Guideline sources The following summarized guidelines for the evaluation and management of cutaneous lupus erythematosus (CLE) are prepared by our editorial team based on guidelines from the American College of Rheumatology (ACR 2023), the European League Against Rheumatism (EULAR 2022), the British Association of Dermatologists (BAD 2021), the German Society of Dermatology (DDG/GKJR/DGRh 2021), the Chinese Society of Dermatology (CSD/ADA/AADV 2021), the Royal College of Ophthalmologists (RCOphth 2020), and the European Academy of Dermatology and Venereology (EADV 2017). 1 2 3 4 5 6 7 8 CalculatorEULAR/ACR classification criteri https://web.pathway.md/diseases/rechQtCFQ0qxf8UQv 1/10 6/23/23, 3:37 AM Cutaneous lupus erythematosus Pathway Guidelines 1. Screening and diagnosis Diagnostic criteria: Use the 2019 EULAR/ACR criteria to differentiate CLE from SLE. A Consider reassessing the 2019 EULAR/ACR criteria either once a year and/or in case of clinical/laboratory changes in any patient with CLE. C Differential diagnosis: as per BAD 2021 guidelines, suspect drug-induced CLE in patients with CLE, particularly subacute CLE, and discontinue any potential causative drug. B 2. Classification and risk stratification Severity assessment: As per DDG 2021 guidelines: Consider using the CLASI or revised CLASI to assess disease activity and intensity in patients with CLE. C Consider using the DLQI or Skindex-29 (skin-specific methods for assessing the quality of life) to assess the quality of life in patients with CLE. C 3. Diagnostic investigations History and physical examination: As per BAD 2021 guidelines, evaluate for SLE by history, examination and targeted laboratory investigations in patients with CLE. B As per DDG 2021 guidelines, assess the patient's medication in cases of drug-induced subacute CLE or deterioration of established subacute CLE. A As per EADV 2017 guidelines, elicit patient's past and present drug history, particularly in patients with subacute CLE. B Evaluation for malignancy: evaluate for a tumor in cases of treatment-refractory subacute CLE, a late manifestation of subacute CLE (> 60 years of age), and symptoms suggestive of carcinoma. A Photoprovocation testing: consider obtaining standardized photoprovocation testing by experienced investigators in special cases, for example, to exclude CLE or to differentiate between CLE and polymorphous light eruption. C Laboratory testing: Do not obtain a routine assessment of glucose-6 phosphate dehydrogenase activity. D Do not obtain a pregnancy test as part of the basic evaluation. D https://web.pathway.md/diseases/rechQtCFQ0qxf8UQv 2/10 6/23/23, 3:37 AM Cutaneous lupus erythematosus Pathway Pretreatment evaluation: screen for HBV infection in all patients eligible for treatment with conventional synthetic, biological, or targeted synthetic DMARDs, immunosuppressants, or corticosteroids (according to dose and duration). B Show 3 more 4. Diagnostic procedures Biopsy and histopathology: perform lesional biopsy for histological confirmation of a clinical diagnosis of CLE, while omitting in cases of butterfly rash or mucosal lesions. A Show 2 more 5. Medical management General principles: manage patients with CLE in the setting of SLE jointly with a rheumatologist. E Topical therapy: As per BAD 2021 guidelines, initiate very potent/potent topical corticosteroids as 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 there is widespread cutaneous and/or SLE involvement. A Show 3 more As per DDG 2021 guidelines, initiate topical corticosteroids in patients with circumscribed CLE lesions. A Show 4 more As per EADV 2017 guidelines, initiate topical corticosteroids as first-line therapy for several weeks in patients with CLE. B Show 4 more Antimalarial agents: As per BAD 2021 guidelines, initiate antimalarials, either alone or with adjunctive topical corticosteroids, as first-line systemic therapy in patients with CLE. A Show 14 more As per DDG 2021 guidelines, initiate