Guidelines for Managing Cutaneous Lupus Erythematosus

Evidence-based guidelines address key issues in the management of cutaneous lupus erythematosus (CLE) in the presence or absence of systemic lupus erythematosus (SLE) in adults, young individuals, and children, as published in the British Journal of Dermatology.

The guidelines are based on a search and review of all relevant literature in the PubMed, MEDLINE, Embase, and the Cochrane databases up to December 2020 and were developed by the Guideline Development Group (GDG) of the British Association of Dermatologists.

The GDG rated the overall certainty of the evidence from the included studies according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system (high, moderate, low, or very low).

The research group strongly recommends use of the Cutaneous Lupus Erythematosus Disease Area and Severity Index-50 (CLASI-50, the percentage of patients achieving ≥50% reduction in CLASI score) as a critical outcome and use of CLASI-20 (percentage of patients with ≥20% reduction in the CLASI score) as an important outcome in determining the clinical effectiveness and safety of local and systemic therapies compared with each other and/or placebo as well as other interventions.

The GDG issued a good practice point (GPP) for managing patients with CLE in the setting of SLE jointly with rheumatology and to consider referral to psychological support services when the impact of CLE may be significant.

The GDG gave a strong recommendation that clinicians should discuss with their patients the importance of lifestyle changes on disease activity and treatment response, including smoking cessation and the need for a variety of photoprotective measures such as a broad-spectrum sunscreen. It also issued a GPP to use caution against use of herbal supplements and traditional medicines in patients with CLE as some supplements may contain corticosteroids or induce disease exacerbation by immune stimulation.

A strong recommendation was given for offering women of child-bearing potential a pregnancy test before commencing methotrexate, mycophenolate mofetil, acitretin, rituximab, belimumab, cyclophosphamide, thalidomide, or lenalidomide therapy for CLE.

For local therapies, the GDG strongly recommends offering very potent or potent topical corticosteroids as a first-line monotherapy option in patients with localized CLE, including the face, for up to 4 weeks, and as an adjuvant to systemic therapy when widespread cutaneous and/or SLE is involved. The group also strongly recommends topical calcineurin inhibitors as first-line monotherapy for patients with localized CLE for up to 12 weeks, and as an adjuvant to systemic therapy when widespread cutaneous and/or SLE is involved.

A strong recommendation was given to offering antimalarials, either alone or with adjunctive topical corticosteroids, as a first-line systemic treatment for patients with CLE. The group also strongly recommends hydroxychloroquine at doses of 200 to 400 mg daily, and that the daily maintenance dose of HCQ should not exceed 5 mg kg^–1 (actual body weight). The GDG recommends annual screening in all patients who have taken HCQ for more than 5 years.

The research group issued a weak recommendation for considering methotrexate (up to 25 mg once weekly) in patients with CLE who have an inadequate response to topical therapy and antimalarials.

A strong recommendation was issued for performing an annual retinal assessment in all patients with CLE who are taking chloroquine (CQ) after 1 year of therapy and for not offering HCQ in combination with CQ owing to the combined risk of retinopathy.

A strong recommendation was given for monitoring signs and symptoms of hemolytic anemia, methemoglobinemia, and agranulocytosis in patients with CLE who are taking dapsone, especially during the first 3 months of treatment, and to only offer acitretin in women of child-bearing potential in exceptional circumstances owing to the risk of teratogenicity during and up to 3 years after treatment.

The GDG strongly recommends caution regarding thalidomide use in patients with an increased risk of thromboembolic events and other comorbidities and to monitor for signs and symptoms of peripheral neuropathy in those who are using thalidomide.

In addition to its recommendations, the GDG also developed a patient management pathway, which advises clinicians to discuss lifestyle changes such as photoprotection and smoking cessation, consider vitamin D supplementation, the potential for drug-induced CLE (especially for subacute CLE), and discontinuing any potential causative drug, and also to consider the presence of SLE using history, examination, and targeted laboratory investigations.

Each CLE subtype has characteristic clinical features, according to the GDG. Acute ACLE (ACLE) generally presents as a macular erythematous rash involving the malar region of the face and is frequently accompanied by oral ulceration. Discoid lupus erythematosus (DLE) generally presents as erythematous, indurated plaques with overlying scale extending into hair follicles on the face, ears, scalp, and neck, with central atrophic scarring and dyspigmentation. Subacute CLE (SCLE) is usually highly photosensitive and typically presents as annular and/or psoriasiform plaques on the upper torso, neck, and arms.

“On routine histology, an interface dermatitis characterized by varying degrees of basal layer degeneration (keratinocyte apoptosis and vacuolization) is seen in all types of CLE where there is epidermal involvement,” stated the research group. “Histology in early lesions, particularly in ACLE, can be nonspecific, whereas in established DLE hyperkeratosis, basement membrane zone thickening, follicular plugging, and perivascular and peri-adnexal inflammation are typically seen.”

According to the study authors, about 80% of patients with SLE will develop CLE, but the risk for SLE in patients with DLE is lower and is 5% for localized disease and 15% for generalized disease. Progression to SLE may be greater in children with chronic CLE (25%-40%).

“There is a paucity of evidence relating to the treatment of CLE in young people and children,” stated the guideline authors. “The GDG is mindful that the presentation of CLE before adulthood is rare and therefore treatment decisions are typically based on available evidence in adults and physicians’ own experience in children and young people with CLE or other inflammatory diseases.”

The GDG comprised 6 consultant dermatologists, a consultant rheumatologist, 2 patient representatives, and a technical team that included an information scientist, a guideline research fellow, and a project manager providing methodologic and technical support.

The investigators noted that limiting the review to English-language references may have excluded important findings published in other languages.

The GDG has proposed 2026 as a revision date for these recommendations.

Disclosure: Several of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

O’Kane D, McCourt C, Meggitt S, et al. British Association of Dermatologists guidelines for the management of people with cutaneous lupus erythematosus 2021. Br J Dermatol. Published online June 25, 2021. doi:10.1111/bjd.20597