How to evaluate and manage a patient with a history of discoid lupus (Systemic Lupus Erythematosus, SLE) presenting with arthralgias, morning stiffness, malar rash, and shortness of breath, with elevated C-Reactive Protein (CRP) and C3 Complement levels, and experiencing Raynaud symptoms?

Evaluation and Management of Suspected SLE Flare with Systemic Manifestations

This patient requires immediate rheumatology referral and comprehensive workup for systemic lupus erythematosus (SLE) flare, as the constellation of polyarticular morning stiffness, malar rash, shortness of breath, Raynaud's phenomenon, and history of discoid lupus strongly suggests progression to systemic disease. 1

Interpretation of Current Laboratory Results

Elevated CRP in Context of SLE

• The elevated CRP is atypical for pure SLE flare and raises concern for superimposed infection, as patients with SLE rarely have elevated CRP levels during disease activity alone 1
• CRP >50 mg/L strongly suggests infection rather than lupus activity, though moderate elevations (15-50 mg/L) can occur with serositis or arthritis 1, 2
• In this patient with arthritis symptoms, the elevated CRP may reflect articular inflammation, but infection must be actively excluded 2

Elevated C3 Complement

• Elevated C3 is inconsistent with active lupus nephritis or severe systemic flare, as complement consumption typically causes low C3/C4 levels during active disease 1
• This finding argues against major organ involvement at present but does not exclude cutaneous, musculoskeletal, or mild systemic disease 2
• Normal or elevated complement with active disease can occur in some patients, particularly with predominantly cutaneous or articular manifestations 2

Essential Additional Laboratory Testing

Immediate workup should include: 1

• Complete blood count (assess for cytopenias: anemia, thrombocytopenia, leukopenia/lymphopenia)
• Comprehensive metabolic panel with serum creatinine and estimated GFR
• Urinalysis with microscopy and urine protein/creatinine ratio (critical for detecting lupus nephritis)
• Anti-dsDNA antibodies (correlates with disease activity and renal involvement)
• Complete complement panel: C3, C4, and CH50 (C3 alone is insufficient)
• ANA with pattern (if not recently documented)
• Anti-Ro/SSA and anti-La/SSB antibodies (relevant for cutaneous disease and Raynaud's)
• Antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, anti-β2-glycoprotein I) given Raynaud's symptoms 1
• Erythrocyte sedimentation rate (ESR) to complement CRP interpretation 2

Infection Workup Given Elevated CRP

• Blood cultures, chest X-ray, and procalcitonin should be obtained to exclude bacterial infection before attributing symptoms solely to lupus flare 3, 4
• The combination of elevated CRP with normal/elevated complement makes infection more likely than isolated SLE flare 4, 2

Clinical Assessment Priorities

Pulmonary Evaluation for Shortness of Breath

• Chest imaging (X-ray minimum, consider CT) is mandatory to evaluate for pleuritis, pneumonitis, pulmonary hemorrhage, or infection 1
• Pulmonary function tests if imaging is unrevealing
• Consider echocardiogram to assess for pericardial effusion or pulmonary hypertension

Cutaneous Assessment

• Dermatology referral for skin biopsy of the facial rash to distinguish between malar rash (acute cutaneous lupus), discoid lupus recurrence, or subacute cutaneous lupus 1, 5
• Biopsy is particularly important given history of discoid lupus to determine if this represents new systemic disease manifestation 5

Renal Surveillance

• Even with normal creatinine, urinalysis is essential as lupus nephritis can be asymptomatic initially 1
• If proteinuria >0.5 g/24h or active sediment present, nephrology referral and consideration for renal biopsy 1

Neuropsychiatric Assessment

• The reported "brain fog" requires formal evaluation for cognitive impairment through focused history assessing attention, concentration, memory, and word-finding difficulties 1

Management Strategy

Immediate Actions

1. Restart hydroxychloroquine immediately (200-400 mg daily) as this is foundational therapy for all SLE manifestations and should never have been discontinued 1, 6
2. Initiate or optimize glucocorticoids based on disease severity pending rheumatology evaluation 1
3. Rule out infection before escalating immunosuppression given elevated CRP 1, 3

Rheumatology Referral (Urgent)

Referral to rheumatology within 1-2 weeks is mandatory for: 1

• Disease activity assessment using validated index (SLEDAI-2K or other)
• Determination of whether this represents progression from discoid to systemic lupus
• Initiation of appropriate immunosuppressive therapy if systemic disease confirmed
• Establishment of monitoring schedule

Additional Immunosuppression Considerations

If systemic SLE is confirmed and hydroxychloroquine plus glucocorticoids are insufficient: 1

• Methotrexate or azathioprine should be considered first-line for articular and cutaneous manifestations
• Mycophenolate mofetil for more severe non-renal manifestations (though teratogenic)
• Avoid cyclophosphamide unless organ-threatening disease develops

Monitoring Schedule

Once diagnosis is established: 1

• Every 3-6 months minimum with active disease
• Each visit: disease activity assessment, complete blood count, CRP, ESR, creatinine, urinalysis
• Every 6-12 months: complement levels (C3, C4), anti-dsDNA, lipid panel, glucose, blood pressure
• Annual ophthalmology examination once hydroxychloroquine restarted (baseline then yearly after 5 years if low-risk) 1

Critical Pitfalls to Avoid

• Never attribute elevated CRP solely to lupus flare without excluding infection, especially with values >15 mg/L 1, 2, 7
• Do not delay urinalysis - lupus nephritis can be silent and early detection dramatically improves outcomes 1
• Elevated complement does not exclude SLE flare but makes major organ involvement less likely 2
• Discontinuing hydroxychloroquine increases flare risk - this medication should be continued indefinitely in SLE 1, 6
• Morning stiffness improving during the day is characteristic of inflammatory arthritis and supports active disease 1