Initial management of discoid lupus erythematosus and subacute cutaneous lupus erythematosus

INTRODUCTION — Discoid lupus erythematosus (DLE) and subacute cutaneous lupus erythematosus (SCLE) are variants of cutaneous lupus erythematosus (cutaneous LE) that may occur independently or as manifestations of systemic lupus erythematosus (SLE). DLE most commonly occurs on the head and is characterized by well-defined, inflammatory plaques that evolve into atrophic, disfiguring scars (picture 1A-B). SCLE typically presents with inflammatory, scaly papules or annular plaques on the neck, upper trunk, and arms (picture 2A-B).

Concern over the appearance of skin lesions leads most patients with DLE or SCLE to desire treatment (algorithm 1). In particular, early treatment of DLE is essential to minimize scarring.

The initial approach to the treatment of patients with DLE or SCLE will be discussed here. The clinical manifestations of DLE and SCLE and the management of patients with refractory disease are discussed separately.

●(See "Overview of cutaneous lupus erythematosus", section on 'Discoid lupus erythematosus'.)

●(See "Overview of cutaneous lupus erythematosus", section on 'Subacute cutaneous lupus erythematosus'.)

●(See "Drug-induced lupus", section on 'Clinical spectrum of drug-induced lupus'.)

●(See "Management of discoid lupus erythematosus and subacute cutaneous lupus erythematosus refractory to antimalarial therapy".)

Risk for progression of DLE or SCLE to SLE is also reviewed separately.

●(See "Overview of cutaneous lupus erythematosus", section on 'Association with systemic lupus erythematosus'.)

OVERVIEW — The primary goal of treatment of DLE and SCLE is resolution of clinical signs of active disease (eg, scale, erythema, and induration). Scarring and dyspigmentation are complications of active disease that may persist despite resolution of active disease.

The management of patients with DLE and SCLE includes measures to achieve resolution of disease activity as well as interventions for associated conditions:

●Interventions for exacerbating factors (eg, sun exposure, medications)

●Pharmacologic treatment

●Monitoring for progression to systemic lupus erythematosus (SLE)

●Psychosocial support

Most patients with DLE or SCLE respond to photoprotection combined with topical anti-inflammatory agents or systemic antimalarial drugs (algorithm 1). Patients with disease refractory to these interventions may benefit from other treatments. (See 'Interventions for exacerbating factors' below and 'Approach to pharmacologic therapy' below and "Management of discoid lupus erythematosus and subacute cutaneous lupus erythematosus refractory to antimalarial therapy".)

Both SCLE and DLE can occur in association with SLE, although co-occurrence of SCLE with SLE is more frequent. Monitoring for signs of SLE aids with identifying patients who require additional interventions for systemic disease. (See "Overview of cutaneous lupus erythematosus", section on 'Association with systemic lupus erythematosus'.)

SCLE and DLE can negatively impact quality of life. Psychologic or psychiatric support may be helpful for addressing psychosocial factors associated with cutaneous lupus erythematosus (cutaneous LE). (See 'Psychosocial support' below.)

INTERVENTIONS FOR EXACERBATING FACTORS — The elimination of exacerbating factors is an important component of long-term management. Key measures include:

●Strict photoprotection

●Discontinuation of photosensitizing medications (if feasible)

●Evaluation for drug-induced disease in patients with SCLE

Photoprotection — Patients with DLE or SCLE should engage in sun-protective measures on a daily basis, including the use of broad-spectrum sunscreens and sun-protective clothing [1]. Exposure to ultraviolet (UV) light and, in rare cases, visible light can be an exacerbating factor for cutaneous lupus erythematosus (cutaneous LE) [1-8]:

●Suggested measures – Given the lack of large-scale, comparative trials addressing the efficacy of different sunscreens in the management of cutaneous LE, patients generally should be advised to use broad-spectrum, water-resistant sunscreens with a sun protection factor (SPF) of at least 30. (See "Selection of sunscreen and sun-protective measures".)

However, typical patient use of sunscreen often provides insufficient protection for the patient who is photosensitive. The importance of other sun-protective behaviors, including the use of sun-protective clothing, broad-brimmed hats, and sun avoidance (particularly during peak midday hours), must be emphasized. Specific products to reduce environmental UV exposure, such as UV-blocking films for car windows, are also available [9]. (See "Overview of cutaneous photosensitivity: Photobiology, patient evaluation, and photoprotection", section on 'Photoprotection' and "Selection of sunscreen and sun-protective measures", section on 'Photoprotective clothing'.)

●Impact of ultraviolet light – In experimental settings, exposure to ultraviolet (UV) light has been shown to induce skin lesions in approximately 70 to 100 percent of patients with SCLE [10-13] and approximately 64 percent of patients with DLE [14]. The latency period between sun exposure and the development of photo-induced skin lesions can last from several days to three weeks [15]. Thus, some patients may fail to associate exacerbations of skin lesions with photosensitivity.

