Case Series Assesses Clinical Features of Pediatric APS

In an effort to elucidate context on disease phenotypes among children with antiphospholipid syndrome (APS), researchers carried out a retrospective review of patients at a tertiary referral center.

Findings were published in Pediatric Rheumatology and revealed a high prevalence of noncriteria clinical manifestations, or those not included in the Sapporo criteria, highlighting the need to “consider these characteristics when developing pediatric-specific classification criteria and when considering this relatively rare diagnosis in pediatric practice,” authors wrote.

APS is a relatively rare systemic autoimmune disease that involves thrombotic events and/or pregnancy morbidity with persistently positive antiphospholipid antibodies (aPL), researchers explained, adding there are currently no pediatric-specific criteria for the disease. It is diagnosed in around 2 of every 100,000 adults in the United States yearly.

The Sapporo criteria are used to formally classify the condition for research purposes in adults, and ongoing efforts continue to develop new criteria specific to pediatric patients with APS.

Previous small case series of this patient population have yielded consistent themes of noncriteria manifestations including livedo reticularis or racemosa, persistent thrombocytopenia, autoimmune hemolytic anemia, choreiform movements, white matter changes, cardiac valve abnormalities, among others.

Current therapeutic approaches for children with the disease are based on adult studies, anecdotal evidence in children, and clinicians’ experience, leading to largely heterogeneous management.

To enable a more personalized and proactive approach to care of children with APS, investigators assessed electronic medical records of 21 children with the condition who presented to Michigan Medicine between 2000 and 2019.

Any patient who failed to meet revised Sapporo Classification criteria by 18 years or younder was excluded from the case series. Of the included patients, 10 patients had primary APS and 11 had secondary APS.

“Among patients with secondary APS and a concomitant rheumatic disease, most (9 or 82%) had a diagnosis of systemic lupus erythematosus (SLE), and there was 1 patient each with ulcerative colitis and microscopic polyangiitis,” authors added.

Median age at diagnosis was 16 years, with a median time of follow-up of 5.8 years; the majority of patients (76%) were female.

Analyses revealed:

• Two thirds of patients (67%) had “noncriteria” manifestations of APS including thrombocytopenia, autoimmune hemolytic anemia, and livedo reticularis/racemose, with no significant differences seen between primary and secondary APS groups.
• Almost half of patients (43%) had recurrent thrombosis, typically when patients were subtherapeutic or nonadherent to anticoagulation.
• Over at least 12 weeks, 64% of the cohort were positive for anti-β2GPI antibodies, 81% for anticardiolipin antibodies, and 52% for lupus anticoagulant.
• Damage Index in Patients with Thrombotic APS (DIAPS) scores indicated a chronic burden of disease in both primary and secondary APS patients.

Based on the findings, researchers advised that pediatric patients who present with autoimmune hemolytic anemia and thrombocytopenia likely warrant APS testing.

“Our data also confirm that testing for ANA [antinuclear antibodies] is not a good screening test for APS because it was only positive in 43% of all patients with APS and none of the patients with primary APS. If a diagnosis of APS is being considered, then screening should be with aPL rather than relying on ANA as a surrogate marker,” they wrote.

In the case series, recurrence was common and nearly all events took place when a patient was not on anticoagulation, underscoring the importance of these patients being prescribed and staying on therapeutic levels of anticoagulation, authors stressed.

Relatively low rates of aspirin use were found especially in primary APS, while this group also reported low utilization of hydroxychloroquine, a common lupus treatment.

“Beyond clots, there is not one definitive feature of this rare disease in children; rather, there is a constellation of symptoms we found among these patients,” said lead study author Jacqueline Madison, MD. “If we can prove these symptoms are related to the condition, then physicians should be able to test for APS sooner and diagnose the disease earlier to prevent potentially catastrophic clots.”

The retrospective nature and small sample size mark limitations to the study, while some included patients were treated by rheumatologists and others by hematologists.

“We have already started a prospective study of this young patient population to better understand how the disease presents in the earliest stages and to try to find even better diagnostic markers in the blood. These are major steps towards limiting blood clots and potential hospitalizations or deaths due to APS in kids,” Madison concluded.

Reference

Madison JA, Gockman K, Hoy C, Tambralli A, Zuo Y, Knight JS. Pediatric antiphospholipid syndrome: clinical features and therapeutic interventions in a single center retrospective case series. Pediatr Rheumatol. Published online February 23, 2022. doi:10.1186/s12969-022-00677-8