Predicting relapsed/refractory disease in childhood hemophagocytic lymphohistiocytosis based on clinical features at diagnosis: A 13-year single-institute retrospective study in Thailand.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease. Relapsed/refractory disease is the main cause of death. This study aims to determine the prognostic indicators for relapsed/refractory disease in childhood HLH (R/R HLH). Infants and children under 18 years of age who were diagnosed with HLH according to HLH-2004 criteria, MAS-HLH criteria for rheumatologic diseases, or H-score undergoing treatment in Chiang Mai University hospital between 2010 and 2022 were included. Demographic data, clinical characteristics, and laboratory parameters were retrospectively reviewed. Out of 86 childhood HLH cases, 30 patients (34.9%) experienced R/R HLH. All patients with primary HLH developed R/R HLH. The most common form of secondary HLH was infection-associated hemophagocytic syndrome (IAHS), comprising 43 cases. Of these, 37.2% had relapsed or refractory disease. Univariable analysis identified several potential risk factors for R/R HLH, including younger age, severe disease status, higher HLH-2004 criteria scores, higher H-scores, overt DIC, higher pSOFA scores, and increased levels of aspartate aminotransferase, total bilirubin, and direct bilirubin. Multivariable logistic regression analysis revealed that a pSOFA score of ≥ 8 and age < 3 years were independent risk factors for R/R HLH, with adjusted odds ratios of 6.35 (95% confidence interval [CI], 1.18-34.19; P = 0.032) and 3.62 (95% CI, 1.04-12.63; P = 0.044), respectively. Children with HLH who have a pSOFA score of ≥ 8, or are younger than 3 years, are at a higher risk of relapsed or refractory disease. Further evaluation of management strategies in this context is warranted.

Timing of Childhood-Onset Systemic Lupus Erythematosus Diagnosis Relative to Menarche and the Impact on Final Adult Height.

OBJECTIVE: The aim of this study was to examine the impact of timing of a childhood-onset systemic lupus erythematosus (SLE) diagnosis relative to menarchal status, on final height, accounting for disease-associated factors. METHODS: We conducted a cohort study of female patients age <18 years at childhood-onset SLE diagnosis, followed at a tertiary care pediatric center from July 1982 to March 2016 and restricted to patients with documented age of menarche and final height. We compared final height between patients diagnosed pre- and postmenarche. We tested the association of the timing of childhood-onset SLE diagnosis with final height, adjusted for ethnicity, in linear regression models. We performed subgroup analyses of patients with growth during follow-up, additionally adjusting for average daily corticosteroid dose and disease activity. RESULTS: Of 401 female childhood-onset SLE patients in the study, 115 patients (29%) were diagnosed premenarche and 286 (71%) postmenarche. Patients diagnosed premenarche were older at menarche compared with patients diagnosed postmenarche (mean ± SD age 13.5 ± 1.4 versus 12.5 ± 1.3 years; P < 0.001). The mean ± SD final height for girls diagnosed postmenarche (161.4 ± 6.9 cm) was greater than for those diagnosed premenarche (158.8 ± 7.3 cm; P = 0.001). In regression analysis, those diagnosed postmenarche were significantly taller than those diagnosed premenarche, as adjusted for ethnicity and disease severity (mean ± SD ß = 2.6 ± 0.7 cm; P = 0.0006). CONCLUSION: In this large cohort study of girls with childhood-onset SLE, patients diagnosed postmenarche achieved a taller final height than those diagnosed premenarche, even after accounting for ethnicity and disease severity.

Hallmark trials in ANCA-associated vasculitis (AAV) for the pediatric rheumatologist.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) refers to a complex group of systemic vasculitides that are characterized by primary small-to-medium sized blood vessel inflammation with the presence of autoantibodies known as ANCA. AAV diseases include Granulomatosis with Polyangiitis (GPA), Eosinophilic Granulomatosis with Polyangiitis (EGPA), and Microscopic Polyangiitis (MPA). AAVs are challenging conditions associated with high cumulative disease and treatment related morbidity and mortality. Given its rarity and the resulting paucity of pediatric-specific clinical trial evidence, pediatric rheumatologists have had to often extrapolate from adult literature for management and therapeutic decisions. The aim of this review is to provide a comprehensive overview of the important findings and overall conclusions of critical landmark clinical trials in the induction and maintenance treatments in adult AAV for the pediatric rheumatologist. This review also highlights the outcomes of recent pediatric AAV observational studies and discusses the future research priorities in pediatric AAV management.

The correlation between the Childhood Health Assessment Questionnaire and disease activity in juvenile idiopathic arthritis.

