What are the symptoms of Antiphospholipid Syndrome (APS) aside from headaches in an 11-year-old patient with a history of Systemic Lupus Erythematosus (SLE) and APS?

Symptoms of Antiphospholipid Syndrome in Pediatric SLE Patients

In an 11-year-old with SLE and APS, you must vigilantly monitor for thrombotic events (venous and arterial), neuropsychiatric manifestations beyond headaches, hematologic abnormalities, and renal involvement, as these represent the most significant threats to morbidity and mortality in this population.

Thrombotic Manifestations

Venous Thrombosis

• Deep vein thrombosis is the most common thrombotic manifestation in APS, particularly in pediatric patients with SLE 1, 2
• Cerebral venous sinus thrombosis presents with intermittent headaches and vomiting and requires immediate brain MRI with gadolinium-enhanced sequences 3
• Thrombosis can occur despite adequate anticoagulation therapy in up to 10% of patients 4

Arterial Thrombosis

• Ischemic stroke and transient ischemic attacks (TIA) comprise over 80% of cerebrovascular disease cases in SLE-APS patients 1
• Myocardial infarction occurs more frequently in APS patients with SLE, though recent data suggests decreasing incidence with modern management 4, 2
• Cerebrovascular disease commonly occurs (50-60%) in the context of high disease activity and persistently positive moderate-to-high titers of antiphospholipid antibodies 1

Neuropsychiatric Manifestations

Cognitive Dysfunction

• Attention deficits, visual memory impairment, verbal memory problems, executive dysfunction, and reduced psychomotor speed are the most commonly affected cognitive domains 1
• Cognitive dysfunction may benefit from anticoagulation therapy in APS patients, though evidence is limited 1
• Brain MRI may reveal cerebral atrophy, white matter lesions, and cerebral infarcts that correlate with severity of cognitive dysfunction 1

Seizure Disorders

• Generalized tonic-clonic seizures occur in 67-88% of SLE patients with seizure disorder 1
• Partial (complex) seizures are less common but significant 1
• Most seizures represent single isolated events; recurrent seizures (epilepsy) occur in 12-22% but have significant impact on morbidity and mortality 1

Movement Disorders

• Chorea (irregular, involuntary, jerky movements) is the best-documented movement disorder in SLE and has been strongly associated with antiphospholipid antibodies and APS 1
• Most patients (55-65%) experience a single episode that subsides within days to a few months 1

Acute Confusional State

• Acute onset with fluctuating level of consciousness and decreased attention characterizes this manifestation 1
• Requires extensive evaluation for underlying precipitating conditions, especially infections and metabolic disturbances 1

Hematologic Manifestations

• Autoimmune hemolytic anemia occurs significantly more frequently in APS patients with SLE compared to primary APS (p < 0.05) 4
• Neutropenia is more common in SLE-APS patients (p < 0.01) 4
• Thrombocytopenia can occur as part of the syndrome 5, 6

Cardiac Manifestations

• Endocardial valve disease (including Libman-Sacks endocarditis) occurs more frequently in patients with APS plus SLE compared to primary APS (p < 0.005) 4
• Heart valve disease represents a significant source of morbidity in this population 4

Renal Manifestations

• APS-associated nephropathy (APSN) is characterized by thrombosis in any kidney vessel 6
• The incidence of APSN in patients with SLE and antiphospholipid antibodies ranges from 11.4% to 39.5% 6
• Glomerular thrombosis occurs more frequently in APS patients with SLE 5
• Chronic kidney disease develops more commonly in SLE patients with APS/antiphospholipid antibodies 6, 2
• Renal biopsy is obligatory for differential diagnosis between lupus nephropathy and APSN 6

Dermatologic Manifestations

• Livedo reticularis (mottled, net-like skin discoloration) occurs more frequently in APS patients with associated SLE 5

Musculoskeletal Manifestations

• Arthralgias and arthritis are more frequently displayed in APS patients with associated SLE 5

Critical Clinical Pitfalls

• Normal laboratory values do not exclude active CNS lupus, as neurological involvement can occur independently of systemic disease activity 3
• The most dangerous error is attributing symptoms to lupus without adequately ruling out infection, particularly in immunosuppressed patients 7
• Patients may develop further thrombotic events despite anticoagulation therapy, requiring vigilant monitoring 4, 2
• Low C4 levels occur more frequently in APS plus SLE patients (p < 0.001) and may indicate higher disease activity 4

Risk Stratification Indicators

• Triple antibody positivity (lupus anticoagulant, anticardiolipin, and anti-β2-glycoprotein I) indicates the highest risk for thrombotic events 8
• Persistently positive moderate-to-high titers of antiphospholipid antibodies represent strong risk factors for cerebrovascular disease 1
• Up to 50-70% of antiphospholipid antibody-positive SLE patients may develop APS during 20 years of follow-up 6