幼年特发性关节炎成人后的临床特点及生物制剂治疗

doi:10.19723/j.issn.1671-167X.2020.06.005

摘要/Abstract

摘要：

目的:探讨幼年特发性关节炎(juvenile idiopathic arthritis, JIA)成人后的临床特点及生物制剂治疗。方法:选择2009年1月1日至2019年1月1日在四川大学华西医院风湿免疫科住院治疗既往病史有JIA诊断的358例患者,对纳入符合条件的90例病例的基本信息、临床症状、诊断指标、治疗方案、门诊随诊(住院患者要求门诊随诊治疗)和诊疗过程等信息进行回顾性分析。观察不同年龄、不同病程的幼年特发性关节炎成人后的临床特点和使用生物制剂治疗6个月的门诊情况。结果:按年龄分为≤26岁组(42例)和>26岁组(48例),在实验室检查[项目包括类风湿因子(rheumatoid factor,RF)、抗核抗体(anti-nuclear antibody、ANA)、抗中性粒细胞抗体(anti-neutrophil antibody,ANCA)、红细胞沉降率(erythrocyte sedimentation rate,ESR)、C-反应蛋白 (C-reactive protein CRP)、白细胞介素-1β(interleukin-1β,IL-1β)、白细胞介素-6(interleukin 6,IL-6)、血红蛋白(hemoglobin,HGB)、白细胞计数(white blood cell count,WBC)、人类白细胞抗原-B27(human leukocyte antigen-B27,HLA-B27)、补体3(complement 3,C3)等]、并发症、治疗和预后上,≤26岁组较>26岁组总体病症轻,即年龄越大,炎症等症状发作时越重、并发症越多、治疗效果越差、预后越差,且差异有统计学意义(P<0.05)。按病程分为≤19年组(46例)和>19年组(44例),在实验室检查(RF、ANA、ANCA、ESR、CRP、IL-1β、IL-6、HGB、HLA-B27、C3等)、并发症、治疗和预后上,病程≤19年组较病程>19年组总体病症轻,即病程越长炎症等症状发作时越重、并发症越多、治疗效果越差、预后越差,差异有统计学意义(P<0.05)。门诊6个月生物制剂治疗发现,生物制剂能改善患者部分临床症状,延缓疾病进一步发展,与非生物制剂治疗组(48例)相比,生物制剂组(42例)受益,且差异有统计学意义(P<0.05)。结论:成人后的JIA虽然被诊断为结缔组织病,但仍然有随着病程和年龄增长而具有特殊的临床特点,因此,建议给予JIA患者成人后特殊关注,要求于成人风湿免疫科规律就诊,按照相应结缔组织病或JIA诊断,规范治疗,同时,重视JIA病史。在生物制剂和非生物制剂治疗对比中,证实生物制剂治疗能有效改善成人后的JIA患者部分临床症状,因此建议在经济条件允许的情况下,可尽早使用生物制剂治疗,延缓疾病发展。

关键词: 成人, 风湿免疫科, 幼年特发性关节炎, 临床特点, 结缔组织病

Abstract:

Objective: To explore the clinical characteristics and biological treatment of juvenile Idiopathic arthritis (JIA) after adulthood. Methods: Selected 358 patients with previous medical history diagnosed by JIA who were hospitalized in the Department of Rheumatology and Immunology, West China Hospital of Sichuan University from January 1, 2009 to January 1, 2019. Perform retrospective analysis of basic information, clinical symptoms, diagnostic indicators, treatment plans, outpatient follow-up (inpatients require outpatient follow-up treatment) and diagnosis and treatment process of 90 eligible cases included, and observe different ages and different courses of disease. The clinical characteristics of young and middle-aged idiopathic arthritis in adults and the outpatient situation of using biological agents for 6 months. Results: According to age, they were divided into ≤26 years old group (42 cases) and >26 years old group (48 cases). Under examination [rheumatoid factor (RF), anti-nuclear antibody (ANA), anti-neutrophil antibody (ANCA), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), interleukin-1β (IL-1β), interleukin 6 (IL-6), hemoglobin (HGB), white blood cell count (WBC), human leukocyte antigen-B27 (HLA-B27), complement 3 (C3), etc.], concurrent in terms of symptoms, treatment and prognosis, the ≤26-year-old group was generally lighter than the >26-year-old group; that was, the older the age, the heavier the onset of inflammation and other symptoms, the more complications, the worse the treatment effect, and the worse the prognosis, and there were statistical differences academic significance (P<0.05). According to the course of disease, they were divided into ≤19 years group (46 cases) and >19 years group (44 cases). In terms of examination (RF, ANA, ANCA, ESR, CRP, IL-1β, IL-6, HGB, HLA-B27, C3, etc.), complications, treatment and prognosis, the course of disease ≤19 years group was compared with the disease course> 19 years group Overall mild; that was, the longer the course of the disease, the more severe the onset of symptoms such as inflammation, the more complications, the worse the treatment effect, and the worse the prognosis, P<0.05, the difference was statistically significant. After 6 months of outpatient treatment with biological agents, it was found that biological agents could improve some of the patients’ clinical symptoms and delay the further development of the disease. Compared with the non-biological agent treatment group (48 cases), the biological agent group (42 cases) benefited, and the difference was statistically significant (P<0.05). Conclusion: Through retrospective analysis, this article believes that although adult JIA is diagnosed as connective tissue disease, it has special clinical characteristics with the course of the disease and age. Therefore, it should be recommended to give special attention to JIA patients after adulthood, require regular medical treatment in the adult rheumatology department, according to the corresponding connective tissue disease or JIA diagnosis, and standard treatment; at the same time, pay attention to the history of JIA. In the comparison of biological and non-biological treatment, it is proved that biological treatment can effectively improve some of the clinical symptoms of JIA patients after adulthood. Therefore, it is recommended that biological treatment be used as soon as possible if economic conditions permit to delay the development of the disease.

