# Lupus Erythematosus: Cutaneous Spectrum

## Overview

Cutaneous lupus erythematosus (CLE) encompasses a spectrum of skin-specific manifestations that may or may not be associated with systemic lupus erythematosus (SLE). The Gilliam classification organizes CLE into **acute, subacute, and chronic** forms. Approximately 70 to 80 percent of SLE patients develop skin involvement during their disease course, and 5 to 25 percent of patients with isolated CLE progress to SLE over time, with risk varying by subtype.

## Acute Cutaneous Lupus Erythematosus (ACLE)

### Malar (Butterfly) Rash

The malar rash is an erythematous, edematous rash over both cheeks and the bridge of the nose. It characteristically **spares the nasolabial folds**, which distinguishes it from seborrheic dermatitis and rosacea, which involve the folds. It is photosensitive, often triggered or exacerbated by UV exposure, and transient, correlating with disease flares. It may be macular, papular, or edematous and can be misdiagnosed as sunburn.

### Generalized ACLE

Generalized ACLE presents as a widespread photodistributed morbilliform or exanthematous eruption. It may involve the dorsal hands while sparing the knuckles -- a distinction from dermatomyositis, which characteristically involves the knuckles. **Bullous lupus** produces subepidermal blisters with a neutrophilic infiltrate and antibodies to type VII collagen.

### Oral Ulceration

Oral ulcers, often painless, occur on the hard palate (classically) or buccal mucosa and are part of the ACR/EULAR classification criteria for SLE.

### Association with Systemic Disease

ACLE is almost always associated with active SLE. Assessment should include evaluation for renal, hematologic, joint, and serosal involvement, with testing for ANA, anti-dsDNA (specific for SLE and correlating with disease activity), and complement levels (C3, C4).

<image>Clinical photograph of the classic malar butterfly rash of acute cutaneous lupus erythematosus showing erythema over both malar eminences and nasal bridge with sparing of the nasolabial folds</image>

## Subacute Cutaneous Lupus Erythematosus (SCLE)

### Clinical Features

SCLE presents in two morphologic patterns. The **annular/polycyclic** pattern shows arcuate or ring-shaped plaques with central clearing and a raised, scaly border. The **papulosquamous (psoriasiform)** pattern produces widespread scaly papules and plaques that can mimic psoriasis. Both are photodistributed, favoring the upper trunk, lateral neck, and extensor arms. Unlike DLE, SCLE heals without scarring, though dyspigmentation may persist. Photosensitivity is a prominent feature.

### Serologic Associations

**Anti-Ro/SSA antibodies** are positive in 70 to 80 percent of cases, and **anti-La/SSB antibodies** in 30 to 50 percent. ANA is positive in 60 to 80 percent, while anti-dsDNA is usually negative and complement levels are usually normal. Approximately 50 percent of patients meet ACR criteria for SLE, but systemic disease is typically mild (arthritis, serositis), and severe nephritis is uncommon.

### Drug-Induced SCLE

Drug-induced SCLE is an important cause that may account for up to one-third of cases. Common culprits include hydrochlorothiazide, terbinafine, calcium channel blockers, ACE inhibitors, proton pump inhibitors, and anti-TNF agents. Anti-Ro/SSA antibodies may become positive. The condition usually resolves with drug discontinuation over weeks to months.

### Neonatal Lupus

Neonatal lupus results from transplacental passage of maternal anti-Ro/SSA and/or anti-La/SSB antibodies. Skin findings include annular erythematous plaques on the face with a periorbital "raccoon eyes" pattern that self-resolve by 6 to 8 months as maternal antibodies clear. The most serious complication is **congenital heart block**, with a 1 to 2 percent risk per pregnancy in anti-Ro-positive mothers, increasing to 20 percent if a prior child was affected. Congenital heart block is irreversible and may require a pacemaker. Hepatobiliary and hematologic involvement may occur but is usually transient.

## Chronic Cutaneous Lupus Erythematosus

### Discoid Lupus Erythematosus (DLE)

DLE is the most common form of chronic CLE. It presents as well-defined, indurated, erythematous plaques with adherent scale and follicular plugging. The **"carpet tack" sign** is produced when the scale is peeled off and shows follicular spikes on the undersurface (keratotic plugs within dilated follicles). Lesions progress to atrophy, scarring, and dyspigmentation (central depigmentation with peripheral hyperpigmentation). Scalp involvement causes scarring alopecia. **Localized DLE** (head and neck only) is the most common form and carries a lower risk of SLE progression (approximately 5 percent). **Generalized DLE** (above and below the neck) has a higher risk of SLE progression (approximately 20 percent). The conchal bowl of the ear is a classic location. Overall, only 5 to 10 percent of DLE patients develop SLE.

