This site is intended for healthcare professionals as a useful source of information on the diagnosis, treatment and support of patients with lupus and related connective tissue diseases.

Introduction

The development of some sort of a rash is one of the commonest features of lupus and is often the first sign of the condition. Frequently, lupus of the skin is the only manifestation and can persist for decades. There are times when recognising the rash and typical histology can clinch the diagnosis. While only rarely life-threatening, involvement of the skin by lupus makes a major contribution to the poor health and psychological trauma frequently felt by people with the condition.

The French physician, Pierre Cazanave, published a clear description of chronic cutaneous lupus in 1833 based on the observations of his professor and mentor, Laurent Biett. Later, in 1851, Cazenave coined the term "lupus erythematosus". It is generally thought that Ferdinand von Hebra, another distinguished 19th century physician, was the first to liken the distribution of the lupus rash on the cheeks and the bridge of the nose to that of a butterfly. It was his son-in-law, Moriz Kaposi, who recognised that some patients with lupus erythematosus could become ill and develop systemic complaints. The butterfly rash is still recognised as the classic sign of lupus but actually only occurs in the minority of patients.

A wide variety of skin lesions can be seen, some of which are highly characteristic of the disease. As shown elsewhere in this guide, lupus presents a broad spectrum of disease. Thus, the spectrum of skin involvement ranges from chronic, localised cutaneous disease to lesions accompanying 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 certain skin lesions.

Skin manifestations

More than two thirds of those with SLE develop a rash. However, for every patient with SLE there are two or three where lupus remains confined to the skin.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 are not so specific for lupus per se, but may be seen in SLE.

The most characteristic histological feature of typical lupus involvement of the skin is an interface dermatitis with inflammation and damage to the basal cell layer of the epidermis, sometimes termed "liquefaction degeneration", due primarily to induction of programmed cell death of keratinocytes (apoptosis). Keratinocytes are normally very resistant to apoptosis and, apart from lupus, this is rarely seen in skin diseases other than dermatomyositis and lichen planus. Additional changes include epidermal atrophy, hyperkeratosis with follicular plugging and atrophy of the adnexal structures. As summarised in Table 1, lupusspecific 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. This is 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 dermoepidermal 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 * 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.

* See chapter - Testing for Lupus

Types of skin lupus

Chronic cutaneous lupus (CCLE) 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.

Lupus tumidus (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, notably the presence of autoantibodies to the nuclear ribonucleoproteins, Ro and La. Affected patients are almost always Caucasian and cutaneous manifestations often dominate the clinical picture. Typically, the rash occurs in a light-exposed distribution and has an annular, polycyclic appearance (Figure 3) and heals with only minimal scarring or atrophy.

Acute cutaneous lupus (ACLE) 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.

Other causes of butterfly rash

A butterfly rash is not always due to lupus and certain common skin conditions can mimic lupus. Rashes commonly mistaken for lupus include rosacea, seborrhoeic dermatitis and, occasionally, allergic reactions of the skin due, for example, to cosmetics.

Photosensitivity

Photosensitivity is common in lupus and a prominent feature of the disease in approximately 40% of lupus patients. Often the rash worsens after sun exposure, but sometimes involvement of UV light is suggested by the distribution of the rash in typical light-exposed areas – the face, back of neck, ears, upper chest, backs of hands and fingers. SCLE is the most photosensitive form of lupus and patients often react to both UVB and UVA. In SLE, sun exposure can aggravate systemic symptoms as well as the rash. People with a light skin tend to be most affected. Sometimes, even visible light aggravates lupus. Occasionally, patients are affected by fluorescent tubes in the home or at work or even photocopiers, which predominantly radiate visible light.

Other 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.

Hair involvement in lupus

Generalised hair loss (alopecia) can accompany a flare of lupus. This is usually not permanent, the hair regrowing once the lupus has been controlled. Some patients with lupus complain of increased fragility of the hair, particularly at the front and at the sides. Hair loss can occur in patches if discoid lupus affects the scalp and is sufficient to damage the hair follicles. Hair loss of this type is usually permanent.

