How should fever be evaluated and managed in a patient with catastrophic antiphospholipid syndrome (CAPS)?

Fever Evaluation and Management in Catastrophic Antiphospholipid Syndrome (CAPS)

Primary Approach to Fever in CAPS

Fever in CAPS patients must be aggressively evaluated for infection as a precipitating or complicating factor, while simultaneously initiating triple therapy (anticoagulation, high-dose glucocorticoids, and plasma exchange/IVIG) without delay, since infection triggers CAPS in a substantial proportion of cases and delays in treatment significantly increase the 25-30% mortality rate. 1, 2, 3

Critical Diagnostic Priorities

Immediate Infection Workup Required

• Obtain blood cultures, urine cultures, and chest radiograph immediately when fever develops in any CAPS patient, as infection is both a common precipitant and complication 4
• The most common infections associated with CAPS include: skin infections (18%), HIV (17%), pneumonia (14%), hepatitis C (13%), and urinary tract infections (10%) 4
• Evaluate for sepsis using SOFA score criteria: look for hypotension (SBP <90 mmHg or MAP <70 mmHg), hypoxemia (PaO₂/FiO₂ <300), hyperbilirubinemia (>2 mg/dL), and hyperlactatemia (>2 mmol/L) 5
• Consider procalcitonin (PCT) measurement: levels ≥1.5 ng/mL have 100% sensitivity and 72% specificity for distinguishing bacterial sepsis from non-infectious inflammation 5

Distinguish Infection from CAPS-Related Inflammation

• Fever in CAPS typically presents with: thrombocytopenia, muscle weakness, visual and cognitive disturbances, abdominal pain, renal failure, and disseminated intravascular coagulation 1
• CAPS causes a "thrombotic storm" with cytokine-mediated inflammation that can produce fever independent of infection 1, 3
• However, 40% of CAPS cases present as catastrophic syndrome triggered by infection, making infection exclusion mandatory 4

Immediate Management Algorithm

Step 1: Empiric Antimicrobial Therapy (Within 1 Hour)

• Initiate broad-spectrum antibiotics within 1 hour if infection is suspected, especially if the patient shows signs of sepsis or is deteriorating 6, 5
• Do not delay antibiotics while awaiting culture results in unstable or high-risk patients 6
• Antibiotic selection should cover: resistant Gram-positive cocci (including MRSA) and Gram-negative bacilli if drug-resistant pathogens are suspected 6

Step 2: Concurrent CAPS-Specific Triple Therapy

• Anticoagulation: Use low molecular weight heparin (LMWH) as the preferred agent due to its anti-inflammatory and anticoagulant properties 1, 2
• High-dose glucocorticoids: Administer immediately; steroid use is associated with improved prognosis (p = 0.024) 2, 4
• Plasma exchange and/or IVIG: Initiate within the first week, performing plasma exchange daily for the first 3 days, then taper based on clinical response 2, 7, 3

Step 3: ICU Admission Criteria

• Admit to ICU if any of the following are present:
  • Requirement for mechanical ventilation 8
  • Shock requiring vasopressors 8
  • Respiratory rate ≥30 breaths/min 8
  • PaO₂/FiO₂ ≤250 8
  • Multilobar infiltrates 8
  • New confusion/disorientation 8
  • Thrombocytopenia <100,000 cells/mm³ 8
  • Hypotension requiring aggressive fluid resuscitation 8

Critical Pitfalls to Avoid

Do Not Delay Treatment for Diagnostic Certainty

• Antiphospholipid antibody levels can fluctuate significantly in CAPS, which complicates diagnosis and can lead to erroneous interpretation of rapidly developing symptoms 1
• Begin triple therapy immediately based on clinical suspicion rather than waiting for antibody confirmation 1, 2

Do Not Withhold Antibiotics Due to Steroid Use

• The combination of appropriate antibiotic coverage with steroids improves prognosis in infection-associated CAPS 4
• Patients given steroids had better outcomes (p = 0.024) even in the presence of infection 4

Monitor for Renal Thrombotic Microangiopathy

• Renal involvement occurs in 35% of CAPS cases, with renal thrombotic microangiopathy (RTMA) carrying worse prognosis (p = 0.001) 4
• Requirement for dialysis also indicates worse prognosis (p = 0.035) 4

Special Considerations

Plasma Exchange Technique

• Use albumin solution as replacement fluid rather than fresh frozen plasma (FFP) when possible, as FFP contains clotting factors, complement activation products, and cytokines that could worsen the thrombotic storm 7
• Perform daily plasma exchange for the first 3 days, then taper based on clinical condition 7

Additional Immunosuppression

• In patients with concurrent systemic lupus erythematosus, consider cyclophosphamide as part of the treatment regimen 2
• For refractory or relapsing cases, rituximab or eculizumab may be considered, though these require further study 2

Monitoring Parameters

• Reassess inflammatory markers: CRP, ESR, and lactate levels to guide treatment response 5
• Monitor for organ dysfunction progression: particularly renal function, platelet count, and respiratory status 1, 4
• Delayed ICU admission is associated with increased mortality, so maintain low threshold for escalation of care 8