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1. Musculoskeletal manifestations of childhood cancer and differential diagnosis with juvenile idiopathic arthritis (ONCOREUM): a multicentre, cross-sectional study

Author

Civino, A, Alighieri, G, Prete, E, Caroleo, A, Magni-Manzoni, S, Vinti, L, Romano, M, Santoro, N, Filocamo, G, Belotti, T, Santarelli, F, Gorio, C, Ricci, F, Colombini, A, Pastore, S, Cesaro, S, Barone, P, Verzegnassi, F, Olivieri, A, Ficara, M, Miniaci, A, Russo, G, Gallizzi, R, Pericoli, R, Breda, L, Mura, R, Podda, R, Onofrillo, D, Lattanzi, B, Tirtei, E, Maggio, M, De Santis, R, Consolini, R, Arlotta, A, La Torre, F, Mainardi, C, Pelagatti, M, Coassin, E, Capolsini, I, Burnelli, R, Tornesello, A, Soscia, F, De Fanti, A, Rigante, D, Pizzato, C, De Fusco, C, Abate, M, Roncadori, A, Rossi, E, Stabile, G, Biondi, A, Lepore, L, Conter, V, Rondelli, R, Pession, A, Ravelli, A, Amatruda, M, Atzeni, C, Bertolini, P, Bigucci, B, Caniglia, M, Cappella, M, Cattalini, M, Cefalo, M, Cellini, M, Cortis, E, Davi, S, De Benedetti, F, Di Cataldo, A, Fabbri, E, Fagioli, F, Fontanili, I, Garaventa, A, Gicchino, M, Ladogana, S, Locatelli, F, Magnolato, A, Marsili, M, Martino, S, Mascarin, M, Messina, C, Micalizzi, C, Porta, F, Rizzari, C, Civino A., Alighieri G., Prete E., Caroleo A. M., Magni-Manzoni S., Vinti L., Romano M., Santoro N., Filocamo G., Belotti T., Santarelli F., Gorio C., Ricci F., Colombini A., Pastore S., Cesaro S., Barone P., Verzegnassi F., Olivieri A. N., Ficara M., Miniaci A., Russo G., Gallizzi R., Pericoli R., Breda L., Mura R., Podda R. A., Onofrillo D., Lattanzi B., Tirtei E., Maggio M. C., De Santis R., Consolini R., Arlotta A., La Torre F., Mainardi C., Pelagatti M. A., Coassin E., Capolsini I., Burnelli R., Tornesello A., Soscia F., De Fanti A., Rigante D., Pizzato C., De Fusco C., Abate M. E., Roncadori A., Rossi E., Stabile G., Biondi A., Lepore L., Conter V., Rondelli R., Pession A., Ravelli A., Amatruda M., Atzeni C., Bertolini P., Bigucci B., Caniglia M., Cappella M., Cattalini M., Cefalo M. G., Cellini M., Cortis E., Davi S., De Benedetti F., Di Cataldo A., Fabbri E., Fagioli F., Fontanili I., Garaventa A., Gicchino M. F., Ladogana S., Locatelli F., Magnolato A., Marsili M., Martino S., Mascarin M., Messina C., Micalizzi C., Porta F., Rizzari C., Civino, A, Alighieri, G, Prete, E, Caroleo, A, Magni-Manzoni, S, Vinti, L, Romano, M, Santoro, N, Filocamo, G, Belotti, T, Santarelli, F, Gorio, C, Ricci, F, Colombini, A, Pastore, S, Cesaro, S, Barone, P, Verzegnassi, F, Olivieri, A, Ficara, M, Miniaci, A, Russo, G, Gallizzi, R, Pericoli, R, Breda, L, Mura, R, Podda, R, Onofrillo, D, Lattanzi, B, Tirtei, E, Maggio, M, De Santis, R, Consolini, R, Arlotta, A, La Torre, F, Mainardi, C, Pelagatti, M, Coassin, E, Capolsini, I, Burnelli, R, Tornesello, A, Soscia, F, De Fanti, A, Rigante, D, Pizzato, C, De Fusco, C, Abate, M, Roncadori, A, Rossi, E, Stabile, G, Biondi, A, Lepore, L, Conter, V, Rondelli, R, Pession, A, Ravelli, A, Amatruda, M, Atzeni, C, Bertolini, P, Bigucci, B, Caniglia, M, Cappella, M, Cattalini, M, Cefalo, M, Cellini, M, Cortis, E, Davi, S, De Benedetti, F, Di Cataldo, A, Fabbri, E, Fagioli, F, Fontanili, I, Garaventa, A, Gicchino, M, Ladogana, S, Locatelli, F, Magnolato, A, Marsili, M, Martino, S, Mascarin, M, Messina, C, Micalizzi, C, Porta, F, Rizzari, C, Civino A., Alighieri G., Prete E., Caroleo A. M., Magni-Manzoni S., Vinti L., Romano M., Santoro N., Filocamo G., Belotti T., Santarelli F., Gorio C., Ricci F., Colombini A., Pastore S., Cesaro S., Barone P., Verzegnassi F., Olivieri A. N., Ficara M., Miniaci A., Russo G., Gallizzi R., Pericoli R., Breda L., Mura R., Podda R. A., Onofrillo D., Lattanzi B., Tirtei E., Maggio M. C., De Santis R., Consolini R., Arlotta A., La Torre F., Mainardi C., Pelagatti M. A., Coassin E., Capolsini I., Burnelli R., Tornesello A., Soscia F., De Fanti A., Rigante D., Pizzato C., De Fusco C., Abate M. E., Roncadori A., Rossi E., Stabile G., Biondi A., Lepore L., Conter V., Rondelli R., Pession A., Ravelli A., Amatruda M., Atzeni C., Bertolini P., Bigucci B., Caniglia M., Cappella M., Cattalini M., Cefalo M. G., Cellini M., Cortis E., Davi S., De Benedetti F., Di Cataldo A., Fabbri E., Fagioli F., Fontanili I., Garaventa A., Gicchino M. F., Ladogana S., Locatelli F., Magnolato A., Marsili M., Martino S., Mascarin M., Messina C., Micalizzi C., Porta F., and Rizzari C.

