LUPUS: A GP Guide to Diagnosis
The Skin and Lupus
Introduction
The French dermatologist, Pierre Cazanave, was the first to describe a patient with a facial eruption characterised by erythema, erosion and follicular plugging which he termed lupus erythematosus (LE). He observed that the lesions were more common in those working outdoors. The initial patient was in good health which Cazanave felt differentiated this condition from lupus vulgaris (cutaneous tuberculosis) although, subsequently, the spectrum of systemic manifestations associated with LE was characterised.
Today, it is recognised that skin involvement is one of the most common manifestations of lupus and is frequently the presenting complaint. A wide variety of skin lesions can be seen, some of which are highly characteristic of the disease and can help in establishing the diagnosis. As shown elsewhere in this guide, lupus presents a broad spectrum of disease ranging, for example, from chronic, localised cutaneous disease to systemic lupus. Rather analogous to leprosy, expression of lupus reflects the response of the immune system, apparently with cell-mediated mechanisms predominating at the localised cutaneous end of the spectrum and striking serological features at the systemic end including potentially pathogenic autoantibodies which, possibly, have a direct role in the pathogenesis of tissue injury including certain skin lesions. Therefore, in addition to being of importance to clinicians, skin disease has been a fruitful subject of research into the pathogenetic mechanisms operating in lupus.
Skin manifestations
The wide variety of skin manifestations in lupus is illustrated in Table 1 which makes a distinction between lesions which clinically and histologically are characteristic of lupus and other forms of skin involvement that can be seen in lupus, usually in the context of systemic lupus, but can also be seen in other conditions. The most characteristic feature of typical lupus involvement of the skin is damage to the basal cell layer of the epidermis, sometimes termed "liquefaction degeneration" due primarily to induction of an active process in the keratinocytes of programmed cell death known as apoptosis. Keratinocytes are normally very resistant to apoptosis and, apart from lupus, are rarely seen in skin disease other than dermatomyositis and lichen planus. A mononuclear infiltrate, initially perivascular, is another common feature and predominantly involves lymphocytes with a T helper phenotype. Additional changes include epidermal atrophy, hyperkeratosis with follicular plugging and atrophy of the adnexal structures. As summarised in Table 1, lupus-specific skin lesions are often categorised into chronic, subacute, or acute based on their clinical features and, in particular, on their ability to produce scarring and atrophy. These are most florid in chronic discoid lesions and least so in the acute erythema of acute cutaneous lupus erythematosus.
Skin tests
Direct immunofluorescence of lesional skin characteristically shows granular deposition of immunoglobulin and complement components at the dermo-epidermal junction in both chronic and acute lesions. In addition, deposition of immunoglobulin and complement also occurs in non-involved skin, particularly from light exposed regions such as the extensor surface of the forearm, in systemic lupus but not in chronic cutaneous lupus. This is the "lupus band test" which has rather fallen out of favour as a diagnostic test for lupus since serological tests (see 'Testing for Lupus') generally provide sufficient support for the clinical diagnosis. However, the presence of granular deposits of lgG with or without complement components has a high degree of specificity for lupus.
Types of skin lupus
- Chronic cutaneous lupus is most often manifested as the discoid LE skin lesion (DLE). It is usually a well-demarcated lesion which begins as an erythematous papule or plaque and, as it progresses, develops increasing hyperkeratosis (scale) and scarring (Figure 1). Typically, it occurs in light exposed areas of the head and neck. As the lesion ages, there is dilatation of the follicular openings which become filled with keratinous debris (follicular plugging). Involvement of the scalp leads to scarring alopecia (Figure 2).
In most cases of DLE the disease is confined to the skin and the ANA test is negative or transiently positive, usually in low titre. Approximately 5-10% of patients, however, develop systemic disease either at onset or later in the course. The risk of systemic disease is increased in certain morphological variants of DLE (Table 1), if multiple DLE lesions extend onto the trunk and extremities or if there are striking serological abnormalities with the presence of autoantibodies particularly characteristic of lupus. Lupus profundus describes indurated lesions due to inflammation of the deep dermis and subcutaneous fat, occurring mainly on the head, face and upper arms, often beneath typical lesions of DLE. - Papular LE is a less emphasised form of cutaneous lupus which also occurs predominantly in light exposed regions. It is characterised histologically by a dense T lymphocyte infiltrate with relatively minor epidermal changes. Sometimes it is difficult to distinguish this from Jessner's lesions. Warty or verrucous LE is another variant in which there is very prominent hyperkeratosis.
