Broad laboratory testing for children with suspected pediatric acute-onset neuropsychiatric syndrome (PANS) may neither distinguish PANS from similar psychiatric conditions nor reliably identify underlying medical causes, according to new data published in JAMA Network Open.

In a case-control study of 109 children, researchers found no significant differences across 56 laboratory variables between those diagnosed with PANS and those with obsessive-compulsive disorder (OCD) or tic disorders.

PANS, which affects an estimated 1 in 200 children, is defined by the sudden onset of OCD, restricted eating, or tics with other neuropsychiatric symptoms and is often suspected to have an autoimmune or postinfectious basis. That hypothesis has driven recommendations for broad testing panels aimed at detecting inflammatory or immune markers.

No Signal in Extensive Lab Panels

The study included 51 children with PANS and 58 children with OCD or tic disorders in the control group. Abnormal laboratory findings were common in both groups: 86.3% of the PANS group and 96.6% of the control group had at least one abnormal result. 

Across 31 prespecified laboratory measures, none differed significantly between groups after adjustment for multiple comparisons (all Benjamini-Hochberg-corrected, P > .05). Children in the control group often had as many, or more, abnormal findings as those with PANS. The following individual biomarkers also failed to discriminate between groups: C-reactive protein (P = .82); erythrocyte sedimentation rate (P = .93); ferritin (P = .95); immunoglobulin G (P = .53); and antinuclear antibody positivity (P = .45).

Group A streptococcal infections were detected in 16.7% of children with PANS and 8.5% of the control group, a nonsignificant difference (P = .62).

According to study author Sara Vasiljevic, a PhD student at Karolinska Institutet in Solna, Sweden, in the few cases where underlying medical conditions were identified, “they were accompanied by clinical somatic signs, not isolated psychiatric symptoms attributed to PANS,” Vasiljevic said.

Vasiljevic said the findings support “a more symptom-driven, targeted approach rather than routine use of large test batteries.”

The results align with more recent guidance from the American Academy of Pediatrics recommending a phased, clinically guided diagnostic strategy rather than routine extensive testing.

“A small subset of patients with atypical presentations, such as focal neurologic signs, systemic symptoms, or an unusual clinical course, may warrant broader investigation,” she said.

Diagnosis Still Clinical

In clinical practice, laboratory testing is only one piece of a much larger diagnostic puzzle, said Ayman Saleh, MD, child psychiatrist and co-founder of the PANS/PANDAS clinic at Children’s National Hospital in Washington, DC. 

Saleh said the study aligns with what clinicians often see: there may be abnormalities, but they are not specific to PANS.

Most patients arrive at Children’s National Hospital having already undergone extensive testing elsewhere, Saleh said.

Instead, PANS remains a diagnosis of exclusion based on clinical presentation.

“If the findings do not support any acute medical illness at that time, we treat it as a psychiatric disorder,” Saleh said.

Low Yield, Potential Downsides 

In the study, clinically actionable diagnoses were rare despite extensive testing. One child in the PANS group was newly diagnosed with celiac disease, and one other had findings suggestive of neuroinflammation without a definitive diagnosis.

Additional neurologic investigations in a subset of patients also had limited utility. Cerebrospinal fluid abnormalities were uncommon (pleocytosis in 7.1%), brain MRI showed no evidence of neuroinflammation, and abnormal electroencephalography findings were infrequent and largely nonspecific.

Saleh said overreliance on broad testing can carry risks. “It can be misleading to the patient and can cause unnecessary intervention.”

He also noted the financial burden, adding that many of these tests are “quite expensive” and may not be covered by insurance.

Instead, Jennifer Vermilion, MD, pediatric neurologist at the University of Rochester Medical Center in Rochester, New York, who was not involved in the study, suggested clinicians look for clinical warning signs. “These ‘red flags’ may include symptoms of psychosis, altered mental status, seizures, or movement disorders other than tics or stereotypes,” she said.

Methodological Concerns Suggest Caution

Caroline De Visscher, MD, PhD, a child and adolescent psychiatrist in Sweden who contributed clinically to the study but declined co-authorship, said the study has key limitations that could affect interpretation.

“The study has two main limitations, lack of sensitivity analyses and a problematic choice of control group,” she said. 

She said that the control group were not healthy children, but rather patients initially referred for suspected PANS who ultimately did not meet the criteria, raising the possibility of misclassification.

“Patients previously fulfilling criteria may be misclassified as controls,” she said, adding that delays between symptom onset and evaluation, as well as prior treatments, may further complicate interpretation.

Time to Rethink Routine Testing?

De Visscher cautioned against narrowing the diagnostic approach too quickly, especially in severely affected patients.

Patients with suspected immunopsychiatric illness, such as PANS, are often very ill, she said. “It is important to continuously take a differential approach in order not to miss other medical conditions.”

De Visscher said it is premature to change practice based on a single study. “I don’t think that the findings of the study are strong enough on their own to be applied in clinical practice,” she said.

For now, experts say the key is balance: avoid unnecessary, low-yield testing while maintaining vigilance for underlying medical conditions.

Ronny Wickström reported receiving honoraria for serving on advisory boards for Eisai, Roche, and Octapharma, and speaker’s fees from Eisai and Sanofi-Genzyme, outside the submitted work. David Mataix-Cols reported receiving personal fees from UpToDate and being a part-owner of Scandinavian E-Health AB, outside the submitted work. Kristina Tedroff reported owning shares in Integrated Research Laboratories AB and Biogaia AB, outside the submitted work. No other disclosures were reported.