Lupus Erythematosus (LE) - Complete Overview

What Is It?

Classification

• Acute CLE (ACLE) - occurs during active, flaring SLE
• Subacute CLE (SCLE) - intermediate severity and SLE association
• Chronic CLE (CCLE) - often occurs without SLE or with mild, smoldering disease

1. Acute Cutaneous Lupus Erythematosus (ACLE)

• Nasolabial folds are characteristically spared (distinguishes from rosacea and seborrheic dermatitis)
• Forehead, chin, and V-area of neck can also be involved
• Generalized ACLE presents as a widespread morbilliform eruption over extensor surfaces of arms and hands, characteristically sparing the knuckles
• An extreme form can simulate toxic epidermal necrolysis (TEN), but differs by involving sun-exposed skin with more insidious onset
• Precipitated/exacerbated by UV light
• Lesions are ephemeral - lasting hours to weeks
• No atrophic scarring unless complicated by secondary infection

2. Subacute Cutaneous Lupus Erythematosus (SCLE)

• Hyperkeratotic papulosquamous plaques, or
• Annular/polycyclic plaques
• Strongly associated with anti-Ro/SS-A antibodies
• Photodistributed but not strictly photodistributed - annular or papulosquamous thin plaques
• Intermediate risk of underlying SLE
• SCLE can also be drug-induced (common triggers: hydrochlorothiazide, diltiazem, terbinafine, proton pump inhibitors, TNF inhibitors, ACE inhibitors, statins, paclitaxel, doxycycline)

3. Chronic Cutaneous Lupus Erythematosus (CCLE)

Discoid LE (DLE) - the most common CCLE subtype

1. Active lesion: erythematous, indurated papule or plaque with adherent scale and follicular plugging
2. Progression: central atrophy, hypopigmentation; hyperpigmented peripheral rim
3. Burnt-out lesion: atrophic, pale scar

• Face (cheeks, nose, ears - especially conchal bowl and outer ear canal)
• Scalp: involved in 60% of DLE patients; irreversible scarring alopecia in one-third
• Localized DLE = lesions only on head/neck
• Generalized DLE = lesions above AND below the neck (higher risk of SLE, more treatment-resistant)

Other CCLE Variants

• Inflammatory lesions of the lower dermis and subcutis
• Firm nodules 1-3 cm on head, proximal arms, chest, breasts, buttocks, thighs
• Overlying skin becomes attached, creating deep saucerized depressions
• Breast involvement can mimic carcinoma (lupus mastitis)
• ~50% of LE panniculitis patients have evidence of SLE

• Purple-red patches, papules, plaques on toes, fingers, and face precipitated by cold/damp conditions
• Associated with anti-Ro/SS-A antibodies and Raynaud phenomenon
• ~20% later develop SLE

4. Systemic Lupus Erythematosus (SLE)

ACR Diagnostic Criteria (11 criteria; 4+ required)

Systemic Manifestations

• Musculoskeletal: non-erosive arthritis/arthralgias (most common)
• Renal: lupus nephritis (major cause of morbidity); WHO/ISN classes I-VI
• Neuropsychiatric: seizures, psychosis, cognitive dysfunction, stroke
• Hematologic: hemolytic anemia, leukopenia, lymphopenia, thrombocytopenia
• Cardiovascular: pericarditis, Libman-Sacks endocarditis, accelerated atherosclerosis
• Pulmonary: pleuritis, pneumonitis, pulmonary hypertension
• Serositis: pleuritis/pericarditis

Hair Loss in SLE

• Lupus hairs: short miniaturized hairs on the anterior scalp
• Diffuse non-scarring alopecia (telogen effluvium) during systemic flares - reversible
• Scarring alopecia from DLE involvement - irreversible

5. Drug-Induced Lupus (DIL)

• Occurs in older patients; affects men as frequently as women
• Symptoms generally mild: fever, myalgias/arthralgias, serositis
• Antibody pattern: positive ANA (homogeneous), antihistone antibodies; negative anti-dsDNA, normal complement
• Resolves on drug withdrawal

Serology / Antibodies

Histopathology

• Hyperkeratosis, follicular plugging
• Interface (vacuolar) dermatitis at the dermoepidermal junction (DEJ)
• Basement membrane zone thickening
• Pigment incontinence
• Dermal mucin deposition
• Perivascular and periadnexal lymphoid infiltrates

Treatment

Sun Protection (All CLE Subtypes)

• Strict UV avoidance, broad-spectrum SPF ≥50 sunscreen, protective clothing
• Vitamin D supplementation (as patients avoid sun)

Topical/Intralesional

• Potent topical corticosteroids (first line for limited disease)
• Intralesional corticosteroids (for resistant DLE plaques)
• Topical calcineurin inhibitors (limited benefit)
• Topical tazarotene (generally disappointing)

Systemic - First Line

• Hydroxychloroquine (HCQ): cornerstone of SLE and CLE management; antimalarial, reduces flares and organ damage; requires ophthalmologic monitoring
• Chloroquine: alternative antimalarial

Systemic - Second Line (CLE and SLE)

• Corticosteroids: for acute flares; long-term use limited by side effects
• Methotrexate
• Mycophenolate mofetil (especially lupus nephritis)
• Azathioprine
• Dapsone
• Thalidomide (highly effective for refractory CLE; strict teratogenicity precautions)
• Retinoids (acitretin)
• Sulfasalazine

Biologics

• Belimumab (anti-BLyS/BAFF): FDA-approved for SLE; reduces flares
• Anifrolumab (anti-IFN-α receptor): FDA-approved for SLE, particularly effective for skin disease
• Rituximab (anti-CD20): used off-label for refractory SLE and lupus nephritis
• Voclosporin + mycophenolate: approved for lupus nephritis

Emerging (2024-2026)

Prognosis

• Most patients with localized DLE have a good prognosis; only ~5% develop SLE
• Generalized DLE carries higher risk of SLE progression
• SLE prognosis has improved dramatically; 10-year survival is now >90% in many cohorts
• Main causes of morbidity and mortality: lupus nephritis, cardiovascular disease (accelerated atherosclerosis), infections from immunosuppression, and neuropsychiatric lupus
• Flares are unpredictable; maintaining low disease activity (LLDAS) significantly reduces damage accrual