Clinical and laboratory features, treatment, and outcomes of macrophage activation syndrome in 80 children: a multi-center study in China.

BACKGROUND: Macrophage activation syndrome (MAS) is a major cause of morbidity and mortality in pediatric rheumatology. We aimed to further understand the clinical features, treatment, and outcome of MAS in China. METHODS: A multi-center cohort study was performed in seven hospitals in China from 2012 to 2018. Eighty patients with MAS were enrolled, including 53 cases with systemic juvenile idiopathic arthritis (SJIA-MAS), 10 cases of Kawasaki disease (KD-MAS), and 17 cases of connective tissue disease (CTD-MAS). The clinical and laboratory data were collected before (pre-), at onset, and during full-blown stages of MAS. We compared the data among the SJIA-MAS, KD-MAS, and CTD-MAS subjects. RESULTS: 51.2% of patients developed MAS when the underlying disease was first diagnosed. In patients with SJIA, 22.6% (12/53) were found to have hypotension before the onset of SJIA-MAS. These patients were also found to have significantly increased aspartate aminotransferase (AST) and lactate dehydrogenase (LDH), as well as decreased albumin (P < 0.05), but no difference in alanine aminotransferase, ferritin, and ratio of ferritin/erythrocyte sedimentation rate (ESR) at onset of MAS when compared to pre-MAS stages of the disease. In addition, ferritin and ratio of ferritin/ESR were significantly elevated in patients at full-blown stages of SJIA-MAS compared to pre-MAS stage. Significantly increased ferritin and ratio of ferritin/ESR were also observed in patients with SJIA compared to in KD and CTD. Receiver-operating characteristic analysis showed that 12,217.5 µg/L of ferritin and 267.5 of ferritin/ESR ratio had sensitivity (80.0% and 90.5%) and specificity (88.2% and 86.7%), respectively, for predicting full-blown SJIA-MAS. The majority of the patients received corticosteroids (79/80), while biologic agents were used in 12.5% (10/80) of cases. Tocilizumab was the most commonly selected biologic agent. The overall mortality rate was 7.5%. CONCLUSIONS: About half of MAS occurred when the underlying autoimmune diseases (SJIA, KD, and CTD) were first diagnosed. Hypotension could be an important manifestation before MAS diagnosis. Decreased albumin and increased AST, LDH, ferritin, and ratio of ferritin/ESR could predict the onset or full blown of MAS in patient with SJIA.

Current status and recent advances on the use of ultrasonography in pediatric rheumatic diseases.

BACKGROUND: Ultrasonography has become a useful tool in the clinical rheumatology settings in the last two decades, but its use has only recently been explored by pediatric rheumatologists. The aim of this article is to review the literature on the current status and recent advances on the use of ultrasound in pediatric rheumatic diseases. DATA SOURCES: We have retrieved and reviewed the relevant articles from MEDLINE/PubMed databases published so far, on the applications of ultrasound in juvenile idiopathic arthritis (JIA), systemic lupus erythematosus, dermatomyositis, enthesitis, Sjogren's syndrome, and other rheumatic diseases. In addition, articles on novel ultrasound imaging technology of potential use in pediatric rheumatology are also reviewed. RESULTS: In JIA, ultrasound can be used to detect subclinical synovitis, to improve the classification of patients in JIA subtypes, to capture early articular damage, to monitor treatment response, and to guide intraarticular injections. Ultrasound is also considered useful in other rheumatic disorders for the evaluation of musculoskeletal symptoms, assessment of parotid gland pathology, and measurement of skin thickness and pathology. Novel ultrasound techniques developed to augment the functionality of ultrasonography may also be applicable in pediatric rheumatic disorders. CONCLUSIONS: Ultrasound shows great promise in the assessment and management of children with rheumatologic disorders. However, standardization and validation of ultrasound in healthy children and in patients with rheumatic diseases are still needed.

[Clinical and laboratory features of macrophage activation syndrome].

