Objective To summarize the clinical and genetic characteristics of patients with erythropoietic protoporphyria (EPP) and explore treatment strategies for this disease. Methods We systematically searched Chinese and English databases (PubMed, China National Knowledge Infrastructure, Wanfang, VIP database, and China Biomedical Literature Service System) for case reports on Chinese (including overseas Chinese) EPP patients published up to November 2025. Data from 7 genetically confirmed patients diagnosed at the Second Hospital of Hebei Medical University were retrospectively analyzed. A descriptive comparison was conducted between the aggregated data of Chinese patients and published large-scale foreign studies with clear population representativeness. Results A total of 46 EPP patients were included, with 44 from China and 2 from Singapore, comprising 40 males (87.0%) and 6 females (13.0%). The median age at onset was 4 years, the median age at diagnosis was 26 years, and the median diagnostic delay was 18.5 years. Patients who initially presented with cutaneous manifestations (n=14) had a significantly shorter diagnostic delay than those presenting with hepatic or other manifestations (n=32) (7 vs. 24.5 years, Z=–2.160, P=0.031). Liver function impairment was present in 92.9% (39/42) of patients. Genetically, 50.0% (23/46) of patients exhibited compound heterozygous pathogenic variants in the FECH gene, and 78.3% (36/46) carried the c.315-48T>C variant. Strict photoprotection served as the cornerstone of management. Patients with concomitant liver disease received additional treatments such as ursodeoxycholic acid, glucocorticoids, plasma exchange, or liver transplantation. Notably, two patients from the Second Hospital of Hebei Medical University showed significant clinical improvement following therapeutic phlebotomy. There were differences in the clinical and genetic characteristics of EPP patients between Chinese and other ethnic groups. Conclusions Chinese (including Singaporean Chinese) EPP patients are characterized by male predominance, a high prevalence of the c.315-48T>C variant, frequent liver injury, and significant diagnostic delay. EPP should be suspected in cases of unexplained photosensitivity accompanied by hepatic dysfunction. Therapeutic phlebotomy may represent a valuable exploratory option for EPP patients.