BACKGROUND: The Childhood Health Assessment Questionnaire (CHAQ) has been adapted from the Stanford Health Assessment Questionnaire for assessing functional ability in children. The present study aimed to determine the correlation between CHAQ and disease activity in juvenile idiopathic arthritis (JIA) during active and inactive disease. METHODS: JIA patients in the Pediatric Department, Ramathibodi Hospital, between January 2011 and December 2013, were included in the study. The CHAQ disability index (DI) and disease activity variables, including active and limited joint count, erythrocyte sedimentation rate, patient's global assessment (PtGA), physician's global assessment (PGA) and 27-joint Juvenile Arthritis Disease Activity Score (JADAS27), were collected from medical records for each patient over six visits. At each visit, each patient was classified as having either active or inactive disease. The correlations between CHAQ-DI and disease activity variables were analysed using Spearman's correlation. RESULTS: The classification of 139 JIA patients consisted of enthesitis-related arthritis (30.9%), systemic JIA (28.1%), oligoarthritis (16.5%), rheumatoid factor (RF)-negative polyarthritis (15.1%), RF-positive polyarthritis (6.5%) and undifferentiated arthritis (2.9%). Out of 812 patient visits, 606 were in active disease and 206 were in inactive disease. RF-negative polyarthritis had the highest CHAQ-DI (0.39 ± 0.66), while oligoarthritis had the lowest (0.20 ± 0.32). There was a good correlation between CHAQ-DI and JADAS27, PGA and PtGA in all JIA subtypes (p < 0.05) during active disease, but a poor correlation between CHAQ-DI and disease activity variables during inactive disease. CONCLUSIONS: CHAQ-DI had a good correlation with disease activity during active disease but a poor correlation during inactive disease. Therefore, CHAQ is only useful for assessing functional ability during active disease.

Subtle inflammation: a possible mechanism of future cardiovascular risk in obese children.

PURPOSE: The risk of cardiovascular disease (CVD) has been shown to be associated with systemic inflammation in obese adults with metabolic syndrome (MetS). The aims of this study were to evaluate the prevalence of MetS and its relation to inflammatory markers in obese Thai children. METHODS: A cross-sectional study was conducted. Children with history of endogenous obesity, chronic diseases, drug ingestion, and any acute illness within 2 weeks prior to enrollment were excluded. Their fasting blood glucose (FBG) levels, oral glucose tolerance tests, insulin, lipid profiles, and selected inflammatory markers, including interleukin-6, tumor necrosis factor-alpha, and high-sensitivity C-reactive protein (hs-CRP) levels, were tested. RESULTS: In this study, 58 obese Thai children (female, 20; male, 38) with a mean body mass index z score of 5.1±2.2 were enrolled. The prevalence of MetS and prediabetes was 31% and 17.2%, respectively. None of the children had diabetes. FBG levels, 2-hour glucose levels, and lipid profiles were not statistically different between those with and without MetS. However, obese children with MetS had higher insulin levels and homeostasis model assessment of insulin resistance values. Elevated hs-CRP levels were found in 69% of the cases, although it was not statistically different between the 2 groups. CONCLUSION: We described a substantial prevalence of MetS in Thai obese children. Regardless of MetS status, two-thirds of the obese children had elevated hs-CRP level, indicating subtle ongoing inflammatory process. This chronic inflammation feasibly predisposes them to CVD in the future, even in children without MetS.

Neurological Involvement and Hepatocellular Injury Caused by a Snake With Hematotoxin Envenomation.

Venomous snakes with hematotoxin-Russell's viper (Daboia spp), Malayan pit viper (Calloselasma rhodostoma), and green pit viper (Cryptelytrops albolabris and C macrops, previously named Trimeresurus spp) are commonly found in Thailand. Coagulation factor activation, thrombocytopenia, hyperfibrinolysis, and disseminated intravascular coagulation are the main mechanisms of hemorrhaging from these snake bites. The neurological involvement and hepatocellular injury after Russell's viper bites were reported in Sri Lanka, but there is no report from Southeast Asia. This case was a 12-year-old hill tribe boy who had ptosis and exotropia of the left eye, respiratory distress, and prolonged venous clotting time, prothrombin time, and activated partial thromboplastin time; low fibrinogen and platelet count; and transaminitis after being bitten by a darkish-colored snake. He did not respond to antivenom for cobra, Malayan pit viper, or Russell's viper. However, his neurological abnormalities, respiratory failure, and hepatocellular injury improved, and coagulopathy was finally corrected after receiving antivenom for green pit viper. The unidentified snake with hematotoxin was alleged for all manifestations in this patient.