Approach Considerations
The goals of management of discoid lupus erythematosus (DLE) are to halt disease activity, thereby preventing scarring, and to prevent the development of further lesions. Advise patients that the development of serious systemic disease is possible, although rare. Regular repeat clinical evaluation with a thorough review of systems accompanied by simple laboratory studies (complete blood cell count, renal function, urinalysis) is usually sufficient to monitor for progression from primary cutaneous disease to systemic involvement.
Therapy begins with the use of sun-protective measures, including sunscreens, photoprotective clothing, wide-brimmed hats, and behavior alteration. Cosmetic measures, such as cover-up makeup or wigs, may be suggested for appropriately selected patients. Makeup used for camouflage includes Covermark and Dermablend.
Standard medical therapy includes topical or intralesional corticosteroids and antimalarials. Topical calcineurin inhibitors have also been used in patients with cutaneous lupus erythematosus (CLE). In addition, topical retinoids have been reported to be helpful. Topical imiquimod was reported to be effective in one patient. Systemic corticosteroids are typically avoided, given that the dose and duration of therapy needed to maintain control of cutaneous disease often results in substantial steroid-related adverse effects. Therefore, for recalcitrant disease, immunosuppressants and immunomodulators, including methotrexate, mycophenolate mofetil, and thalidomide, amongst others, should be considered.
Activity
Since chronic CLE is exacerbated by sunlight and other UV exposure, advise patients to take precautions by limiting exposure to sunlight to the early morning or late afternoon, when the sun is less intense. Even during these times, strict photoprotective measures should be practiced. Advise patients to avoid artificial light sources, such as tanning beds.
Consultations
Consultation with the following specialists may be helpful:
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Rheumatologist - For joint involvement or to evaluate for systemic involvement
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Nephrologist - For renal involvement
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Internist - To evaluate for systemic involvement
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Ophthalmologist - To monitor therapy with hydroxychloroquine or chloroquine
Antimalarial Therapy
Antimalarial therapy seems to lessen the progression to systemic lupus erythematosus (SLE) and to lower the risk of thrombovascular disease. [27, 28] Alternative therapies include immunosuppressive agents, [29, 30] thalidomide or lenalidomide, [27, 31, 32, 33, 34, 35] and oral or topical retinoids. These agents are typically used in antimalarial-resistant patients. In most patients, the antimalarial should be continued during treatment with other agents, unless a complication due to the antimalarial occurs. The rationale for continuing the antimalarial therapy includes its ability to reduce the risk of disease progression to SLE as well as its photoprotective benefits.
Hydroxychloroquine is the first-line systemic agent for discoid lupus erythematosus (DLE), whereas chloroquine is considered second-line antimalarial therapy in the United States. Both hydroxychloroquine and chloroquine may cause deposits in the retina and cause irreversible retinopathy. Therefore, these two agents should not be used concomitantly because of the increased risk of ocular toxicity when used in combination. [36]
Quinacrine has also been used for recalcitrant cutaneous lupus erythematosus (CLE) as combination therapy with either hydroxychloroquine or chloroquine. [37] A retrospective cohort study demonstrated that the combination of quinacrine with other antimalarials does not increase the risk for ocular toxicity compared with monotherapy with hydroxychloroquine or chloroquine. [38] Of note, quinacrine is not associated with retinal toxicity and can be considered in patients who are at risk for or who have experienced antimalarial-induced retinopathy. Quinacrine down-regulates responses of toll-like receptor (TLR)–3, TLR-4, and TLR-8. [39] Of note, quinacrine is not commercially available in the United States and is available only from compounding pharmacies. It is not currently approved for human use in the United States.
Traditionally, antimalarials have been considered less effective in patients who smoke; however, it is also possible that DLE is worse in these patients. A 2011 study demonstrated that cigarette smoking did not have a significant impact on response to hydroxychloroquine in patients with DLE. Rather, disseminated DLE and the presence of concomitant SLE were both significantly associated with decreased therapeutic efficacy. [40] However, a 2015 meta-analysis concluded that patients with CLE who smoke have a 2-fold decreased chance of cutaneous improvement with antimalarial therapies. [41]
Efforts regarding smoking cessation are advisable in patients with DLE who smoke or who are exposed to secondary smoke. [42, 43, 44] Furthermore, a 2012 study demonstrated that patients with CLE who smoked had more severe cutaneous disease, had inferior quality of life, and were more frequently treated with a combination of hydroxychloroquine and quinacrine than were nonsmokers. [45]
Ocular toxicity is a well-known risk of both hydroxychloroquine and chloroquine, as they can deposit in the retina with subsequent irreversible retinopathy. Thus, these two medications should not be used in combination. The American Academy of Ophthalmology 2016 guidelines recommend a baseline fundus examination with subsequent annual screening after 5 years of treatment. [46] High dose and long duration of treatment are the most significant risk factors for retinopathy. The risk of toxicity at the recommended dose up to 5 years is under 1%, and up to 10 years is 2%. After 20 years of treatment, however, risk of toxicity rises to almost 20%. Despite these guidelines, in clinical practice, ocular examinations are still typically recommended at baseline (within 3 months of initiating the antimalarial agent) and annually thereafter.
