Rare cutaneous lupus erythematosus (ORPHA:535)
Rare cutaneous lupus erythematosus (CLE) is an autoimmune disease that denotes a heterogeneous spectrum of clinical manifestations affecting the skin and can be divided into 4 categories: acute CLE (ACLE); subacute CLE (SCLE); chronic CLE (CCLE; the most diverse form); and intermittent CLE (ICLE). CLE can either occur alone or associated with systemic lupus erythematosus (SLE).
Epidemiology
Incidence is estimated to be 1/25,000 in USA, and it affects predominantly women. CLE occurs more in patients with a family history of lupus or other autoimmune diseases.
Clinical description
CLE usually appears between 20-70 years but it has also been described in children (0-18 years). There are 4 main types of CLE: ACLE which presents as prominent non scarring-rash on cheeks and nose (''butterfly rash'', localized form) or more rarely, by a widespread eruption of red, symmetric, maculopapular lesions with accentuation of the UV-exposed areas (''maculopapular lupus rash'', generalized form); SCLE which presents with red, raised, scaly rash on sun-exposed areas of the body (annular/polycyclic form or papulosquamous form); CCLE which presents either as red to purple, well demarcated, scaly rash on the scalp, face, ears, and other sun-exposed areas (discoid LE; DLE), as frostbites (Chilblain LE; ChLE), or as painful subcutaneous nodules (LE profundus; LEP); and ICLE or LE tumidus (LET) presenting as red, swollen, urticaria-like plaques. Cutaneous manifestations appear in 72-85% of SLE patients.
Etiology
Etiology is still elusive but it is thought to be multifactorial, involving a genetic predisposition. The disease is then triggered by UV radiation, infections (cytomegalovirus, hepatitis C, Epstein-Barr virus), hormones (estrogens, prolactin), and exposure to drugs and chemicals, which initiate an inflammatory process. Cytokines and chemokines are involved in propagating inflammatory responses, suppressing tolerogenic components of the immune system. Autoreactive B cells are intrinsic to lupus pathogenesis.
Diagnostic methods
Diagnosis is based on family history, clinical and laboratory findings (detection of antibodies anti-nuclear antigens (ANA)), histological examinations of skin biopsy which show superficial and deep perivascular and periadnexal lymphocytic infiltrate, interface-dermatitis and thickening of the basement membrane as a late consequence. The epidermis is atrophic with necrotic keratinocytes. Diagnosis is confirmed by direct immunofluorescence (detects deposits of immunoglobulins and complement component C3 and IgG at the dermo epidermal junction) and photoprovocation.
Differential diagnosis
Differential diagnosis depends on subtypes and includes: ACLE: dermatomyositis, erythema multiforme, drug-induced photosensitivity, dermatitis (atopic, contact), exanthema (viral, drug-induced), rosacea, seborrheic dermatitis. SCLE: classic mycosis fungoides, pityriasis rubra pilaris, vitiligo, tinea corporis, erythema anulare centrifugum, granuloma annulare, erythema gyratum repens, psoriasis. DLE: sarcoidosis, tuberculosis, leprosy, classic mycosis fungoides, cutaneous pseudolymphoma, granuloma faciale, nummular eczema, psoriasis, squamous and basal cell carcinoma, rosacea, lichen planus. ChLE: frostbites. LEP: subcutaneous panniculitis-like T-cell lymphoma, erythema nodosum. LET: Jessner lymphocytic infiltration of the skin, polymorphous light eruption, reticular erythematosus mucinosis.
Management and treatment
Treatment goals are to improve skin appearance, limit scarring, and prevent new skin lesions. This includes use of UV light protection; topical therapy (corticosteroids and/or calcineurin inhibitors); and antimalarial therapy that may improve CLE and delay progression to SLE. For patients refractory to antimalarials, immunosupressive and immunomodulatory therapy (systemic corticosteroids, methotrexate, oral retinoids) may be proposed.
Prognosis
CLE is a chronic skin disease, with significant impact on the patients' quotidian. Risk of SCLE and CCLE patients developing SLE is <10%. ACLE is associated with SLE.

                            Last update: 
                            June 2015


                            - Expert reviewer(s): 
                            Pr Marzia CAPRONI  - Dr Carla CARDINALI  - Pr Paolo FABBRI  - Dr Barbara GIOMI