Civino Adele, Alighieri Giovanni, Prete Eleonora, Caroleo Anna Maria, Magni-Manzoni Silvia, 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, Podda Rosa Anna, Onofrillo Daniela, Lattanzi Bianca, Tirtei Elisa, Maggio Maria Cristina, De Santis Raffaela, Consolini Rita, Arlotta Annalisa, La Torre Francesco, Mainardi Chiara, Pelagatti Maria Antonietta, Coassin Elisa, Capolsini Ilaria, Burnelli Roberta, Tornesello Assunta, Soscia Francesca, De Fanti Alessandro, Rigante Donato, Pizzato Cristina, De Fusco Carmela, Abate Massimo Eraldo, Roncadori Andrea, Rossi Elisa, Stabile Giulia, Biondi Andrea, Lepore Loredana, Conter Valentino, Rondelli Roberto, Pession Andrea, Ravelli Angelo
Unità di Reumatologia e Immunologia Pediatrica, Ospedale Vito Fazzi, Lecce, Italy.
Unità di Pediatra-UTIN, Azienda Ospedaliera Cardinale G Panico, Tricase, Italy.
Lancet Rheumatol. 2021 Jul;3(7):e507-e516. doi: 10.1016/S2665-9913(21)00086-2. Epub 2021 May 11.
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.
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.
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]).
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.
Associazione Lorenzo Risolo.
儿童癌症的症状可能与风湿性疾病相似。然而，用于指导鉴别诊断的证据仍然很少。因此，预防错误或延迟诊断对于避免糖皮质激素或免疫抑制治疗的不当使用以及预后恶化很重要。为此，我们旨在评估癌症发病时患者出现的肌肉骨骼表现的患病率和特征，并确定区分伴有关节病的儿童恶性肿瘤与幼年特发性关节炎的因素。
我们在意大利的25个儿科血液肿瘤中心和22个儿科风湿病中心进行了一项多中心横断面研究。我们前瞻性招募了年龄小于16岁、新诊断为癌症或幼年特发性关节炎的患者。我们排除了接受过糖皮质激素预处理的患者（口服泼尼松≥1mg/kg/天或等效剂量连续≥2周）。我们使用由Cineca大学间联盟提供支持的基于网络平台的电子病例报告表，收集新诊断为癌症或幼年特发性关节炎患者的数据。主要结局是描述癌症发病时肌肉骨骼表现的频率和特征；次要结局是使用多变量逻辑回归分析确定可区分伴有或不伴有其他肌肉骨骼症状的关节病性恶性肿瘤与幼年特发性关节炎的因素。
在2015年5月1日至2018年5月31日期间，1957名患者符合条件，其中1277名（65%）患有癌症，680名（35%）患有幼年特发性关节炎。1277名癌症患者中有324名（25%[95%CI 23.0 - 27.8]）出现肌肉骨骼症状，其中207名有关节病。恶性骨肿瘤患者的肌肉骨骼症状发生率最高（66名中的53名[80%]），其次是朗格汉斯细胞组织细胞增多症患者（34名中的16名[47%]）、白血病患者（582名中的189名[32%]）、软组织肉瘤患者（68名中的16名[24%]）和神经母细胞瘤患者（109名中的21名[19%]）。在324名有癌症和肌肉骨骼症状的患者中，最常见的主诉是关节疼痛（199名[61%]），其次是四肢骨疼痛（112名[35%]）。关节受累以单关节模式为主（207名中的100名[48%]）和少关节模式（86名[42%]累及2 - 4个关节，20名[10%]累及>4个关节），最常受累的关节是髋关节（207名中的88名[43%]）和膝关节（81名[39%]）。多变量分析显示，四肢骨疼痛是与癌症最密切相关的独立变量（比值比[OR]87.80[95%CI 18.89 - 408.12]），其次是体重减轻（59.88[6.34 - 565.53]）、血小板减少（12.67[2.40 - 66.92]）、单关节受累（11.30[4.09 - 31.19]）、髋关节受累（3.30[1.13 - 9.61]）和男性（2.40[1.03 - 5.58]）。与幼年特发性关节炎独立相关的因素是晨僵（OR 0.04[95%CI 0.01 - 0.20]）、关节肿胀（0.03[0.01 - 0.09]）和手部小关节受累（0.02[0 - 1.05]）。
我们的研究提供了关于儿童癌症出现的肌肉骨骼表现的详细信息，并突出了对与幼年特发性关节炎进行鉴别诊断最有帮助的临床和实验室特征。
洛伦佐·里索洛协会。
