Musculoskeletal Symptoms and Misdiagnoses in Children With Acute Myeloid Leukaemia: A Nationwide Cohort Study

Eur J Haematol. 2024 Sep 18. doi: 10.1111/ejh.14303. Online ahead of print.

Abstract

Objectives: Childhood cancer often presents with non-specific signs and symptoms that might mimic non-malignant disorders including musculoskeletal diseases, potentially leading to rheumatic and orthopaedic misdiagnoses. We aimed to compare clinical presentation, diagnostic interval and survival in paediatric acute myeloid leukaemia (AML) with and without initial musculoskeletal symptoms.

Methods: This nationwide retrospective, cohort study reviewed medical records of 144 children below 15 years diagnosed with AML in Denmark from 1996 to 2018.

Results: Musculoskeletal symptoms occurred in 29% (42/144) of children with AML and 8% (11/144) received an initial musculoskeletal misdiagnosis, being mainly non-specific and pain-related. The children with and without musculoskeletal symptoms did not differ markedly up to the diagnosis of AML and blood counts were affected equally in both groups. However, the children with prior musculoskeletal symptoms were more likely to have elevated levels of LDH and ferritin. Furthermore, they revealed a tendency towards a longer total interval (median 53 days vs. 32 days, p = 0.07), but the overall survival did not differ.

Conclusion: AML should be considered as an underlying cause in children with unexplained musculoskeletal symptoms and abnormal blood counts. Concomitant elevation of LDH and ferritin should strengthen the suspicion.

Keywords: acute myeloid leukaemia; adolescent; child; delayed diagnosis; diagnostic error; differential diagnosis; infant; musculoskeletal diseases; retrospective studies.