Aetiopathogenesis

There is increasing evidence that the induction of autoantibodies against self-proteins derives from an impaired ability to clear dying (apoptotic) cells. Both genetic (human leucocyte antigen (HLA)) and environmental (toxins, drugs, UV radiation, viruses) factors have been implicated in disease pathogenesis.

Pathology

Discoid lesions show epidermal atrophy, hyperkeratosis and basal layer degeneration. Subacute lesions show greater atrophy but the other features are less evident. Systemic lesions have similar changes with dermal oedema and fibrinoid change, inflammatory infiltrate and sometimes vasculitis. Direct immunofluorescence shows a ‘lupus band’ at the dermoepidermal junction in lesional systemic and discoid LE, but this is also found in approximately 20% of healthy individuals on sun-exposed skin.

Clinical presentation

Systemic lupus erythematosus (99% ANA, 50% Ro, 60% dsDNA positive)

Skin signs are found in 80%. The facial butterfly eruption (Fig. 1) is characteristic, but photosensitivity, discoid lesions, diffuse alopecia, mouth lesions and vasculitis also occur. Multisystem involvement with serological or haematological abnormalities must be demonstrated to diagnose systemic LE (Table 1). The female : male ratio is 8 : 1.

Fig. 1 Systemic LE.

The typical butterfly eruption is present on the face.

Table 1 Organ involvement in systemic LE

Organ	Involvement
Skin	Photosensitivity, facial rash, vasculitis, hair loss, Raynaud’s phenomenon
Blood	Anaemia, thrombocytopenia
Joints	Arthritis, tenosynovitis, calcification
Kidney	Glomerulonephritis, nephrotic syndrome
Heart	Pericarditis, endocarditis, hypertension
Central nervous system	Psychosis, infarction, neuropathy
Lungs	Pneumonitis, effusion

Discoid lupus erythematosus (35% ANA, 2% Ro, <5% dsDNA positive)

One or more round or oval plaques appear on the face, scalp or hands (Fig. 2). The lesions are well demarcated, red, atrophic, scaly and show keratin plugs in dilated follicles. Scarring leaves alopecia on the scalp and hypopigmentation in those with a pigmented skin. Remission occurs in over 50%. Internal involvement is not a feature, and only 6% develop systemic LE. Women outnumber men by 2 : 1.

Fig. 2 Discoid LE on the forehead.

Differential diagnosis

Discoid LE can usually be differentiated from other facial rashes such as rosacea, seborrhoeic dermatitis, lupus vulgaris or psoriasis. A biopsy should be performed. The photosensitive eruption of systemic LE may resemble polymorphic light eruption, dermatomyositis or drug reaction.

Management

Immunological screening is important for diagnosis and to predict complications (e.g. anti-Ro and congenital heart block; anticardiolipin and thromboses and spontaneous abortions; antihistone and drug-induced lupus). Discoid LE usually responds to potent or very potent topical steroids which, in this instance, can be applied to the face. Sunblock creams are essential. Widespread disease may need systemic therapy with hydroxychloroquine; the small risk of retinopathy demands monitoring of visual acuity. The treatment of systemic LE depends on the type of involvement. Sunscreens reduce photosensitivity but, if there is internal disease, antimalarials and systemic steroids are required, often with immunosuppressive agents.

Aetiopathogenesis

Dysregulated transforming growth factor (TGF)-β-induced fibroblast overproduction of collagen is central to tissue fibrosis. However, endothelial cell damage by T cells and macrophages may also be important.

Clinical presentation

Raynaud’s phenomenon (p. 70) is frequently the presenting sign. The skin of the fingers, forearms and lower legs becomes tight, waxy and stiff, and the finger pulps are resorbed (Fig. 3). Facial signs include perioral furrowing, telangiectasia (p. 115) and restricted mouth opening. Internal organ involvement, e.g. renal failure, may prove fatal (Table 2). Women are affected more than men (F : M ratio 4 : 1). Some 90–95% of cases are ANA positive. The diagnosis is rarely in doubt in diffuse disease, although chronic graft-versus-host disease shows similar changes. Limited cutaneous systemic sclerosis has a better prognosis and usually affects only the neck, forearms and lower legs. A subset described as CREST syndrome, is confined to Calcinosis, Raynaud’s phenomenon, oEsophageal dysmotility, Sclerodactyly and Telangiectasia.

Fig. 3 Systemic sclerosis.

Note the tightly bound waxy skin on the fingers (sclerodactyly) and resorption of the finger pulps.

Table 2 Organ involvement in systemic sclerosis

Management

Treatment is mainly supportive. Nifedipine can help Raynaud’s phenomenon. Hypertension is controlled. Systemic steroids, penicillamine and immune-suppressives have been used with little benefit. Photophoresis may be tried (p. 115). Renal crises (associated with antiRNA polymerase I and III antibodies) should be managed aggressively with angiotensin converting enzyme (ACE) inhibitors.

Clinical presentation

In dermatomyositis/polymyositis, skin changes or muscle weakness may predominate. The typical eruption is a lilac–blue discoloration around the eyelids, cheeks and forehead, often with oedema. Bluish–red papules or streaks on the dorsal aspects of the hands (Fig. 5), elbows and knees are seen, sometimes with pigmentation and nail fold telangiectasia. Photosensitivity is common. There is no strong association with autoantibodies, although anti-Jo-1 antibodies predict lung involvement. An association with malignancy exists in patients over 40 years, 40% of whom have an underlying tumour, usually of the lung, breast or stomach. A childhood variant mainly affects the muscles and causes calcinosis and contractures.

Fig. 5 Dermatomyositis.

A streaky eruption is seen on the dorsal aspects of the hands.

Management

Investigations must define the degree of myositis and, in adults, exclude the possibility of underlying neoplasia. Treatment is with systemic steroids in moderate to high dosage, often with an immunosuppressive such as azathioprine or methotrexate. Immunoglobulin infusion and possibly photophoresis (p. 115) may help.