What are the key differences in diagnosis and treatment between cutaneous lupus (lupus 1) and systemic lupus erythematosus (lupus 2)?

Differentiating Cutaneous Lupus from Systemic Lupus Erythematosus

The key distinction is that cutaneous lupus erythematosus (CLE) affects only the skin, while systemic lupus erythematosus (SLE) involves multiple organ systems with potential for life-threatening complications—this differentiation requires skin biopsy, comprehensive serological testing, and systematic evaluation for internal organ involvement. 1, 2

Clinical Presentation Differences

Cutaneous Lupus (CLE) Features

• Skin-limited disease with three main subtypes: acute cutaneous LE (ACLE), subacute cutaneous LE (SCLE), and chronic cutaneous LE (CCLE), each with distinct morphology and prognosis 3, 2
• Chronic cutaneous LE is the most common subtype and typically remains localized to the skin, though 25% may eventually develop systemic features 3
• Subacute cutaneous LE represents a distinct subset with photosensitive, annular or papulosquamous lesions, typically without systemic involvement 2, 4
• Lesions are frequently triggered or aggravated by UV light exposure and typically appear in sun-exposed areas 3, 4

Systemic Lupus Erythematosus (SLE) Features

• Multi-organ involvement including kidneys (lupus nephritis), central nervous system (neuropsychiatric lupus), hematologic abnormalities, and cardiovascular complications 1
• Five-fold increased mortality risk compared to general population, primarily from infections, cardiovascular disease, and malignancies 1, 5
• Acute cutaneous lupus (malar/butterfly rash) is strongly associated with active systemic disease 6, 7
• Renal involvement occurs frequently with risk of doubling serum creatinine in 14-18% at 10 years 1

Diagnostic Approach

Essential Skin Evaluation

• Skin biopsy with histological analysis is mandatory for all suspected lupus cases, as many conditions mimic lupus erythematosus 1, 6
• Evaluation by an experienced dermatologist is recommended due to diagnostic complexity 1, 6
• Follow-up repeat biopsy should be performed if clinical morphology changes or treatment fails 1, 6
• Consider using the Cutaneous Lupus Disease Area and Severity Index (CLASI) for monitoring patients with predominant skin manifestations 1, 6

Laboratory Differentiation

• Complete immunological panel: ANA, anti-dsDNA, anti-Ro/SSA, anti-La/SSB, anti-RNP, antiphospholipid antibodies, complement levels (C3, C4) 1, 6
• Anti-dsDNA and low complement are more specific for SLE and correlate with disease activity, particularly renal involvement 1
• Anti-Ro/SSA antibodies are commonly positive in subacute cutaneous lupus but can occur without systemic disease 1, 2
• Complete blood count to detect cytopenias (anemia, thrombocytopenia, leukopenia, lymphopenia) which suggest systemic involvement 1, 6

Organ System Assessment for SLE

• Renal evaluation: serum creatinine, urinalysis, urine protein/creatinine ratio, and blood pressure monitoring 1, 6
• Neuropsychiatric assessment: clinical history for headache, mood disorders, seizures, cognitive impairment, and cerebrovascular symptoms 1
• Cardiovascular screening: assess for traditional risk factors, as SLE patients have markedly increased atherosclerosis risk 1, 5
• C-reactive protein (CRP): typically normal or minimally elevated in SLE unless superimposed infection is present (>50 mg/L suggests infection) 1

Treatment Differences

Cutaneous Lupus Treatment

• First-line: Topical glucocorticoids for localized lesions plus hydroxychloroquine (not exceeding 5 mg/kg actual body weight) 6, 8
• Photoprotection is essential to prevent flares triggered by UV exposure 1, 6
• Second-line for refractory disease: Methotrexate (preferred first choice due to cost and availability), mycophenolate mofetil, or azathioprine 5, 6
• Short-term systemic glucocorticoids may be added for widespread or severe cutaneous disease 6, 4
• Ophthalmological screening required at baseline, after 5 years, then yearly for hydroxychloroquine retinal toxicity 6, 8

Systemic Lupus Erythematosus Treatment

• Foundation therapy for all SLE patients: Hydroxychloroquine is mandatory unless contraindicated, as it reduces disease activity, prevents flares, and improves survival 5, 8
• Glucocorticoids: Low-dose (≤7.5 mg/day prednisone) when needed, with goal to minimize and withdraw to prevent organ damage 5
• Immunosuppressive therapy for organ-threatening disease: Mycophenolate mofetil or cyclophosphamide for lupus nephritis, with kidney biopsy essential before initiating therapy 5
• Biologic therapies: Belimumab should be added for inadequate response to standard therapy (hydroxychloroquine + glucocorticoids ± immunosuppressants) 5, 9
• Adjunct therapies: Low-dose aspirin for patients with antiphospholipid antibodies or cardiovascular risk factors; calcium and vitamin D for those on long-term glucocorticoids 1, 5

Critical Pitfalls to Avoid

• Never assume skin-limited disease without comprehensive evaluation—25% of chronic cutaneous lupus patients develop systemic features 3
• Do not delay kidney biopsy in suspected lupus nephritis—treatment decisions depend on histological classification and early aggressive therapy prevents irreversible damage 5
• Avoid prolonged high-dose glucocorticoids (>7.5 mg/day)—they increase irreversible organ damage risk in SLE patients 5
• Never withhold hydroxychloroquine without clear contraindication—non-adherence is associated with higher flare rates and mortality in SLE 5
• Do not ignore comorbidity screening in SLE—infections, cardiovascular disease, hypertension, diabetes, osteoporosis, and malignancies (non-Hodgkin lymphoma, lung cancer, hepatobiliary cancer) are common causes of morbidity and mortality 1, 5