Few studies have addressed the efficacy of sunscreen in preventing the development of skin lesions. The following data support sunscreen use in this population:

•In a company-sponsored, randomized, intraindividual trial of 25 patients with cutaneous LE (17 with lupus erythematosus tumidus, five with DLE, and three with SCLE), experimental ultraviolet A (UVA) or ultraviolet B (UVB) irradiation failed to induce skin lesions in all sites treated with an SPF 60 sunscreen containing ethylhexyl methoxycinnamate, titanium dioxide, zinc oxide, and methylene bis-benzotriazolyl tetramethylbutylphenol [16]. In contrast, skin lesions consistent with cutaneous LE developed in untreated or vehicle-treated sites in 16 patients (64 percent) and 14 patients (56 percent), respectively. (See "Overview of cutaneous photosensitivity: Photobiology, patient evaluation, and photoprotection", section on 'Photoprotection'.)

•An intraindividual study of 11 patients with DLE or SCLE compared the ability of three different broad-spectrum sunscreens to protect against the development of skin lesions after exposure to UVA and UVB [17]. All three sunscreens had protective effects. The most protective sunscreen prevented the development of skin lesions in all patients and had an SPF of 60. This sunscreen contained octocrylene, avobenzone, ecamsule, drometrizole trisiloxane, and titanium dioxide.

•A retrospective study found that an SPF 30 broad-spectrum sunscreen containing avobenzone, octocrylene, ethylhexyl triazone, drometrizole trisiloxane, and titanium dioxide was highly effective in preventing new lesions following irradiation with UVA and UVB in 49 out of 51 patients with cutaneous LE (primarily DLE or lupus tumidus) [18].

•An eight-week, open-label study, in which subjects with DLE and SCLE were instructed to apply a broad-spectrum sunscreen with an SPF greater than 15 that contained avobenzone and padimate O, demonstrated that daily use of this sunscreen led to a decrease in disease severity [19].

Avoidance of exacerbating drugs — Drug-induced SCLE presents with cutaneous and serologic findings similar to idiopathic disease. Medications that are associated with drug-induced SCLE should be discontinued or avoided when possible in patients with SCLE (table 1). (See "Overview of cutaneous lupus erythematosus", section on 'Drug-induced subacute cutaneous lupus erythematosus'.)

Withdrawal of the culprit agent often leads to resolution of the skin disease. However, many patients have persistently detectable autoantibodies (SSA/Ro antibodies or SSB/La antibodies), and a minority have persistent skin disease [20].

In addition, medications that are known to cause photosensitivity may exacerbate symptoms in patients with idiopathic DLE or SCLE and should be avoided [20]. (See "Photosensitivity disorders (photodermatoses): Clinical manifestations, diagnosis, and treatment", section on 'Photosensitivity due to exogenous agents'.)

APPROACH TO PHARMACOLOGIC THERAPY — In addition to photoprotection and avoidance of other exacerbating factors, most individuals with DLE or SCLE require pharmacologic therapy to control active disease. The extent and severity of skin involvement influences the approach to initial treatment (algorithm 1). (See 'Limited disease' below and 'Extensive disease or disease resistant to local therapy' below and 'Aggressive disease' below.)

Limited disease — Limited disease may be considered disease that is unlikely to cause disfigurement (eg, scarring or dyspigmentation on the face) and consists of a degree of skin involvement for which daily topical therapy is often manageable (eg, a limited amount of skin in body site[s] the patient can easily reach).

Approach — Patients with DLE or SCLE involving a limited body surface area can often be treated with local therapy. Topical corticosteroids are an appropriate first-line therapy (algorithm 1) [21,22]. Topical calcineurin inhibitors (tacrolimus or pimecrolimus) and intralesional corticosteroid injections are alternative local therapies.

Initial treatment with topical corticosteroids is often preferred over topical calcineurin inhibitors because of the higher cost of topical calcineurin inhibitors compared with some topical corticosteroids. In addition, in DLE, some studies suggest greater efficacy of super high-potency topical corticosteroids compared with topical tacrolimus. (See 'Topical calcineurin inhibitors' below.)

However, the lack of risk for corticosteroid-induced skin atrophy is a favorable characteristic of topical calcineurin inhibitors, particularly for patients requiring long-term topical therapy on sites at greatest risk for cutaneous atrophy (eg, face or intertriginous areas). In accordance, some authors have suggested using high-potency topical corticosteroids for the initial treatment of severe, acute flares of DLE and SCLE, followed by the use of a topical calcineurin inhibitor once control of the acute flare has been achieved [23]. (See 'Topical calcineurin inhibitors' below.)

Intralesional corticosteroid injections are often reserved for patients who fail topical therapy, given the discomfort associated with multiple injections. However, some patients may prefer the intermittent nature of interlesional therapy over daily application of topical corticosteroid therapy. Intralesional therapy is most applicable for the treatment of a few small areas of skin involvement. (See 'Intralesional corticosteroids' below.)

