Cutaneous lupus erythematosus
What is lupus erythematosus?
Lupus erythematosus (LE) is an autoimmune connective tissue disorder that can affect one or several organs. Circulating autoantibodies and immune complexes are due to loss of normal immune tolerance and are pathogenic. Clinical features of LE are highly variable. LE nearly always affects the skin to some degree.
What is cutaneous lupus erythematosus?
Cutaneous LE comprises several chronic and relapsing LE-specific and LE-nonspecific inflammatory conditions. There can be some overlap.
- LE-specific cutaneous LE has been classified as acute, subacute, intermittent and chronic. Lesions may be localised or generalised. In LE-specific cutaneous LE, lesions are often induced by exposure to sunlight.
- LE-nonspecific cutaneous LE may relate to systemic LE or other autoimmune disease.
Who gets cutaneous lupus erythematosus?
Cutaneous LE most often affects young to middle-aged adult women (aged 20–50 years) but children, the elderly, and males may be affected.
Important predisposing factors for cutaneous LE include:
- Female gender
- Genes: ≥ 25 risk loci have been identified and there are HLA associations
- Skin of colour
What causes lupus erythematosus?
LE is classified as autoimmune, as it is associated with pathogenic antibodies directed against components of cell nuclei in various tissues. UVB irradiation causes keratinocyte necrosis, immune system activation and antibody formation.
Factors that aggravate LE include:
There are various types of cutaneous LE, classified as acute, subacute, intermittent and chronic cutaneous LE. The revised Cutaneous Lupus Erythematosus Disease Area and Severity Index (RCLASI) can be used to assess disease activity and damage.
Acute cutaneous LE affects at least 50% of patients with systemic lupus erythematosus (SLE). Many are sick, young, fair-skinned females.
Specific features of acute cutaneous LE may include:
- Malar eruption or ‘butterfly rash’ (erythema and oedema of cheeks, sparing nasolabial folds) lasting hours to days
- Erythematous papular rash on arms, sometimes forming large plaques and spreading widely
- Photosensitivity (a rash on all recently sun-exposed skin)
- Cheilitis and mouth ulcers
- Blisters (bullous LE) and erosions
About 15% of patients with cutaneous LE have subacute cutaneous LE. One-third of cases are due to previous drug exposure.
Features of subacute cutaneous LE include:
- Precipitation or aggravation by sun exposure
- Non-itchy psoriasis-like papulosquamous rash on the upper back, chest and upper arms
- Annular or polycyclic plaques that clear centrally
- Absence of scarring on resolution
Up to 50% of patients with subacute cutaneous LE may also have a mild form of SLE, resulting in arthralgia (painful joints) or arthritis (joint disease) and low blood counts. Severe SLE is rare in patients with subacute cutaneous LE.
Drug-induced subacute cutaneous LE
More than 100 drugs have been associated with the onset of subacute cutaneous LE. They include:
- Tumour necrosis factor-alpha (TNF-α) inhibitors (biologics)
- Proton-pump inhibitors
Neonatal cutaneous lupus erythematosus
Neonatal cutaneous LE arises within 2 months of birth to mothers with known or subclinical subacute cutaneous LE.
Features of neonatal cutaneous LE may include:
- An annular erythematous rash, which slowly resolves over 6 months
- Rash is most often periorbital
- Blood count abnormalities: haemolytic anaemia, leukopenia, thrombocytopenia
- Hepatobiliary disease
- Persistent congenital heart block
A paediatrician should assess all babies born to mothers with subacute LE (or carrying anti-Ro/La) at birth. Mortality in babies with heart block is up to 20%, despite pacemaker implantation.
Intermittent cutaneous LE, more often known as lupus tumidus, is a dermal form of lupus.
Features of lupus tumidus include:
- Affects sun-exposed sites such as cheeks, neck, anterior chest
- Erythematous, urticaria-like patches and plaques with a smooth surface
- Round or annular shapes
- Clears during the winter months
Lupus tumidus is similar to Jessner lymphocytic infiltrate, in which diagnostic criteria for lupus are absent.
Chronic cutaneous LE accounts for 80% of presentations with cutaneous LE. About 25% of patients with chronic cutaneous LE also have systemic LE.
Discoid LE is the most common form of chronic cutaneous LE. It is more prevalent in patients with skin of colour, who are at greater risk of postinflammatory hyperpigmentation and hypertrophic scarring.
- Discoid LE is confined to the skin above the neck in most patients, but can spread below the neck to affect upper back, V of neck, forearms and backs of hands.
- Scalp, ears, cheeks, nose are the most common sites.
- Most patients have photosensitivity.
- New lesions are destructive, erythematous scaly plaques with follicular prominence.
