富马酸替诺福韦二吡呋酯在慢性乙型肝炎患者中诱导的范科尼综合征并低磷软骨病一例

Tenofovir dipifurate fumarate induced Fanconi syndrome combined with hypophosphatemic osteomalacia in a patient with chronic hepatitis B

目的探讨富马酸替诺福韦二吡呋酯(TDF)在慢性乙型肝炎(CHB)患者中诱导的范科尼综合征(FS)并低磷软骨病(HO)的临床诊断学特征。方法回顾性分析2022年5月3日济宁市第一人民医院收治的1例继发性FS并HO的CHB患者的临床资料,并进行文献复习。结果患者女性,66岁,因“双下肢反复疼痛1年余”入院,既往CHB病史20余年,口服TDF治疗5年余。患者1年前无明显诱因出现双下肢疼痛麻木不适,以右下肢为重,疼痛较为剧烈,活动后加重,休息后可减轻。血钾3.00 mmol/L,血钙2.18 mmol/L,血磷0.32 mmol/L;血尿素氮、肌酐水平无异常。反复多次尿检,尿糖±~2+,尿蛋白0~2+;24 h尿磷23.25 mmol。双侧踝关节MRI平扫示双踝关节组成骨、跗骨及跖骨多发骨质异常信号,可见假骨折线。患者诊断为TDF诱导的继发性FS并HO。停用TDF,更换为富马酸丙酚替诺福韦抗病毒治疗,并加用维生素D钙咀嚼片、维生素D2软胶囊、甘油磷酸钠等纠正钙磷代谢紊乱,患者症状明显改善。结论对于服用TDF治疗CHB的患者,应该警惕继发性FS并HO的发生,在治疗前和治疗中,均应进行血肌酐、血磷、尿糖和尿蛋白的监测。

Objective To explore the clinical diagnostic features of Fanconi syndrome(FS)combined with hypophosphatemic osteomalacia(HO)induced by tenofovir dipifurate fumarate(TDF)in a patient with chronic hepatitis B(CHB).Methods The clinical data of a case of CHB with FS and HO admitted to the Jining No.1 People′s Hospital on May 3,2022 were reviewed retrospectively,and the literature was reviewed.Results The 66-year-old female had a history of more than 20 years of CHB treated with TDF for more than 5 years before she was admitted to hospital due to"recurrent pain of both lower limbs for more than 1 year".The patient had pain,numbness and discomfort in both lower limbs without obvious inducement 1 year ago,especially in the right lower limb.The pain was more severe,worsened after activity and could be alleviated after rest.Her serum potassium was 3.00 mmol/L,calcium was 2.18 mmol/L,phosphorus was 0.32 mmol/L,and there was no abnomality in blood urea nitrogen and creatinine.Repeated urine tests showed urine glucose±-2+,urine protein 0-2+.The 24-hour total urinary phosphorus was 23.25 mmol.Plain MRI scan of bilateral ankle joints showed multiple bone abnormalities in constituent,tarsal and metatarsal bones of both ankles,and false fracture lines were found.The diagnosis was secondary FS with HO caused by TDF.TDF was discontinued,and antiviral therapy was replaced with tenofovir alafenamide fumarate,vitamin D calcium chewable tablets,vitamin D2 softgel capsules,sodium glycerophosphate,and other medications to correct calcium and phosphorus metabolism disorders,and the patient′s symptoms improved significantly.Conclusions Patients with CHB treated with TDF should be aware of the possibility of FS complicating with HO.Clinicians should monitor blood creatinine,blood phosphorus,urine glucose,and urine protein levels both before and during treatment.