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NSAID Anti-Inflammatories

Oral nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or naproxen may be beneficial for PANS/PANDAS patients. The medications appear to be particularly useful for exacerbations (or “mini-flares”) which occur in the weeks following immunotherapy. Assuming that the PANS and PANDAS condition is the result of an immune system disorder, reducing inflammation would have a beneficial effect for patients. Dosing levels are provided on the manufacturer’s label and by the PANS/PANDAS Research Consortium published guidelines. The cyclo-oxygenase inhibitor, celecoxib, is another NSAID that has been reported to be helpful. Mechanisms of action are unknown. All the NSAIDS carry risks of GI bleeding and other side effects, so they should be used with caution, following manufacturers’ guidelines for dosage and duration of therapy. See the PANS/PANDAS treatment flowchart for additional information.
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Case reports to PPN include PANDAS and PANS children who have symptom exacerbations related to Candida albicans (yeast) infections. Even if the child takes probiotics, children on antibiotic therapy or prophylaxis are susceptible to candida overgrowth. Most physicians do not think to check for candida albicans in the oral cavity or other mucosal surfaces (vagina, rectum and urethra). Examining patients for yeast infections is imperative for all children whose PANS symptoms exacerbate during antibiotic treatment or prophylaxis, as well as for those with urinary frequency or other UTI-related symptoms. In young women, they are typically not yet at the age of gynecologic exams, and pediatricians rarely include yeast as a possible issue, even when urinary frequency or other urinary issues are present. If yeast is present, azole antifungals such as fluconazole (Diflucan) or nystatin may help alleviate the PANDAS exacerbation.
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Antihistamines (H1 and H2 Blockers)

Antihistamines block effects of histamine and include H1 and H2 blockers. The H1 blockers include diphenhydramine, fexofenadine, loratadine, cetirizine and others; H2 blockers include cimetidine, ranitidine and nizatidine, among others. These drugs have a variety of anti-inflammatory and immunomodulatory activities. In addition to their immunologic properties, the H1 blockers (such as diphenhydramine or Benadryl) are “soporific” drugs which produce sleepiness; this side effect can be useful for PANDAS children with initial insomnia. However, paradoxical behavioral adverse events can occur with antihistamines, and instead of getting sleepy, the children become agitated, “wild” or out-of-control. These idiosyncratic reactions cannot be predicted, so initial doses of antihistamines should be administered with close parental supervision.
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Vitamin D

Indirect evidence supports optimization of Vitamin D levels among PANDAS and PANS children. Patients may be treated with vitamin D3 as needed to maintain serum 25-hydroxy vitamin D level above 30 ng/mL (75 nmol/L).
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While there have been no published research on the effect of tonsillectomy on PANS or PANDAS patients, there has been unpublished findings and anecdotal evidence that show tonsillectomy may have benefit. Many PANS/PANDAS patients have damaged or cryptic tonsils, but the potential benefit of tonsillectomy is not limited to patients with those tonsil characteristics. In an unpublished research study done at Georgetown Medical Center, PANDAS patients had their tonsils removed, analyzed, and the children subsequently tracked for over six months. The tonsils relative to non-PANDAS patients had many pathogens, most prominent being staphylococcus (staph). Streptococcus pyogenes was not found in PANDAS patients but was present in non-PANDAS controls. Other notable pathogens included MRSA, E. coli, Pseudomonas and Serratia marcens. The absence of Streptococcus in the PANDAS cohort suggests that once the patient has been “sensitized” other pathogens can induce neurologic symptoms in susceptible patients.

In addition, the tonsils belonging to PANDAS patients contained elevated levels of TH17, indicating a consistent immune response to the pathogens lodged within the tonsils. TH17 has been found in animal PANDAS research to be a potential agent for opening the blood brain barrier, allowing inflammation in targeted regions of the brain.

The Georgetown study and physician experience indicates that removal of the tonsils can provide remission of PANS & PANDAS symptoms for some patients. There is no marker to determine which patient a tonsillectomy will result in remission of PANS/PANDAS symptoms.

A clear benefit of tonsillectomy that was found in the Georgetown study and further observed by practitioners who see many PANS/PANDAS patients, is that those PANS/PANDAS cases that have undergone tonsillectomy, have a significantly lower chance of recurrence post-immunotherapy such as IVIG. Since immunotherapy suppresses the potential cause of basal ganglia encephalitis and in some cases like IVIG “reboots” the immune response, then removing a consistent infectious trigger housed within the tonsil or removing a repository for new pathogen agitators would most likely be beneficial.
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The Selective Serotonin Reuptake Inhibitors (“SSRIs”) may be helpful for the treatment of OCD and anxiety symptoms in PANDAS/PANS. The SSRIs include fluoxetine, fluvoxamine, sertraline, and paroxetine. Although all have a primary effect on serotonin reuptake, each has additional therapeutic effects which cause a variety of side effects. For example, some SSRIs (such as fluoxetine) can cause significant “activation” and should be avoided in children who are already having insomnia and sleep difficulties.

Clinical experience with PANDAS and PANS patients suggests that using a low dose and slow titration minimizes the risks of activation, agitation, akathisia, and other adverse effects of the drugs. The medications MUST be started at an extremely low dose (e.g., 1/4th or less of that used for a typical child). Upward titrations should be adjusted no faster than 2-week intervals. An adequate trial of an SSRI is 10-12 weeks at maximum dosage.

An electrocardiogram (EKG) should be obtained before and during treatment with antipsychotics to monitor the QTc interval—excessive prolongation (QTc >450 mseconds) is a contraindication to use of antipsychotic medications.

Although most side effects are easily managed, the development of suicidal thoughts and/or actions is a cause for immediate concern. The SSRIs are known to cause suicidality in children (the mechanism is unknown) and because of this, the FDA has issued a “black box” warning for their use in pediatric patients. The risk of suicidal thoughts is low and the risk of suicidal behaviors is lower, but even one child is too many – so caution must be exercised with use of the SSRIs. If suicidal thoughts/behaviors develop, the child must be monitored closely as the SSRI is discontinued (remembering that some of the drugs will require tapering to avoid additional adverse effects). In most patients, the therapeutic benefits outweigh the possible adverse effects. Parents should be aware of reports of suicidal thoughts and behaviors developing during SSRI administration.
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Special Consideration: Probiotics

In order to maintain a proper balance in the microbiome while a PANS/PANDAS patient is undergoing antibiotic therapy or prophylaxis, the providers caring for PANS/PANDAS patients should consider multi-strain probiotics. Probiotics are available in colony forming units (“CFU’s) and the correct CFU dosage for children and adults must be considered as part of the therapy.
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