combination treatment with antimalarial drugs in patients with extensive lesions, an inclination to scarring, or insufficient response. A Show 3 more As per EADV 2017 guidelines, initiate antimalarials as first-line and long-term systemic therapy in all patients with CLE with severe or widespread skin lesions, particularly in patients with the risk of scarring and development of systemic disease. B Show 7 more Systemic corticosteroids: https://web.pathway.md/diseases/rechQtCFQ0qxf8UQv 3/10 6/23/23, 3:37 AM Cutaneous lupus erythematosus Pathway As per BAD 2021 guidelines, consider initiating concomitant tapering courses of oral or IV corticosteroids (such as methylprednisolone) in patients with severe or disseminated CLE, or subtypes with the greatest risk of scarring (such as discoid lupus erythematosus with a high risk of permanent damage, high disease burden). E Show 2 more As per DDG 2021 guidelines, initiate systemic corticosteroids, in addition to antimalarial drugs, as first-line therapy for a limited period of time in patients with severe or disseminated CLE lesions. Taper off systemic corticosteroids as soon as possible. A As per EADV 2017 guidelines, initiate systemic corticosteroids first-line therapy in addition to antimalarials in patients with severe or widespread active CLE lesions. B Show 2 more Methotrexate: As per BAD 2021 guidelines, consider initiating methotrexate up to 25 mg once weekly in patients with CLE with an inadequate response to topical therapy and antimalarials. C Show 2 more As per DDG 2021 guidelines, initiate methotrexate as systemic second-line therapy at doses of up to 25 mg per week and, if possible, in combination with antimalarial drugs. A As per EADV 2017 guidelines, initiate methotrexate up to 20 mg/week as second-line therapy, primarily in patients with subacute CLE, preferably SC and in addition to antimalarials. B Systemic retinoids: As per BAD 2021 guidelines, consider initiating acitretin 25-50 mg daily as second-line systemic therapy in patients with CLE. C Show 2 more As per DDG 2021 guidelines, initiate retinoids, preferably in combination with antimalarial drugs, as second-line systemic therapy in patients with hypertrophic CLE lesions. A Consider initiating retinoids as second-line systemic therapy in all other forms of CLE. B As per EADV 2017 guidelines, initiate systemic retinoids as second-line therapy in selected patients with CLE unresponsive to other treatments, preferably in addition to antimalarials. B Dapsone: As per BAD 2021 guidelines, consider initiating dapsone (typically at 50 mg daily and escalated to 150 mg daily, depending on response and tolerability) as first-line systemic therapy in patients with subacute CLE and bullous SLE. E Show 2 more As per DDG 2021 guidelines: Consider initiating dapsone as first-line therapy in patients with bullous CLE and as second- line therapy, preferably in combination with antimalarial drugs, in patients with refractory CLE. C Start dapsone at low doses (50 mg/day) and increase the dose to a maximum of 1.5 mg/kg body weight depending on clinical response and side effects. Monitor glucose-6 phosphate dehydrogenase activity before initiating treatment. A https://web.pathway.md/diseases/rechQtCFQ0qxf8UQv 4/10 6/23/23, 3:37 AM Cutaneous lupus erythematosus Pathway As per EADV 2017 guidelines, consider initiating dapsone as first-line therapy in patients with bullous lupus erythematosus. C Show 3 more Mycophenolate mofetil: As per BAD 2021 guidelines, consider initiating oral mycophenolate mofetil (typically at 500 mg BID and escalated to 1.5 g BID, dependent on response and tolerability) in pateints with CLE with an inadequate response to topical therapy and antimalarials. C Show 2 more As per DDG 2021 guidelines: Consider initiating mycophenolate mofetil, preferably in combination with antimalarial drugs, as third-line therapy in patients with refractory CLE lesions. Start mycophenolate mofetil at a dose of 500 mg BID with a