Clinical features and prognosis of 118 children with histiocytic necrotizing lymphadenitis / 中华儿科杂志

Objective: To explore the clinical features and prognosis of children with histiocytic necrotizing lymphadenitis (HNL). Methods: The clinical data of 118 children with HNL diagnosed and treated in the Department of Rheumatology and Immunology of Children's Hospital, Capital Institute of Pediatrics from January 2014 to December 2021 were retrospectively analyzed. The clinical symptoms, laboratory examination, imaging examination, pathological findings, treatment and follow-up were analyzed. Results: Among the 118 patients, 69 were males and 49 were females. The age of onset was 10.0 (8.0, 12.0) years, ranging from 1.5 to 16.0 years. All the children had fever lymph node enlargement, blood system involvement in 74 cases (62.7%), skin injury in 39 cases (33.1%). The main manifestations of laboratory examination were increased erythrocyte sedimentation rate in 90 cases (76.3%), decreased hemoglobin in 58 cases (49.2%), decreased white blood cells in 54 cases (45.8%) and positive antinuclear antibody in 35 cases (29.7%). Ninety-seven cases (82.2%) underwent B-mode ultrasound of lymph nodes, showing nodular lesions with low echo in the neck; 22 cases (18.6%) underwent cervical X-ray and (or) CT; 7 cases (5.9%) underwent cervical magnetic resonance imaging. Lymph node biopsy was performed in all 118 cases, and the pathological results did not support malignant diseases such as lymphoma or Epstein-Barr virus infection, suggesting HNL. Fifty-seven cases (48.3%) recovered without treatment, 61 cases (51.7%) received oral steroid therapy, and 4 cases (3.4%) received indomethacin as anal stopper. The 118 cases were followed up for 4 (2, 6) years, ranging from 1 to 7 years, 87 cases (73.7%) had one onset and did not develop into other rheumatological diseases, and 24 cases (20.3%) had different degrees of recurrence, 7 cases (5.9%) had multiple system injuries, and all of the tested autoantibodies were positive for medium and high titers. All of them developed into other rheumatic immune diseases, among which 5 cases developed into systemic lupus erythematosus and 2 cases developed into Sjogren's syndrome; 7 cases were given oral steroid therapy, including 6 cases plus immunosuppressant and 2 cases receiving methylprednisolone 20 mg/kg shock therapy. Conclusions: The first-onset HNL portion is self-healing, hormone-sensitive and has a good prognosis. For HNL with repeated disease and multiple system injury, antinuclear antibody titer should be monitored during follow-up, and attention should be paid to the possibility of developing into other rheumatological diseases, with poor prognosis.

Treatment of 11 cases of juvenile idiopathic arthritis by intra-articular injection of adalimumab / 中华儿科杂志

Objective: To evaluate the efficacy and safety of intra-articular injection of adalimumab (ADA) in the treatment of refractory oligoarticular juvenile idiopathic arthritis (JIA). Methods: This was a retrospective study. Clinical data on age, gender, and symptoms of joint swelling and pain were collected from 11 children with refractory oligoarticular JIA involving only knee joints admitted to Department of Rheumatism and Immunology of Children's Hospital, Capital Institute of Pediatrics from November 2019 to October 2020. The physician and parent-child evaluation of disease activity, the number of active joints, and the level of erythrocyte sedimentation rate (ESR) at different treatment time points were analyzed at every 4-week observation point after drug administration, and the non-parametric Kruskal-Wallis test was used to compare the differences in clinical evaluation indicators and changes in laboratory tests at different treatment times. The follow-up period was 6 months. Results: Among the 11 children, 5 were boys and 6 were girls. The age was 3.0 (2.8) years. All 11 children had symptoms of joint swelling and pain as well as limitation of movement. After 3 intra-articular injections of ADA, the joint symptoms of 11 children were better than before treatment; the joint symptoms of 7 children disappeared completely, and no recurrence occurred during the 6-month follow-up period. At different treatment times, physician and parent-child evaluation of disease activity, a gradual decrease in the number of active joints in the children, ESR, and juvenile arthritis disease activity score with 27 joints were all statistically significant (χ2=53.99, 59.37, 32.87, 40.07, 54.00, all P<0.001).No significant adverse drug reactions were observed in any of the 11 children during treatment and follow-up. Conclusion: Intra-articular injection of ADA in the treatment of refractory oligoarticular JIA has a significant effect in controlling joint symptoms and is relatively safe.

Relationship between specific microRNAs in plasma and juvenile idiopathic arthritis / 中华实用儿科临床杂志

