Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Harvard Medical School, Boston, Massachusetts.
Arthritis Care Res (Hoboken). 2024 Mar;76(3):328-339. doi: 10.1002/acr.25234. Epub 2023 Nov 27.
Systemic juvenile idiopathic arthritis-associated lung disease (SJIA-LD) is a life-threatening disease complication. Key questions remain regarding clinical course and optimal treatment approaches. The objectives of the study were to detail management strategies after SJIA-LD detection, characterize overall disease courses, and measure long-term outcomes.
This was a prospective cohort study. Clinical data were abstracted from the electronic medical record, including current clinical status and changes since diagnosis. Serum biomarkers were determined and correlated with presence of LD.
We enrolled 41 patients with SJIA-LD, 85% with at least one episode of macrophage activation syndrome and 41% with adverse reactions to a biologic. Although 93% of patients were alive at last follow-up (median 2.9 years), 37% progressed to requiring chronic oxygen or other ventilator support, and 65% of patients had abnormal overnight oximetry studies, which changed over time. Eighty-four percent of patients carried the HLA-DRB1*15 haplotype, significantly more than patients without LD. Patients with SJIA-LD also showed markedly elevated serum interleukin-18 (IL-18), variable C-X-C motif chemokine ligand 9 (CXCL9), and significantly elevated matrix metalloproteinase 7. Treatment strategies showed variable use of anti-IL-1/6 biologics and addition of other immunomodulatory treatments and lung-directed therapies. We found a broad range of current clinical status independent of time from diagnosis or continued biologic treatment. Multidomain measures of change showed imaging features were the least likely to improve with time.
Patients with SJIA-LD had highly varied courses, with lower mortality than previously reported but frequent hypoxia and requirement for respiratory support. Treatment strategies were highly varied, highlighting an urgent need for focused clinical trials.
全身性幼年特发性关节炎相关肺疾病（SJIA-LD）是一种危及生命的疾病并发症。关于临床病程和最佳治疗方法仍存在关键问题。本研究的目的是详细描述 SJIA-LD 检测后的管理策略，描述整体疾病过程，并测量长期结果。
这是一项前瞻性队列研究。从电子病历中提取临床数据，包括当前临床状况和诊断后的变化。测定血清生物标志物，并与 LD 的存在相关联。
我们纳入了 41 例 SJIA-LD 患者，85%至少有一次巨噬细胞活化综合征发作，41%对生物制剂有不良反应。尽管 93%的患者在最后一次随访时仍存活（中位数 2.9 年），但 37%进展为需要慢性吸氧或其他呼吸机支持，65%的患者夜间血氧饱和度研究异常，且随时间变化。84%的患者携带 HLA-DRB1*15 单倍型，明显多于无 LD 的患者。SJIA-LD 患者的血清白细胞介素-18（IL-18）明显升高，C-X-C 基序趋化因子配体 9（CXCL9）也存在可变性，基质金属蛋白酶 7 显著升高。治疗策略显示抗 IL-1/6 生物制剂的使用存在差异，并添加了其他免疫调节治疗和肺部靶向治疗。我们发现了广泛的当前临床状况，与从诊断到持续生物治疗的时间无关。变化的多领域测量显示，影像学特征随时间的推移最不可能改善。
SJIA-LD 患者的病程差异很大，死亡率低于先前报道，但缺氧和呼吸支持需求频繁。治疗策略差异很大，这突出表明迫切需要进行有针对性的临床试验。
