Low‐dose interleukin‐2 for the treatment of systemic lupus erythematosus with recurrent rash

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies against self-antigens, leading to widespread inflammation and multi-organ involvement. It can affect almost all organ systems, resulting in various clinical manifestations and numerous complications.1 Skin and mucosal lesions are observed in most patients with SLE. Typical manifestations include the characteristic butterfly-shaped facial erythema, subacute cutaneous lupus, and chronic cutaneous lupus erythematosus, with other forms presenting as lupus panniculitis, chilblain lupus erythematosus, and discoid lupus erythematosus.2 Here, we report a case of a patient with persistent facial butterfly erythema that did not respond to standard treatments. A 57-year-old female patient experienced recurrent facial erythema for one year and was diagnosed with SLE at the Affiliated Hospital of North Sichuan Medical College. Initial treatment included hydroxychloroquine (0.2 g, twice daily) and prednisone (50 mg, daily, with gradual tapering). However, due to an allergy to oral hydroxychloroquine, the regimen was changed to total glucoside (0.6 g, twice daily), resulting in gradual improvement of the facial erythema. One month prior to admission, the patient developed erythema on her face and hands. Upon admission, she presented with well-defined, butterfly-shaped erythema on both cheeks, sparing the nasal wings. Additionally, erythema was visible on the back of both hands, punctate erythema was noted on the neck, and no joint swelling, clubbing, or skin discoloration was present on the extremities. Laboratory tests, including routine urine and fecal analyses, biochemical tests, erythrocyte sedimentation rate, C-reactive protein, phospholipid antibody, muscle enzyme spectrum, and neutrophil antibody tests, were within normal ranges. Her glycosylated hemoglobin level was 7.84%. Blood tests revealed a leukocyte count of 3.2 × 109/L (Normal range: 3.5–9.5 × 109/L), platelet count of 75 × 109/L (100–300 × 109/L), hemoglobin level of 92 g/L (115–150 g/L), complement 4 level of 114 mg/L (160–380 mg/L), and complement 3 level of 372 mg/L (790–1520 mg/L). Immunologic tests showed positive antinuclear antibody in sera at 1:100 dilution, with elevated anticentromere antibody >400.00 RU/mL (0–19.99 RU/mL), anti-Ro52 antibody 344.85 RU/mL (0–19.99 RU/mL), anti-splice complex protein antibody >400.00 RU/mL (0–19.99 RU/mL), anti-SS-A antibody 183.36 RU/mL (0–19.99 RU/mL), and anti-Sm antibody 54.29 RU/mL (0–19.99 RU/mL). The patient's 24-hour urinary protein quantification was 824.6 mg. High-resolution chest computed tomography revealed interstitial changes along with mild inflammatory and fibrotic lesions in the left lung's upper lobe lingual segment. Based on the 2019 European League Against Rheumatism/American College of Rheumatology classification criteria, she scored 27 points,3 confirming diagnoses of SLE, lupus nephritis, hematologic abnormalities, and interstitial lung disease. Her SLE disease activity index (SLEDAI) score was 11. As the patient was intolerant to mycophenolate mofetil and azathioprine, she received intravenous methylprednisolone (40 mg daily) and subcutaneous telitacicept (160 mg weekly). Despite this regimen, her skin rashes showed minimal improvement. Subsequently, low-dose interleukin-2 (IL-2) therapy was initiated at 500,000 IU, administered subcutaneously every other day for a total of five treatments, to modulate immune function. Following IL-2 therapy, erythema on her face and hands gradually resolved (Figure 1). Blood tests post-treatment revealed a leukocyte count of 7.11 × 109/L, platelet count of 125 × 109/L, hemoglobin level of 121 g/L, complement 4 level of 170 mg/L, and complement 3 level of 667 mg/L. All values were significantly higher than those previously reported. IL-2, primarily produced by CD4+ T cells, also appears in small quantities from CD8+ T cells and natural killer cells. Known as a “T cell growth factor”, IL-2 supports the long-term growth of T cells in vitro.4 In cellular immune processes, IL-2 modulates the balance between regulatory T cells (Tregs) and helper T cells (Th17). Low-dose IL-2 selectively promotes Treg proliferation and differentiation over Th17 cells, thereby correcting Treg/Th17 imbalances found in autoimmune diseases. In SLE, Treg levels tend to decrease, and Th17 levels increase, correlating with disease activity as measured by scores like SLEDAI.5 Low-dose IL-2 therapy enhances Treg counts, reducing the function of effector T cells, helping to restore immune homeostasis and suppress immune overactivity. For patients with recurrent facial erythema and those intolerant to traditional immunosuppressants, combined low-dose IL-2 therapy may offer an effective adjunctive treatment option. Jirong Cheng designed the study, drafted the manu- script, and created the figure. Miao He, Di Ma, and Xing Li participated in the collection and interpretation of the data. All authors critically revised the manuscript and approved the final manuscript. This work was supported by a grant from the Municipal School Cooperative Research Special Project (Sichuan North Medical College) in Nanchong, Sichuan Province, Grant/Award Number: 19SXHZ0140. The authors declare no conflict of interest. This study was approved by the Institutional Medical Ethics Committee of the Affiliated Hospital of North Sichuan Medical College (2023ER180-1). The data used in this article are available from the corresponding author upon reasonable request.