Objective To investigate the potential possibilities of specific microRNA in plasma as novel biomarkers for the early diagnosis in juvenile idiopathic arthritis (JIA).Methods This research was be segmented into 4 stages.1.Screened candidate microRNAs:5 candidate plasma microRNAs were detected by biochips of microRNAs,corresponding 5 JIA patients with onset of oligoarthritis,5 JIA patients with onset of polyarthritis and 3 age-matched and sex-matched healthy controls individual.2.The feasibility of the microRNAs as novel biomarkers was validated by Realtime quantitative polymerase chain reaction (RT-PCR) in plasma on 80 JIA patients (43 oligoarthritis,37 polyarthritis),29 juvenile ankylosing spondylitis(JAS) patients and 30 healthy control individuals.3.The change of microRNAs was observed by RT-PCR in plasma from another 9 JIA patients before and 3 months after anti-rheumatic drug treatment.4.The correlation between the levels of candidate plasma microRNAs and clinical parameters of JIA patients was analyzed.Results Plasma concentrations of miR-16,miR-146a and miR-223 in JIA patients,including oligoarthritis and polyarthritis,were significantly higher than those in healthy subjects (all P ＜ 0.05) and JAS patients (all P ＜ 0.001),and plasma concentration of miR-132 in JIA were significantly lower than those in healthy subjects and JAS patients (all P ＜ 0.001).Although the plasma concentration of miR-16 in polyarthritis JIA patients was considerably higher than that in oligoarthritis JIA patients (all P ＜ 0.01),the plasma concentrations of miR-146a,miR-223 and miR-132 were no difference between the 2 subtypes of JIA(all P ＞0.05).More importantly,it was found that the expression of miR-16 was considerably reduced in the post-treatment plasma samples when compared to the pre-treatment samples(P =0.061).In addition,the levels of miR-16 in JIA plasma inversely corrected with tender joint.Conclusions Plasma levels of miR-16 were well-discriminated between JIA patients and healthy subjects or JAS patients.It is suggested that plasma miR-16 might serve as a novel and potential biomarker for screening JIA.Furthermore,it might serve as a novel biomarker for joint inflammation but not specifically for differentiating the subtypes of JIA.

Application of Infliximab in treating of severe polyarticular juvenile idiopathic arthritis / 中华实用儿科临床杂志

Objective To investigate the safety and efficacy of infliximab in the treatment of severe polyarticular juvenile idiopathic arthritis(JIA).Methods Forty-four patients with severe polyarticular JIA were treated with infliximab (3 mg/kg) on week 0,2 and 6,respectively,and then they were treated every 8 weeks,plus methotrexate or and leflunomide for oral intake,and meanwhile physical therapy and functional rehabilitation were carried out.Patients were assessed by the American College of Rheumatology (ACR) response criteria (30,50,70) on week 2,6 and 14 and followed up,including swollen joint count,tender joint count,duration of morning stiffness and fever,body functions,lab inflammatory index like CRP,ESR changes.Results Among 44 cases,according to ACR response criteria,which represents 30％,50％,70％ improvement from baseline,the cure rates with infliximab therapy in swollen joint count,tender joint count,duration of morning stiffness,CRP,ESR were achieved in 47.7％ (21/44 cases),20.5％ (9/44 cases),and 11.4％ (5/44 cases) of patients with JIA on week 2 ; 63.6％ (28/44 cases),43.2％ (19/44 cases),and 13.6％ (6/44 cases) of patients on week 6 ;81.8％ (36/44 cases),52.2％ (23/44 cases),27.2％ (12/44 cases) on week 14,respectively.Inflammatory index like CRP,ESR with infliximab treatment decreased considerably compared that before treatment(P ＜0.05).Side effects from infliximab treatment were well-tolerated.There was no abnormality in the liver and kidneys or complicated infections,and no negative cases turned into the positive.Conclusions Treating severe polyarticular JIA with infliximab showed a rapid cure rate,safety and better tolerance.

Rituximab therapy for severe pediatric systemic lupus erythematosus / 中华儿科杂志

<p><b>OBJECTIVE</b>To analyze the safety and efficacy of anti-CD20 monoclonal antibody in treatment of severe pediatric systemic lupus erythematosus (PSLE).</p><p><b>METHOD</b>The diagnosis of PSLE was made according to the criteria for the classification of systemic lupus erythematosus revised by the American College of Rheumatology in 1997. Severe cases with PSLE was selected by the following criteria: age ≤ 16 years, number of important organs involved > 1, SLEDAI score > 10 points and poor response to conventional immunosuppressive treatment. These patients received 2 doses of 375 mg/m(2) rituximab (RTX), 2 weeks apart. Clinical, laboratory findings and drug side effects were recorded at RTX initiation, 2 weeks, 1 month, 3, 6 and 12 months after infusion.</p><p><b>RESULT</b>A total of 20 patients. Male to female ratio was 1:3, were enrolled. They were 5-16 years old. The course of disease was (3.0 ± 2.5) years (range: 1 month-7 years), patients were followed up for 12 - 36 months [median: (27.0 ± 7.8) months]. Delirium and cognitive disorders were significantly improved in 10 cases of lupus encephalopathy after 1 month. Lupus nephritis in children were eased slowly, 14/15 patients with lupus nephritis were improved after 2-3 months. Four cases of lupus pneumonia were significantly improved within 1 month. Decreased blood cells counts were relieved at 1 month in 16/18 cases. Cellular immune function was assessed 2 weeks after application of anti-CD20 monoclonal antibody; we found B-cell clearance in 19 patients (95%). B lymphocyte count of 18 patients (90%) was restored within one year. SLEDAI score was reduced obviously. Dose of corticosteroid ranged from (45.0 ± 4.7) mg/m(2) before drug use to (12.0 ± 2.7) mg/m(2) 12 months later (P < 0.001). After the drug use, 5 patients had pneumonia within 6 months; 2 cases who suffered from aspergillus pneumonia and Pneumocystis carinii pneumonia respectively were severe. They accepted mechanical ventilation and anti-inflammatory support after being transferred to the intensive care unit, and their conditions improved at last. No death occurred. In 2 patients the disease recurred with B-cell recovery after 15 months and 18 months. Administration of another cycle of rituximab resulted in remission again in one case but not in the other.</p><p><b>CONCLUSION</b>Anti-CD20 monoclonal antibody is effective and safe in treatment of severe PSLE. But severe infections may occur in some cases. Focusing on prevention and early treatment can reduce the probability of adverse reactions.</p>