Treatment

Table 4 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. Treatment of the skin in lupus often needs a multidisciplinary approach. Involvement of a dermatologist with experience of treating lupus is invaluable, together with input from other health professionals such as a specialist nurse to help with non-medical aspects of management. The emphasis is on self-management. Adequate education about the condition itself and the goals of treatment are essential.

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. Patients should also avoid lengthy exposure to direct sunlight and wear a hat and long sleeves to provide a barrier. 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, with a star rating of at least four, are needed to protect against UVA.

Table 2 lists some of the topical treatments for skin involvement. 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.

There is anecdotal evidence that a variety of other agents used topically can be effective in cases not responding satisfactorily to local corticosteroids. None as yet have been subjected formal randomised controlled studies. An example is the topical use of the macrolide immunosuppressants, tacrolimas and picrolimas.

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. Smoking reduces efficacy of antimalarials and in those who are still unresponsive it is worth trying combination antimalarials, for example hydroxychloroquine and mepacrine.

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. They are generally used in the context of severe acute systemic lupus but have been used for severe refractory skin disease per se. For example, thalidomide can be effective in difficult cases. However, tolerability is a problem even with small doses, as well as being highly terratogenetic. Sensory neuropathy is a particular problem and often limits long term use.

Scarring of the skin

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. Discoid lupus erythematosus
Figure 2. Scarring alopecia
Figure 3. The typical annular rash of SCLE
Figure 4. "Butterfly" rash

Table 1 - Skin lesions associated with lupus erythematosus

CLINICAL VARIANT

A. Lesions with typical LE histology

1. Chronic cutaneous LE (CCLE)
   a) Classical discoid LE (DLE)
     i. Localised DLE
     ii. Generalised DLE
   b) Hypertrophic DLE
   c) Papular LE
   d) Chilblain LE (perniotic lupus)
   e) Lupus profundus
   f) Mucosal DLE

2. Subacute cutaneous LE (SCLE)
   a) Annular SCLE
   b) Papulosquamous SCLE

3. Acute cutaneous LE (ACLE)
   a) Localised ACLE ("Butterfly" rash)
   b) Generalised maculopapular ACLE
SYSTEMIC FEATURES






Uncommon
More common
Uncommon
Uncommon
More common
More common
Uncommon
B. Non-specific skin lesions

1. Cutaneous vascular disease
  a) Vasculitis
   i. Small vessel (purpura; urticarial)
   ii. PAN-like
  b) Livedo reticularis
2. Non-scarring alopecia
3. Panniculitis
4. Bullous lesions





Usual
Usual
Thrombotic tendency
Usual
Usual
Usual

Table 2 - Local therapy for lupus skin disease

Corticosteroids
Tacrolimas
Picrolimas
Tretinoin
Calcipotriol

Table 3 - Drugs used for refractory lupus skin disease

Thalidomide
Dapsone
Acitretin
Auranofin
Clofazimine
Pulse IV methylprednisolone
High dose IV immunoglobulin
Immunosuppressive agents
    Incl: azathioprine
      methotrexate
      ciclosporin A
      mycophenolate
      rituximab
(CCLE; SCLE)
(DLE; SCLE; vasculitis; bullous LE)
(CCLE, especially hypertrophic LE)
(CCLE)
(CCLE)
(ACLE; extensive photosensitive eruption)
(Refractory skin disease)
(Refractory skin disease)

Table 4 - A suggested algorithm for treating cutaneous lupus

Supportive

Mild, localised
Severe, widespread
Refractory
regular sun blocking agent
cosmetic camouflage
topical corticosteroids
topical corticosteroids plus hydroxychloroquine
hydroxychloroquine plus mepacrine

dapsone or retinoids

thalidomide or auranoffin or clofazamine

azathioprine or methotrexate or mycophenolate plus corticosteroids

IV immunoglobulin or rituximab
Prof Peter Maddison
North West Wales Rheumatology Service
Ysbyty Gwynedd
Bangor LL28 5SL