病例报告
ENGLISH ABSTRACT
阿达木单抗诱发颈部淋巴结结核
吴桂英
穆桂兰
乌日力嘎
李鸿斌
王勇
白丽杰
作者及单位信息
·
DOI: 10.3760/cma.j.cn114015-20240103-00002
Adalimumab-induced cervical lymph node tuberculosis
Wu Guiying
Mu Guilan
Wuriliga
Li Hongbin
Wang Yong
Bai Lijie
Authors Info & Affiliations
Wu Guiying
Department of Rheumatology and Immunology, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010050, China
Mu Guilan
Department of Infectious Diseases, Inner Mongolia Fourth Hospital, Hohhot 010020, China
Wuriliga
Department of Rheumatology and Immunology, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010050, China
Li Hongbin
Department of Rheumatology and Immunology, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010050, China
Wang Yong
Department of Rheumatology and Immunology, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010050, China
Bai Lijie
Department of Rheumatology and Immunology, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010050, China
·
DOI: 10.3760/cma.j.cn114015-20240103-00002
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摘要

1例38岁男性强直性脊柱炎患者接受阿达木单抗40 mg皮下注射、1次/2周治疗,21个月后出现发热、乏力、右侧颈部淋巴结和咽喉部肿痛。实验室检查示结核菌素试验强阳性,结核杆菌γ-干扰素释放试验1 911.98 ng/L,红细胞沉降率27 mm/1 h。右侧颈部淋巴结活检示淋巴结肉芽肿性炎。诊断为颈部淋巴结结核。考虑与阿达木单抗有关。停用该药,予抗结核治疗。次日,患者体温恢复正常,5 d后颈部淋巴结、咽喉部肿痛及乏力等症状缓解。45 d后门诊复查,患者上述症状消失。

结核,淋巴结;肿瘤坏死因子抑制剂;阿达木单抗
ABSTRACT

A 38-year-old male patient with ankylosing spondylitis received subcutaneous injection of adalimumab 40 mg once every 2 weeks. After 21 months of medication, the patient developed fever, fatigue, swelling, and pain in the right neck lymph node and throat. Laboratory tests showed that the tuberculin test was strong positive, mycobacterium tuberculosis γ-interferon release test was 1 911.98 ng/L, and erythrocyte sedimentation rate was 27 mm/1 h. The biopsy of right neck lymph node showed granulomatous inflammation of the lymph node. The patient was diagnosed with cervical lymph node tuberculosis, which was considered to be related to adalimumab. The drug was stopped and anti-tuberculosis treatments were given. The next day, the patient′s temperature returned to normal. After 5 days, the swelling and pain of cervical lymph nodes and throat, and the fatigue were relieved gradually. After 45 days, the above symptoms in the patient disappeared.

Tuberculosis, lymph node;Tumor necrosis factor inhibitors;Adalimumab
Bai Lijie, Email: mocdef.3ab613002jsmn
引用本文

吴桂英,穆桂兰,乌日力嘎,等. 阿达木单抗诱发颈部淋巴结结核[J]. 药物不良反应杂志,2025,27(03):188-189.