Key words: Adults, Department of rheumatology and immunology, Juvenile idiopathic arthritis, Clinical features, Connective tissue diseases

中图分类号:

R593

魏士雄,黎苏佳,刘毅. 幼年特发性关节炎成人后的临床特点及生物制剂治疗[J]. 北京大学学报（医学版）, 2020, 52(6): 1014-1022.

Shi-xiong WEI,Shu-jia LI,Yi LIU. Clinical characteristics and biological treatment of adult patient with juvenile idiopathic arthritis[J]. Journal of Peking University (Health Sciences), 2020, 52(6): 1014-1022.

图/表 4

表1

不同年龄组患者的临床特征"

Clinical features	≤26 years	>26 years	P
Cases, n(%)	52 (57.78)	38 (42.22)	-
Female, n(%)	27 (51.92)	32 (84.21)	-
Male, n(%)	25 (48.08)	6 (15.79)	-
Disease duration/years, $x - ± s$	14.35 ± 6.09	23.22±6.28	0.436
Medical check(+)
RF/(IU/mL), $x - ± s$	63.33±25.44	69.12±28.21	<0.05^*
ANA(+/-), n(%)	17 (32.69)	14 (36.84)	-
ANCA(+/-), n(%)	12 (20.69)	9 (23.68)	-
ESR/(mm/h), $x - ± s$	77.42±28.23	79.71±31.22	<0.05^*
CRP/(mg/L), $x - ± s$	23.57±7.58	27.59±3.46	<0.05^*
IL-1β/(ng/L), $x - ± s$	17.35±5.45	19.55±7.32	<0.05^*
IL-6/(ng/L), $x - ± s$	1.472±0.212	1.379±0.293	0.172
HGB/(g/L), $x - ± s$	97.38±19.86	93.26±21.50	0.420
WBC/(×10⁹/L), $x - ± s$	13.83±4.58	12.37±2.68	0.356
HLA-B27(+/-), n(%)	7 (13.46)	15 (39.47)	-
C3/(g/L), $x - ± s$	0.514±0.210	0.496±0.257	<0.05^*
Abnormal X and CT images of joints, n(%)	52 (100.00)	38 (100.00)	-
Treatment (In hospital)
NSAIDs treatment, n(%)	5 (100.00)	0	-
Biological agent treatment, n(%)	17 (40.48)	25 (59.52)	-
Hormone therapy, n(%)	14 (38.89)	22 (61.11)	-
Immunosuppressive therapy, n(%)	9 (60.00)	6 (40.00)	-
Other treatment, n(%)	0	3 (100.00)	-
Pay a return visit
DAS28, $x - ± s$	3.58±1.75	4.67±1.50	<0.05^*
SF-36, $x - ± s$	83.78±11.51	91.35±10.52	<0.01^*
JADI-A, $x - ± s$	7.28±2.58	7.89±3.15	<0.05^*
JADI-E, $x - ± s$	3.93±1.65	4.82±2.12	<0.05^*
Number of complications, $x - ± s$	6.52±1.76	7.97±2.53	<0.05^*

表1

表2

不同病程组患者的临床特征"

