TY - JOUR
T1 - Musculoskeletal manifestations of childhood cancer and differential diagnosis with juvenile idiopathic arthritis (ONCOREUM)
T2 - a multicentre, cross-sectional study
AU - Italian Association of Paediatric Haematology and Oncology
AU - Italian Paediatric Rheumatology Study Group
AU - Civino, Adele
AU - Alighieri, Giovanni
AU - Prete, Eleonora
AU - Caroleo, Anna Maria
AU - Magni-Manzoni, Silvia
AU - Vinti, Luciana
AU - Romano, Micol
AU - Santoro, Nicola
AU - Filocamo, Giovanni
AU - Belotti, Tamara
AU - Santarelli, Francesca
AU - Gorio, Chiara
AU - Ricci, Francesca
AU - Colombini, Antonella
AU - Pastore, Serena
AU - Cesaro, Simone
AU - Barone, Patrizia
AU - Verzegnassi, Federico
AU - Olivieri, Alma Nunzia
AU - Ficara, Monica
AU - Miniaci, Angela
AU - Russo, Giovanna
AU - Gallizzi, Romina
AU - Pericoli, Roberta
AU - Breda, Luciana
AU - Mura, Rossella
AU - Podda, Rosa Anna
AU - Onofrillo, Daniela
AU - Lattanzi, Bianca
AU - Coassin, Elisa
AU - Rigante, Donato
AU - Abate, Massimo Eraldo
AU - Rossi, Elisa
AU - Lepore, Loredana
AU - Rondelli, Roberto
AU - Pession, Andrea
AU - Ravelli, Angelo
AU - Cappella, M.
AU - Cefalo, M. G.
AU - Davì, S.
AU - De Benedetti, F.
AU - Di Cataldo, A.
AU - Garaventa, A.
AU - Ladogana, S.
AU - Locatelli, F.
AU - Magnolato, A.
AU - Martino, S.
AU - Mascarin, M.
AU - Messina, C.
AU - Micalizzi, C.
N1 - Funding Information:
This work was funded by Associazione Lorenzo Risolo, which supported the platform CINECA. We thank Martina Amatruda (Roma, Italy), Catia Atzeni (Cagliari, Italy), Patrizia Bertolini (Parma, Italy), Barbara Bigucci (Rimini, Italy), Maurizio Caniglia (Perugia, Italy), Michela Cappella (Reggio Emilia, Italy), Marco Cattalini (Brescia, Italy), Maria Giuseppina Cefalo (Rome, Italy), Monica Cellini (Modena, Italy), Elisabetta Cortis (Orvieto, Italy), Sergio Davì (Genova, Italy), Fabrizio De Benedetti (Roma, Italy), Andrea Di Cataldo (Catania, Italy), Elena Fabbri (Rimini, Italy), Franca Fagioli (Torino, Italy), Ilaria Fontanili (Parma, Italy), Alberto Garaventa (Genova, Italy), Maria Francesca Gicchino (Napoli, Italy), Saverio Ladogana (San Giovanni Rotondo, Italy), Franco Locatelli (Roma, Italy), Andrea Magnolato (Trieste, Italy), Manuela Marsili (Chieti, Italy), Silvana Martino (Torino, Italy), Maurizio Mascarin (Aviano, Italy), Chiara Messina (Padova, Italy), Concetta Micalizzi (Genova, Italy), Fulvio Porta (Brescia, Italy), and Carmelo Rizzari (Monza, Italy) for participating in data collection and patient assessment at their respective centre.