Patients with limited disease that responds insufficiently to one or more local therapies are candidates for systemic antimalarial therapy. (See 'Extensive disease or disease resistant to local therapy' below.)

Topical corticosteroids — Topical corticosteroids are appropriate first-line therapies for patients with limited DLE or SCLE, and some patients with limited disease can be adequately managed with photoprotection and topical corticosteroids alone (algorithm 1) [21,24-27]:

●Administration – The approach to topical corticosteroid therapy differs slightly for DLE and SCLE:

•Discoid lupus erythematosus – We suggest twice-daily application of a super high-potency or high-potency topical corticosteroid (groups 1 or 2), such as clobetasol propionate, as first-line therapy for acute flares of DLE (table 2) [28,29].

Although the use of high-potency topical corticosteroids on the face is typically avoided, they are often used for the treatment of facial DLE because of the importance of disease control for the minimization of scarring. (See 'Approach' above.)

•Subacute cutaneous lupus erythematosus – We suggest twice-daily application of a super high-potency to medium-potency topical corticosteroid (class 1 to 4) as initial therapy for acute flares of SCLE (table 2).

Improvement in DLE and SCLE with topical corticosteroids is typically noted within days to two weeks of the initiation of therapy. If an acute flare of DLE or SCLE has not responded to a high-potency topical corticosteroid after two to four weeks, we proceed to an alternative therapy (algorithm 1).

For patients who exhibit continuing improvement with topical corticosteroid therapy but have residual disease activity after four weeks, topical corticosteroid therapy can be continued at the lowest potency and frequency that supports continued improvement provided there are no signs of corticosteroid-induced cutaneous atrophy. When all signs of disease activity (eg, scale, erythema, induration) are absent, treatment can be discontinued. Scarring and dyspigmentation will be unaffected by continued treatment.

Data on topical corticosteroid maintenance regimens are lacking. For patients who achieve resolution of disease activity with topical corticosteroids but experience rapid recurrence of disease activity upon the withdrawal of topical corticosteroid therapy, we typically initiate a long-term maintenance regimen with a topical corticosteroid or topical calcineurin inhibitor. We use the lowest potency topical corticosteroid and lowest frequency of application that maintains improvement:

•For maintenance therapy on the face, we typically use up to twice-daily application of a low-potency topical corticosteroid (groups 6 or 7), such as hydrocortisone 1% or 2.5%, as long as evidence of disease activity persists (erythema and scale) (table 2).

•For maintenance therapy on the trunk, extremities, or scalp, we typically use up to twice-daily application of medium-potency to high-potency topical corticosteroids (groups 2 to 4), such as triamcinolone acetonide 0.1% cream or fluocinonide 0.05% cream, as long as evidence of disease activity persists.

●Efficacy – High-quality studies on the efficacy of topical corticosteroids for DLE and SCLE are limited, and the use of topical corticosteroids for DLE as first-line agents is primarily based upon documentation of successful treatment from early case reports and studies [24-27]:

•In a double-blind trial (n = 20) in which two lesions on each patient were treated with either fluocinolone acetonide 0.025% ointment (a medium-potency topical corticosteroid) three times daily or a vehicle control, fluocinolone was superior to the vehicle for the treatment of DLE [25]. The same authors reported efficacy of fluocinolone acetonide 0.025% ointment in a series of 28 patients. After 18 days, 14 patients showed complete or almost complete regression of skin lesions, and only two patients failed to improve.

•The use of very low-potency agents for DLE is discouraged by the results of a randomized trial (n = 78) in which application of fluocinonide 0.05% cream was superior to hydrocortisone 1% cream for the treatment of DLE (27 versus 10 percent, respectively, achieved complete clearance or excellent improvement after six weeks of therapy) [28].

Although there are no high-quality studies of the efficacy of topical corticosteroids for the treatment of SCLE, our experiences and the clinical experiences of others suggest efficacy of this therapy [11].

●Adverse effects – Cutaneous atrophy is a potential side effect of the long-term use of topical corticosteroids, particularly higher-potency agents. Patients should be advised to limit the application of topical corticosteroids to the involved skin only and should be followed closely for the development of atrophy. Adverse effects related to systemic absorption may also occur with topical corticosteroid use, especially when treating large areas of involvement. (See "Topical corticosteroids: Use and adverse effects", section on 'Adverse effects'.)

Topical calcineurin inhibitors — Topical calcineurin inhibitors are alternative anti-inflammatory drugs for the treatment of DLE or SCLE (algorithm 1) [23,30-32].

