RESUMO
Skin is the forestage for a series of many-sided functions of tumor necrosis factor-alpha (TNF-α), a proinflammatory cytokine with staggering versatility and sizable implications for tissue homeostasis, immune responses, angiogenesis, apoptosis, local and systemic inflammation. An aberrant TNF-α-mediated crosstalk has been linked to the pathogenesis of acute and chronic skin inflammatory diseases, and indeed, TNF-α dysregulation can contribute to the development and progression of psoriasis, vitiligo, local damage following exposition to ultraviolet light radiations, cutaneous lupus erythematosus, and acne vulgaris. Therapies that target TNF-α are conspicuously used in the treatment of different skin disorders, aiming to modulate the in vivo immune functions triggered by many cutaneous cells, including keratinocytes, mast cells, or Langerhans cells, and reduce inflammation taking place within the skin. Herein, we focus on the key relationships between TNF-α and distinct skin non-neoplastic inflammatory or physiologic conditions, showing that a natural induction of TNF-α may have a protective significance but that TNF-α overproduction may be harmful or even lethal. Many questions remain unraveled in the therapeutic practice, and caution should be exercised due to eventual backlashes exerted by TNF-α in maintaining skin health or in provoking skin disease.
Assuntos
Pele , Fator de Necrose Tumoral alfa , Fator de Necrose Tumoral alfa/metabolismo , Humanos , Pele/metabolismo , Pele/patologia , Pele/efeitos da radiação , Animais , Dermatopatias/metabolismo , Dermatopatias/etiologia , Dermatopatias/patologia , Inflamação/metabolismo , Inflamação/patologiaRESUMO
BACKGROUND: Lymphatic malformations are vascular developmental anomalies varying from local superficial masses to diffuse infiltrating lesions, resulting in disfigurement. Patients' outcomes range from spontaneous regression to severe sequelae notwithstanding appropriate treatment. The current classification guides, in part, clinicians through the decision-making process, prognosis prediction and choice of therapeutic strategies. Even though the understanding of molecular basis of the disease has been recently improved, a standardized management algorithm has not been reached yet. RESULTS: Here, we report our experience on five children with different lymphatic anomalies of the head and neck region treated by applying a multidisciplinary approach reaching a consensus among specialists on problem-solving and setting priorities. CONCLUSIONS: Although restitutio ad integrum was rarely achieved and the burden of care is challenging for patients, caregivers and healthcare providers, this study demonstrates how the referral to expert centres can significantly improve outcomes by alleviating parental stress and ameliorating patients' quality of life. A flow-chart is proposed to guide the multidisciplinary care of children with LMs and to encourage multidisciplinary collaborative initiatives to implement dedicated patients' pathways.
Assuntos
Anormalidades Linfáticas , Humanos , Anormalidades Linfáticas/terapia , Anormalidades Linfáticas/patologia , Feminino , Masculino , Criança , Pescoço/patologia , Cabeça , Pré-Escolar , Lactente , Qualidade de VidaRESUMO
Introduction: An aberrant immune response involving yet unidentified environmental and genetic factors plays a crucial role in triggering Kawasaki disease (KD). Aims: The aim of this study was to assess general and laboratory data at the onset of KD in a single-center cohort of children managed between 2003 and 2023 and retrospectively evaluate any potential relationship with the development of KD-related cardiovascular abnormalities (CVAs). Patients and methods: We took into account a total of 65 consecutive children with KD (42 males, median age: 22 months, age range: 2-88 months) followed at the Department of Life Sciences and Public Health in our University; demographic data, clinical signs, and laboratory variables at disease onset, before IVIG infusion, including C-reactive protein, hemoglobin, white blood cell (WBC) count, neutrophil count, platelet count, aminotransferases, natremia, albumin, total bilirubin, and 25-hydroxyvitamin D were evaluated. Results: Twenty-one children (32.3% of the whole cohort) were found to have echocardiographic evidence of CVAs. Univariate analysis showed that diagnosis of KD at <1 year or >5 years was associated with CVAs (p = 0.001 and p = 0.01, respectively); patients with CVAs had a longer fever duration and mostly presented atypical or incomplete presentations. Interestingly, all patients with CVAs had lower levels of vitamin D (less than 30 mg/dL, p = 0.0001) and both higher WBC and higher neutrophil counts than those without CVAs (p = 0.0001 and p = 0.01, respectively). Moreover, blood levels of albumin were significantly lower in KD patients with CVAs compared to those without (11/21, 52% versus 13/44, 30%, p = 0.02). Multiple logistic regression with correction for sex showed that serum vitamin D < 30 ng/mL, WBC count > 20.000/mm3, and age > 60 months at KD onset were the only independent factors statistically associated with CVAs. Conclusions: Hypovitaminosis D, WBC count over 20.000/mm3, and age above 5 years at KD onset emerged as independent factors statistically associated with the occurrence of CVAs.