Funding Information:
This work was funded by Associazione Lorenzo Risolo, which supported the platform CINECA. We thank Martina Amatruda (Roma, Italy), Catia Atzeni (Cagliari, Italy), Patrizia Bertolini (Parma, Italy), Barbara Bigucci (Rimini, Italy), Maurizio Caniglia (Perugia, Italy), Michela Cappella (Reggio Emilia, Italy), Marco Cattalini (Brescia, Italy), Maria Giuseppina Cefalo (Rome, Italy), Monica Cellini (Modena, Italy), Elisabetta Cortis (Orvieto, Italy), Sergio Dav? (Genova, Italy), Fabrizio De Benedetti (Roma, Italy), Andrea Di Cataldo (Catania, Italy), Elena Fabbri (Rimini, Italy), Franca Fagioli (Torino, Italy), Ilaria Fontanili (Parma, Italy), Alberto Garaventa (Genova, Italy), Maria Francesca Gicchino (Napoli, Italy), Saverio Ladogana (San Giovanni Rotondo, Italy), Franco Locatelli (Roma, Italy), Andrea Magnolato (Trieste, Italy), Manuela Marsili (Chieti, Italy), Silvana Martino (Torino, Italy), Maurizio Mascarin (Aviano, Italy), Chiara Messina (Padova, Italy), Concetta Micalizzi (Genova, Italy), Fulvio Porta (Brescia, Italy), and Carmelo Rizzari (Monza, Italy) for participating in data collection and patient assessment at their respective centre.
Publisher Copyright:
© 2021 Elsevier Ltd
PY - 2021
Y1 - 2021
N2 - Background: Presenting symptoms of childhood cancers might mimic those of rheumatic diseases. However, the evidence available to guide differential diagnosis remains scarce. Preventing wrong or delayed diagnosis is therefore important to avoid incorrect administration of glucocorticoid or immunosuppressive therapy and worsening of prognosis. As such, we aimed to assess the prevalence and characteristics of presenting musculoskeletal manifestations in patients at cancer onset and to identify the factors that differentiate childhood malignancies with arthropathy from juvenile idiopathic arthritis. Methods: We did a multicentre, cross-sectional study at 25 paediatric haemato-oncology centres and 22 paediatric rheumatology centres in Italy. We prospectively recruited patients who were younger than 16 years that were newly diagnosed with cancer or juvenile idiopathic arthritis. We excluded patients with glucocorticoid pre-treatment (>1 mg/kg per day of oral prednisone or equivalent for ≥2 consecutive weeks). We collected data for patients with a new diagnosis of cancer or juvenile idiopathic arthritis using an electronic case report form on a web-based platform powered by the Cineca Interuniversity Consortium. The primary outcome was to describe the frequency and characteristics of musculoskeletal manifestations at cancer onset; and the secondary outcome was to identify factors that could discriminate malignancies presenting with arthropathy, with or without other musculoskeletal symptoms, from juvenile idiopathic arthritis using multivariable logistic regression analysis. Findings: Between May 1, 2015, and May 31, 2018, 1957 patients were eligible, of which 1277 (65%) had cancer and 680 (35%) had juvenile idiopathic arthritis. Musculoskeletal symptoms occurred in 324 (25% [95% CI 23·0–27·8]) of 1277 patients with cancer, of whom 207 had arthropathy. Patients with malignant bone tumours had the highest frequency of musculoskeletal symptoms (53 [80%] of 66), followed by patients with Langerhans histiocytosis (16 [47%] of 34), leukaemia (189 [32%] of 582), soft-tissue sarcomas (16 [24%] of 68), and neuroblastoma (21 [19%] of 109). In the 324 patients with cancer and musculoskeletal symptoms, the most common complaints were joint pain (199 [61%]), followed by limb bone pain (112 [35%]). Joint involvement had a prevalent monoarticular pattern (100 [48%] of 207) and oligoarticular pattern (86 [42%] had 2–4 joints involved and 20 [10%] had >4 joints involved), with the most frequently involved joints being the hip (88 [43%] of 207) and knee (81 [39%]). On multivariable analysis, limb bone pain was the independent variable most strongly associated with cancer (odds ratio [OR] 87·80 [95% CI 18·89–408·12]), followed by weight loss (59·88 [6·34–565·53]), thrombocytopenia (12·67 [2·40–66·92]), monoarticular involvement (11·30 [4·09–31·19]), hip involvement (3·30 [1·13–9·61]), and male sex (2·40 [1·03–5·58]). Factors independently associated with juvenile idiopathic arthritis were morning stiffness (OR 0·04 [95% CI 0·01–0·20]), joint swelling (0·03 [0·01–0·09]), and involvement of the small hand joints (0·02 [0–1·05]). Interpretation: Our study provides detailed information about presenting musculoskeletal manifestations of childhood cancers and highlights the clinical and laboratory features that are most helpful in the differential diagnosis with juvenile idiopathic arthritis. Funding: Associazione Lorenzo Risolo.
