Is fever present in catastrophic antiphospholipid antibody syndrome (CAPS)?

Fever in Catastrophic Antiphospholipid Antibody Syndrome

Yes, fever is a prominent and characteristic feature of catastrophic antiphospholipid antibody syndrome (CAPS), occurring in the majority of patients and often serving as one of the initial presenting symptoms of this life-threatening condition. 1, 2

Clinical Presentation of Fever in CAPS

• Fever is a cardinal presenting symptom in CAPS, typically appearing at disease onset alongside the rapid development of multiorgan thrombosis 1, 2
• The fever in CAPS is often precipitated by an infectious trigger, with the febrile illness serving as the "second hit" that transforms underlying antiphospholipid antibody positivity into the catastrophic thrombotic storm 3, 1
• Fever in CAPS is accompanied by a constellation of other symptoms including thrombocytopenia, muscle weakness, visual and cognitive disturbances, abdominal pain, renal failure, and disseminated intravascular coagulation 2

Diagnostic Challenges Related to Fever

• The presence of fever in CAPS creates significant diagnostic confusion because the clinical presentation mimics severe sepsis and other thrombotic microangiopathies, often leading to delayed diagnosis 3, 4
• The non-specific nature of fever combined with multiorgan involvement means that CAPS is frequently misdiagnosed initially, contributing to its high mortality rate 1
• When evaluating a febrile patient with suspected CAPS, clinicians must rule out infections as both a precipitating factor and a concurrent complication, as infections are common triggers for CAPS and can coexist with the syndrome 3, 2

Fever as Part of the "Two-Hit Hypothesis"

• The pathophysiology of CAPS follows a "two-hit hypothesis" where antiphospholipid antibodies represent the first hit (creating a prothrombotic state), and a second trigger such as infection with associated fever precipitates the catastrophic thrombotic event 3
• Common precipitating events that cause fever and trigger CAPS include infections (particularly cytomegalovirus and other viral or bacterial infections), trauma, and surgical procedures 3, 4, 2

Clinical Implications for Management

• The presence of fever in a patient with known antiphospholipid antibodies or systemic lupus erythematosus should raise immediate suspicion for CAPS, particularly if accompanied by evidence of multiorgan involvement 3, 1
• Empirical treatment for infections is warranted in febrile patients while simultaneously pursuing the diagnosis of CAPS, as infection may be both a trigger and a comorbid condition 3
• Early recognition of fever as part of the CAPS presentation is critical because timely diagnosis and intervention with triple therapy (anticoagulation, plasmapheresis, and high-dose glucocorticosteroids) significantly improves survival 4, 2

Key Distinguishing Features

• Unlike the isolated fever seen in other conditions, fever in CAPS is accompanied by rapid-onset multiorgan failure, particularly affecting the kidneys, lungs, central nervous system, and heart 4, 1
• The fever occurs in the context of laboratory findings showing thrombocytopenia, microangiopathic hemolytic anemia, and elevated antiphospholipid antibodies (lupus anticoagulant, anticardiolipin antibodies, or anti-beta-2-glycoprotein I antibodies) 4, 2