which antibod- ies from a streptococcal infection attack the heart valves, joints, and brain and result in heart disease, arthritis, and Sydenham’s Chorea. Although bacteria set the vicious cycle in motion, the real damage in this type of autoimmune disorder stems from the antibodies and the inappropriate immune response. While the exact mechanism of the autoimmune process in-
volved with PANDAS is still under investigation, research published in The Journal of Neuroimmunology in 2006 by Kirvan, et al suggests the mechanism involves antibody-mediated cell-signaling post group A streptococcal infections. The antibodies produced in group A streptococcal infections are thought to penetrate the blood brain bar- rier (BBB) and activate a brain enzyme (CaM kinase II) with multiple functions that are negatively impacted in various neuropsychiatric disorders. The article notes that those with PANDAS have higher CaM kinase II activation than those with non-PANDAS OCD, tic, and ADHD groups not associated with streptococcal infection. Although PANDAS is a clinical diagnosis, the traditional criteria
for PANDAS include:
1. OCD and/or Tic Disorder 2. Pediatric onset of symptoms (age 3 to puberty) – sudden/dra- matic onset
3. Episodic course of symptom severity (waxes and wanes) 4. Association with group A beta-hemolytic streptococcal infec- tion (such as through a positive throat culture for strep or history of Scarlet Fever)
5. Association with neurologic abnormalities (such as motoric hyperactivity, choreiform movements, etc.)
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Clinical experience reveals that traditional criteria for PANDAS do not capture the full scope and complexity of what is involved with the presentation, diagnosis, and treatment of this disorder. One must also consider the presence of other signs/ symptoms/ comor- bidities, frequent lack of known strep exposure/illness, specific lab abnormalities (or lack thereof), and response to treatment. These other signs, symptoms, and comorbid diagnoses include
irritability, personality changes, aggression, uncontrolled agitation, fear about bedtime regimen, fidgetiness, emotional lability, anxiety, enuresis, motoric symptoms (tics, handwriting changes, motoric hyperactivity, compulsive rituals), sensory defensiveness, impulsiv- ity, depression, dysthymia, separation anxiety, anorexia, ADD, and ADHD.
Laboratory tools are limited and the traditional abnormalities of increased blood strep titers (ASO and DNAseB antibodies) and a positive throat culture are not always present. In other words, normal levels of strep antibodies and negative cultures do not exclude the PANDAS diagnosis. On the flip side, streptococcal bacteria found in gastrointestinal testing may provide a clue, given other signs and symptoms consistent with PANDAS, but it is not enough to make a diagnosis. The emerging research involving CaM kinase and anti-neuronal antibodies (noted above) is promising and has important diagnos- tic and therapeutic implications. These newer tests are particularly helpful when blood ASO and DNAseB antibodies and other tests are negative in a child in whom PANDAS is suspected, however they are not yet commercially available. As mentioned earlier, the real problem is thought to be the damage resulting from the inappropriate immune response to the bacterial infection. Damage from the antibodies recurs with each subsequent streptococcal exposure and PANDAS flare. Research studies have shown that antibodies alone are enough to cause the behavioral and movement problems noted in those with PANDAS. This is a crucial point, in that adequate PANDAS treatment requires comprehensive immune therapy, in addition to antibiotics. One is not enough without the other, and immune therapy is likely the more important of the two treatment arms. Treatments to consider for PANDAS (one should discuss with the primary doctor involved, but referral to an Immunologist experi- enced in PANDAS diagnosis and treatment is also recommended):
1. Antibiotics (used daily for treatment and sometimes less fre quently for prophylaxis – zithromax, omnicef, penicillin, IM bicil lin, clindamycin, etc.)
2. Immune Modulation Therapy a. Corticosteroids (short-term use of tapering dose – a positive response often indicates the patient is more likely to respond posi- tively to Intravenous immunoglobulin (IVIG), but no response does not mean IVIG will be ineffective)
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