### Histopathology of DLE

DLE shows **interface dermatitis** (vacuolar type) with basal layer damage, **follicular plugging** with keratin-filled dilated follicles, a **thickened basement membrane zone** (PAS-positive), and a **superficial and deep perivascular and periadnexal lymphocytic infiltrate**. **Dermal mucin deposition** (Alcian blue-positive) is present. Late lesions show dermal fibrosis and loss of adnexal structures. DIF (lupus band test) reveals granular IgG, IgM, IgA, and/or C3 at the BMZ, positive in approximately 90 percent of lesional DLE skin. The test is positive in sun-protected non-lesional skin in SLE but not in isolated CLE.

### Lupus Profundus (Lupus Panniculitis)

Lupus profundus involves subcutaneous fat and may occur with or without overlying DLE changes. It presents as firm, deep subcutaneous nodules or plaques on the proximal extremities, face, trunk, and buttocks that heal with **lipoatrophy** (depressed, atrophic areas). Histopathology shows lobular panniculitis with lymphocytic infiltrate, hyaline fat necrosis, lymphoid follicles, and calcification. Patients are often ANA-positive, and approximately 50 percent have concurrent SLE.

### Chilblain Lupus

Chilblain lupus produces tender, violaceous papules and plaques on the fingers, toes, heels, and ears, precipitated by cold exposure. It resembles chilblains (pernio) but is persistent and associated with lupus serologies. Histology shows interface dermatitis with perivascular and periadnexal lymphocytic infiltrate. It may be associated with familial chilblain lupus (TREX1 mutations; Aicardi-Goutieres syndrome).

### Tumid Lupus (Lymphocytic Infiltrate of Jessner Overlap)

Tumid lupus presents as urticarial-like, succulent, erythematous plaques without surface change (no scale, no follicular plugging). It is extremely photosensitive. Histology shows a dense superficial and deep perivascular and periadnexal lymphocytic infiltrate with prominent dermal mucin but **no interface change**, distinguishing it from other forms of CLE. DIF is typically negative. The prognosis is excellent with very low risk of SLE, and it responds well to antimalarials and photoprotection. Whether tumid lupus is truly CLE or a separate entity remains debated.

<image>Clinical photographs showing the spectrum of chronic cutaneous lupus: discoid lupus (scarring plaque with follicular plugging and dyspigmentation), lupus profundus (deep subcutaneous nodule with overlying atrophy), and tumid lupus (succulent urticarial-like plaque without surface change)</image>

## Lupus-Specific vs. Lupus-Nonspecific Skin Findings

### Lupus-Specific (Histology Shows Interface Dermatitis)

Lupus-specific findings include ACLE (malar rash, generalized), SCLE (annular, papulosquamous), DLE, lupus profundus, chilblain lupus, and tumid lupus.

### Lupus-Nonspecific (Reflect Systemic Disease Activity)

Lupus-nonspecific findings include vascular manifestations (Raynaud phenomenon, livedo reticularis, thrombophlebitis, periungual telangiectasias), nonscarring alopecia (diffuse "lupus hair" with short broken hairs at the frontal hairline), oral and nasal ulcers, urticarial vasculitis (hypocomplementemic), and calcinosis cutis (rare in SLE; more common in dermatomyositis and scleroderma).

| CLE Subtype | Morphology | Scarring | SLE Risk | Key Serology |
|-------------|-----------|---------|---------|-------------|
| ACLE (malar) | Erythema sparing nasolabial folds | No | ~100% (nearly always SLE) | ANA, anti-dsDNA |
| SCLE | Annular/polycyclic or papulosquamous | No (dyspigmentation) | ~50% (mild) | Anti-Ro/SSA (70–80%) |
| DLE (localized) | Scarring plaques, follicular plugging | Yes | ~5% | ANA (30–50%) |
| DLE (generalized) | Scarring plaques above + below neck | Yes | ~20% | ANA |
| Lupus profundus | Deep subcutaneous nodules, lipoatrophy | Yes (depressed) | ~50% | ANA |
| Chilblain lupus | Violaceous papules on fingers/toes (cold) | Variable | Variable | ANA, anti-Ro |
| Tumid lupus | Succulent plaques, no surface change | No | Very low | Often negative |

## Systemic Workup

### When to Suspect SLE in a CLE Patient

SLE should be suspected with generalized DLE, SCLE, or ACLE presentations, positive anti-dsDNA antibodies, low complement levels (C3, C4), cytopenias, proteinuria, serositis, arthritis, or multiple lupus-specific and nonspecific skin findings.