RESUMO
Background: A correlation between plasma lipids and timing of pubertal development has been hypothesized, though lipid influence remains unclear in central precocious puberty (CPP). Aim: To assess any possible alterations in the lipid profile and triglyceride glucose index (TyG) in children diagnosed with CPP. Patients and Methods: Retrospective single-center study conducted on children (aged 6.3 ± 2.1 years) evaluated for the suspicion of CPP. Results: Based on the results of the gonadotropin releasing hormone (GnRH) test, considering 5 IU/L as cut-off of the luteinizing hormone peak, CPP was confirmed in 43 patients (57.3%). Sixteen (37.2%) had a pathologic body mass index (BMI), with 9 (20.9%) being overweight and 7 (16.27%) obese. High total cholesterol was found in 3 patients with CPP (6.97%), high triglycerides were found in 11 patients with CPP (25.58%), high LDL cholesterol was found in 5 patients with CPP (11.62%), low HDL cholesterol was found in 12/43 patients with CPP (27.9%), a pathologic TyG was found in 13/43 patients with CPP (30.23%). No significant association was observed in the lipid profile for patients with or without CPP, except for HDL cholesterol, which was lower in the CPP group (47.1 ± 10.9; p = 0.033). However, the association between serum HDL cholesterol and CPP was not confirmed at the multivariate logistic regression analysis adjusted for patients' sex and age (p = 0.1; OR: 1.035; 95% CI: 0.993-1.078). Conclusion: The overall lipid profile of our pediatric patients diagnosed with CPP did not differ from patients having idiopathic precocious thelarche or normal variants of puberty development.
RESUMO
BACKGROUND: Wernicke encephalopathy (WE) is an acute and potentially fatal neuropsychiatric disorder resulting from thiamine deficiency: its etiology and clinical presentation can be heterogeneous and arduously recognized, especially in children and adolescents. CASE PRESENTATION: An 8-year-old girl arrived to the emergency room with ataxic gait, nystagmus, and mental confusion after a 10-day history of repeated severe vomiting; her recent clinical history was characterized by restricted nutrition due to a choking phobia, which caused substantial weight loss. Brain magnetic resonance imaging revealed a bilaterally increased T2 signal in the medial areas of the thalami and cerebral periaqueductal region. Diagnosis of WE based on clinical and neuroradiological findings was established and confirmed after labwork showing low serum thiamine. Following psychiatric evaluation, the patient was also diagnosed with avoidance-restrictive food intake disorder (ARFID), which required starting cognitive behavioral therapy and introducing aripiprazole. The patient displayed improvement of the radiological findings after one month and complete resolution of her neurological symptoms and signs. CONCLUSIONS: Eating disorders like ARFID might forerun acute signs of WE; this possibility should be considered even in pediatric patients, especially when atypical neurological pictures or feeding issues come out.
RESUMO
BACKGROUND: Individuals with hyperinsulinemia may initially not meet any diagnostic criteria for metabolic syndrome, though displaying a higher risk of cardiovascular complications combined with obesity, diabetes, and hypertension. AIM: The main objective of our study was to assess the diagnostic accuracy of various cardiovascular risk indices in hyperinsulinemic children and adolescents; a secondary objective was to estimate the optimal cut-offs of these indices. PATIENTS AND METHODS: This retrospective single-center study was conducted on 139 patients aged 12.1 ± 2.9 years, managed for hyperinsulinism. RESULTS: We found statistically significant differences in homeostasis model assessment of insulin resistance index (HOMA-IR), triglyceride glucose index (TyG), TyG-body mass index, visceral adiposity index, lipid accumulation product index, fatty liver index, and hepatic steatosis index. At the linear logistic regression assessment, we found that insulin growth factor-1 (IGF-1), HOMA-IR, and ALT/AST ratio were independently associated with confirmed hyperinsulinism. At the multivariate analysis, IGF-1 levels over 203 ng/mL and HOMA-IR higher than 6.2 were respectively associated with a 9- and 18-times higher odds ratio for hyperinsulinism. The other investigated parameters were not significantly related to hyperinsulinism, and could not predict either the presence of hyperinsulinemia or a subsequent cardiovascular risk in our patients. CONCLUSION: Commonly used indices of cardiovascular risk in adults cannot be considered accurate in confirming hyperinsulinism in children, with the exception of HOMA-IR. Further studies are needed to verify the usefulness of specific cardiovascular risk indices in hyperinsulinemic children and adolescents.
