What is the differential diagnosis and necessary lab tests for a female patient presenting with a facial rash sparing the nasolabial fold, fever, and joint pain?

Differential Diagnosis and Laboratory Testing

Primary Diagnosis: Systemic Lupus Erythematosus (SLE)

The clinical triad of facial rash sparing the nasolabial fold (malar/butterfly rash), fever, and joint pain in a female patient is highly suggestive of systemic lupus erythematosus and warrants immediate autoimmune workup. 1, 2

Why SLE is Most Likely

• Malar rash sparing the nasolabial folds is a pathognomonic feature of acute cutaneous lupus erythematosus, distinguishing it from other facial rashes 1, 2
• Female predominance is characteristic of SLE, with women affected 9-10 times more frequently than men 2
• Constitutional symptoms (fever), mucocutaneous manifestations (facial rash), and musculoskeletal symptoms (joint pain) represent the classic triad of early SLE presentation 2
• The combination of symmetric joint pain with inflammatory features and photosensitive rash are key features warranting ANA testing 3

Secondary Differential Diagnoses

Dermatomyositis

• Can present with facial rash (heliotrope rash on eyelids), fever, and joint pain 1
• However, dermatomyositis typically involves periorbital edema and violaceous discoloration, not the classic malar distribution sparing nasolabial folds 1
• Gottron's papules on hands and muscle weakness would be expected 1

Adult-Onset Still's Disease

• Presents with high spiking fevers, salmon-pink evanescent rash (not fixed facial rash), and arthritis 1
• Rash typically appears on trunk and extremities during fever spikes, not as persistent facial erythema 1

Drug Hypersensitivity Reaction

• Can cause maculopapular rash, fever, and arthralgias 4
• Requires recent medication exposure (antibiotics, NSAIDs, anticonvulsants) within 2-3 weeks 4
• Rash distribution is typically more generalized, not specifically malar with nasolabial sparing 4

Essential Laboratory Tests

First-Line Autoimmune Panel (Order Immediately)

Antinuclear Antibody (ANA) Testing:

• ANA by immunofluorescence is positive in nearly 100% of SLE cases and is the essential screening test 2, 3
• If ANA is positive, reflex testing should include ANA titer and pattern 3

Specific Autoantibodies:

• Anti-double-stranded DNA (anti-dsDNA) antibodies - highly specific for SLE 2, 3
• Anti-Smith (anti-Sm) antibodies - highly specific for SLE 2, 3
• Anti-Ro/SSA and anti-La/SSB antibodies - associated with photosensitive rashes and subacute cutaneous lupus 1, 2

Complement Levels:

• C3 and C4 levels - hypocomplementemia indicates active disease and immune complex consumption 2

Complete Blood Count with Differential

• Look for cytopenias: leukopenia, lymphopenia, thrombocytopenia, or hemolytic anemia 2, 3
• Cytopenias are key features warranting ANA testing and support SLE diagnosis 3

Comprehensive Metabolic Panel

• Assess renal function (creatinine, BUN) for lupus nephritis 2
• Evaluate for electrolyte abnormalities 2

Urinalysis with Microscopy

• Screen for proteinuria and hematuria indicating renal involvement 2
• Cellular casts suggest active lupus nephritis 2

Inflammatory Markers

• Erythrocyte sedimentation rate (ESR) - typically elevated in active SLE 2
• C-reactive protein (CRP) - may be normal or mildly elevated in SLE (helps distinguish from infection) 2

Additional Testing if Dermatomyositis Suspected

• Creatine kinase (CK) and aldolase - elevated with muscle involvement 1
• Myositis-specific antibodies (anti-Jo-1, anti-MDA-5, anti-TIF1-γ) 1

Antiphospholipid Antibodies (If History Suggests)

• Lupus anticoagulant, anticardiolipin antibodies, anti-β2-glycoprotein I antibodies 2
• Order if history of thrombosis, recurrent miscarriages, or thrombocytopenia 2

Critical Management Considerations

Do not delay referral to rheumatology while awaiting laboratory results - early diagnosis and treatment improve outcomes and prevent organ damage 2

Avoid empiric doxycycline unless there is specific epidemiologic risk for tickborne illness (tick exposure, endemic area, outdoor activities in wooded regions) 5, 6 - the facial rash sparing nasolabial folds is not consistent with Rocky Mountain Spotted Fever, which presents with peripheral petechial rash starting on wrists/ankles 6

Screen for life-threatening complications: assess for neurologic symptoms (seizures, psychosis), severe cytopenias, renal failure, or cardiopulmonary involvement requiring urgent intervention 2