Prompt, symptomatic, multidisciplinary treatment is the best way to curtail the symptoms of pediatric acute-onset neuropsychiatric syndrome (PANS) and pediatric autoimmune neuropsychiatric syndrome associated with streptococcal infection (PANDAS), according to new guidelines.

Clinicians should tailor treatment to symptoms, wrote Margo Thienemann, MD, of Stanford (Calif.) University and her coauthors in the clinical management section of the guidelines. For example, children with mild psychiatric symptoms might only need cognitive-behavioral therapy (CBT), while more severe symptoms can merit a slow up-titration of psychoactive medications.

PANS presents as a “lightning-like” onset of obsessive-compulsive disorder (OCD) or eating restrictions plus at least two of these symptoms: anxiety (especially separation anxiety), emotional lability or depression, irritability, aggression or severely oppositional behaviors, cognitive and attentional deficits that undermine school performance, sensory or motor abnormalities, and somatic symptoms such as sleep disturbances or enuresis. Acute-onset PAN triggered by Group A streptococcal infection meets criteria for PANDAS. To help guide treatment of both conditions, the PANS Research Consortium of immunologists, rheumatologists, neurologists, infectious disease experts, general pediatricians, psychiatrists, nurse practitioners, and other scientists published the three-part recommendations online July 19 in a special issue of the Journal of Child and Adolescent Psychopharmacology, the first part of which discusses psychiatric and behavioral interventions for the syndromes’ symptoms (2017 Jul 19. doi: 10.1089/cap.2016.0145).

Clinical management of PANS/PANDAS includes psychoeducational, psychotherapeutic, behavioral, family- and school-based, and pharmacologic interventions, Dr. Thienemann and her associates wrote. Starting CBT (exposure-response prevention) has the best chance of halting OCD behaviors. Acutely ill children might not be ready for CBT, but parents still can learn to “hold the line” to avoid accommodating and worsening irrational fears.

Options for psychoactive medications include benzodiazepines for anxiety; aripiprazole, risperidone, olanzapine, haloperidol, or quetiapine for psychosis; and SSRIs, such as fluoxetine, sertraline, and fluvoxamine for depression and OCD. Severe depression merits both psychotherapy and an SSRI. Antipsychotics are not indicated for OCD unless children are incapacitated and only if their QTc interval does not exceed 450 milliseconds. Because PANS/PANDAS patients can react severely to psychotropics, clinicians should “start low” at about a quarter of a typical dose and “go slow,” gradually titrating up.

It’s best to rule out other medical disorders first when patients refuse or restrict food or fluids. Next, clinicians should assess medical stability and support nutrition and hydration while treating underlying brain inflammation. “Feeding tubes may be necessary, at least during the acute phases of the illness,” the authors wrote. Chronic symptoms can warrant treatments for eating disorders.

Bouts of aggression or irritability are classic and can be especially challenging for families. Parents can refocus the child with toys or by dancing, singing, or acting silly but should also make a safety plan, such as calling 911, if aggressive behaviors are endangering the patient or family members. Pharmacologic options for aggression include diphenhydramine, benzodiazepines, and antipsychotics.

For tics, options include comprehensive behavioral intervention for tics, habit reversal training, and cautiously monitored pharmacotherapy with alpha-2 adrenergic agonists, clonidine, guanfacine, or short-course antipsychotics. Symptoms of attention-deficit/hyperactivity disorder merit classroom accommodations; methylphenidate compounds can be added if needed. For children with sleep disturbances, the best strategy is to focus on sleep hygiene before considering low-dose diphenhydramine, melatonin, cyproheptadine, clonidine, trazodone, or zolpidem. Pain, however, needs early treatment to stop it from becoming refractory. Pain and stiffness after awakening can signal arthritis, enthesitis, or inflammatory back pain and warrant physical therapy and evaluation by a pediatric rheumatologist or pain specialist.

Part II of the guidelines covers immunomodulators. As in other severe brain disorders, early treatment improves outcomes and helps prevent relapses, wrote Jennifer Frankovich, MD, also of Stanford University, and her associates. Clinicians should start second-line therapies if first-line treatment fails. Acute impairment can remit with NSAIDs or a short course of oral corticosteroids, but chronic symptoms often need more aggressive and prolonged immunotherapy. Children with moderate to severe impairment should receive intravenous immunoglobulins, and those with severe, chronic impairment may need bursts of high-dose corticosteroids or longer-term corticosteroids with taper. Patients with extreme or life-threatening impairment should receive first-line therapeutic plasma exchange alone or with intravenous immunoglobulins, high-dose intravenous corticosteroids, and rituximab.

Part III of the guidelines covers infections. Most cases involve group A streptococci (GAS), but other culprits include Mycoplasma pneumoniae and viruses, such as influenza, wrote Michael S. Cooperstock, MD, MPH, of the University of Missouri-Columbia and his associates. They recommend antistreptococcal treatment for “essentially all” newly diagnosed cases. They also suggest secondary antistreptococcal prophylaxis for severe neuropsychiatric symptoms or intermittent exacerbations associated with GAS. “For all other [cases], vigilance for GAS infection in both the patient and close contacts is recommended,” they wrote. “Since any intercurrent infection may induce a symptom flare, close observation with appropriate therapy for any treatable intercurrent infection is warranted.” They also recommend standard childhood immunizations and monitoring vitamin D levels.

The National Institutes of Health supported the research summarized in the guidelines. Dr. Thienemann disclosed grants from Auspex, Shire, Pfizer, F. Hoffmann-La Roche, AstraZeneca, Sunovion, Neurocrine Biosciences, Psyadon, and the PANDAS Network, as well as personal fees from the International OCD Foundation and the Tourette Syndrome Association. Dr. Frankovich and Dr. Cooperstock had no relevant disclosures.

Emily M. Godfrey, MD, MPH

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