Persistent osteoarticular pain in children: early clinical and laboratory findings suggestive of acute lymphoblastic leukemia (a multicenter case-control study of 147 patients)

Abstract

Background: The aim of this study was to identify early clinical and laboratory features that distinguish acute lymphoblastic leukemia (ALL) from juvenile idiopathic arthritis (JIA) in children presenting with persistent bone or joint pain for at least 1 month.

Methods: We performed a multicenter case-control study and reviewed medical records of children who initially presented with bone or joint pain lasting for at least 1 month, all of whom were given a secondary diagnosis of JIA or ALL, in four French University Hospitals. Each patient with ALL was paired by age with two children with JIA. Logistic regression was used to compare clinical and laboratory data from the two groups.

Results: Forty-nine children with ALL and 98 with JIA were included. The single most important feature distinguishing ALL from JIA was the presence of hepatomegaly, splenomegaly or lymphadenopathy; at least one of these manifestations was present in 37 cases with ALL, but only in 2 controls with JIA, for an odds ratio (OR) of 154 [95%CI: 30-793] (regression coefficient: 5.0). If the presence of these findings is missed or disregarded, multivariate analyses showed that non-articular bone pain and/or general symptoms (asthenia, anorexia or weight loss) (regression coefficient: 4.8, OR 124 [95%CI: 11.4-236]), neutrophils < 2 × 10⁹/L (regression coefficient: 3.9, OR 50 [95%CI: 4.3-58]), and platelets < 300 × 10⁹/L (regression coefficient: 2.6, OR 14 [95%CI: 2.3-83.9]) were associated with the presence of ALL (area under the ROC curve: 0.96 [95%CI: 0.93-0.99]).

Conclusions: Based on our findings we propose the following preliminary decision tree to be tested in prospective studies: in children presenting with at least 1 month of osteoarticular pain and no obvious ALL in peripheral smear, perform a bone marrow examination if hepatomegaly, splenomegaly or lymphadenopathy is present. If these manifestations are absent, perform a bone marrow examination if there is fever or elevated inflammatory markers associated with non-articular bone pain, general symptoms (asthenia, anorexia or weight loss), neutrophils < 2 × 10⁹/L or platelets < 300 × 10⁹/L.

Keywords: Arthralgia; Bone pain; Childhood acute lymphoblastic leukemia; Diagnosis; Juvenile idiopathic arthritis.

Fig. 1

Decision tree proposal for children presenting with at least 1 month of osteoarticular pain. * “Elevated inflammatory markers” were defined as C-reactive protein > 6 mg/L and/or the 1st hour’s erythrocyte sedimentation rate > 20 mm. ** “General symptoms” were defined as the presence of at least one of the following parameters: anorexia, weight loss or asthenia.