OBJECTIVE: To study the clinical and laboratory features of macrophage activation syndrome (MAS) at the early stage of diagnosis, and to explore a method for early identification of MAS. METHODS: A retrospective analysis was performed for the demographic data, clinical and laboratory features, and treatment outcomes of 21 MAS patients. RESULTS: Of the 21 MAS patients, 14 had systemic juvenile idiopathic arthritis, 5 had Kawasaki disease (KD), and 2 had connective tissue disease (CTD) as primary diseases. The median time of MAS onset was 19 days. The KD patients had the shortest time of MAS onset, while the CTD patients had the longest onset time (P=0.009). The top 10 clinical symptoms were fever (95%), rash (86%), lymph node enlargement (67%), hemophagocytic phenomenon in bone marrow (63%), pulmonary disease (62%), serous effusion (62%), hepatomegaly (52%), cerebrospinal fluid abnormalities (50%), central nervous system damage (43%), and splenomegaly (38%). The median of hemoglobin level was lower than the normal value. The medians of C-reactive protein level and erythrocyte sedimentation rate were higher than the normal values. There were significant increases in serum ferritin, glutamic-pyruvic transaminase, aspartate aminotransferase, lactate dehydrogenase, and triglyceride. The median of fibrinogen level was lower than the normal value. There were significant increases in D-dimer, interleukin-6 (IL-6), interleukin-10 (IL-10), and interferon-γ (IFN-γ). Of the 21 patients, 20 were improved and discharged. CONCLUSIONS: If patients with rheumatic disease have persistent fever, hepatic dysfunction, coagulation disorders, multiple organ impairment, significantly increased IL-10 and IFN-γ, and a persistent increase in serum ferritin, the development of MAS should be considered.

[Association of vitamin D concentrations with juvenile idiopathic arthritis].

OBJECTIVE: 25-Hydroxyvitamin D3 [25(OH)D3] is the main product of vitamin D and can reflect the absolute concentration of active vitamin D in the body. This study examined serum 25(OH)D3 levels in children with juvenile idiopathic arthritis (JIA) in order to explore the association of vitamin D concentrations with the pathogenesis and disease activity of JIA. METHODS: Serum samples were collected from 53 children confirmed as having JIA between January 2013 and March 2014, as well as 106 healthy children (control group) who underwent physical examination in the same period. Serum concentrations of 25(OH)D3 were measured using ELISA and compared between the cases and healthy controls. The association of serum 25(OH)D3 levels with JIA subtypes, ACR Pediatric 30 Score, peripheral blood C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were analyzed in children with JIA. RESULTS: Compared with the control group, the JIA group had significantly reduced serum 25(OH)D3 levels (median: 42.6 nmol/L vs 49.9 nmol/L; P<0.01). The percentage of subjects with severe deficiency of vitamin D in the JIA group was significantly higher than that in the control group (17.0% vs 6.6%; P<0.05). Serum 25(OH)D3 showed no significant correlations with JIA subtypes, ACR Pediatric 30 Score, CRP, and ESR in children with JIA. CONCLUSIONS: Vitamin D concentrations are significantly decreased in children with JIA. Decreased vitamin D concentrations may be associated with the pathogenesis of JIA. However, vitamin D concentrations may have no correlations with JIA subtypes, disease severity, and disease activity.

[Serum cytokine levels in children with newly diagnosed active systemic juvenile idiopathic arthritis].

OBJECTIVE: To study the changes in serum cytokines levels in children with newly diagnosed active systemic juvenile idiopathic arthritis (SJIA) and to explore the role of cytokines in the development and progression of SJIA. METHODS: Seventy-four pediatric patients with active SJIA between January 2010 and December 2013 were included in the study. Serum levels of interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukine-10 (IL-10), tumor necrosis factor (TNF), and interferon gamma (IFN-γ) were measured by flow cytometry in these patients. The levels of cytokines were also determined in 202 healthy children as the control group. Routine laboratory parameters including white blood cell (WBC) count, percentage of neutrophils, hemoglobin level, platelet count, hypersensitive C-reactive protein (hs-CRP), and erythrocyte sedimentation rate (ESR) were monitored in the patient group. RESULTS: The WBC count, percentage of neutrophils, hs-CRP, and ESR in 74 cases of SJIA were significantly above the normal range, their platelet counts were within the normal range, whereas hemoglobin levels were below the normal range. Compared with the control group, the patient group showed a significantly increased level of IL-6 (P<0.01) and significantly reduced levels of IL-4, IL-10, and TNF (P<0.01). However, there were no significant changes in serum levels of IL-2 and IFN-γ in the patient group (P>0.05). In SJIA children, IL-6 level, which was significantly elevated, was negatively correlated with hemoglobin level, which was significantly reduced (r=-0.244, P<0.05). CONCLUSIONS: Serum level of IL-6 is significantly increased in children with SJIA, and it has a negative correlation with anemia.

