What is the likely diagnosis and treatment for a young female with skin lesions, alopecia, oral ulcers, and a high Antinuclear Antibody (ANA) titer?

Systemic Lupus Erythematosus (SLE)

This young female with skin lesions, alopecia, oral ulcers, and ANA titer of 1:320 most likely has systemic lupus erythematosus (SLE), and should be started on hydroxychloroquine 200 mg twice daily along with systemic corticosteroids, with close monitoring for renal and hematologic involvement.

Diagnostic Certainty

The combination of skin lesions, alopecia, oral ulcers, and high ANA titer (>1:320) strongly indicates SLE and warrants immediate treatment initiation. 1

• Skin disease occurs in up to 70% of SLE patients during the course of disease, with malar rash (40%), alopecia (24%), and oral ulcers (19%) being the most frequent mucocutaneous manifestations 1
• High ANA titers (>1:320) combined with arthralgias are risk factors that signal transition from cutaneous to systemic lupus, requiring close monitoring 1
• The clinical triad of skin lesions, alopecia, and oral ulcers fulfills multiple American College of Rheumatology criteria for SLE diagnosis 2

Critical Initial Workup Required

Order the following tests immediately to assess disease severity and organ involvement:

• Complete blood count to evaluate for anemia, leukopenia, lymphopenia, or thrombocytopenia (hematologic involvement) 3, 4
• Comprehensive metabolic panel including creatinine and electrolytes to assess renal function 3
• Urinalysis with protein-creatinine ratio to detect lupus nephritis (proteinuria >0.5 g/g is significant) 3
• Anti-Smith antibody (highly specific for SLE when positive) 3
• Anti-Ro/SSA and anti-La/SSB antibodies (important even if ANA is positive, as some patients can be ANA-negative with positive anti-Ro) 5, 4
• Complement levels (C3, C4) to assess disease activity 2
• ESR to evaluate inflammatory activity (elevated ESR >100 mm/h suggests active disease) 3

Important Diagnostic Pitfall

Do not dismiss this diagnosis even if initial ANA is negative on repeat testing—4-13% of SLE cases are ANA-negative, particularly those with anti-Ro positivity. 4

• ANA-negative SLE patients with positive anti-Ro antibodies typically present with vasculitic skin lesions, photosensitivity, renal disease, and can have multiple organ involvement 4
• Always order anti-extractable nuclear antigens (ENA) panel including anti-Ro/SSA when clinical suspicion for SLE is high, regardless of ANA result 4

Differential Diagnosis Consideration

Rule out Rowell syndrome if the skin lesions have target-like or erythema multiforme (EM) characteristics:

• Rowell syndrome presents with SLE, EM-like lesions, and speckled pattern ANA, requiring the same immunosuppressive treatment as SLE 3, 5
• EM-like lesions in Rowell syndrome show predominant truncal distribution (versus extremity distribution in classic EM) 3
• The presence of recurrent EM-like eruptions without identifiable drug trigger should raise suspicion for underlying lupus 3

Treatment Algorithm

Initiate treatment immediately upon clinical diagnosis without waiting for all serologic results:

First-Line Therapy

• Hydroxychloroquine 200 mg twice daily as disease-modifying therapy 3, 5
• High-dose systemic corticosteroids (typically prednisone 1 mg/kg/day) for acute disease control 3, 5

Second-Line Immunosuppression (if inadequate response or steroid-sparing needed)

• Mycophenolate mofetil 1 g twice daily for 6 months, particularly if renal involvement present 3
• Azathioprine 50 mg twice daily as maintenance therapy after initial disease control 3

Adjunctive Measures

• Topical corticosteroids for localized skin lesions 6
• Sun protection counseling as photosensitivity is common 2
• Supportive care for oral ulcers (topical anesthetics, chlorhexidine rinses) 6

Monitoring Strategy

Reassess at 6 weeks, 3 months, and 6 months with:

• Clinical examination for skin lesion improvement, hair regrowth, and resolution of oral ulcers 3
• Repeat urinalysis and protein-creatinine ratio to monitor renal response (target <0.5 g/g) 3
• Complete blood count to monitor for hematologic improvement 3
• ESR to assess inflammatory activity reduction 3

Red Flags Requiring Urgent Nephrology Referral

Immediately refer if any of the following develop:

• Protein-creatinine ratio >1.0 g/g suggesting significant lupus nephritis 3
• Rising creatinine indicating declining renal function 3
• Active urinary sediment with RBC casts 3
• Nephrotic-range proteinuria (>3.5 g/day) 3

Expected Timeline for Response

• Skin lesions and oral ulcers: Begin improving within 2-4 weeks of treatment initiation 3
• Alopecia: Hair regrowth typically takes 3-6 months due to hair follicle cycle lag 7
• Renal parameters: Should show improvement by 3-6 months if lupus nephritis present 3
• Constitutional symptoms: Fever, malaise, and joint pain resolve within days to weeks of corticosteroid therapy 3