The investigators hypothesize that topical application of Tapinarof, an FDA-approved topical Aryl hydrocarbon receptor (AHR) agonist for the treatment of plaque psoriasis, would inhibit lupus-causing T cells and lead to improvement of cutaneous lupus lesions. To test this hypothesis, the investigators will perform a prospective, interventional clinical trial in patients with chronic and/or subacute cutaneous lupus. This trial will include outcomes analyzing the change in cutaneous lupus lesions using standardized assessments, but also analyze pre- and post-treatment skin and blood immune parameters to elucidate the immune effects and changes in lupus as a result of topical AHR agonist application. The goals are to 1) identify if topical AHR agonism leads to improvement in cutaneous lupus, and 2) examine the immunopathology of cutaneous lupus and its alteration with topical AHR agonist treatment.

Inclusion Criteria:

• Age 18 years and older
• Patients with a histopathological or clinical diagnosis of chronic and/or subacute CLE
• Patients with at least one active cutaneous lupus lesion with a diameter ≥ 1cm and CLA-IGA-R score of ≥ 3 at screening and baseline

Exclusion Criteria:

• Unwillingness or inability to complete informed consent process or comply with the study protocol
• Patients who are pregnant or breast-feeding
• Other dermatologic diseases whose presence or treatments would interfere with evaluation of the study drug or interpretation of participant safety or trial results
• History of allergy, hypersensitivity reaction, or anaphylaxis to any component of the study drug
• Application to cutaneous lupus lesion(s) being assessed of topical corticosteroids, topical calcineurin inhibitors, or topical janus kinase inhibitors within 1 weeks of study drug initiation
• Application to cutaneous lupus lesion(s) being assessed of topical tapinorof within 4 weeks of study drug initiation
• Prior use of anifrolumab within the last 6 months
• New initiation of systemic immunosuppressive or immunomodulating drugs (e.g. oral or injectable corticosteroids, methotrexate, cyclosporine, mycophenolate mofetil, azathioprine, belimumab), antimalarials (hydroxychloroquine, chloroquine, quinacrine), or systemic janus kinase inhibitors within 12 weeks of study drug initiation
• For patients already on the following treatment(s) prior to enrollment: unstable or changing of dosing of systemic immunosuppressive or immunomodulating drugs (e.g. oral or injectable corticosteroids, methotrexate, cyclosporine, mycophenolate mofetil, azathioprine, belimumab), antimalarials (hydroxychloroquine, chloroquine, quinacrine), or systemic janus kinase inhibitors within 4 weeks of study drug initiation
• Patients with active infections.