We typically use topical calcineurin inhibitors for patients who have failed treatment with topical corticosteroids or for long-term therapy for thin lesions in atrophy-prone areas, such as the face. Topical calcineurin inhibitors may be slower acting than topical corticosteroids but do not induce cutaneous atrophy. Concerns have also been raised over the ability of these agents to penetrate thick, hypertrophic lesions of DLE [23]:

●Administration – Topical calcineurin inhibitors used for DLE and SCLE include pimecrolimus 1% cream and tacrolimus 0.03% or 0.1% ointment. We typically treat with the 0.1% concentration of tacrolimus. Topical calcineurin inhibitors are applied to the affected areas twice daily.

In general, improvement in symptoms can be expected within the first four weeks of treatment, and complete clearance of thin patches or plaques may occur within two months [23].

●Efficacy – The efficacy of topical calcineurin inhibitors for cutaneous lupus erythematosus (cutaneous LE) has been evaluated in a few randomized trials with limited numbers of patients and variable results [33-36]. A 12-week, vehicle-controlled trial of topical tacrolimus 0.1% ointment in 30 patients with various forms of cutaneous LE refractory to topical corticosteroid therapy found limited evidence for the efficacy of tacrolimus specifically for DLE and SCLE [33]. In the trial, which included 14 patients with DLE and 4 patients with SCLE, improvement in lesion severity was noted in tacrolimus-treated patients, but the degree of improvement was not superior to the improvement detected in vehicle-treated patients.

Although these findings raise doubt about the efficacy of topical tacrolimus for DLE and SCLE, the number of patients with DLE and SCLE was small, the study included patients who were failing to respond sufficiently to systemic therapies, and encouragement of patient sunscreen use may have contributed to lesion regression. In contrast, two small, randomized trials comparing topical tacrolimus and pimecrolimus with topical corticosteroids, which are generally accepted to be effective for cutaneous LE, suggest benefit from calcineurin inhibitors:

•In an eight-week trial in which 10 patients with DLE were treated with either twice-daily application of pimecrolimus 1% cream or twice-daily application of betamethasone 17-valerate 0.1% cream (a medium-potency topical corticosteroid), there was no significant difference in efficacy or adverse effects between the two agents [34]. The mean clinical severity scores in the trial decreased by 86 and 73 percent, respectively.

•Another trial investigating the efficacy of tacrolimus 0.1% ointment versus clobetasol propionate 0.05% ointment (a superpotent topical corticosteroid) for various forms of cutaneous LE reported similar efficacy but found an increased risk for the development of telangiectasias in subjects treated with clobetasol propionate [35]. The efficacy data from this trial may be less applicable since only 5 out of 20 patients in the trial had DLE or SCLE.

Other studies suggest greater efficacy of super high-potency topical corticosteroids in DLE:

•In a split-body, randomized trial in which 21 patients with DLE applied tacrolimus 0.1% ointment to one randomly assigned side of the body and clobetasol propionate 0.05% ointment to the contralateral side for six weeks, both treatments were associated with reductions in disease activity scores, but clobetasol demonstrated a greater median reduction [36].

•A nonrandomized, comparative study (n = 40) compared the efficacy of tacrolimus 0.1% with halobetasol propionate 0.05% (a super high-potency topical corticosteroid) in patients receiving hydroxychloroquine for DLE. After eight weeks, there were statistically significant reductions in the erythema, scale/hypertrophy, and total disease activity scores in both groups but a greater reduction in the scale/hypertrophy scores in the halobetasol propionate group [37].

Uncontrolled studies also suggest efficacy of topical calcineurin inhibitors in small numbers of patients [38-40].

Simultaneous therapy with topical tacrolimus and clobetasol propionate has also been used with success in cutaneous LE [41,42].

●Adverse effects – Both pimecrolimus and tacrolimus are generally well tolerated. The most common side effect is a transient burning or stinging sensation after application that typically resolves within the first one to two weeks of use.

In 2006, the US Food and Drug Administration (FDA) placed a black box warning on topical calcineurin inhibitors due to a concern for their potential carcinogenesis based on animal studies. However, a causal relationship has not been established. (See "Treatment of atopic dermatitis (eczema)", section on 'Topical calcineurin inhibitors'.)

Intralesional corticosteroids — Intralesional corticosteroid injections are an alternative local therapy (algorithm 1). In addition, patients with focal lesions that do not respond to topical corticosteroids or topical calcineurin inhibitors can be treated with intralesional corticosteroid injections:

●Administration – Triamcinolone acetonide in concentrations ranging from 3 to 5 mg/mL is typically used. A small-diameter needle (ideally 30 gauge) is used to inject approximately 0.1 mL of the medication into the target site. Multiple injections within a single lesion should be placed approximately 1 cm apart. For patients who cannot tolerate the pain associated with injection, a topical anesthetic can be applied prior to the procedure. (See "Intralesional corticosteroid injection".)

Injections are repeated every three to four weeks until erythema and scale are no longer present. If no response has occurred after two to three injections, alternative treatment should be considered.

Some patients, most often those with SCLE, have too many lesions to treat successfully with intralesional corticosteroids alone due to the large number of injections that would be required [9]. In the author's clinical practice, most patients are treated with less than 10 mg of triamcinolone acetonide per session.