- Subacute cutaneous lupus (SCLE) is a term used to describe a subset of patients with lupus with a very characteristic pattern of disease expression and serological findings. Affected patients are almost always Caucasian and cutaneous manifestations often dominate the clinical picture. Characteristics of SCLE are summarised in Table 2. The eruption is usually widespread, predominantly affecting light exposed regions. Often it shows a typical morphology, either annular (Figure 3) or papulosquamous, and heals with only minimal scarring or atrophy.
Acute cutaneous lesions are associated with systemic disease and are frequently transient, episodic and reflect disease activity. The classical "butterfly" rash (Figure 4) is characterised by erythema and oedema of the malar skin. This occurs in about a third of patients with lupus.
Photosensitivity
Photosensitivity is common in lupus and a prominent feature of the disease in approximately 40% of lupus patients. There is a particular association with the presence of autoantibodies to a ribonucleoprotein auto-antigen, termed Ro. Anti-Ro antibodies are not necessary for photosensitivity but are related to the degree of epidermal damage. Irradiation with UVB, which is highly reactive and produces important changes in DNA and other potential auto-antigens, is a key factor but UVA is also commonly involved. This means that some patients react to sunlight even behind window glass which filters out UVB.
Cutaneous lesions
Table 1 lists a variety of cutaneous lesions which are seen in lupus but are not LE-specific. These manifestations tend to be a feature of active, systemic disease and include purpura, similar to that seen in Henoch Schönlein purpura, due to small vessel vasculitis. Livedo reticularis is a mottled red or bluish discoloration of the skin with a netlike pattern. It results from stagnation of blood in dilated superficial capillaries and venules and is associated with the presence of antiphospholipid antibodies and an increased risk of recurrent vascular thromboses and miscarriages.
Treatment
Table 3 summarises an approach to treating lupus skin disease. The goals of management are to improve the appearance of the skin and to prevent scarring and telangiectasia. The emphasis is on symptomatic treatment and only very rarely is it necessary to resort to high-dose systemic steroids or immunosuppressive agents for skin disease per se. Experience has shown that the great majority of cases, even with severe skin involvement, can be managed with a combination of effective protection against UV irradiation, the judicious use of topical corticosteroids and antimalarial agents.
Sunscreens represent a cornerstone of therapy and in some patients with SCLE is all the treatment that is needed. Preparations with a high sun-protective factor are required (SPF 15 or higher) and need to be used regularly. The SPF value applies only to UVB and often total sun blocks containing zinc oxide or titanium dioxide are needed to protect against UVA. Topical corticosteroids can be very effective for patients with chronic or subacute cutaneous lupus. Potent preparations are often needed to begin with but excessive use of potent topical steroids can induce atrophy and follicular inflammation and should be avoided especially on the face. Stubborn lesions may require polythene occlusion and for small chronic lesions, especially on the extremities, flurandrenolone tape can be cut to size. Rarely, intralesional triamcinolone (10mg/mI) is necessary, particularly for lesions on the ears and nose. Injections should be directed as superficially as possible, but even so there is still a risk of atrophic scarring. When severe inflammation has settled, it is better to maintain improvement with medium or low potency preparations. If topical therapy fails, or the lesions are too extensive, antimalarials such as hydroxychloroquine can be very effective. Ocular toxicity with this drug has been greatly exaggerated and is very unusual if the dose does not exceed 6mg/kg body weight/day. New monitoring guidelines avoiding repeated and unnecessary trips to the ophthalmologists are currently being drawn up. As summarised in Table 3, a number of medications, or combinations of these, have proved to be effective as second line agents in refractory cases.
Further help
When scarring or telangiectasia has occurred, especially on the face, cosmetic camouflage can be vitally important to the patient. The Red Cross provides a service to teach patients and can be accessed via a dermatologist. Disfiguring lesions may respond well to excision and grafting or even dermabrasion. CO2 laser therapy is an alternative destructive technique.
 Figure 1. DLE |
 Figure 2. Scarring alopecia |
 Figure 3. SCLE, annular |
 Figure 4. "Butterfly" rash |
Table 1 - Skin lesions associated with lupus erythematosus
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Table 2 - Features of subacute cutaneous lupus erythematosus (SCLE) Caucasian female |
Table 3 - A suggested algorithm for treating cutaneous lupus
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Prof. Peter Maddison
Consultant Rheumatologist
Ysbyty Gwynedd
Penrhosgarnedd
Bangor
Gwynedd, LL57 2PW