Cutaneous lupus erythematosus (CLE) encompasses a spectrum of lupus-specific skin diseases that may occur with or without systemic lupus erythematosus (SLE). Major subtypes include acute CLE (ACLE), subacute CLE (SCLE), and chronic CLE (CCLE; e.g., discoid lupus erythematosus, DLE). Pathogenesis involves genetic susceptibility, type I interferon signaling, autoantibodies, UV-driven keratinocyte injury, and dysregulated innate/adaptive immunity. Diagnosis integrates clinical morphology, histopathology, direct immunofluorescence, and serology. Management prioritizes photoprotection, smoking cessation, trigger avoidance, topical anti-inflammatories, and stepwise systemic therapy (antimalarials as cornerstone), with emerging roles for biologics targeting interferon pathways.
Epidemiology
- CLE may present alone or with SLE; risk of systemic disease varies by subtype (highest in ACLE).
- SCLE: commonly middle-aged women; strongly photosensitive.
- DLE: most common CCLE; can scar and cause dyspigmentation and alopecia; higher prevalence in people of African ancestry.
Pathophysiology
- UV radiation induces keratinocyte apoptosis, nucleic acid release, and plasmacytoid dendritic cell activation with type I interferon production.
- Autoantibodies (anti-Ro/SSA, anti-La/SSB more typical of SCLE; ANA frequently positive in ACLE) contribute to cutaneous and systemic disease.
- Smoking reduces response to antimalarials and worsens CLE severity.
Clinical Subtypes
- ACLE: malar “butterfly” rash sparing nasolabial folds; generalized morbilliform/edematous photosensitive eruption; strong SLE association.
- SCLE: annular or papulosquamous, non-scarring, highly photosensitive lesions on V of chest, shoulders, extensor arms; anti-Ro positivity common; drug-induced variants (e.g., PPIs, thiazides, terbinafine, TNF inhibitors, ICIs).
- CCLE:
- Discoid LE (DLE): indurated erythematous plaques with adherent scale, follicular plugging; atrophy, scarring, dyspigmentation; scalp involvement may cause scarring alopecia.
- Lupus panniculitis (lupus profundus), chilblain lupus.
- Nonspecific LE skin findings: livedo, vasculitic lesions, urticaria, Raynaud phenomenon.
Differential Diagnosis
- Rosacea, seborrheic dermatitis (for facial erythema); psoriasis/tinea (for annular plaques); lichen planopilaris and central centrifugal cicatricial alopecia (for scarring alopecia); dermatomyositis (for photosensitive eruptions).
Diagnostic Workup
- Skin biopsy with histology (interface dermatitis) and direct immunofluorescence (granular IgG/IgM/C3 at dermoepidermal junction).
- Serology: ANA, anti-dsDNA, anti-Sm, anti-Ro/SSA, anti-La/SSB, complements; CBC, urinalysis, creatinine to assess systemic involvement.
- Assess photosensitivity history and medication list for drug-induced SCLE.
Management
- Universal measures
- Rigorous photoprotection: broad-spectrum SPF 50+, UV-protective clothing, hats; behavioral sun avoidance.
- Smoking cessation.
- Gentle skin care; camouflage for dyspigmentation if desired.
- Topical therapy
- Topical corticosteroids (potency matched to site; limit high-potency on face).
- Topical calcineurin inhibitors (tacrolimus/pimecrolimus) for face/intertriginous sites or maintenance.
- Intralesional triamcinolone for hypertrophic DLE plaques.
- Systemic therapy
- Antimalarials: hydroxychloroquine (HCQ) first-line; consider chloroquine or quinacrine adjunct in refractory cases.
- Dosing HCQ ≤5 mg/kg/day (real body weight) to limit retinal toxicity; baseline and annual ophthalmologic screening per guidelines after 5 years or earlier if risk factors.
- Refractory disease: add or switch to methotrexate, mycophenolate mofetil, azathioprine, dapsone (especially for bullous LE), thalidomide/lenalidomide (teratogenic, neuropathy risk), or short courses of systemic corticosteroids for flares.
- Biologics and targeted agents:
- Anifrolumab (type I IFN receptor blocker) approved for SLE; some benefit in cutaneous activity; consider in SLE with significant cutaneous disease.
- Belimumab (anti-BAFF) improves mucocutaneous SLE activity in many.
- JAK inhibitors and other interferon-pathway inhibitors under study.
- Special sites
- Scalp DLE: early aggressive treatment to prevent scarring alopecia; intralesional steroids, HCQ, adjunct immunosuppressants.
- Chilblain lupus: cold avoidance, vasodilators (e.g., nifedipine), antimalarials.
Prognosis and Monitoring
- DLE can cause permanent scarring and dyspigmentation; early control prevents damage.
- Risk of progression to SLE is higher in ACLE/SCLE than in localized DLE; monitor systemic symptoms/labs periodically.
- Monitor for antimalarial retinal toxicity and systemic agent adverse effects.
References (recent guidelines and key reviews)
- EULAR/ACR guidance on SLE with cutaneous involvement, 2023–2024.
- European/North American CLE management guidelines and consensus statements, 2022–2024.
- Reviews on type I interferon targeting in CLE/SLE, 2022–2024.
- Ophthalmology guidelines on hydroxychloroquine screening, 2023 update.