●Efficacy – Although this modality has been utilized by multiple experts for DLE and SCLE [9,11,43-48], there are no high-quality studies of intralesional corticosteroids for these indications. In one series of patients with DLE, a clinical response characterized as very good or excellent was achieved by 26 out of 40 patients treated with 3 or 4 mg/mL of triamcinolone acetonide [46].

●Adverse effects – As with topical corticosteroids, cutaneous atrophy and pigmentary changes can occur with intralesional administration of corticosteroids. Periocular injections should be approached with caution, as central retinal artery occlusion leading to visual impairment is a potential adverse event [49].

Systemic absorption also occurs with intralesional administration. In addition to the practical limitations of numerous injections, the risk of systemic side effects limits the use of this modality to disease involving small amounts of skin surface area. (See "Intralesional corticosteroid injection", section on 'Adverse effects and pitfalls'.)

Extensive disease or disease resistant to local therapy — Extensive disease may be considered a degree of skin involvement for which daily topical therapy would be challenging for many patients.

Patients with aggressive, rapidly progressing disease may benefit from the addition of systemic corticosteroid therapy (algorithm 1). (See 'Aggressive disease' below.)

Approach — When local treatment is impractical due to the presence of extensive disease or limited disease fails to respond adequately to local treatment, systemic antimalarial therapy is our preferred treatment (algorithm 1) [21,22].

Local therapies (topical corticosteroids, topical calcineurin inhibitors, or intralesional corticosteroids) may be beneficial as adjunctive therapy. In particular, topical corticosteroids are useful as a bridge therapy during the first few weeks of treatment while awaiting the onset of slower-acting systemic agents.

Hydroxychloroquine is the most common agent used in the treatment of cutaneous LE and our preferred first-line treatment. Other antimalarial drugs are generally reserved for patients with inadequate responses to hydroxychloroquine. (See 'Antimalarial drugs' below.)

Other immunosuppressive or immunomodulatory therapies may be tried if antimalarial therapy fails or cannot be tolerated. (See "Management of discoid lupus erythematosus and subacute cutaneous lupus erythematosus refractory to antimalarial therapy".)

Antimalarial drugs — Hydroxychloroquine and chloroquine are the primary antimalarial agents that are utilized in the treatment of DLE and SCLE (algorithm 1). Hydroxychloroquine and chloroquine are 4-aminoquinoline antimalarial compounds that have very similar pharmacokinetics, action, and metabolism [50,51] (see "Antimalarial drugs in the treatment of rheumatic disease"):

●Administration – Treatment of DLE or SCLE with antimalarial drugs is most often initiated with hydroxychloroquine because it is generally accepted to have the best side effect profile. Chloroquine has a greater risk of retinal toxicity and gastrointestinal intolerance, and quinacrine is more likely to cause hematologic adverse effects [52]:

•Regimen – We treat most adult patients with a starting dose of hydroxychloroquine of 200 mg/day, followed by an increase to 200 mg twice daily after one to two weeks if the drug is well tolerated. Starting with the once-daily dose may reduce gastrointestinal side effects. The dose of hydroxychloroquine should not exceed 5 mg/kg of real body weight per day to minimize risk for retinopathy [53]. The safety of hydroxychloroquine in pregnancy is reviewed separately. (See "Safety of rheumatic disease medication use during pregnancy and lactation", section on 'Hydroxychloroquine'.)

Because there is a delay in the onset of action of antimalarials, six to eight weeks should elapse before efficacy is assessed. Once satisfactory improvement is attained with hydroxychloroquine, the dose can be decreased to 200 mg/day for maintenance therapy [9].

Many patients with purely cutaneous disease can discontinue their antimalarials during winter months, when photoexacerbation is less of a problem.

•Patients with insufficient responses to hydroxychloroquine – If hydroxychloroquine therapy does not result in resolution of disease activity, the antimalarial regimen can be adjusted, or therapies for refractory disease can be utilized:

-Chloroquine may be substituted for hydroxychloroquine because there is a small subset of patients who respond preferentially to this drug [9,54]. Limiting the chloroquine dose to less than or equal to 2.3 mg/kg of real body weight per day is suggested to minimize risk for retinopathy [53]. Chloroquine and hydroxychloroquine should not be used together because of an unacceptably high risk of retinal toxicity. (See "Antimalarial drugs in the treatment of rheumatic disease", section on 'Ocular effects'.)

-The selection of therapy for refractory disease is reviewed separately. (See "Management of discoid lupus erythematosus and subacute cutaneous lupus erythematosus refractory to antimalarial therapy".)

Some authors suggest the addition of quinacrine (100 mg per day) to hydroxychloroquine as a next step when monotherapy with hydroxychloroquine is unsuccessful [55-58]. However, in some countries (including the United States), quinacrine can only be obtained through specialty compounding pharmacies, and shortages and manufacturing difficulties have made it difficult to obtain. Quinacrine also lacks regulatory approval for any medical indication.

