Clinical, Laboratory Features Differentiate Musculoskeletal Manifestations of Childhood Cancers From Juvenile Idiopathic Arthritis

child in hospital with IV
Researchers assessed the prevalence and characteristics of musculoskeletal manifestations of childhood cancers and identified the factors that differentiated them from juvenile idiopathic arthritis.

Clinical and laboratory features, such as limb bone pain, weight loss, thrombocytopenia, monoarticular and hip involvement, may differentiate musculoskeletal manifestations of childhood cancers from juvenile idiopathic arthritis (JIA), according to study results published in Lancet Rheumatology.

Children with cancer may present with similar symptoms to JIA. Studies have shown that up to 2% of children with musculoskeletal symptoms who were initially referred to rheumatology were ultimately diagnosed with cancer. This study was initiated to assess the prevalence and characteristics of musculoskeletal symptoms in children with newly diagnosed cancer and to identify factors that differentiated childhood malignancies with arthropathy from JIA.

Using a multicenter cross-sectional study, the researchers collected data from 25 pediatric hemato-oncology centers and 22 pediatric rheumatology centers in Italy. Patients younger than 16 years with onset cancer were prospectively enrolled in the study between May 2015 and May 2018. Exclusion criteria was pretreatment with glucocorticoids.

The primary study outcome was the frequency and characteristics of musculoskeletal symptoms at the onset of cancer. The secondary outcome was the identification of factors that could distinguish between malignancies presenting with arthropathy, with or without other musculoskeletal symptoms, and JIA.

A total of 1957 patients, of whom 1277 had cancer and 680 had JIA, were included in the study. Among patients with cancer, 324 (25%) experienced musculoskeletal symptoms. The frequency of musculoskeletal symptoms varied by the type of malignancy – 80% with malignant bone tumors; 47% with Langerhans histiocytosis; 32% with leukemia; 24% with soft-tissue sarcomas; and 19% with neuroblastoma. The most common symptoms were joint pain (61%) and limb bone pain (35%). Of the 324 patients with cancer and musculoskeletal symptoms, 207 had arthropathy with involvement of 1 joint (48%), 2 to 4 joints (42%), or more than 4 joints (10%). The most frequently involved joints were the hip (43%) and knee (39%).

Limb bone pain was most strongly associated with cancer (odds ratio [OR], 87.80; 95% CI, 18.89-408.12; P <.0001), followed by weight loss (OR, 59.88; 95% CI, 6.34-565.53; P <.0001), thrombocytopenia (OR, 12.67; 95% CI, 2.40-66.92; P =.003), monoarticular involvement (OR, 11.30; 95% CI, 4.09-31.19; P <.0001), hip involvement (OR, 3.30; 95% CI, 1.13-9.61; P =.029), and male sex (OR, 2.40; 95% CI, 1.03-5.58, P =.043). Factors independently associated with JIA were morning stiffness (OR, 0.04; 95% CI, 0.01-0.20; P <.0001), joint swelling (OR, 0.03; 95% CI, 0.01-0.09; P <.0001), and involvement of small hand joints (OR, 0.02; 95% CI, 0.00-1.05; P =.053)

Limitations of the study included overestimation of musculoskeletal symptoms due to a higher frequency of leukemia and lower frequency of central nervous system neoplasms in the study population compared with the Italian cancer registry; the low numbers of some JIA subtypes in the study population; and the fact that laboratory measurements were collected for the first time at the center, but not necessarily at the onset of clinical symptoms.

“These findings confirm the high frequency of musculoskeletal presentation among patients with [pediatric] cancers and underscore the diagnostic difficulties that might be posed by the occurrence of musculoskeletal symptoms in isolation,” the researchers concluded. “Altogether, the results of our analysis increase the knowledge of musculoskeletal manifestations of childhood cancer and help to define the optimal diagnostic algorithm for children who present with unexplained joint involvement,” they added.


Civino A, Alighieri G, Prete E, et al; on behalf of the Italian Association of Paediatric Haematology and Oncology and the Italia Paediatric Rheumatology Study Group. Musculoskeletal manifestations of childhood cancer and differential diagnosis with juvenile idiopathic arthritis (ONCOREUM): a multicentre, cross-sectional study. Lancet Rheumatol. Published online May 11, 2011. doi:10.1016/ S2665-9913(21)00120-X