What is the most likely diagnosis and recommended work‑up for a patient who presents with a rash confined to the bilateral cheeks, nasal folds, and chin?

Diagnosis: Acute Cutaneous Lupus Erythematosus (Malar Rash)

The most likely diagnosis is acute cutaneous lupus erythematosus (ACLE) presenting as a malar rash, and the recommended work-up includes skin biopsy for histology and direct immunofluorescence, complete blood count, comprehensive metabolic panel, urinalysis, antinuclear antibody (ANA), anti-dsDNA, anti-Sm, anti-Ro/SSA, anti-La/SSB, and complement levels (C3, C4). 1, 2

Key Diagnostic Features

The distribution described—bilateral cheeks including the nasal folds and chin—is the critical distinguishing feature:

• Classic malar ("butterfly") rash of systemic lupus erythematosus typically spares the nasolabial folds, making this presentation atypical for standard ACLE 1, 2
• However, ACLE can present with erythematous macules, telangiectasia, or papulosquamous lesions affecting the face more diffusely, including areas beyond the classic butterfly distribution 2
• The involvement of nasolabial folds and chin suggests either an atypical ACLE presentation or consideration of alternative diagnoses 1, 3

Essential Work-Up Components

Skin Biopsy (Mandatory)

• Obtain two punch biopsies from perilesional skin: one for routine histology and one for direct immunofluorescence (DIF) 4, 1
• Histology in ACLE shows interface dermatitis with basal cell vacuolar degeneration, lymphocytic infiltrate, and dermal mucin deposition 1, 5
• DIF demonstrates immunoglobulin and complement deposition at the dermal-epidermal junction (positive "lupus band test") in lesional skin in 90% of ACLE cases 1, 5

Serologic Testing

• ANA (antinuclear antibody): Positive in >95% of systemic lupus erythematosus cases 1, 5
• Anti-dsDNA and anti-Sm antibodies: Highly specific for SLE 1, 5
• Anti-Ro/SSA and anti-La/SSB: Associated with photosensitivity and subacute cutaneous LE, but can be present in ACLE 1, 5
• Complement levels (C3, C4): Low levels suggest active systemic disease 1, 5
• Complete blood count: Assess for cytopenias (leukopenia, lymphopenia, thrombocytopenia, anemia) 1, 5
• Comprehensive metabolic panel: Evaluate renal and hepatic function 1, 5
• Urinalysis with microscopy: Screen for proteinuria, hematuria, and cellular casts indicating lupus nephritis 1, 5

Critical Differential Diagnoses to Exclude

Secondary syphilis must be ruled out, as it can mimic malar rash with facial involvement including nasolabial folds, and presents with similar systemic symptoms (fever, arthralgias, lymphadenopathy) 3:

• Order RPR (rapid plasma reagin) and confirmatory treponemal testing (FTA-ABS or TP-PA) 3

Seborrheic dermatitis commonly affects nasolabial folds and can be confused with lupus 1, 3:

• Distinguished by greasy yellow scales and lack of systemic symptoms 1

Rosacea affects central face including nasolabial folds 1, 3:

• Look for flushing, telangiectasia, and papulopustular lesions without systemic features 1

Drug-induced lupus should be considered 1, 5:

• Obtain detailed medication history for the past 2 months, including over-the-counter medications 4
• Common culprits include hydralazine, procainamide, isoniazid, minocycline, and anti-TNF agents 1, 5

Common Pitfalls to Avoid

• Do not rely on nasolabial fold sparing as an absolute criterion: While classic teaching emphasizes sparing of nasolabial folds in malar rash, ACLE can present with more diffuse facial involvement 2, 6
• Do not skip DIF: Routine histology alone may be nonspecific; DIF provides critical diagnostic confirmation 4, 1
• Do not assume isolated cutaneous disease: 51% of patients with ACLE have systemic involvement at presentation, requiring full systemic evaluation 2, 5
• Do not overlook infectious mimics: Always test for syphilis in patients with facial rash and systemic symptoms, as clinical and even histopathological overlap exists 3

Additional Considerations

• Photosensitivity history: 63% of SLE patients report photosensitivity; ask specifically about sun exposure preceding rash onset 2
• Associated mucosal involvement: Check for oral ulcers (present in 31.5% of SLE patients), nasal ulcers, and conjunctival injection 2, 5
• Vascular phenomena: Examine for Raynaud's phenomenon (60% of SLE patients), livedo reticularis, and periungual telangiectasia 2, 5
• Alopecia: Assess for non-scarring alopecia (40% of SLE patients) or scarring alopecia from chronic discoid lesions 2, 5