### Laboratory Panel

**ANA** is positive in more than 95 percent of SLE, 60 to 80 percent of SCLE, and 30 to 50 percent of DLE. **Anti-dsDNA** is specific for SLE and correlates with disease activity and nephritis. **Anti-Ro/SSA and anti-La/SSB** are associated with SCLE, neonatal lupus, and Sjogren overlap. **Anti-Smith** is the most specific antibody for SLE but has low sensitivity (approximately 25 percent). **Anti-RNP** suggests mixed connective tissue disease overlap. Complement levels (C3, C4, CH50) are low in active SLE. The panel should also include CBC, CMP, urinalysis with microscopy, and antiphospholipid antibodies (anticardiolipin, lupus anticoagulant, anti-beta2-glycoprotein I).

## Treatment

### Topical Therapy

**Sunscreen and photoprotection** are the cornerstone for all CLE subtypes, with broad-spectrum SPF 50 or higher providing UVA and UVB protection alongside protective clothing. **Topical corticosteroids** of mid-to-high potency for the body and low potency for the face are first-line for limited DLE and SCLE. **Topical calcineurin inhibitors** (tacrolimus 0.1 percent, pimecrolimus) are useful for facial and periorbital lesions to avoid corticosteroid atrophy. **Intralesional triamcinolone** at 3 to 10 mg/mL is used for hypertrophic DLE plaques.

### Systemic Therapy

**Hydroxychloroquine** is the first-line systemic therapy for all CLE subtypes, dosed at 5 mg/kg real body weight per day or less (per revised AAO guidelines to reduce retinal toxicity risk). It inhibits TLR7/9 signaling, reduces type I interferon, and inhibits antigen presentation, with onset of action at 2 to 3 months. Retinal toxicity screening requires a baseline eye exam and then annual examination after 5 years (or sooner with risk factors). Beyond skin benefit, HCQ reduces SLE flare risk, thrombosis risk, and mortality in SLE. **Chloroquine** is an alternative antimalarial with higher retinal toxicity risk. **Quinacrine** can be added to HCQ (but not combined with chloroquine due to additive retinal risk) at 100 mg daily. It does not cause retinal toxicity but produces yellow skin discoloration and carries risk of hemolytic anemia in G6PD deficiency.

Additional systemic options include **methotrexate** (10 to 25 mg weekly, effective for refractory DLE), **mycophenolate mofetil** (for refractory CLE or concurrent systemic disease), **dapsone** (particularly useful for bullous lupus), and **thalidomide/lenalidomide** (highly effective for refractory CLE but teratogenic with neuropathy risk). **Belimumab** (anti-BLyS/BAFF) is FDA-approved for SLE with some benefit in CLE. **Anifrolumab** (anti-IFNAR1) is FDA-approved for SLE with significant skin response (BICLA) and emerging data for refractory CLE. **Rituximab** is used for refractory cases, and **JAK inhibitors** have emerging data for refractory CLE.

<image>Treatment algorithm for cutaneous lupus erythematosus showing stepwise approach from photoprotection and topical therapy through antimalarials to second-line and third-line systemic agents based on disease severity and subtype</image>

## Clinical Pearls

The malar rash of ACLE spares the nasolabial folds, which distinguishes it from the butterfly-distribution rash of seborrheic dermatitis and rosacea, which involve the folds. The "carpet tack sign" of DLE is a highly characteristic finding -- adherent scale with keratotic follicular plugs visible on the undersurface. Anti-Ro/SSA-positive women of childbearing age must be counseled about neonatal lupus risk, particularly congenital heart block (1 to 2 percent per pregnancy); serial fetal echocardiography starting at 16 weeks is recommended. Drug-induced SCLE is increasingly recognized and may account for one-third of cases; always review the medication list when a patient presents with new SCLE. Hydroxychloroquine is the single most important systemic therapy for CLE; retinal screening guidelines have shifted to 5 mg/kg/day or less dosing to minimize long-term retinal toxicity risk.

## References
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