RESUMO
Objective: Inflammation has been associated with an increased risk for cancer development, while innate immune system activation could counteract the risk for malignancies. Familial Mediterranean fever (FMF) is a severe systemic inflammatory condition and also represents the archetype of innate immunity deregulation. Therefore, the aim of this study is to investigate the risk for cancer development in FMF. Methods: The risk ratio (RR) for malignancies was separately compared between FMF patients and fibromyalgia subjects, Still's disease patients and Behçet's disease patients. Clinical variables associated with cancer development in FMF patients were searched through binary logistic regression. Results: 580 FMF patients and 102 fibromyalgia subjects, 1012 Behçet's disease patients and 497 Still's disease patients were enrolled. The RR for the occurrence of malignant neoplasms was 0.26 (95% Confidence Interval [CI.] 0.10-0.73, p=0.006) in patients with FMF compared to fibromyalgia subjects; the RR for the occurrence of malignant cancer was 0.51 (95% CI. 0.23-1.16, p=0.10) in FMF compared to Still's disease and 0.60 (95% CI. 0.29-1.28, p=0.18) in FMF compared to Behçet's disease. At logistic regression, the risk of occurrence of malignant neoplasms in FMF patients was associated with the age at disease onset (ß1 = 0.039, 95% CI. 0.001-0.071, p=0.02), the age at the diagnosis (ß1 = 0.048, 95% CI. 0.039-0.085, p=0.006), the age at the enrolment (ß1 = 0.05, 95% CI. 0.007-0.068, p=0.01), the number of attacks per year (ß1 = 0.011, 95% CI. 0.001- 0.019, p=0.008), the use of biotechnological agents (ß1 = 1.77, 95% CI. 0.43-3.19, p=0.009), the use of anti-IL-1 agents (ß1 = 2.089, 95% CI. 0.7-3.5, p=0.002). Conclusions: The risk for cancer is reduced in Caucasic FMF patients; however, when malignant neoplasms occur, this is more frequent in FMF cases suffering from a severe disease phenotype and presenting a colchicine-resistant disease.
Assuntos
Febre Familiar do Mediterrâneo , Neoplasias , Sistema de Registros , Humanos , Febre Familiar do Mediterrâneo/complicações , Febre Familiar do Mediterrâneo/epidemiologia , Neoplasias/epidemiologia , Neoplasias/etiologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Fatores de Risco , Estudos de Coortes , Adulto Jovem , Fibromialgia/epidemiologia , Fibromialgia/etiologia , Síndrome de Behçet/epidemiologia , Síndrome de Behçet/complicaçõesRESUMO
Juvenile dermatomyositis (JDM) is the most common inflammatory myopathy affecting children, being marked by chronic inflammation which mostly impacts on both skin and skeletal muscles; diagnostic criteria of JDM include an unforeseeable mixture of clinical features, while treatment modalities commonly require corticosteroids or immunosuppressant agents. Although the pathogenesis of JDM is not completely understood, several infectious triggers have been linked to its priming via anecdotal reports related to children. Pediatric cases of recent-onset JDM have been temporally associated to an infectious disease by the power of increased titers of circulating antibodies to a putative infectious agent, including parasites, and/or detectable viral RNA or bacterial DNA. With this narrative review we offer an update about JDM association with a host of infections, namely parvovirus B19, Epstein-Barr virus, Coxsackie virus, human immune deficiency virus, severe acute respiratory syndrome coronavirus 2, Mycoplasma pneumoniae and Toxoplasma gondii, as resulting from the medical literature. Few are the evidence-proved results addressing JDM as an unambiguous post-infectious disorder and available data specifically related to children are poor, highlighting the need of further research into the exploration between environmental cut-out factors and JDM.
