This article reports the diagnosis and treatment process of a 52-year-old female patient who was finally diagnosed with POEMS syndrome. Her main clinical manifestations included Raynaud phenomenon of both hands, skin pigmentation, swelling of both hands and feet, and numbness of both feet. The patient was admitted to the Department of Rheumatology and Immunology, Peking University People's Hospital on April 8, 2024, due to "purplish red skin on the neck and chest for 1.5 years, swelling of both hands for 1 year, and numbness of both feet for 8 months". One and a half years ago, she was diagnosed with systemic sclerosis (SSc) in another hospital, based on evidence from a series of clinical manifestations. Her main symptoms were Raynaud phenomenon of both hands, skin pigmentation, swelling of both hands and feet, and numbness of both feet, which met the 2013 classification criteria for SSc by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR). During the disease course, the patient received regular treatment with glucocorticoids and disease-modifying antirheumatic drugs (DMARDs), but her condition still progressed continuously. Eight months ago, she developed new-onset numbness in both her feet accompanied by pinprick-like pain, indicating the complexity of the condition and the need for further investigation of the etiology. Differential diagnosis should consider possibilities, such as mixed connective tissue disease, eosinophilic fasciitis, and malignant tumors. Auxiliary examinations showed that the patient's serum antinuclear antibody, anti-topoisomerase Ⅰ(Scl-70) antibody, anti-U1 ribonucleoprotein (RNP) antibody, and antineutrophil cytoplasmic antibody were all negative. Imaging examinations revealed no pulmonary arterial hypertension or pulmonary interstitial fibrosis. In addition, the patient had multiple endocrine abnormalities and responded poorly to treatment with glucocorticoids and DMARDs, suggesting the need to be alert to the possibility of lymphoproliferative diseases. Further examinations including vascular endothelial growth factor detection, whole-body bone scan, and bone marrow aspiration and biopsy were performed, and the final diagnosis of POEMS syndrome was confirmed. The patient was then transferred to the Department of Hemato-logy and received treatment with the pomalidomide combined with dexamethasone regimen, and her clinical symptoms gradually relieved. This case suggests that POEMS syndrome is similar to rheumatological and immunological diseases such as SSc in terms of clinical manifestations. Clinicians should be more vigilant during diagnosis and treatment, and pay attention to differentiation, so as to reduce missed diagnoses and misdiagnoses, thereby formulating more accurate and effective treatment plans for patients.

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