DOI:10.3760/cma.j.cn114015-20240103-00002

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患者男,38岁,因双侧腹股沟区疼痛2年余,无明显诱因出现咽喉部肿痛、发热3周,于2023年10月10日收入内蒙古自治区第四医院感染性疾病科。2年余前,患者无明显诱因出现双侧腹股沟区疼痛,晨起明显,伴晨僵,活动后缓解,同时出现腰背部疼痛,晨起和夜间明显,自行口服塞来昔布0.2 g、1~2次/d。服用3个月后,上述症状逐渐加重,遂就诊于内蒙古医科大学附属医院风湿免疫科门诊。实验室检查示人类白细胞抗原B27阳性,骶髂关节CT示双侧骶髂关节炎,骶髂关节增强+脂肪抑制序列磁共振成像示双侧骶髂关节骶骨面、髂骨骨髓水肿。诊断:强直性脊柱炎。强直性脊柱炎病情活动度评分(ankylosing spondylitis activity score,ASDAS)2.46。胸部CT、结核杆菌感染T细胞及病毒性肝炎等相关检查结果可排除结核病及病毒性肝炎。予阿达木单抗40 mg皮下注射、1次/2周。治疗1个半月后上述症状减轻,ASDAS评分为0.64。继续规律应用阿达木单抗,每3~4个月门诊随访1次,症状控制可,共治疗21个月。23 d前,因发热、乏力、右侧颈部淋巴结和咽喉部肿痛就诊于内蒙古医科大学附属医院耳鼻喉科门诊,考虑急性扁桃体炎,给予抗感染治疗后咽喉部肿痛减轻,但仍间断发热,体温37.3 ℃~38.4 ℃,明显乏力,颈部淋巴结肿大。结核菌素试验强阳性,γ-干扰素释放试验1 911.98 ng/L(参考值:<14.00 ng/L)。右侧颈部淋巴结活检示淋巴结肉芽肿性炎,考虑为结核性。为进一步诊治,患者至内蒙古自治区第四医院感染性疾病科就诊并收入院。患者既往无特殊疾病史及家族史。否认药物、食物过敏史。
入院体检:体温36.2 ℃,心率80次/min,呼吸20次/min,血压114/75 mmHg(1 mmHg=0.133 kPa)。心、肺、腹部检查未见明显异常。实验室检查:红细胞沉降率27 mm/1 h,C反应蛋白,血、尿、粪常规,肝、肾功能,血糖,类风湿因子未见异常,胸部CT未见异常。考虑为阿达木单抗所致颈部淋巴结结核。入院当日停用该药,予异烟肼0.6 g口服、1次/d,利福平0.6 g口服、1次/d,乙胺丁醇0.75 g口服、1次/d,吡嗪酰胺0.5 g口服、3次/d。次日,患者体温恢复正常,5 d后乏力、颈部淋巴结肿痛及咽喉部肿痛逐渐缓解,20 d后出院。出院医嘱:继续按上述剂量服用抗结核药,予塞来昔布0.2 g口服、2次/d和柳氮磺吡啶1 g口服、3次/d治疗强直性脊柱炎。45 d后门诊复查,患者咽喉部肿痛、发热、乏力等不适症状消失,嘱患者定期复诊。
讨论
本例患者因强直性脊柱炎给予阿达木单抗,治疗21个月后出现淋巴结结核,停用该药并予四联抗结核治疗,症状逐渐缓解。患者入院时强直性脊柱炎病情稳定,淋巴结结核与原发疾病无关。有文献报道阿达木单抗可诱发结核 [ 1 ],美国药品食品管理局发布的阿达木单抗药品说明书已警示该药可诱发结核。采用Naranjo不良反应因果关系评估量表 [ 2 ]评价阿达木单抗与本例患者颈部淋巴结结核的因果关系,评分为7分(很可能有关)。
强直性脊柱炎主要侵犯中轴骨骼,其特征性表现为骶髂关节和脊柱炎症性背痛,影像学改变为骶髂关节炎。肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)在该病发病中起重要作用,阻断TNF-α通路是治疗该病的有效方法。阿达木单抗通过阻断TNF-α与p55和p57细胞表面肿瘤坏死因子受体的相互作用而拮抗TNF-α的生物活性,被用于治疗强直性脊柱炎等自身免疫疾病 [ 3 ]。其常见不良反应是感染、注射部位反应 [ 4 ],偶见严重感染、新发结核和结核病再活化 [ 5 ]。使用TNF-α抑制剂的患者较未使用者发生结核病的风险增加约4倍 [ 6 ]。蔡俊等 [ 7 ]的一项文献分析显示,在39例使用阿达木单抗致结核的患者中,37例结核发病时间在用药后3年内,14例发生在用药后6~12个月。
TNF-α抑制剂引发的结核中2/3为肺外结核,其中约50%为播散型结核 [ 8 ]。肺外结核可发生在淋巴结、腹膜、胸膜等部位,无论使用哪种TNF-α抑制剂,其诱发结核的病死率均高于结核的全因死亡率 [ 9 ]。使用阿达木单抗治疗的患者即使在用药前进行了结核筛查以及预防性抗结核治疗,发生结核的风险仍为健康人群的2.93倍 [ 10 ]。卫菁等 [ 11 ]分析了167例使用TNF-α抑制剂后发生结核病的患者临床资料,发现用药前行结核筛查者152例,其中42例为阳性,110例为阴性。提示无论患者使用阿达木单抗前结核病筛查结果如何,都应警惕新发结核感染以及结核活化的风险。
本例提示,阿达木单抗可致颈部淋巴结结核。用药前需仔细询问患者病史并完善相关检查,用药后仍需密切随诊,一旦确诊应立即予以抗结核治疗,并根据原发疾病的情况调节或更换治疗方案。
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