Clinical features	≤19 years	>19 years	P
Age/years, $x - ± s$	20.42±7.61	25.35±8.53	0.723
Female, n(%)	27 (51.92)	32 (61.54)	-
Male, n(%)	19 (61.29)	12 (38.71)	-
Cases, n(%)	46 (51.11)	44 (48.89)	-
Medical check(+)
RF/(IU/mL), $x - ± s$	61.53±24.35	72.39±23.18	<0.01^*
ANA(+/-), n(%)	18 (39.13)	13 (29.55)	-
ANCA(+/-), n(%)	13 (28.26)	8 (18.18)	-
ESR/(mm/h), $x - ± s$	75.37±24.41	82.56±23.87	<0.05^*
CRP/(mg/L), $x - ± s$	23.85±6.78	29.52±5.61	<0.05^*
IL-1β/(ng/L), $x - ± s$	18.23±4.75	19.33±5.32	0.046
IL-6/(ng/L), $x - ± s$	1.517±0.179	1.254±0.288	0.058
HGB/(g/L), $x - ± s$	99.54±17.53	90.11±19.44	<0.05^*
WBC/(×10⁹/L), $x - ± s$	12.64±4.13	13.43±5.56	0.063
HLA-B27(+/-), n(%)	14 (30.43)	8 (18.18)	-
C3/(g/L), $x - ± s$	0.565±0.177	0.460±0.233	<0.05^*
Abnormal X and CT images of joints, n(%)	46 (100.00)	44 (100.00)	-
Treatment (In hospital)
NSAIDs Treatment, n(%)	4 (80.00)	1 (20.00)	-
Biological agent treatment, n(%)	14 (33.33)	28 (66.67)	-
Hormone therapy, n(%)	15 (41.67)	21 (58.33)	-
Immunosuppressive therapy, n(%)	7 (46.67)	8 (53.33)	-
Other treatment, n(%)	0 (-)	3 (100.00)	-
Pay a return visit
DAS28, $x - ± s$	3.25±1.79	5.01±1.99	<0.01^*
SF-36, $x - ± s$	85.53±12.34	90.01±11.56	<0.05^*
JADI-A, $x - ± s$	6.79±1.39	8.21±2.14	<0.01^*
JADI-E, $x - ± s$	3.76±1.13	4.15±0.93	<0.05^*
Number of complications, $x - ± s$	5.64±1.57	8.07±1.35	<0.01^*

表2

表3

治疗组的基线特征"

Demographic/clinical characteristics	Biological agents treatment group (n=42)	Non-biological agents treatment group (n=48)
Age/years, $x - ± s$	24.75±5.32	22.53±6.31
Female, n(%)	27 (64.29)	32 (66.67)
Course of the disease/years, $x - ± s$	22.17±7.25	20.54±7.85
Previously took DMARDs, n(%)	42 (100.00)	48 (100.00)
Taking corticosteroids, n(%)	42 (100.00)	48 (100.00)
Taking immunosuppressants, n(%)	42 (100.00)	48 (100.00)
CRP/(mg/L), $x - ± s$	25.40±6.67	26.22±7.18
RF/(IU/mL), $x - ± s$	63.26±24.78	63.88±25.15
ANA(+), n(%)	35.71	33.33
ANCA(+), n(%)	26.19	20.83
ESR/(mm/h), $x - ± s$	76.53+29.10	77.13±28.48
IL-1β/(ng/L), $x - ± s$	18.41±7.32	17.54±6.57
IL-6/(ng/L), $x - ± s$	1.531±0.214	1.41±0.274
HGB/(g/L), $x - ± s$	96.40±20.21	92.82±23.31
WBC/(×10⁹/L), $x - ± s$	14.38±4.19	14.01±5.45
Radiographic progression/units	0	0
DAS28, $x - ± s$	5.23±1.39	4.57±1.86
SF-36, $x - ± s$	97.30±14.25	94.04±12.45
JADI-A, $x - ± s$	8.05±2.54	7.75±2.63
JADI-E, $x - ± s$	4.01±0.94	3.35±1.21

表3

表4

生物制剂组和非生物制剂组6个月治疗后临床特点"

Clinical features	Biological agents treatment group 6 months after treatment (n=42)	Non-Biological agents treatment group 6 months after treatment (n=48)
CRP/(mg/L), $x - ± s$	9.52±5.51	24.57±8.62^#
RF/(IU/mL), $x - ± s$	27.64±18.34	57.50±23.32^#
ANA(+)/%	9.52	12.50
ANCA(+)/%	14.29	14.58
ESR/(mm/h), $x - ± s$	30.58±16.43	69.22±26.30^#
IL-1β/(ng/L), $x - ± s$	8.33±7.32	17.35±6.27^#
IL-6/(ng/L), $x - ± s$	0.934±0.444	0.937±0.572
HGB/(g/L), $x - ± s$	113.62±14.16	96.23±24.45^#
WBC/(10⁹ /L), $x - ± s$	10.25±2.47	12.35±3.73
Radiographic progression: first month, second months, third months, fourth months, fifth months, sixth month	0.56, 0.82, 0.89, 1.11, 1.17, 1.19	0.58, 0.95, 1.42, 1.85, 2.01, 2.39^#
DAS28, $x - ± s$	2.95±1.21	4.31±1.45^#
SF136, $x - ± s$	103.86±11.43	97.30±12.96^#
JADI-A, $x - ± s$	6.55±1.87	6.41±2.02
JADI-E, $x - ± s$	3.18±1.02	2.92±1.53

表4

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