Cutaneous Lupus Erythematosus (CLE)

Epidemiology

• Systemic lupus erythematosus (SLE) is common with significant morbidity and mortality.

• Risk is strongly influenced by sex, with women outnumbering men by at least 9:1.

• SLE primarily affects women during childbearing years, indicating a likely hormonal influence. Rare in prepubertal children.

• Patients with only cutaneous lesions have a lower female-to-male ratio (approximately 3:1), but female predominance remains.

• Ethnicity is a significant risk factor, nearly as influential as sex.

• In the US, SLE prevalence is fourfold higher in African-American women than in White women (211 vs. 64 per 100,000).

• African-Americans tend to develop SLE at an earlier age and exhibit a higher mortality rate.

• Likely similar prevalence in Asian, Latin American, and European White populations compared to US Whites.

• Approximately as many patients have cutaneous lupus erythematosus (LE) without concurrent SLE as those with SLE.

Pathogenesis

• Pathogenesis of cutaneous lupus erythematosus (LE) involves genetic and environmental factors.

• Environmental triggers include ultraviolet radiation (UVR), medications, cigarette smoking, and possibly viruses.

• Interaction of these factors causes an inflammatory cascade with cytokine and chemokine responses.

• A lichenoid tissue reaction is common, characterized by epidermal basal cell damage and lymphocytic infiltrate in the dermis.

• Various genes involved in B and T cell function and immune responses may contribute to disease variability.

• UVB and UVA are linked to exacerbation of cutaneous LE, with UVB being a more potent inducer of skin changes.

• UVR leads to apoptosis, translocation of antigens, and increased production of autoantibodies and type I interferons (IFNs).

• Proinflammatory cytokines such as TNF, IL-1, and IFN-γ are induced by UVR.

• Dendritic cells contribute to T cell activation and can prime CD8+ T cells against keratinocyte-derived antigens.

• An increase in plasmacytoid dendritic cells and cytotoxic T cells is noted within cutaneous LE lesions.

• UV radiation initiates a complex immune response, leading to a positive feedback loop and exacerbation of skin lesions.

Variants and subtypes

• Acute Cutaneous LE (ACLE):

• Subacute Cutaneous LE (SCLE):

• Chronic Cutaneous LE (CCLE):

  • Includes several subtypes

  • Discoid LE (DLE):

    • Lesions are frequently long-lived and intensely inflammatory.

    • Can lead to permanent disfiguring scars.

    • Active lesions are typically thicker and firmer than surrounding skin due to pronounced superficial and deep dermal inflammatory infiltrate.

    • Features include follicular plugging, scarring alopecia, and dyspigmentation with hypopigmentation centrally and hyperpigmentation peripherally.

      • sometimes can also present as vitiligo-like depigmentation

    • Can rarely also present as hypertrophic (verrucous) DLE - characterised by thick scaling overlying the discoid lesion or occurring at the periphery of the discoid lesion - mainly on extensor surfaces of the arms but face and trunk may also be involved

      
      
      

    • Adnexa are prominently involved.

    • May be localized or widespread.

    • Rarely, squamous cell carcinoma can develop in a long-standing discoid lesion.

  

  • Lupus Erythematosus Tumidus (LET):

    • Typically presents with firm, erythematous plaques that lack scale or follicular plugging.

    • Intense perivascular and periadnexal inflammatory infiltrate within the dermis with mucin deposition.

  • Lupus Panniculitis (Lupus Profundus):

    • A variant of lupus panniculitis, with inflammation in the subcutaneous fat.

  • Chilblain Lupus:

    • Presents with red or dusky purple lesions on the fingers, toes, elbows, knees and lower legs.

• Other Variants:

  • Neonatal LE: Can present with annular erythematous plaques on the forehead and scalp

  • Rowell Syndrome: Erythema multiforme-like lesions.

  • Bullous LE: Blistering eruption similar to toxic epidermal necrolysis or erythema multiforme major.

• Diagnostic Criteria:

  • The Systemic Lupus International Collaborating Clinics (SLICC) classification system requires at least 4 of 17 criteria (including at least one clinical and one immunologic criterion), or biopsy-proven lupus nephritis with ANAs or anti-dsDNA antibodies.

  • The American College of Rheumatology (EULAR/ACR) classification criteria require a score of 10 or more with entry criteria fulfilled.

Diagnosis and Investigations

• Histopathology:

  • SCLE: More obvious interface dermatitis and perivascular inflammation.

  • DLE: Focal interface dermatitis and dense perivascular lymphoid infiltrates throughout the dermis.

    • May also show periadnexal inflammation, follicular plugging and scarring.

  • LET: Prominent dermal mucin deposition and dermal perivascular and periadnexal lymphocytic infiltrates with a lack of epidermal change.

  • Lupus Panniculitis: Prominent inflammatory infiltrates within the lobules of the subcutaneous fat.

    • May have overlying changes of DLE.

  • Some of the more distinctive histologic features include basal cell damage, lymphohistiocytic inflammatory infiltrates admixed with CD123+ plasmacytoid dendritic cells, and periadnexal inflammation (primarily in discoid lesions), follicular plugging, and scarring.

• Direct Immunofluorescence (DIF):

  • Granular deposits of IgM at the dermal-epidermal junction are characteristic of lupus.

  • Antibody deposits at the dermal-epidermal junction are the most characteristic immunohistologic finding in lesions of cutaneous lupus.

• Laboratory Tests:

  • ANA with profile (anti-dsDNA, -Sm).

  • Urinalysis.

  • CBC with differential and platelet count.

  • Chemistries (BUN, creatinine).

  • ESR, CRP.

  • Complement levels (C3, C4).

  • Antiphospholipid antibodies, PT/PTT.

  • Autoantibodies to dsDNA and Sm are relatively specific for SLE.

  • Autoantibodies to SSA/Ro, SSB/La, U1RNP, histones, and ssDNA are common in patients.

• A diagnostic algorithm for cutaneous lupus involves initial evaluation, a lesional biopsy for histology and DIF, and systemic evaluation if needed.

Differential Diagnosis

• ACLE/Malar Rash: Rosacea, Seborrheic dermatitis, Sunburn, Drug-induced photosensitivity, Dermatomyositis.

• SCLE: Psoriasis, Dermatophytosis, Polymorphous light eruption, Granuloma annulare, Pemphigus foliaceus.

• Discoid Lesions: Lichen planus, Sarcoidosis, Tinea faciei, Follicular mucinosis, Non-melanoma skin cancer.

• Lupus Tumidus: Urticarial vasculitis

• Chilblain Lupus: Pernio, acrocyanosis

Treatment/Management

• General measures include avoiding photosensitizing medications and smoking cessation.

• Sun protection is essential, including sunscreens, protective clothing and sun avoidance.

• Careful attention should be given to vitamin D and calcium intake.

• Topical corticosteroids, antimalarials and dapsone may also be considered.

Complications

• Scarring and disfigurement.

• Dyspigmentation.

• Scarring alopecia.

• Progression to systemic lupus erythematosus (SLE).

• Rarely, squamous cell carcinoma in long-standing discoid lesions.

Additional Notes

• The three major types of cutaneous LE (ACLE, SCLE, CCLE) are not mutually exclusive.

• Drug-induced lupus should be considered in the differential diagnosis of CLE.

• Cutaneous lesions of LE can indicate internal disease.

Let me know if you need further clarification or have any additional questions.