A large single-center cohort study demonstrated a reasonable safety profile for antimalarials in the treatment of lupus, with less than 20% of patients presenting with at least one adverse effect during treatment. [47] While most common adverse effects were mild-to-moderate cutaneous and gastrointestinal manifestations, ocular alterations were the most common cause for treatment discontinuation.
Corticosteroid and Immunomodulator Therapy
Topical corticosteroids are selected for the type of lesion under treatment and for the site of involvement. For example, solutions, lotions, oil, or foams are preferred for the scalp, weaker agents are used on the face, and superpotent agents are used under occlusion for hypertrophic lesions. Topical calcineurin inhibitors may also be used, most often for facial lesions when the patient is taking appropriate breaks from topical corticosteroids.
Intralesional injection of corticosteroids (typically, the authors use triamcinolone acetonide 3 mg/mL) is useful as adjunctive therapy for individual lesions. Potential for atrophy relates to the amount of corticosteroid injected in any one area; therefore, dilute concentrations and low volumes are preferred. In addition, the treating physician must take care to limit the total dose of the injections at any given clinic visit to avoid systemic toxicity from the steroids; for example, if a patient is given 10 mL of triamcinolone 3 mg/mL, this means that the patient has received a total of 30 mg, and toxicity is similar as if it had been delivered orally or by intramuscular injection.
Among immunosuppressives, methotrexate, mycophenolate mofetil, and azathioprine, amongst others, may be considered. [29, 30] Two reports have documented the value of mycophenolate mofetil for treatment of cutaneous lesions of lupus erythematosus, including one study that used mycophenolate mofetil in antimalarial-resistant subjects. [48, 49]
Multiple other agents have case reports, case series, or early clinical trials to support their use in cutaneous lupus erythematosus (CLE), including lenalidomide, [50, 51] tofacitinib, [7, 52] apremilast, [53] intravenous immunoglobulin, [54] belimumab, [55, 56] and sirolimus. [57]
In the authors’ experience, systemic corticosteroids are rarely effective and frequently lead to steroid-related adverse effects at the doses needed to manage cutaneous disease.
Excision and Laser Therapy
Excision of burned-out, scarred lesions is possible; however, reactivation of inactive lesions has been reported in some patients.
Laser therapy may be useful for lesions with prominent telangiectasias; however, one must consider the risk of reactivation with this form of therapy. An open trial in a small group of patients has demonstrated the efficacy of pulsed-dye laser (PDL) therapy for discoid lupus erythematosus (DLE) lesions. Another randomized controlled trial involving 48 lesions in 9 DLE patients failed to demonstrate a significant difference in modified CLASI scores with PDL compared with a control group. [58] Before using this therapy in patients, at a minimum, a test area should be treated to make certain that the DLE does not flare. [59]
Long-Term Monitoring
Follow patients with discoid lupus erythematosus (DLE) at regular intervals. Response to therapy varies from several weeks to several months. At each visit, question the patient about new symptoms that may reflect systemic disease. At regular intervals, perhaps annually in otherwise asymptomatic patients, perform routine laboratory studies for assessment, including complete blood cell count, renal function tests, and urinalysis. Repeat antibody testing is needed only if a change in symptomatology is noted.
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Discoid lupus erythematosus on the face.
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Chronic scarred lesion of discoid lupus erythematosus.
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Lesions of discoid lupus erythematosus in the conchal bowl demonstrate patulous follicles with follicular plugging.
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Palmar lesions of discoid lupus erythematosus.
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Scarring alopecia of discoid lupus erythematosus.
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Widespread scarring alopecia.
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Hypertrophic lesions of chronic cutaneous lupus erythematosus on the dorsal hands. Characteristic lesions were observed elsewhere.