subsequent dose increase to 2 g/day. B Consider initiating mycophenolic acid as an alternative to mycophenolate mofetil. C As per EADV 2017 guidelines, initiate mycophenolate mofetil as third-line therapy in patients with refractory CLE, preferably in addition to antimalarials. B Show 2 more Other immunosuppressants: As per DDG 2021 guidelines: Consider offering azathioprine or cyclosporin for the treatment of patients with CLE. (No recommendation. Do not use cyclophosphamide for the treatment of patients with CLE. D As per EADV 2017 guidelines: Avoid using azathioprine, cyclophosphamide and cyclosporine for the treatment of patients with CLE without systemic involvement. D Do not use leflunomide for the treatment of patients with CLE. D Thalidomide and lenalidomide: As per BAD 2021 guidelines, consider initiating thalidomide as third-line therapy in patients with treatment-resistant CLE. C Show 4 more As per DDG 2021 guidelines, consider initiating thalidomide, preferably in combination with antimalarial drugs, in selected patients with refractory CLE lesions. As per EADV 2017 guidelines, initiate thalidomide in selected patients with refractory CLE, preferably in addition to antimalarials. B Show 4 more Monoclonal antibodies: As per BAD 2021 guidelines: Consider initiating rituximab on a case-by-case basis in patients with treatment-resistant CLE, if conventional systemic therapies have failed. C https://web.pathway.md/diseases/rechQtCFQ0qxf8UQv 5/10 6/23/23, 3:37 AM Cutaneous lupus erythematosus Pathway Consider initiating belimumab in eligible patients with SLE with cutaneous involvement, if conventional systemic therapies have failed. C As per DDG 2021 guidelines, consider initiating belimumab or rituximab in patients with CLE. As per EADV 2017 guidelines, avoid using belimumab for the treatment of patients with CLE without systemic involvement. D Show 2 more Other agents: As per BAD 2021 guidelines, consider administering IVIG only on a case-by-case basis in patients with treatment-resistant CLE, if conventional systemic therapies have failed. C Show 2 more As per DDG 2021 guidelines: Consider administering IVIG in patients with CLE. Do not use antibiotics for the treatment of patients with CLE. D As per EADV 2017 guidelines: Do not use antibiotics/antimicrobials (clofazimine, sulfasalazine, cefuroxime axetil) and interferon-alpha for the treatment of patients with CLE. D Avoid using intravenous IgAnd danazol for the treatment of patients with CLE. D 6. Nonpharmacologic interventions Lifestyle modifications: As per BAD 2021 guidelines, counsel patients with CLE about the importance of lifestyle changes on disease activity and treatment response, such as smoking cessation and the need for a range of photoprotective measures, including the use of a broad-spectrum sunscreen. A As per DDG 2021 guidelines, advise using sunscreen in exposed areas in addition to sun protective clothing in patients of all stages irrespective of the extent and the topical or systemic medication used. A As per DDG 2021 guidelines, advise avoiding active and passive exposure to tobacco smoke in patients with CLE. A As per EADV 2017 guidelines, advise avoiding unprotected UV exposure and using daily preventive (chemical and physical) measures in all patients with CLE. B Show 2 more Vitamin D supplementation: As per BAD 2021 guidelines, consider offering vitamin D supplementation in patients with CLE. C As per DDG 2021 guidelines, consider offering vitamin D3 supplementation in patients with CLE. https://web.pathway.md/diseases/rechQtCFQ0qxf8UQv 6/10 6/23/23, 3:37 AM Cutaneous lupus erythematosus Pathway As per EADV 2017 guidelines, consider offering vitamin D supplementation in all patients with CLE. C Herbal products: caution patients with CLE against herbal supplements and traditional medicines as some may contain corticosteroids or induce disease exacerbation by immune stimulation. E Psychological support: consider referring patients to available