●Efficacy – Many patients with cutaneous LE will respond to monotherapy with hydroxychloroquine [46,54,59,60]. In a randomized trial comparing treatment of cutaneous LE with hydroxychloroquine with treatment with acitretin (n = 58), 50 percent of patients with DLE or SCLE treated with 400 mg/day of hydroxychloroquine and 46 percent of patients treated with acitretin achieved complete clearance or marked improvement after eight weeks of therapy [59]. Treatment success was also evident in a series of 34 patients with DLE [46]. Twenty-four patients (70 percent) achieved a good to excellent response with hydroxychloroquine (200 to 400 mg/day) for at least six weeks.

Although the limited availability of quinacrine is often prohibitive, results from the following studies suggest that combination therapy with hydroxychloroquine and quinacrine may be associated with improved response:

•In a retrospective study of patients with various forms of cutaneous LE who failed to respond to hydroxychloroquine alone (19 patients with DLE and 10 with SCLE), combination therapy led to an 84 percent response rate and a statistically significant improvement in disease activity among the subjects with DLE [55]. Among the patients with SCLE, 60 percent showed improvement on clinical examination. However, the decrease in disease activity was not statistically significant.

•A prospective cohort study composed of patients with various forms of cutaneous LE found that combination therapy with hydroxychloroquine and quinacrine significantly reduced disease activity in patients who had previously failed hydroxychloroquine [54]. Ten out of 15 patients (67 percent) improved with combination therapy. Due to the small number of patients, subtype-specific response rates could not be reliably assessed.

In a prospective study of 300 patients with cutaneous LE, serum levels of hydroxychloroquine correlated with treatment efficacy, suggesting that laboratory testing may be of value for distinguishing true resistance to hydroxychloroquine from factors such as poor patient compliance and inadequate drug dosing [61]. Further studies are necessary to determine the role of quantitative drug levels in the identification of antimalarial-resistant DLE and SCLE. The availability of the test is limited.

The impact of smoking on the effectiveness of antimalarial drugs is unclear. (See 'Smoking cessation' below.)

●Adverse effects – Antimalarial drugs are generally well tolerated. Adverse effects include gastrointestinal distress; ocular toxicity (chloroquine and hydroxychloroquine); and neuropsychiatric, neuromuscular, or hematologic abnormalities. Patients receiving hydroxychloroquine or chloroquine therapy should receive a baseline ophthalmologic examination and periodic ophthalmologic examinations thereafter. (See "Antimalarial drugs in the treatment of rheumatic disease", section on 'Adverse effects' and "Antimalarial drugs in the treatment of rheumatic disease", section on 'Routine eye examinations'.)

Cutaneous alterations may also occur with antimalarial therapy, including blue-gray pigmentation on the shins, face, or palate, as well as bleaching of lightly pigmented hair. In addition, diffuse, yellow discoloration of the skin, sclera, and body secretions is a frequent side effect of quinacrine therapy.

Aggressive disease — Occasionally, patients present with disease that is rapidly progressing or associated with risk for worsening scarring or cosmetically significant pigmentary alteration (eg, progressive DLE on the face) (algorithm 1). Such patients should proceed directly to oral antimalarial therapy rather than topical monotherapy. In addition, we suggest a short course of systemic corticosteroid therapy [21,22].

Systemic corticosteroids — The goal of systemic corticosteroid therapy is to attain rapid control of disease while awaiting the onset of oral antimalarial drugs. Systemic corticosteroids should not be used as primary therapy because of a risk for severe adverse effects with long-term therapy. (See "Major adverse effects of systemic glucocorticoids".)

Typical dosing for systemic corticosteroid therapy for adults consists of 0.5 to 1 mg/kg per day of prednisone administered for two to four weeks, with the aim of subsequent tapering and discontinuation [21].

A cohort study that assessed the efficacy of multiple treatments in 1002 patients with various forms of cutaneous LE suggests benefit of systemic corticosteroids [62]. Benefit was reported in greater than 90 percent of patients with DLE (n = 128) or SCLE (n = 99) treated with systemic corticosteroids.

MONITORING FOR PROGRESSION TO SYSTEMIC LUPUS ERYTHEMATOSUS — Patients with SCLE and DLE are at risk for the coexistence or future development of systemic lupus erythematosus (SLE). Risk varies with the clinical presentation, with risk in patients with SCLE higher than in patients with limited or generalized DLE. (See "Overview of cutaneous lupus erythematosus", section on 'Association with systemic lupus erythematosus'.)

Patients should be evaluated for SLE at the time of diagnosis. This typically includes a clinical history with a particular focus on a rheumatologic review of systems, a physical examination, and select laboratory studies. (See "Overview of cutaneous lupus erythematosus", section on 'Diagnosis' and "Clinical manifestations and diagnosis of systemic lupus erythematosus in adults", section on 'Evaluation' and "Childhood-onset systemic lupus erythematosus (SLE): Clinical manifestations and diagnosis", section on 'Diagnostic approach'.)

