Seronegative synovitis with depressed edema syndrome is a group of symmetrical, edematous, and remissionable disorders of acute onset with a negative rheumatoid factor and an underlying lesion of synovitis, which is considered a specific subtype of rheumatoid arthritis. Seronegative synovitis with depressed edema syndrome, also known as RS3PE syndrome, is a disease whose etiology has not yet been clarified. Patients may present with depressed edema of the extremities and symmetric polyarthritis, which may resolve spontaneously, and is most common in older men. Patients with this disease are often rheumatoid factor negative and have few erosive changes on X-ray. Small-dose hormones, nonsteroidal anti-inflammatory drugs and slow-acting antirheumatic drugs are effective. Low-dose hormones such as prednisone acetate are more effective in reducing swelling and have a rapid onset of symptomatic relief within 24 hours, with most taking several weeks. Slow-acting drugs such as methotrexate or sulfasalazine are generally used, which have some effect, but long-term application is not recommended. All of the above medications should be taken as prescribed by a physician. It is recommended that patients with seronegative synovitis with depressed edema syndrome go to the Department of Rheumatology and Immunology of a regular hospital for standardized diagnosis and treatment under the guidance of a doctor.