psychological support services (such as a psychiatrist, clinical psychologist or patient support group) if the psychological impact of CLE is significant. E 7. Therapeutic procedures Intralesional corticosteroids: as per BAD 2021 guidelines, consider administering intralesional triamcinolone (0.1 mL/cm field, starting at 2.5-5 mg/mL for sites at higher risk of atrophy including the face and 10 mg/mL for other sites) as a local treatment option in patients with localized discoid lupus erythematosus or as an adjunctive therapy for persistent lesions. E Physical modalities: As per BAD 2021 guidelines, insufficient evidence to recommend pulsed dye laser for the treatment of patients with CLE. I As per DDG 2021 guidelines, do not offer terapeutic UV irradiation in patients with CLE. D Show 2 more As per EADV 2017 guidelines, do not offer any UV light therapy in patients with CLE. D Show 3 more 8. Specific circumstances Considerations for contraception: As per DDG 2021 guidelines, consider preferring non-hormonal contraceptives or progestin-only contraceptives. C Show 2 more As per EADV 2017 guidelines: Do not use estrogen-containing hormonal contraception in patients with CLE and associated antiphospholipid syndrome. D Avoid using estrogen replacement therapy in patients with CLE. D Patients contemplating pregnancy: counsel female patients of reproductive age with CLE about possible difficulties with pregnancy as a precautionary measure. A Show 3 more Pregnant patients: As per BAD 2021 guidelines, obtain additional monitoring by the obstetric team to identify congenital heart block in the fetuses of female patients with CLE with anti-Ro/SSA and/or anti- La/SSB antibodies becoming pregnant. E https://web.pathway.md/diseases/rechQtCFQ0qxf8UQv 7/10 6/23/23, 3:37 AM Cutaneous lupus erythematosus Pathway Show 2 more As per DDG 2021 guidelines, obtain serial fetal echocardiography starting at the 16th week of gestation in patients positive for anti-Ro/SSA and/or anti-La/SSB antibodies with a previous congenital heart block pregnancy. A Show 4 more As per EADV 2017 guidelines, initiate hydroxychloroquine at usual dosage as first-line therapy in patients with active CLE during pregnancy or breastfeeding. B Show 5 more 9. Patient education General counseling: As per BAD 2021 guidelines: Offer obtaining a pregnancy test in female patients of child-bearing potential before initiating methotrexate, mycophenolate mofetil, acitretin, rituximab, belimumab, cyclophosphamide, thalidomide or lenalidomide therapy. Counsel them regarding the risk of teratogenicity, advise pregnancy prevention and instigate the pregnancy prevention program. A Advise using reliable contraception as a precautionary measure in sexually active male patients during methotrexate, mycophenolate mofetil, thalidomide and lenalidomide therapy, during dose interruption (where applicable) and for periods of time following the cessation of treatment. A As per DDG 2021 guidelines, inform patients with CLE about the possibility of Koebner phenomenon. A Show 2 more 10. Preventative measures Routine immunizations: As per ACR 2023 guidelines, consider offering high-dose or adjuvanted influenza vaccination, rather than regular-dose influenza vaccination, in 65 years old patients with rheumatic or musculoskeletal diseases and in 18-65 years old patients with rheumatic or musculoskeletal diseases on immunosuppressive medications. C Show 17 more As per DDG 2021 guidelines, evaluate and vaccinate patients before and during immunosuppressive/immunomodulating treatment according to current guidelines. Offer annual influenza vaccination. A Prophylaxis for Pneumocystis jirovecii pneumonia: consider administering prophylaxis against P. jirovecii pneumonia in patients initiating high-dose corticosteroids, especially in combination with immunosuppressants and depending on the risk-benefit ratio. C https://web.pathway.md/diseases/rechQtCFQ0qxf8UQv 8/10 6/23/23, 3:37 AM Cutaneous lupus erythematosus