A 11-year-old girl presented with recurrent fever and erythema for 2 months. Her medical history included episodes of fever, accompanied by painful subcutaneous nodules on her extremities and buttocks. The patient initially responded well to treatment with dexamethasone (5 mg, intramuscular injection) instead of antibiotics; however, she experienced symptomatic relapse approximately 2 weeks later. Physical examination revealed multiple tender erythematous nodules in the upper and lower extremities. Physical examination results were otherwise unremarkable. Complete blood count (CBC) showed normal levels of hemoglobin and platelets, with slightly elevated leukocytes (13.01 × 109/L with 87.5% neutrophils). High acute phase reactants, C-reactive protein (CRP) (32.7-105 mg/L; normal < 10 mg/L) and erythrocyte sedimentation rate (ESR) (36-53 mm/h; normal < 20 mm/h), were observed. A detailed clinical assessment was performed to identify the risk factors for panniculitis, including anti-streptolysin O (ASO), T-SPOT.TB, tuberculin purified protein derivative test, blood culture, antinuclear antibody (ANA), anti-double-stranded DNA (anti-dsDNA), extractable nuclear antigen, perinuclear and cytoplasmic anti-neutrophil cytoplasmic antibody (p-ANCA and c-ANCA), antiphospholipid antibodies, lupus anticoagulant, serum levels of C3 and C4, and alpha 1-antitrypsin were detected, and all were negative or within the normal range. Abdominal ultrasonography and computed tomography (CT) of the abdomen revealed no abnormalities. Histopathological examination of the skin biopsy specimen obtained from a representative nodule revealed lobular panniculitis with moderate infiltration of lymphocytes and histiocytes. No evidence of vasculitis, necrosis, or infection caused by bacteria, fungi, or mycobacteria was observed in the biopsy specimen. Based on the present case report and a combination of serological tests and histopathological examination, we diagnosed the patient with panniculitis. The patient received prednisone (1.5 mg/kg/day) combined with mycophenolate mofetil (MMF) (300 mg/m2/dose) as glucocorticoid-sparing therapy which showed obvious improvement. However, with prednisone tapered to 10 mg/day for approximately 10 months, the girl suffered again from high fever and tenderness nodular, along with new symptoms: her left ankle and foot became swollen and there was point tenderness on the dorsal side of the talonavicular joint. Her medical history revealed no history of acute anterior uveitis or IBD. Laboratory examination results, including those for ASO, human leukocyte antigen 27 (HLA-B*27), rheumatoid factor, anti-cyclic citrullinated peptide, and ANA, were negative. Magnetic resonance imaging (MRI) of the left foot showed that the tarsal area involvement with bone marrow edema in the cuboid and cuneiform bones, indicating enthesitis. A second skin biopsy revealed a small aggregation of lymphocytes and histiocytes in the fat lobules. Therefore, prednisone treatment was increased to 15 mg/day, and ibuprofen (7.5 mg/kg/dose) was prescribed as well. However, the patient had recurrent episodes of painful erythema and swelling in her left foot, with gradual low back pain 1 year before admission. CT of the sacroiliac joint (SIJ) revealed sacroiliitis with bone destruction and the hip MRI showed inflammation in the fat layer. Finally, the patient was diagnosed with panniculitis and ERA, with the latter diagnosed based on the International League of Associations for Rheumatology classification criteria for JIA 2001 []. Anti-tumor necrosis factor alpha (anti-TNF-α) antibody infliximab (IFX) (5 mg/kg at 2-week intervals initially, repeated in monthly intervals three times, currently at 8-week intervals) plus methotrexate (15 mg/m2) was chosen as therapy, whereas prednisone and MMF were gradually discontinued. She experienced an improvement in both joints and panniculitis. Laboratory tests showed that CBC and serum acute phase reactants returned to the normal range. Furthermore, CT revealed no further progression of bone destruction in the SIJ, and inflammation of the fat layer on the buttocks was significantly reduced. At 2-year follow-up, her skin lesions and arthritis remained stable.