Lupus erythematosus

• Cazenave and Schedel, 1833
• Kaposi, 1872
• Leloir, 1890

Lupus erythematosus, LE, erythematodes, butterfly lichen, Leloir's disease

Chronic autoimmune disease of the skin and/or internal organs, mediated by loss of immune tolerance, autoantibody production, and interferon-driven inflammation.

• Peak onset: 20th to 40th year of life
• Female : male = approx. 9:1 (in SLE)
• Cutaneous lupus erythematosus (CLE) is 2–3× more common than SLE
• Higher prevalence in individuals with skin of colour
• Worldwide SLE prevalence: 20–150/100,000

Systemic lupus erythematodes (SLE)

Cutaneous lupus erythematosus (CLE)

• Acute cutaneous lupus erythematosus (ACLE)
  • Localised ACLE
  • Generalised ACLE
• Subacute cutaneous lupus erythematosus (SCLE)
  • Annular SCLE
  • Papulosquamous SCLE
• Chronic cutaneous lupus erythematosus (CCLE)
  • Discoid lupus erythematosus (DLE)
    • Localised DLE
    • Generalised DLE
  • Mucosal DLE (oral/conjunctival)
  • Lupus erythematosus verrucosus (hypertrophicus)
  • Lupus erythematosus profundus (panniculitis)
• Intermittent CLE
  • Lupus erythematosus tumidus (LET)

Special forms:

• Rowell's syndrome
• Chilblain lupus
• Drug-induced lupus erythematosus
   

• Genetic predisposition (HLA-DR2/DR3, IRF5, STAT4, TYK2, PTPN22)
• Breakdown of immune tolerance
• Pathogenic autoantibodies: ANA, anti-dsDNA, anti-Sm, anti-Ro/SSA, anti-La/SSB
• Type I interferon axis activation (IFN-α, IFNAR1 signaling)
• Dysregulated NETosis, oxidative stress
• Environmental triggers: UV radiation, smoking, viral infections, drugs (e.g. hydralazine, procainamide)
   

• ACLE: malar (butterfly) erythema, widespread photosensitive rash
• SCLE: annular or psoriasiform plaques, symmetrical on sun-exposed areas
• DLE: erythematous plaques with scale, follicular plugging, scarring and pigment changes
• LET: smooth, erythematous, oedematous plaques without surface changes
• Mucosal LE: oral ulcers, rarely conjunctival involvement
• Nailfold signs: periungual telangiectasias, nail dystrophy
   

• Classification of SLE should follow the 2019 EULAR/ACR criteria, which require a positive ANA (≥1:80 on HEp-2 cells) as the entry criterion, followed by additive weighted clinical and immunological criteria. A total score of ≥10 points confirms the diagnosis of SLE.
• ANA testing is mandatory because it is the required entry criterion in the 2019 classification. ANA positivity reflects underlying B-cell activation and serves as a highly sensitive (but non-specific) marker of systemic autoimmunity. In CLE, ANA can also support the diagnosis and help identify patients at risk for systemic progression.
• Clinical diagnosis supported by laboratory and histology
• Serology: ANA, anti-dsDNA, anti-Sm, anti-Ro/SSA, anti-La/SSB
• Complement (C3/C4), ESR/CRP, urinalysis
• Skin biopsy: interface dermatitis, lymphocytic infiltrates, basement membrane thickening
• Direct immunofluorescence (DIF): linear IgG, C3 at dermoepidermal junction (Lupus band test)
• CLASI (Cutaneous Lupus Erythematosus Disease Area and Severity Index) for scoring
   

• ACLE: face (malar), upper trunk, arms
• SCLE: upper chest, upper back, shoulders, arms
• DLE: scalp, face, ears; can cause scarring alopecia
• LET: face, neck, upper torso
• Lupus profundus: subcutis of upper arms, thighs, buttocks
• Chilblain LE: acral areas during cold exposure
   

• Fluctuating course with environmental (e.g. UV light) or hormonal triggers
• Family history of autoimmune disease common

• Interface dermatitis with basal vacuolization
• Follicular plugging, hyperkeratosis
• Dermal mucin deposition
• Periadnexal and perivascular lymphocytic infiltrates
• DIF: positive lupus band test (IgG/C3 along basement membrane)
   

• DLE: scarring, dyspigmentation, secondary infection
• Risk of squamous cell carcinoma in long-standing DLE lesions
• SCLE: ~15–20% transition to systemic lupus
• Systemic complications in SLE: lupus nephritis, CNS involvement, cytopenias, serositis
   

• Strict photoprotection (broad-spectrum sunscreen ≥ SPF 50)
• Smoking cessation
• Screening for and managing comorbid autoimmune diseases
• Vitamin D supplementation as needed
   

• Variable depending on subtype
• LET: good prognosis, no scarring
• DLE: potential for permanent scarring
• SCLE: relapsing, potential SLE progression
• SLE: prognosis determined by organ involvement (e.g. renal, CNS)
   

Topical therapy:

• Potent/very potent corticosteroids (mometasone, clobetasol)
• Calcineurin inhibitors (tacrolimus, pimecrolimus)
• Topical JAK inhibitors (off-label; case reports)

Systemic therapy:

• Antimalarials (first-line): Hydroxychloroquine 200–400 mg/day
• Systemic corticosteroids for flares (e.g. prednisolone)
• Immunosuppressants for refractory CLE: methotrexate, mycophenolate mofetil, azathioprine
• Biologics:
  • Anifrolumab (Saphnelo®): anti-IFNAR1 monoclonal antibody; Swissmedic-approved since 2023 for moderate to severe SLE
  • Belimumab (Benlysta®): anti-BLyS monoclonal antibody; approved for SLE including lupus nephritis
• Retinoids for hypertrophic LE
   

1. Fanouriakis A et al. 2023 EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis. 2023;82:15–27.
2. Kuhn A et al. Updated classification and pathogenesis of cutaneous lupus erythematosus. J Eur Acad Dermatol Venereol. 2022;36(8):1214–1224.
3. Stannard J et al. Anifrolumab in moderate to severe cutaneous lupus erythematosus: a phase 3 trial. N Engl J Med. 2023;388(9):841–851.
4. Durosinmi-Etti F et al. Cutaneous lupus erythematosus: diagnostic and therapeutic updates. JAMA Dermatol. 2024;160(2):125–134.
5. Swissmedic. Saphnelo® Zulassung für systemischen Lupus erythematodes. Swissmedic Bulletin. 2023.