###### Abstract  
Systemic lupus erythematosus (SLE) is a clinically heterogeneous autoimmune disease, and organ manifestations, such as lupus nephritis (LN) or skin disease, may be refractory to standard treatment. Therefore, new agents are required to allow for a more personalized therapeutic approach. Recently, several new therapies have been approved internationally, including cyclosporine for LN and anifrolumab for moderately to severely active SLE. Here, we report a case of SLE with a predominant and refractory cutaneous manifestation despite combination treatment with glucocorticoids, hydroxychloroquine, mycophenolate mofetil, and belimumab, which had been present for more than 12 months. Belimumab was switched to anifrolumab, and the patient responded quickly after two infusions (eight weeks) with a reduction in the Cutaneous Lupus Assessment and Severity Index (CLASI) from 17 to 7. In addition, we review the available clinical trial data for anifrolumab with a focus on cutaneous outcomes. Based on phase II and III clinical trials investigating the intravenous administration, a consistent CLASI improvement was observed at 12 weeks. Interestingly, in a phase II trial of subcutaneous anifrolumab application, CLASI response was not different from placebo at 12 weeks but numerically different at 24 and 52 weeks, respectively. Thus, anifrolumab emerges as an attractive new therapeutic option suggesting a possible domain-based approach.  
systemic lupus erythematosus; anifrolumab; interferon; cutaneous lupus erythematosus  
202202013 June 2022015 June 202202015 June 202202  
She presented in October 2021 to her routine visit and complained of worsening skin lesions and joint pain over the preceding three months (Figure 1A-C).  
Her skin lesions consisted of non-prurritic erythematous lesions distributed symmetrically over the upper trunk and back, as well as the face, arms, and hands. There were no areas of scarring. Her skin rash was most consistent with subacute cutaneous lupus erythematosus (SCLE). The Cutaneous Lupus Erythermatosus Disease Area and Severity Index (CLASI) was determined with a score of 17.  
The metacarpophalangeal II to V and proximal interphalangeal joints II to V were slightly swollen and tender to palpation. Anti-dsDNA abs were elevated at 114 IU/mL (normal range [NR] <15 IU/mL), C3 was 0.71 g/L (NR 0.82-1.93 g/L), and C4 was 0.08 g/L (NR 0.15-0.57 g/L). The Systemic Lupus Erythermatosus Disease Activity Index 200 (SLEDAI-2K) was calculated as 10.  
Previous therapy included hydroxychloroquine (200 mg/day), azathioprine, and varying doses of prednisolone. Three courses of medium to high oral prednisolone doses (0.5-1 mg/kg of body weight) to control her skin disease and flares of polyarthritis were given over the previous six months.  
Her current SLE treatment included hydroxychloroquine (200 mg/day), low-dose prednisone (5 mg/day), mycophenolate mofetil (500 mg twice daily, higher doses not tolerated), and subcutaneous belimumab (BEL) (200 mg/week), which had been started more than 12 months before. In this refractory patient with active cutaneous and joint disease, BEL was switched to ANI.  
Anifrolumab treatment was initiated in January 2022. Eight weeks later, after receiving two intravenous infusions of 300 mg four weeks apart, the skin lesions had improved significantly (Figure 1D-F).  
In addition, her complement levels and anti-dsDNA antibody titer improved moderately (Figure 2A,B). The CLASI improved from 17 to 7 (Figure 2C). Joint pain and swelling also improved with treatment. No side effects or infusion reactions occurred, and the patient has lowered her prednisolone dose to 2 mg/day. After four infusions, the patient reduced her dose of mycophenolate mofetil to 500 mg/day. Follow-up is ongoing.  
Figure 1: Cutaneous manifestations of the patient before (**A–C**) and eight weeks after the initiation of anifrolumab treatment (**D–F**).