What is the appropriate management for a patient with prolonged fever, anemia (low hemoglobin), and a new onset purpura rash?

Urgent Evaluation for Tickborne Rickettsial Disease or Systemic Vasculitis

A patient presenting with 3 months of fever, anemia, and new-onset purpura requires immediate empiric doxycycline therapy while pursuing urgent diagnostic workup for Rocky Mountain spotted fever (RMSF) or other life-threatening systemic vasculitides, as delayed diagnosis of RMSF is associated with significantly increased mortality. 1

Immediate Management Priority

Start empiric doxycycline 100 mg twice daily immediately if RMSF or other tickborne rickettsial disease is suspected, without waiting for diagnostic confirmation. 1 Lack of rash or late-onset rash in RMSF has been associated with delays in diagnosis and increased mortality, with case-fatality rates of 5-10%. 1

Key Clinical Features Suggesting RMSF:

• Fever with petechial purpura that may involve palms and soles 1
• Thrombocytopenia and anemia (both present in your patient) 1
• Hyponatremia and slightly increased hepatic transaminases 1
• Late-stage manifestations can include cutaneous necrosis and purpura fulminans that mimics meningococcemia 1

Critical Differential Diagnoses to Exclude

1. Thrombotic Thrombocytopenic Purpura (TTP)

RMSF-associated neurologic manifestations, renal failure, and thrombocytopenia are frequently confused with TTP. 1 Check:

• Complete blood count with peripheral smear for schistocytes 1
• Renal function (creatinine, BUN) 1
• LDH, indirect bilirubin (elevated in hemolysis) 1
• ADAMTS13 activity if TTP suspected 2, 3

If TTP is confirmed: Initiate urgent plasma exchange, which has increased survival from 10% to >90%. 2, 3 Plasmapheresis should be started immediately, not delayed for diagnostic confirmation. 3

2. Infective Endocarditis with Immune Complex Glomerulonephritis

Prolonged fever with purpura and anemia can represent infective endocarditis. 4, 5 Obtain:

• Blood cultures (at least 3 sets from different sites) 4, 5
• Echocardiography (transthoracic initially, transesophageal if high suspicion) 4
• Urinalysis for hematuria and proteinuria 4, 5
• Complement levels (C3, C4 may be low) 5
• Serum immune complexes 5

If endocarditis confirmed: Start appropriate antibiotics immediately and consider plasmapheresis if crescentic glomerulonephritis develops, as this has shown dramatic improvement in refractory cases. 4

3. IgA Vasculitis (Henoch-Schönlein Purpura)

While typically acute in children, HSP can present with prolonged symptoms in adults. 6 Look for:

• Palpable purpura on lower extremities and buttocks 6
• Abdominal pain or gastrointestinal bleeding 6
• Joint involvement (arthralgias or arthritis) 6
• Hematuria or proteinuria indicating nephritis 6

Diagnostic confirmation: Skin biopsy showing leukocytoclastic vasculitis with IgA-dominant immune deposits. 6 If renal involvement present, document as "IgA vasculitis with glomerulonephritis." 6

4. Ehrlichiosis

Consider Ehrlichia chaffeensis ehrlichiosis, which presents with: 1

• Fever, headache, malaise, myalgia 1
• Rash in approximately 30% of adults (60% in children), appearing median 5 days after illness onset 1
• Leukopenia, thrombocytopenia, increased hepatic transaminases, hyponatremia, anemia 1
• Case-fatality rate of 3% 1

Treatment: Doxycycline covers both RMSF and ehrlichiosis. 1

Essential Diagnostic Workup

Immediate Laboratory Tests:

• CBC with differential: Assess for thrombocytopenia, leukopenia, anemia severity 1
• Peripheral blood smear: Evaluate for schistocytes (TTP), morulae (ehrlichiosis), or malaria parasites 1
• Comprehensive metabolic panel: Check renal function, electrolytes (hyponatremia common in rickettsial disease) 1
• Hepatic transaminases: Elevated in rickettsial diseases 1
• Coagulation studies: PT/PTT, fibrinogen, D-dimer 1
• Inflammatory markers: CRP, ESR, ferritin 1
• Blood cultures × 3: Rule out endocarditis and bacteremia 4, 5

Specialized Testing:

• Rickettsial serology: Acute and convalescent titers for RMSF, ehrlichiosis 1
• ADAMTS13 activity: If TTP suspected 2, 3
• Complement levels (C3, C4): Low in immune complex disease, normal in HSP 6
• ANCA and anti-GBM antibodies: Exclude other vasculitides 6
• Autoimmune panel: ANA, RF, anti-dsDNA if systemic autoimmune disease suspected 1

Imaging and Tissue Diagnosis:

• Chest radiograph: Evaluate for pneumonia or acute chest syndrome 1
• Skin biopsy of purpuric lesion: Obtain for immunofluorescence (IgA deposits in HSP) and histopathology 6
• Echocardiogram: If endocarditis suspected 4

Management Algorithm Based on Clinical Presentation

If Hemodynamically Unstable or Severe Manifestations:

1. Admit to ICU immediately 1
2. Start empiric doxycycline 100 mg IV twice daily (covers RMSF, ehrlichiosis) 1
3. Add broad-spectrum antibiotics (vancomycin + ceftriaxone or piperacillin-tazobactam) to cover endocarditis and sepsis until cultures negative 1
4. Fluid resuscitation: 20 mL/kg isotonic crystalloid boluses if hypotensive 1
5. Initiate plasma exchange urgently if TTP suspected (don't wait for ADAMTS13 results) 2, 3

If Stable but Concerning Features:

1. Start empiric doxycycline 100 mg PO twice daily 1
2. Admit for observation and serial monitoring 1
3. Complete diagnostic workup as above 1, 6
4. Monitor for progression: Serial CBCs, renal function, vital signs every 4-6 hours 1

Critical Pitfalls to Avoid

Never delay doxycycline therapy while awaiting serologic confirmation of rickettsial disease—serology is often negative early in illness, and delayed treatment increases mortality. 1

Do not assume viral illness in a patient with prolonged fever and new purpura—this constellation demands aggressive workup for life-threatening causes. 1

Avoid aspirin or NSAIDs until dengue and other viral hemorrhagic fevers are excluded, as these increase bleeding risk. 7

Do not give prophylactic platelet transfusions in TTP, as this can worsen thrombosis—transfuse only for severe bleeding or before invasive procedures when platelets <20,000/mm³. 8

Recognize that RMSF can mimic TTP, meningococcemia, or acute vasculitis—maintain broad differential and treat empirically for the most immediately life-threatening diagnosis. 1