Although there is general agreement that patients diagnosed with SCLE or DLE should receive long-term monitoring for the development of SLE, approaches to subsequent evaluation vary. We typically perform at least the following:

●Review of systems at each follow-up visit

●Annual full history and physical examination

●Annual complete blood count with differential

●Annual urinalysis

Patients who exhibit signs or symptoms suggestive of SLE should receive the standard diagnostic work-up of other patients with suspected SLE. Repetition of an antinuclear antibody (ANA) titer is not indicated for patients who had a positive ANA at the time of the cutaneous lupus erythematosus (cutaneous LE) diagnosis. (See "Clinical manifestations and diagnosis of systemic lupus erythematosus in adults", section on 'Evaluation' and "Childhood-onset systemic lupus erythematosus (SLE): Clinical manifestations and diagnosis", section on 'Diagnostic approach'.)

PSYCHOSOCIAL SUPPORT — Cutaneous lupus erythematosus (cutaneous LE) has been associated with negative effects on quality of life, increased risk for depression, and other psychosocial challenges [63,64]. A Danish, cross-sectional study that included 1424 patients with cutaneous LE, 2065 patients with systemic lupus erythematosus (SLE), and approximately 35,000 matched controls found an adjusted hazard ratio of depression of 2.07 (95% CI 1.55-2.75) for patients with cutaneous LE [63]. In a separate study that included 49 patients seen at an autoimmune skin disease clinic for cutaneous LE, 17 patients (35 percent) met criteria for depression and/or anxiety, with need for intervention based upon scores on validated questionnaires [65].

Awareness of the association of cutaneous LE with psychosocial effects and psychiatric disorders is helpful for identifying patients who may benefit from professional evaluation or intervention. Examples of additional resources for social support and information that patients may find helpful include:

●Lupus Foundation of America

●Lupus Canada

●Lupus UK

OTHER INTERVENTIONS

Smoking cessation — The impact of smoking cessation on the treatment of DLE and SCLE is unclear:

●Impact on disease – Smoking has been associated with the development of cutaneous lupus erythematosus (cutaneous LE) and may contribute to the development of more severe disease [66-70]. In a case-control study of 108 patients with cutaneous LE (majority with DLE or SCLE), patients with cutaneous LE were more likely to be smokers than matched controls (odds ratio [OR] 2.77, 95% CI 1.63-4.76) [70]. Smoking preceded the onset of symptoms in 91 percent of the affected smokers. Additional studies are necessary to determine the effect of smoking cessation on disease activity.

●Impact on antimalarial therapy – There is uncertainty about the impact of smoking on the efficacy of antimalarial therapy for DLE and SCLE. A meta-analysis of observational studies that assessed the impact of smoking on the response of cutaneous LE to antimalarial drugs found a twofold reduction in the likelihood of clinical improvement among smokers compared with nonsmokers (pooled OR 0.53, 95% CI 0.29-0.98) [71]. This meta-analysis, however, did not limit the analysis to studies including only patients with DLE or SCLE.

Moreover, no studies have identified smoking as an independent risk factor for antimalarial failure in patients with cutaneous LE. One large, retrospective cohort study failed to demonstrate reduced antimalarial efficacy among smokers with DLE [72], and a prospective cohort study has shown increased responsiveness of cutaneous LE to antimalarial therapy among smokers with mild disease as compared with nonsmokers with mild disease [73].

Additional research will be useful for clarifying the impact of smoking on antimalarial therapy. It is possible that factors such as increased disease severity among subjects who smoke and nonadherence to antimalarial therapy in smokers may be responsible for antimalarial failure in some patients who smoke. If smoking has a negative effect on antimalarial therapy, nicotine interference with uptake of drug into cell lysosomes or the acceleration of the metabolic clearance of these medications is a potential mechanism [74]. It is unclear whether the use of nicotine substitutes (eg, chewing gums, patches, or inhalers) could have a similar effect, so when possible, smoking cessation without the use of these aids is preferable. (See "Overview of smoking cessation management in adults".)

Assessment for vitamin D deficiency — Vitamin D deficiency may have deleterious effects on multiple organ systems. In addition to diet as a source of vitamin D, vitamin D is synthesized in the skin after sun exposure. Thus, the possibility of vitamin D deficiency should be considered in patients with cutaneous LE, particularly those who engage in strict sun-protective measures [75-77]. Due to the potential adverse effects of vitamin D deficiency, we typically test patients with cutaneous LE annually for this disorder. (See "Vitamin D and extraskeletal health" and "Vitamin D deficiency in adults: Definition, clinical manifestations, and treatment".)