[Risk factors for pleural lung disease in children with juvenile idiopathic arthritis].

OBJECTIVE: To investigate the risk factors for pleural lung disease (PLD) in children with juvenile idiopathic arthritis (JIA) and to provide a basis for the early diagnosis and timely treatment of this disease. METHODS: A total of 360 children with a confirmed diagnosis of JIA were enrolled, and their clinical data were retrospectively analyzed. All patients underwent a chest X-ray. The patients with PLD were assigned to PLD group, while those without PLD were assigned to non-PLD group. The clinical, imaging, and laboratory results of JIA patients with PLD were analyzed. RESULTS: Among the 360 JIA patients, 43 (11.9%) had PLD, and 9 (21%) of them had respiratory symptoms. Chest X-ray findings mainly included interstitial pneumonitis (53.5%) and pleurisy and/or pleural effusion (38.1%). In the 43 cases of JIA-PLD, 4 (9.3%) had normal chest X-ray findings but abnormal chest CT findings. The incidence of PLD was relatively high in patients aged under 3 years and those aged 12 years or above. Children with systemic JIA had a relatively high incidence of PLD. Compared with the non-PLD group, the PLD group had a significantly higher incidence of anemia, elevated white blood cell (WBC) count and IgG levels in peripheral blood, and positive rheumatoid factors or antinuclear antibodies (P<0.05). CONCLUSIONS: Among children with JIA, PLD is mostly seen in patients with systemic JIA or aged <3 years or ≥ 12 years, especially those with anemia, elevated WBC count and IgG levels, and positive rheumatoid factors or antinuclear antibodies. For JIA patients with PLD, interstitial pneumonitis is usually seen on chest X-ray or CT, but respiratory symptoms are rarely observed. Routine use of high-resolution chest CT is recommended for early diagnosis and timely treatment of PLD in children with JIA.

[Clinical features of recurrent Kawasaki disease in 20 children].

OBJECTIVE: To investigate the clinical features of recurrent Kawasaki disease (KD) and the relationship of recurrent KD with coronary artery lesions. METHODS: The medical data of 20 children with recurrent KD who were admitted to the Children's Hospital from January 1998 to May 2007 were retrospectively studied. Their clinical features were compared with those of children with initial KD. RESULTS: The incidence of recurrent KD was 1.34% (20/1489). KD relapsed 2 months to 4.6 years (average: 1.2 years) after the first episode in the 20 children. Compared with the initial KD group, the clinical symptoms in the recurrent KD group were incomplete, complicated and less severe. The period of fever, platelet count, C-reactive protein and ESR were remarkably reduced in the recurrent KD group, but the incidence of coronary artery lesions increased significantly compared with the initial KD group (40% vs 25%; P<0.05). CONCLUSIONS: The clinical symptoms of recurrent KD were incomplete in children. Recurrent KD was associated with an increased incidence of coronary artery lesions.

Analysis of urinary proteomic patterns for diabetic nephropathy by ProteinChip.

Diabetic nephropathy (DN) is the main cause of mortality for diabetic patients. The objective of this work was to develop a proteomic approach to detect proteins or peptides in urine for identifying individuals in the early stage of DN. We obtained urine samples from 106 diabetic patients and 50 healthy subjects. Early stage of DN was defined as urine albumin-to-creatinine ratio between 30 to 299 mg/g. Mass spectra were generated using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Peaks were detected by Ciphergen SELDI software version 3.1. Over 1000 proteins or peptides were obtained using ProteinChip. About 200 of them, the m/z values were in the range from 1008.5 to 79 942.3 Da. These values were significantly differentiated between diabetic patients and contro1 subjects. A mathematical analysis revealed that a cluster of 8 up-regulated proteins and 16 down-regulated proteins was in the diabetic patients, with m/z values from 2197.3 to 79 613 Da. Four top-ranked proteins, with m/z values of 4139.0, 4453.5, 5281.1, and 5898.5 Da, were selected as the potential fingerprints for detection of early stage DN with a sensitivity of 75% and a specificity of 80%. ProteinChip technology may be a novel non-invasive method for detecting early stage DN.