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

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 652 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\ub70\u201327\ub78]) 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\u20134 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\ub780 [95% CI 18\ub789\u2013408\ub712]), followed by weight loss (59\ub788 [6\ub734\u2013565\ub753]), thrombocytopenia (12\ub767 [2\ub740\u201366\ub792]), monoarticular involvement (11\ub730 [4\ub709\u201331\ub719]), hip involvement (3\ub730 [1\ub713\u20139\ub761]), and male sex (2\ub740 [1\ub703\u20135\ub758]). Factors independently associated with juvenile idiopathic arthritis were morning stiffness (OR 0\ub704 [95% CI 0\ub701\u20130\ub720]), joint swelling (0\ub703 [0\ub701\u20130\ub709]), and involvement of the small hand joints (0\ub702 [0\u20131\ub705]). 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

Rapporto i.c.a.i. Storia e risultati, di una strategia di ricerca epidemiologica e strumentale

It identifies also a group of vascular surgeons and angiologists, who in the last few years have been undertaking a permanent research program in this area, which is still 'orphan', with respect to the availability of reliable epidemiological data and standardized clinical procedures. Stimulated by the suggestions of an European consensus, the i.c.a.i. group addresses several unsettled issues of CLI: it drew a profile of the different diagnostic and therapeutic interventions used in CLI, in order to assess the consistency of the current procedures with the recommendations of the consensus as well as their practicability. This epidemiological survey served also as a feasibility phase of subsequent intervention studies: it provided information on the prognostic profile of a real population observed in routine conditions of care, thus allowing a careful estimation of the population to be recruited in clinical trials conducted in the same setting. A large scale randomised trial was actually performed, addressing a long unanswered question, it provided evidence of some benefits of the use of prostanoids in CLI. Though small and short-lasting, the advantage is of apparent clinical relevance for a severe clinical condition for which effective treatments were so far unavailable. On its turn, the trial data base (including over 1,500 patients) offers now an epidemiological background suitable to identify the outcome predictive factors in the natural history of CLI, generate further hypothesis related to particular risk subgroups and revise the adequacy of the consensus recommendations

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

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

A prospective epidemiological survey of the natural history of chronic critical leg ischaemia

Objective: To draw a picture of the different practices adopted for the diagnosis, specific treatment and general care of critical leg ischaemia (CLI) in the light of the recommendations of the recent Consensus Document. Design: Prospective observational study. Setting: A representative sample of vascular and general surgery, angiology, general medicine departments of the Italian National Health Service. Subjects: Patients with leg ischaemia considered as chronic and critical according to the definition and diagnostic criteria adopted in each centre. Chief outcome measures: Epidemiological profile of the standard population; prevalence of definition criteria and of diagnostic and therapeutic procedures; short and medium-term clinical outcome as well as of the general vascular morbidity and mortality. Main results: Over a 3 month period, 574 patients were recruited in 69 centres mainly on the basis of clinical findings of CLI (rest pain and/or trophic lesions). They had an adequate diagnostic assessment of their vascular lesions and a high cardiovascular risk in terms of prior morbidity and presence of risk factors, Over half of the patients underwent revascularisation and three quarters were given pharmacological treatments. At the end of the observation period, 50 patients had died (8.7%), three had had a myocardial infarction (0.5%), six a stroke (1.0%), 70 a major amputation (12.2%) and 103 had persistent CLI (17.9%). Conclusions: This survey confirms the dramatic prognosis of patients with CLI and provides an appropriate background and setting to conduct experimental clinical studies in this field