Abstract

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 b

Published
2021

2. Studio Multicentrico prospettico osserva zionale sui sintomi muscolo scheletrici all’esordio in oncologia pediatrica e i fattori predittivi nella diagnosi differenziale con l’atrite idiopatica giovanile. Analisi preliminare

Author

Civino, A., Alighieri, G., Davi, S., Pession, A., Ravelli, A., Santoro, N., Belotti, T, Martino, S., Cesaro, Simone, Filocamo, G., Marino, S., Magnolato, A., Colombini, A., Ricci, F., Suffia, C., Galizzi, R., Palmisani, E., Verzegnassi, F., Olivieri, A. N., Tirtei, E., Gerloni, V, Gorio, C., Lattanzi, B., Pizzati, C., Soscia, F., Vinti, L., De Fanti, A., Ficara, M., Magni Manzoni, S., Boaro, M. P., Prete, E., Quartulli, L., La Torre, F., Onofrillo, D., Rigante, D., Capolsini, I., Maggio, C., Ladogana, S., Marsali, M., Burnelli, R., Coassin, E., Pelegatti, M. A., Arlotta, A., Lepore, L., Conter, V., Biondi, A., Fagioli, F., and Rondelli, R.

Subjects
diagnosi, leucemia acuta, sintomi, diagnosi, sintomi, leucemia acuta
Published
2016

4. Musculoskeletal manifestations of childhood cancer and differential diagnosis with juvenile idiopathic arthritis (ONCOREUM): a multicentre, cross-sectional study