- Scalp discoid LE presents as red, scaly and bald plaques.
- Slow healing leads to postinflammatory pigmentation and white scars.
- Hair growth may partially or completely recover with treatment. Cicatricial (scarring) alopecia can be permanent.
Hypertrophic LE is a variant of discoid LE in which there are thickened and warty plaques resembling viral warts or skin cancers. Hypertophic LE can occur on palms and/or soles. This is also called palmoplantar LE, and is a form of acquired keratoderma.
Mucosal LE presents with plaques, ulcers and scaling. Mucosal lesions may predispose to squamous cell carcinoma.
- Lips and inside the mouth
- Lower eyelid with madarosis (loss of eyelashes)
- Rarely, vulva/penis
Lupus profundus affects subcutaneous tissue. Other names for lupus profundus are lupus panniculitis and subcutaneous LE.
- Lupus profundus may develop at any age, including childhood.
- It may involve face, buttocks, limbs or anywhere.
- Firm deep and tender nodules persist for some months.
- Lesions resolve leaving dented, atrophic scars (lipoatrophy).
LE nonspecific cutaneous features are most often associated with SLE. They include:
- Diffuse hair thinning
- Raynaud phenomenon: abnormal blanching of fingers and toes in response to cold weather, followed by numbness and slow rewarming by the fingers which go blue then red.
- Lupus chilblains: painful erythematous nodules on fingers and toes during cooler months.
- Dilated periungual telangiectasia, ragged cuticles and nail dystrophy
- Digital ulcers and pitting scars
- Papular and nodular mucinosis on cheeks, upper chest, upper arms or back.
- Vasculitis: small vessel vasculitis, urticarial vasculitis and less often, vasculitis of medium and large vessels
- Livedo reticularis and antiphospholipid syndrome
Complications of cutaneous lupus erythematosus
Chronic cutaneous LE causes facial deformity and scarring. Active and burned-out disease can lead to social isolation and depression.
How is cutaneous lupus erythematosus diagnosed?
- SLE is associated with high titre antinuclear antibodies
- About 70% of patients with subacute LE have antiRo/La extractable nuclear antigens (ENA)
- The severity of LE may be reflected in the titre of ANA and/or ENA.
- ANA and ENA are often negative in a patient with chronic cutaneous LE.
- Mild anaemia or leukopenia may be present in patients that do not have SLE
Skin biopsy may be diagnostic, showing a lichenoid tissue reaction and features specific to the kind of cutaneous LE. Direct immunofluorescence tests may show positive antibody deposition along the basement membrane (lupus band test).
Diagnostic features on biopsy are more likely to be found in LE-specific skin lesions than in LE-nonspecific cutaneous LE.
How can cutaneous lupus erythematosus be prevented?
- Carefully protect all exposed skin from sun exposure with covering clothing and SPF50+ broad-spectrum sunscreen (see sun protection)
- Smoking cessation is essential – it is best to avoid nicotine replacement as nicotine in any form may exacerbate cutaneous LE
- If subacute LE is drug-induced, stop the responsible medication.
What is the treatment for cutaneous lupus erythematosus?
The aim of treatment for cutaneous LE is to prevent flares, improve appearance and to prevent scarring.
- Potent or ultrapotent topical steroids are applied to chronic discoid LE plaques
- Calcineurin inhibitors, pimecrolimus cream or tacrolimus ointment can be used instead of topical steroids
- Intralesional corticosteroid can be injected into small lesions resistant to topical therapy
- Topical retinoids, calcipotriol and imiquimod have also been reported to be helpful in a few patients.
- Cosmetic camouflage may be used to disguise unsightly plaques.
Treatment for cutaneous and systemic LE may include:
- Antimalarials especially hydroxychloroquine
- Immune modulators such as methotrexate, mycophenolate, dapsone, ciclosporin
- Retinoids, ie acitretin, isotretinoin
- Systemic corticosteroids
- If sun protection is strict, vitamin D supplementation.
Severe disease may require more aggressive treatment:
- Intravenous immunoglobulin
- Monoclonal antibodies targeting T and B cells and cytokines: rituximab
- Phototherapy using UVA1 may be useful to treat skin lesions of cutaneous LE
- Photodynamic therapy (PDT) has been reported to clear chronic cutaneous LE
- Vascular laser can reduce telangiectasia
- Surgery may improve appearance of disfiguring scars
What is the outlook for cutaneous lupus erythematosus?
The prognosis for cutaneous LE is variable.
The skin involvement in SLE tends to mirror systemic involvement.
Drug-induced SCLE clears within a few weeks of withdrawal of the responsible drug.
Untreated chronic cutaneous LE tends to persist, but severity is lessened by strict sun protection and avoidance of nicotine.