Identifying acute lymphoblastic leukemia mimicking juvenile idiopathic arthritis in children

OBJECTIVE:Acute lymphoblastic leukemia (ALL) may present with arthritis implying the risk of being misdiagnosed as juvenile idiopathic arthritis (JIA). The aim of this study was to identify predictors for ALL based on clinical and laboratory information. METHODS:This cross-sectional, retrospective study compared clinical presentation and laboratory results of 26 children with ALL and arthritis versus 485 children with JIA (433 non-systemic, 52 systemic JIA). Using a Bayesian score approach the findings were evaluated by calculating odds ratios (OR) and lnOR as a measure of diagnostic weight. RESULTS:Distinction on clinical grounds was difficult, as even a high number of joints involved did not exclude ALL. One or more hematologic cell counts were low (Hb <10 g/dL, platelet count <100 x 109/L, neutrophil count < 1.0 x 109/L) in 92% with ALL, 25% with systemic JIA and 10% with non-systemic JIA. Neutropenia and thrombocytopenia had the highest ORs of 128 (95% CI 43-387) and 129 (95% CI 26-638), each giving a diagnostic weight of 4. The estimated risks of ALL were 0.2% with normal cell counts and 9%, 67% and 100% when one, two or three cell lines were affected. CONCLUSION:A simple count of cell lines with low counts can serve as a basic diagnostic strategy. Children with tri- or bilinear involvement should be referred to a bone marrow, and those with unilinear involvement a thorough screen for further evidence of ALL (organomegaly, ESR, LDH, uric acid, and blood smear)

Musculoskeletal misdiagnoses in children with brain tumors:A nationwide, multicenter case-control study

ObjectiveChildhood brain tumors belong to the cancer type with the longest diagnostic delay, the highest health care utilization prior to diagnosis, and the highest burden of long-term sequelae. We aimed to clarify whether prior musculoskeletal diagnoses in childhood brain cancer were misdiagnoses and whether it affected the diagnostic delay.Study designIn this retrospective, chart-reviewed case-control study we compared 28 children with brain tumors and a prior musculoskeletal diagnosis to a sex and age-matched control group of 56 children with brain tumors and no prior musculoskeletal diagnosis. Using the Danish registries, the cases were identified from consecutive cases of childhood brain cancers in Denmark over 23 years (1996-2018).ResultsOf 931 children with brain tumors, 3% (28/931) had a prior musculoskeletal diagnosis, of which 39% (11/28) were misdiagnoses. The misdiagnoses primarily included torticollis-related diagnoses which tended to a longer time interval from first hospital contact until a specialist was involved: 35 days (IQR 6-166 days) compared to 3 days (IQR 1-48 days), p = 0.07. When comparing the 28 children with a prior musculoskeletal diagnosis with a matched control group without a prior musculoskeletal diagnosis, we found no difference in the non-musculoskeletal clinical presentation, the diagnostic time interval, or survival. Infratentorial tumor location was associated with a seven-fold risk of musculoskeletal misdiagnosis compared to supratentorial tumor location.ConclusionMusculoskeletal misdiagnoses were rare in children with brain tumors and had no significant association to the diagnostic time interval or survival. The misdiagnoses consisted primarily of torticollis- or otherwise neck-related diagnoses

Inflammatory Biomarkers Can Differentiate Acute Lymphoblastic Leukemia with Arthropathy from Juvenile Idiopathic Arthritis Better Than Standard Blood Tests

Objective - To evaluate the predictive value of biomarkers of inflammation like phagocyte-related S100 proteins and a panel of inflammatory cytokines in order to differentiate the child with acute lymphoblastic leukemia (ALL) from juvenile idiopathic arthritis (JIA). Study design - In this cross-sectional study, we measured S100A9, S100A12, and 14 cytokines in serum from children with ALL (n = 150, including 27 with arthropathy) and JIA (n = 236). We constructed predictive models computing areas under the curve (AUC) as well as predicted probabilities in order to differentiate ALL from JIA. Logistic regression was used for predictions of ALL risk, considering the markers as the respective exposures. We performed internal validation using repeated 10-fold cross-validation and recalibration, adjusted for age. Results - In ALL, the levels of S100A9, S100A12, interleukin (IL)-1 beta, IL-4, IL-13, IL-17, matrix metalloproteinase-3, and myeloperoxidase were low compared with JIA (P Conclusions - The biomarkers S100A9, IL-4, and IL-13 might be valuable markers to differentiate ALL from JIA

Arthritis as presenting manifestation of acute lymphoblastic leukaemia in children

BackgroundAt disease onset, children with acute lymphoblastic leukaemia (ALL) may present with arthralgia or even signs of arthritis. This might cause misdiagnosis and thereby lead to prolonged diagnostic delay. The present study aimed to identify children with ALL with joint involvement and to compare their characteristics and outcome with children with ALL without joint involvement.MethodsCase records of 286 children diagnosed with ALL between 1992 and 2013 were reviewed and analysed in this retrospective, descriptive study.ResultsFifty-three (18.5%) children with ALL presented with localised joint pain, and half of them had objective signs of arthritis. The mean number of joints involved was 2.5, most frequently presenting as asymmetric oligoarthritis. The suspected misdiagnosis were reactive arthritis (19/53), osteomyelitis (9/53) and juvenile idiopathic arthritis (8/53). Children with joint involvement had less objective signs of haematological disease. Cytopenia was absent in 24% in children with joint involvement (vs 8% without, p=0.001), 50% had only one cell line affected (vs 21%, p=0.0005) and 44% had no organomegaly (vs 29%, p=0.05). Median diagnostic delay was 4 vs 2 weeks. The 5-year event-free and overall survival was superior for children with joint involvement: 94% vs 87% (p=0.049), and 96% vs 83% (p=0.044).ConclusionsALL with joint involvement is a frequent finding (18.5%). The clinical signs of leukaemia are less prominent, but non-articular pain should alert the clinician of a possible diagnosis of leukaemia. The overall and event-free survivals were superior compared with the children without joint involvement.</jats:sec