Author

Giovanna Russo, Valentino Conter, M Caniglia, A Garaventa, Giulia Stabile, MF Gicchino, Elisa Rossi, Annalisa Arlotta, S Ladogana, C Atzeni, Rita Consolini, Luciana Vinti, Daniela Onofrillo, Roberto Rondelli, Nicola Santoro, Loredana Lepore, F Locatelli, Elisa Coassin, Monica Ficara, Micol Romano, S Martino, Roberta Burnelli, I Fontanili, Francesca Soscia, Eleonora Prete, Francesca Santarelli, Romina Gallizzi, Patrizia Barone, MG Cefalo, E Cortis, Giovanni Filocamo, M Amatruda, Angela Miniaci, Anna Maria Caroleo, Massimo Eraldo Abate, Maria Cristina Maggio, M Mascarin, Simone Cesaro, E Fabbri, F De Benedetti, Angelo Ravelli, Alma Nunzia Olivieri, C Micalizzi, A Magnolato, B Bigucci, Francesca Ricci, Elisa Tirtei, Antonella Colombini, Luciana Breda, Tamara Belotti, Raffaela De Santis, Roberta Pericoli, Serena Pastore, Silvia Magni-Manzoni, Rosa Anna Podda, Chiara Mainardi, Donato Rigante, Federico Verzegnassi, C Messina, Adele Civino, Cristina Pizzato, M Marsili, Chiara Gorio, Rossella Mura, M Cattalini, Andrea Pession, M Cappella, A Di Cataldo, Francesco La Torre, Assunta Tornesello, Andrea Roncadori, F Porta, Maria Antonietta Pelagatti, F Fagioli, P Bertolini, Ilaria Capolsini, C Rizzari, M Cellini, Bianca Lattanzi, Alessandro De Fanti, S Davì, Carmela De Fusco, Giovanni Alighieri, Andrea Biondi, Civino, Adele, Alighieri, Giovanni, Prete, Eleonora, Maria Caroleo, Anna, SilviaMagni-Manzoni, Vinti, Luciana, Romano, Micol, Santoro, Nicola, Filocamo, Giovanni, Belotti, Tamara, Santarelli, Francesca, Gorio, Chiara, Ricci, Francesca, Colombini, Antonella, Pastore, Serena, Cesaro, Simone, Barone, Patrizia, Verzegnassi, Federico, Olivieri, Alma Nunzia, Ficara, Monica, Miniaci, Angela, Russo, Giovanna, Gallizzi, Romina, Pericoli, Roberta, Breda, Luciana, Mura, Rossella, Annapodda, Rosa, Onofrillo, Daniela, Lattanzi, Bianca, Elisatirtei, Cristina Maggio, Maria, De Santis, Raffaela, Ritaconsolini, Arlotta, Annalisa, La Torre, Francesco, Mainardi, Chiara, Antonietta Pelagatti, Maria, Coassin, Elisa, Capolsini, Ilaria, Burnelli, Roberta, Tornesello, Assunta, Soscia, Francesca, De Fanti, Alessandro, Donatorigante, Pizzato, Cristina, De Fusco, Carmela, Eraldo Abate, Massimo, Roncadori, Andrea, Rossi, Elisa, Stabile, Giulia, Biondi, Andrea, Lepore, Loredana, Conter, Valentino, Rondelli, Roberto, Pession, Andrea, Ravelli, Angelo, Association of Paediatric Haematology and Oncology†and the Italian Paediatric Rheumatology Study Group†, Italian, Amatruda, M, Atzeni, C, Pbertolini, Bigucci, B, Caniglia, M, Cappella, M, Cattalini, M, Cefalo, Mg, Cellini, M, Cortis, E, Davì, S, De Benedetti, F, Di Cataldo, A, Fabbri, E, Fagioli, F, Fontanili, I, Garaventa, A, Gicchino, MARIA FRANCESCA, Ladogana, S, Locatelli, F, Magnolato, A, Marsili, M, Martino, S, Mascarin, M, Messina, C, Micalizzi, C, Porta, F, Rizzari, C, Civino A., Alighieri G., Prete E., Caroleo A.M., Magni-Manzoni S., Vinti L., Romano M., Santoro N., Filocamo G., Belotti T., Santarelli F., Gorio C., Ricci F., Colombini A., Pastore S., Cesaro S., Barone P., Verzegnassi F., Olivieri A.N., Ficara M., Miniaci A., Russo G., Gallizzi R., Pericoli R., Breda L., Mura R., Podda R.A., Onofrillo D., Lattanzi B., Tirtei E., Maggio M.C., De Santis R., Consolini R., Arlotta A., La Torre F., Mainardi C., Pelagatti M.A., Coassin E., Capolsini I., Burnelli R., Tornesello A., Soscia F., De Fanti A., Rigante D., Pizzato C., De Fusco C., Abate M.E., Roncadori A., Rossi E., Stabile G., Biondi A., Lepore L., Conter V., Rondelli R., Pession A., Ravelli A., Amatruda M., Atzeni C., Bertolini P., Bigucci B., Caniglia M., Cappella M., Cattalini M., Cefalo M.G., Cellini M., Cortis E., Davi S., De Benedetti F., Di Cataldo A., Fabbri E., Fagioli F., Fontanili I., Garaventa A., Gicchino M.F., Ladogana S., Locatelli F., Magnolato A., Marsili M., Martino S., Mascarin M., Messina C., Micalizzi C., Porta F., Rizzari C., Civino, A, Alighieri, G, Prete, E, Caroleo, A, Magni-Manzoni, S, Vinti, L, Romano, M, Santoro, N, Filocamo, G, Belotti, T, Santarelli, F, Gorio, C, Ricci, F, Colombini, A, Pastore, S, Cesaro, S, Barone, P, Verzegnassi, F, Olivieri, A, Ficara, M, Miniaci, A, Russo, G, Gallizzi, R, Pericoli, R, Breda, L, Mura, R, Podda, R, Onofrillo, D, Lattanzi, B, Tirtei, E, Maggio, M, De Santis, R, Consolini, R, Arlotta, A, La Torre, F, Mainardi, C, Pelagatti, M, Coassin, E, Capolsini, I, Burnelli, R, Tornesello, A, Soscia, F, De Fanti, A, Rigante, D, Pizzato, C, De Fusco, C, Abate, M, Roncadori, A, Rossi, E, Stabile, G, Biondi, A, Lepore, L, Conter, V, Rondelli, R, Pession, A, Ravelli, A, Bertolini, P, Cefalo, M, Davi, S, and Gicchino, M

Subjects
medicine.medical_specialty, business.industry, Immunology, Arthritis, Cancer, Odds ratio, Musculoskeletal manifestation, Juvenile idiopathic arthritis, medicine.disease, Histiocytosis, Rheumatology, Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, Prednisone, Internal medicine, Joint pain, Arthropathy, Musculoskeletal manifestations, childhood cancer, juvenile idiopathic arthritis, medicine, childhood cancer, Immunology and Allergy, Differential diagnosis, medicine.symptom, business, medicine.drug
Abstract

Summary 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.

Published
2021

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