Assuntos
Dermatomiosite , Humanos , Dermatomiosite/imunologia , Criança , COVID-19/imunologia , SARS-CoV-2/imunologiaRESUMO
INTRODUCTION: Vascular events account for a considerable burden of morbidity and mortality in Behçet syndrome (BS). Thrombosis occurs in 1.8-21 % pediatric BS patients, even if the real prevalence is still largely unknown. OBJECTIVES: To report clinical features and outcomes of pediatric BS patients with thrombosis and to compare the demographic and clinical characteristics of BS patients with and without thrombosis. METHODS: Retrospective data collection of BS patients with thrombosis (T+) included in the EUROFEVER registry. BS patients without thrombosis (T-), belonging to the same rheumatology units, were matched in a 2:1 ratio. RESULTS: 37 T+ were compared to 74 T- patients. At onset, ICBD criteria fulfillment was higher in the T- group (p = 0.015). Caucasian patients were more often T-, Turkish patients were more frequent in T+ group (p = 0.002). At onset, pustulosis was most frequently observed in the T- (p < 0.001) as well as gastrointestinal symptoms (p < 0.001) and ocular involvement (p = 0.022). Neurological symptoms were more often described in T+ (p = 0.034). As for T+, thrombosis was reported at BS presentation in 8/37 (21.6 %). For the T + e patients who developed thrombosis later, oral aphthosis (p = 0.003), genital aphthosis (p = 0.014) were more frequently observed at BS onset, while pustulosis (p = 0.005) and fever (p = 0.043) coexisted with thrombosis. Thrombosis was mainly venous (26/37,70.3 %), involving the cerebral sinuses (21/37, 56.8 %). After thrombosis, 35/37 (94.6 %) T+ patients received an immunomodulatory treatment compared with 16/29 (55.2 %) pre-thrombosis. A recurrence was reported in 6/31(19.4 %). CONCLUSION: Thrombosis was reported at BS presentation in one fifth of cases. Pustolosis and fever were more frequently concomitant to thrombosis. Sinus veins were the most frequent site.
Assuntos
Síndrome de Behçet , Sistema de Registros , Trombose , Humanos , Síndrome de Behçet/complicações , Síndrome de Behçet/epidemiologia , Masculino , Feminino , Criança , Adolescente , Estudos Retrospectivos , Trombose/etiologia , Trombose/epidemiologia , Europa (Continente)/epidemiologia , PrevalênciaRESUMO
Achondroplasia (ACH), the most common form of skeletal dysplasia, is characterized by severe disproportionate short stature, rhizomelia, exaggerated lumbar lordosis, brachydactyly, macrocephaly with frontal bossing and midface hypoplasia. Ligamentous laxity has been reported as a striking feature of ACH, but its prevalence and characteristics have not been systematically evaluated yet. There is growing evidence that ligamentous laxity can be associated with chronic musculoskeletal problems and may affect motor development leading to abnormal developmental trajectories. This study aimed to assess the prevalence of ligamentous laxity in children with ACH through standardized tools, the Beighton scale and its modified version for preschool-age children. A total of 33 children (mean age 6.4 ± 3.2 years; age range 1-12.5 years) diagnosed with ACH by the demonstration of a pathogenic variant in the FGFR3 gene and 33 age- and sex-matched healthy controls were included in the study. Both ligamentous laxity assessment and neurological examinations were performed; medical history was also collected from caregivers. Children with ACH showed a 2 times higher risk of ligamentous laxity than the group without skeletal dysplasia (OR = 2.2; 95% CI = 1.0 to 4.7), with 55% of children meeting the diagnostic criteria for hypermobility. No significant difference in ligamentous laxity was observed between males and females. Joint involvement analysis revealed characteristic patterns, with knee hypermobility observed in 67% of patients, while rare was elbow hypermobility. Longitudinal assessments indicated a decreasing trend in ligamentous laxity scores over time, suggesting a potential decrease in hypermobility issues during adulthood. The findings of this study provide valuable insights into the prevalence and characteristics of ligamentous laxity in ACH. Implementation of standardized ligamentous laxity assessments might guide patients' follow-up and facilitate early interventions, helping to prevent pain and improve outcomes and quality of life for such patients. Further prospective studies are needed to explore the natural history of ligamentous laxity in ACH and investigate the potential impact of emerging pharmacological treatments upon hypermobility.
Assuntos
Acondroplasia , Instabilidade Articular , Osteocondrodisplasias , Masculino , Criança , Pré-Escolar , Feminino , Humanos , Adulto , Lactente , Prevalência , Qualidade de Vida , Instabilidade Articular/epidemiologia , Acondroplasia/epidemiologia , Acondroplasia/genética , Estudos ProspectivosRESUMO
BACKGROUND: Among aneuploidies compatible with life, trisomy 22 mosaicism is extremely rare, and only about 25 postnatal and 18 prenatal cases have been described in the literature so far. The condition is mainly characterized by facial and body asymmetry, cardiac heart defects, facial dysmorphisms, growth failure, delayed puberty, and variable degrees of neurodevelopmental delay. PROBLEM: The scattered information regarding the condition and the dearth of data on its natural history and developmental outcomes restrict genetic counseling, particularly in prenatal settings. Moreover, a prompt diagnosis is frequently delayed by the negative selection of trisomic cells in blood, with mosaicism percentage varying among tissues, which often entails the need for further testing. Purpose/topic: The aim of our work is to provide assistance in prenatal and postnatal genetic counseling by systematically delineating the current knowledge of the condition. This entails defining the prenatal and postnatal characteristics of the condition and presenting novel data from three cases, both prenatally and postnatally. Additionally, we report the developmental outcomes observed in two new patients.
