What is the appropriate diagnostic and treatment approach for targetoid macules on the hands and feet with a family history of Systemic Lupus Erythematosus (SLE) and psoriasis?

Diagnostic and Treatment Approach for Targetoid Macules on Hands and Feet with Family History of SLE and Psoriasis

This presentation of sharply demarcated, targetoid macules with dark red centers symmetrically distributed on palms and soles in a patient with parental history of both SLE and psoriasis requires immediate evaluation for cutaneous lupus erythematosus, particularly subacute cutaneous lupus erythematosus (SCLE), with skin biopsy and comprehensive autoimmune workup to exclude systemic lupus erythematosus. 1, 2

Immediate Diagnostic Workup

Skin Biopsy

• Perform skin biopsy immediately for histological confirmation, as this is mandatory for diagnosing cutaneous lupus erythematosus and cannot be bypassed 3, 1
• The targetoid morphology with symmetric palmoplantar distribution is highly suggestive of SCLE, which is frequently associated with anti-Ro/SSA antibodies 1
• Repeat biopsy if clinical morphology changes or treatment fails 3

Comprehensive Autoantibody Panel

Order the following baseline tests immediately 1, 2, 4:

• ANA (using 1:160 dilution cutoff) 2
• Anti-dsDNA antibodies (use double-screening: solid phase assay first, then Crithidia luciliae immunofluorescence for confirmation) 2
• Anti-Ro/SSA and anti-La/SSB antibodies (critical given the targetoid presentation and family history, as these are strongly associated with SCLE and neonatal lupus) 3, 1
• Anti-RNP, anti-Sm antibodies 1, 2
• Anti-phospholipid antibodies (lupus anticoagulant, anticardiolipin, anti-β2-glycoprotein I) 3, 1
• C3 and C4 complement levels 1, 2

Essential Laboratory Tests

Obtain baseline labs to assess for systemic involvement 1, 2:

• Complete blood count (to detect cytopenias associated with SLE) 3, 1
• Erythrocyte sedimentation rate and C-reactive protein 1, 2
• Serum creatinine and albumin 3, 1
• Urinalysis with microscopy and urine protein/creatinine ratio 3, 1

Excluding Systemic Lupus Erythematosus

Renal Assessment

• If urinalysis is abnormal or creatinine elevated, immediately obtain urine protein/creatinine ratio, urine microscopy, and renal ultrasound 1, 4
• Consider referral for kidney biopsy if renal abnormalities persist 1, 4

Neuropsychiatric Screening

Specifically assess for 1, 4:

• Seizures, paresthesiae, numbness, weakness
• Headaches (particularly new-onset or severe)
• Depression, cognitive impairment (memory, attention, concentration, word-finding difficulties)

Multi-System Review

Evaluate for involvement of at least two organ systems 2:

• Musculoskeletal: arthritis, arthralgias
• Hematologic: anemia, thrombocytopenia, leukopenia, lymphopenia 3
• Cardiopulmonary: serositis (pleuritis, pericarditis)
• Constitutional symptoms: fever, malaise, weight loss

Differential Diagnosis Considerations

Primary Considerations

Given the targetoid morphology and distribution, prioritize:

• Subacute cutaneous lupus erythematosus (most likely given symmetric palmoplantar targetoid lesions) 1
• Erythema multiforme major (though typically has mucosal involvement) 3
• Drug-induced SCLE (inquire about recent medication changes, particularly thiazides, calcium channel blockers, ACE inhibitors) 1

Secondary Considerations

• Psoriasis (given family history, but targetoid macules are atypical for psoriasis) 3
• Psoriatic arthritis with palmoplantar involvement 3
• Stevens-Johnson syndrome/toxic epidermal necrolysis (though presentation lacks blistering and mucosal involvement) 3

Treatment Approach

If Cutaneous Lupus Confirmed Without Systemic Disease

First-line therapy 1:

• Strict photoprotection is mandatory (broad-spectrum sunscreen SPF 50+, protective clothing, sun avoidance) 3, 1
• Ultrapotent topical corticosteroids for localized lesions 3
• Hydroxychloroquine 200-400 mg daily (5-6.5 mg/kg/day) as systemic therapy 5

Critical caveat: If family history of psoriasis is strong and patient develops psoriatic features, hydroxychloroquine may exacerbate psoriasis and should be used cautiously 6, 7

Second-line options if refractory 1:

• Azathioprine for third-line treatment
• Consider methotrexate (particularly useful if psoriasis coexists) 8, 7

If Systemic Lupus Erythematosus Confirmed

Apply EULAR/ACR 2019 classification criteria 2:

• Systemic corticosteroids (dose depends on severity and organ involvement) 3
• Hydroxychloroquine as maintenance therapy 3, 5
• Immunosuppressive agents (azathioprine, mycophenolate mofetil, or methotrexate) for steroid-sparing and disease control 3

Monitoring Strategy

Initial Phase (First 6 Months)

Monitor every 3 months 1, 4:

• Disease activity using CLASI (Cutaneous Lupus Disease Area and Severity Index) 3, 1
• CBC, ESR, CRP, serum albumin, creatinine 1, 4
• Urinalysis and urine protein/creatinine ratio 1, 4
• Anti-dsDNA, C3, C4 levels 1, 4

Maintenance Phase (After 6 Months)

Monitor every 6-12 months if disease stable 1, 4:

• Same laboratory parameters as initial phase
• Reassess for new systemic manifestations

Hydroxychloroquine Monitoring

Baseline and annual ophthalmologic examination 3:

• Risk of retinopathy increases with doses >6.5 mg/kg/day, duration >5 years, age >60 years, renal insufficiency 3

Critical Pitfalls to Avoid

• Do not rely solely on ANA testing, as it can be positive in other conditions and may be negative in some lupus patients 1, 4
• Do not delay skin biopsy—clinical diagnosis alone is insufficient 3, 1
• Be aware that hydroxychloroquine can exacerbate psoriasis if the patient develops psoriatic features given the family history 6, 7
• Do not miss anti-Ro/SSA and anti-La/SSB testing, as these are critical for SCLE diagnosis and have implications for future pregnancy (neonatal lupus, congenital heart block risk) 3, 1
• Avoid mycophenolate mofetil, cyclophosphamide, and methotrexate if pregnancy is planned 1
• Do not assume isolated cutaneous disease—always screen for systemic involvement given the strong family history 1, 2