AB - Background: Presenting symptoms of childhood cancers might mimic those of rheumatic diseases. However, the evidence available to guide differential diagnosis remains scarce. Preventing wrong or delayed diagnosis is therefore important to avoid incorrect administration of glucocorticoid or immunosuppressive therapy and worsening of prognosis. As such, we aimed to assess the prevalence and characteristics of presenting musculoskeletal manifestations in patients at cancer onset and to identify the factors that differentiate childhood malignancies with arthropathy from juvenile idiopathic arthritis. Methods: We did a multicentre, cross-sectional study at 25 paediatric haemato-oncology centres and 22 paediatric rheumatology centres in Italy. We prospectively recruited patients who were younger than 16 years that were newly diagnosed with cancer or juvenile idiopathic arthritis. We excluded patients with glucocorticoid pre-treatment (>1 mg/kg per day of oral prednisone or equivalent for ≥2 consecutive weeks). We collected data for patients with a new diagnosis of cancer or juvenile idiopathic arthritis using an electronic case report form on a web-based platform powered by the Cineca Interuniversity Consortium. The primary outcome was to describe the frequency and characteristics of musculoskeletal manifestations at cancer onset; and the secondary outcome was to identify factors that could discriminate malignancies presenting with arthropathy, with or without other musculoskeletal symptoms, from juvenile idiopathic arthritis using multivariable logistic regression analysis. Findings: Between May 1, 2015, and May 31, 2018, 1957 patients were eligible, of which 1277 (65%) had cancer and 680 (35%) had juvenile idiopathic arthritis. Musculoskeletal symptoms occurred in 324 (25% [95% CI 23·0–27·8]) of 1277 patients with cancer, of whom 207 had arthropathy. Patients with malignant bone tumours had the highest frequency of musculoskeletal symptoms (53 [80%] of 66), followed by patients with Langerhans histiocytosis (16 [47%] of 34), leukaemia (189 [32%] of 582), soft-tissue sarcomas (16 [24%] of 68), and neuroblastoma (21 [19%] of 109). In the 324 patients with cancer and musculoskeletal symptoms, the most common complaints were joint pain (199 [61%]), followed by limb bone pain (112 [35%]). Joint involvement had a prevalent monoarticular pattern (100 [48%] of 207) and oligoarticular pattern (86 [42%] had 2–4 joints involved and 20 [10%] had >4 joints involved), with the most frequently involved joints being the hip (88 [43%] of 207) and knee (81 [39%]). On multivariable analysis, limb bone pain was the independent variable most strongly associated with cancer (odds ratio [OR] 87·80 [95% CI 18·89–408·12]), followed by weight loss (59·88 [6·34–565·53]), thrombocytopenia (12·67 [2·40–66·92]), monoarticular involvement (11·30 [4·09–31·19]), hip involvement (3·30 [1·13–9·61]), and male sex (2·40 [1·03–5·58]). Factors independently associated with juvenile idiopathic arthritis were morning stiffness (OR 0·04 [95% CI 0·01–0·20]), joint swelling (0·03 [0·01–0·09]), and involvement of the small hand joints (0·02 [0–1·05]). Interpretation: Our study provides detailed information about presenting musculoskeletal manifestations of childhood cancers and highlights the clinical and laboratory features that are most helpful in the differential diagnosis with juvenile idiopathic arthritis. Funding: Associazione Lorenzo Risolo.
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U2 - 10.1016/S2665-9913(21)00086-2
DO - 10.1016/S2665-9913(21)00086-2
M3 - Article
AN - SCOPUS:85107036569
VL - 3
SP - e507-e516
JO - The Lancet Rheumatology
JF - The Lancet Rheumatology
SN - 2665-9913
IS - 7
ER -