In a study of 52 patients with cutaneous LE, 65 percent exhibited 25-hydroxyvitamin D levels of less than 75 nmol/L (30 ng/mL), a level that is often defined as vitamin D insufficiency [75]. Vitamin D levels were significantly lower in subjects who engaged in daily sunscreen use or sun avoidance compared with those who did not.

Low levels of vitamin D may play a role in autoimmunity [78], and it is unknown whether low levels of vitamin D increase the risk for cutaneous LE or augment the severity of the disease. One small, uncontrolled study reported no change in disease activity with vitamin D supplementation in patients with cutaneous LE and vitamin D deficiency [79]. There are no high-quality studies investigating the effect of vitamin D supplementation on the prevention or treatment of cutaneous LE. (See "Vitamin D and extraskeletal health", section on 'Immune system'.)

Topical retinoids — Systemic retinoids have been used in the treatment of refractory cutaneous LE, but evidence to support the efficacy of topical retinoids for this indication is limited to case reports describing the use of tretinoin 0.05% cream and tazarotene 0.05% gel for hypertrophic lesions of DLE [80,81]. (See "Management of discoid lupus erythematosus and subacute cutaneous lupus erythematosus refractory to antimalarial therapy", section on 'Oral retinoids'.)

The basis for the use of topical retinoids in cutaneous LE is the ability of these drugs to decrease inflammation and slow abnormal differentiation and hyperproliferation of keratinocytes. We do not routinely use topical retinoids in the management of cutaneous LE.

Topical retinoids are not recommended in pregnancy. The most common side effect of topical retinoids is cutaneous irritation.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cutaneous lupus erythematosus".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Discoid lupus (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Rationale for treatment – Discoid lupus erythematosus (DLE) and subacute cutaneous lupus erythematosus (SCLE) may occur independently or in association with systemic lupus erythematosus (SLE). Concern over the appearance of skin lesions drives many patients to seek therapy. Treatment of DLE early in the course of the disease is essential to minimize the development of scarring. (See 'Introduction' above and 'Overview' above.)

●Components of management – Key components of the management of DLE and SCLE include interventions for exacerbating factors, pharmacologic therapy, monitoring for SLE, and psychologic support. (See 'Overview' above and 'Monitoring for progression to systemic lupus erythematosus' above and 'Psychosocial support' above.)

●Interventions for exacerbating factors:

•Photoprotection – Sun-protective measures are an important component of the management of DLE and SCLE. Patients should use broad-spectrum sunscreen with a sun protection factor (SPF) ≥30 on a daily basis. Other sun-protective measures, such as hats, protective clothing, and sun avoidance, are an integral part of the treatment regimen. (See 'Photoprotection' above.)

•Medication review – Certain medications can incite or exacerbate cutaneous lupus erythematosus (cutaneous LE) (table 1). In patients with SCLE, medications that can induce the disorder should be identified and discontinued. Medications that increase photosensitivity also should be avoided or discontinued in patients with cutaneous LE. (See 'Avoidance of exacerbating drugs' above.)

●Initial pharmacologic therapy:

•Limited disease – For the initial treatment of most patients with limited DLE or SCLE, we suggest local therapy rather than systemic therapy (algorithm 1) (Grade 2C).

For most patients, we suggest initial treatment with topical corticosteroids rather than topical calcineurin inhibitors or intralesional corticosteroid injections (Grade 2C). Topical calcineurin inhibitors are more expensive than some topical corticosteroids, and limited data suggest greater efficacy of super high-potency topical corticosteroids for DLE. Topical calcineurin inhibitors are useful for long-term therapy for lesions in areas of the skin where there is high risk for corticosteroid-induced atrophy (eg, face or intertriginous areas).

Intralesional corticosteroid therapy may be beneficial for lesions that fail to improve with topical therapy but requires multiple injections and is most appropriate for the treatment of limited skin areas. (See 'Limited disease' above.)

•Extensive disease – For the initial treatment of most patients with extensive DLE or SCLE, we suggest systemic therapy with hydroxychloroquine rather than other therapies (algorithm 1) (Grade 2C). (See 'Extensive disease or disease resistant to local therapy' above.)

•Rapidly progressing, severe disease – Rapid attainment of disease control is desirable for patients with disease that is progressing rapidly or is associated with cosmetically significant scarring or pigmentary alteration. For these patients, we suggest combining hydroxychloroquine treatment with a short course of prednisone rather than hydroxychloroquine monotherapy or local therapy (algorithm 1) (Grade 2C). (See 'Aggressive disease' above.)

●Failure of initial local treatment – Patients who fail initial treatments for DLE and SCLE may benefit from other interventions. When limited disease cannot be controlled with local therapy, we suggest proceeding to hydroxychloroquine (algorithm 1) (Grade 2C). Patients with disease that does not respond to antimalarial treatment are candidates for other therapies. (See 'Antimalarial drugs' above and "Management of discoid lupus erythematosus and subacute cutaneous lupus erythematosus refractory to antimalarial therapy".)