Assuntos
Cromossomos Humanos Par 22 , Mosaicismo , Trissomia , Humanos , Trissomia/genética , Feminino , Cromossomos Humanos Par 22/genética , Gravidez , Diagnóstico Pré-Natal , Masculino , Aconselhamento Genético , Dissomia Uniparental/genética , Recém-Nascido , Transtornos Cromossômicos/genética , Transtornos Cromossômicos/diagnósticoRESUMO
Background and objective: IgA vasculitis (IgAV), a predominantly pediatric leukocytoclastic disease, has an unpredictable, though largely benign, evolution. The aim of this study was to retrospectively investigate any potential clinical or laboratory predictors of gastrointestinal involvement in a single-center cohort of children with IgAV. Patients and methods: A total of 195 children with a history of IgAV, regularly followed-up for an average period of 1 ± 2.6 years via outpatients clinics of the pediatric rheumatology unit in our University, were assessed, analyzing their clinical and laboratory variables in relationship with their disease evolution and outcome. Results: Univariate analysis showed that a higher neutrophil granulocyte count and lower lymphocyte count (expressed as a percentage of the total white blood cells) were significantly associated with the presence of gastrointestinal involvement at the first examination (65.2 ± 13% versus 58.8 ± 12%, p = 0.02, and 26.4 ± 11% versus 32.1 ± 11%, p = 0.02, respectively). A positive pharyngeal swab for Streptococcus pyogenes, a deficiency of 25-hydroxyvitamin D, a persistence of purpuric rash for more than 1 month, and purpuric lesions in the genital area were also associated with gastrointestinal involvement (p = 0.0001, p = 0.0001, p = 0.007 and p = 0.001, respectively). However, multiple logistic regressions with correction for the patients' sex and age showed that lower 25-hydroxyvitamin D levels, persistent rash, and genital lesions were independently and significantly associated with signs of gastrointestinal involvement. We then performed a secondary analysis (both univariate and multivariate) to investigate whether vitamin D deficiency was associated with other IgAV manifestations: we found that only 25-hydroxyvitamin D deficiency remained significantly associated with gastrointestinal involvement in IgAV. Conclusions: Patients with IgAV and vitamin D deficiency might be more prone to developing gastrointestinal manifestations of variable severity.
RESUMO
OBJECTIVES: Limited information is available on the clinical features, treatment modalities and outcomes of the juvenile idiopathic arthritis (JIA) categories of enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA). This study was aimed to describe the characteristics of Italian children with ERA and JPsA and to compare them with those of patients with the other categories of JIA. METHODS: Patients were part of a multinational sample included in a study aimed to investigate the prevalence of disease categories, treatment approaches, and disease status in patients from across different geographical areas (EPOCA Study). All patients underwent a retrospective assessment, based on the review of clinical chart, and a cross-sectional evaluation, which included assessment of physician- and parent-reported outcomes and laboratory tests, and recording of ongoing therapies. RESULTS: Of the 9081 children with JIA enrolled in the EPOCA Study, 1300 were recruited at 18 paediatric rheumatology centres in Italy. 45 (3.5%) had ERA and 49 (3.8%) had JPsA. Several remarkable differences in demographic features and frequency of articular and extra-articular manifestations, disease damage, impairment in physical function and health-related quality of life, school-related problems, comorbidities, and ongoing treatments were observed between ERA and JPsA and the other JIA categories. CONCLUSIONS: We described the characteristics of Italian children with ERA and JPsA and highlighted their peculiarities and their differences from the other JIA subsets. These data provide useful insights for future revisions of JIA classification and a benchmarking against which the features from other cohorts may be compared.
Assuntos
Artrite Juvenil , Criança , Humanos , Artrite Juvenil/diagnóstico , Artrite Juvenil/tratamento farmacológico , Artrite Juvenil/epidemiologia , Estudos Retrospectivos , Estudos Transversais , Qualidade de Vida , Resultado do TratamentoRESUMO
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.