Pathway 11. Follow-up and surveillance Assessment of treatment response: As per DDG 2021 guidelines, consider using the CLASI or the revised CLASI for monitoring therapeutic response. C As per DDG 2021 guidelines: Assess the efficacy of systemic treatment for CLE after a minimum of 3 months and a maximum of 6 months (except for corticosteroids). A Continue systemic treatment for up to 1 year after the skin lesions have resolved in patients without any immunological disorders or systemic symptoms. Individualize the decision on treatment continuation for all other patients. A Monitoring of chloroquine/chloroquine treatment: As per DDG 2021 guidelines: Obtain ophthalmological evaluation in all patients with CLE during the first year of treatment with antimalarial drugs, and every year after five years of treatment. A Obtain ophthalmological evaluation before initiating treatment with antimalarial drugs in patients with preexisting ocular disease. Obtain yearly ophthalmological monitoring in patients with risk factors (especially renal failure). A Follow-up: As per DDG 2021 guidelines, consider reassessing the 2019 EULAR/ACR criteria either once a year and/or in case of clinical/laboratory changes in patients with CLE. C Show 3 more As per DDG 2021 guidelines: Obtain routine evaluation of basic laboratory parameters used in normal patient care during chloroquine/hydroxychloroquine treatment. Do not obtain additional monitoring. Monitor all other treatments according to the guideline for bullous dermatitis/psoriasis. A Evaluate and monitor patients before and during immunosuppressive/immunomodulating treatment according to current guidelines. A Surveillance for malignancy: advise participation in the generally recommended cancer screening examinations (skin, colon, gynecology, prostate) in patients with CLE. A Monitoring of hydroxychloroquine/chloroquine treatment: as per RCOphth 2020 guidelines, obtain annual monitoring for retinopathy in all patients receiving hydroxychloroquine for > 5 years or chloroquine for > 1 year. B Show 17 more References 1. Anne R Bass, Eliza Chakravarty, Elie A Akl et al. 2022 American College of Rheumatology Guideline for Vaccinations in Patients With Rheumatic and Musculoskeletal Diseases. Arthritis Rheumatol. 2023 Jan 4. Online ahead of print. Open https://web.pathway.md/diseases/rechQtCFQ0qxf8UQv 9/10 6/23/23, 3:37 AM Cutaneous lupus erythematosus Pathway 2. D O'Kane, C McCourt, S Meggitt et al. British Association of Dermatologists guidelines for the management of people with cutaneous lupus erythematosus 2021. Br J Dermatol. 2021 Dec;185 6 1112 1123. Open 3. A Kuhn, E Aberer, Z Bata-Cs rg et al. S2k guideline for treatment of cutaneous lupus erythematosus - guided by the European Dermatology Forum EDF in cooperation with the European Academy of Dermatology and Venereology EADV . J Eur Acad Dermatol Venereol. 2017 Mar;31 3 389 404. Open 4. Margitta Worm, Miriam Zidane, Lisa Eisert et al. S2k guideline: Diagnosis and management of cutaneous lupus erythematosus Part 2 Therapy, risk factors and other special topics. J Dtsch Dermatol Ges. 2021 Sep;19 9 1371 1395. Open 5. Qianjin Lu, Hai Long, Steven Chow et al. Guideline for the diagnosis, treatment and long-term management of cutaneous lupus erythematosus. J Autoimmun. 2021 Sep;123 102707. Open 6. Margitta Worm, Miriam Zidane, Lisa Eisert et al. S2k guideline: Diagnosis and management of cutaneous lupus erythematosus Part 1 Classification, diagnosis, prevention, activity scores. J Dtsch Dermatol Ges. 2021 Aug;19 8 1236 1247. Open 7. George E Fragoulis, Elena Nikiphorou, Mrinalini Dey et al. 2022 EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in adults with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis. 2022 Nov 3;ard-2022 223335. Open 8. The Royal College of Ophthalmologists. Hydroxychloroquine and Chloroquine Retinopathy: Recommendations on Monitoring. RCOphth. 2020 Dec. Open https://web.pathway.md/diseases/rechQtCFQ0qxf8UQv 10/10