Effectiveness and safety of bisphosphonates therapy in secondary osteoporosis in children.

INTRODUCTION: There are few studies on effectiveness and safety of bisphosphonate therapy in secondary osteoporosis in children. The aim of this research was to analyse effectiveness and safety of bisphosphonates in secondary osteoporosis in children. PATIENTS AND METHODS: Multicentre retrospective study in patients younger than 18 suffering from secondary osteoporosis and who have received bisphosphonates. Clinical data were recorded. Bone mineral density (BMD) was assessed in terms of BMD Z-score in lumbar spine (ZBMDls) measured by dual-energy X-ray absorptiometry (DXA). Effectiveness was valued at changes in ZBMDls one and two years after the onset of bisphosphonates and at the decrese in the number of fractures a year. Adverse events reported were recorded. Descriptive and bivariant analysis was performed. RESULTS: 32 patients were recruited. ZBMDls increased one year after the onset of treatment ((-2.46 ± 0.96) vs. (-1.54 ± 1.38); p < .001). Fractures a year dicreased significantly (1 (1-2) vs. 0 (0-0.61); p < .001). ZBMDls increase was higher in patients who were able to walk (1.88 ± 0.72 vs. 0.55 ± 0.82; p = .07) and correlated positively with body mass index (BMI)- for- age percentile (rho: 0.564; p < .001). The decrease in the number of fractures a year was higher in patients with lower initial fracture rate (rho: -0,47; p = .006) and with higher initial ZBMDls (rho: -0.47; p = .07). 10 adverse events were reported in 7 patients (22%), all of them intravenous bisphosphonates related. No association was found between adverse events and studied variables. CONCLUSIONS: Bisphosphonates are effective in secondary osteoporosis in children. Response seems to be better in patients who are able to walk, well-nourished and in the early stages of the disease. Adverse events were frequent but mild.

Longitudinal Study of Cognitive Functioning in Adults with Juvenile Idiopathic Arthritis.

OBJECTIVE: To prospectively evaluate possible decline of cognitive functions in adult patients with juvenile idiopathic arthritis (JIA) and identify associated factors. PATIENTS AND METHODS: We performed a 24-month prospective observational study of adults (≥16 years) with JIA. The primary outcome measure was decline in cognitive function defined as a worsening of ≥2 points on the scales of the subsets administered to evaluate the different cognitive areas using the Wechsler Adult Intelligence Scale (WAIS) after 24 months: attention/concentration (digit span); verbal function (vocabulary); visual-spatial organization (block design); working memory (letter-number sequencing); and problem solving (similarities). Other variables included average inflammatory activity using C-reactive protein and composite activity indexes, comorbidity, and treatment. Logistic regression was performed to identify factors associated with cognitive decline. RESULTS: The study population comprised 52 patients with JIA. Of these, 15 (28.8%) had cognitive decline at V24. The most affected functions were working memory (17.3%), attention/concentration (9.6%), verbal function (7.7%), visual-spatial organization (7.7%), and problem solving (3.8%). There were no significant differences in the median direct or scale scores for the cognitive functions evaluated between V0 and V24 for the whole sample. The factors associated with cognitive decline in patients with JIA were average C-reactive protein (OR [95% CI], 1.377 [1.060-1.921]; p = 0.039), depression (OR [95% CI], 3.691 [1.294-10.534]; p = 0.015), and treatment with biologics (OR [95% CI], 0.188 [0.039-0.998]; p = 0.046). CONCLUSION: Cognitive decline was detected in almost one third of adults with JIA after 24 months of follow-up. Systemic inflammatory activity in JIA patients was related to cognitive decline. Patients treated with biologics had a lower risk of decline in cognitive functions.

Digital ischemia as the initial presentation of catastrophic antiphospholipid syndrome.

Catastrophic antiphospholipid syndrome is an infrequent disease in children, but of major relevance because of its high morbidity and mortality. We report the case of a child with digital ischaemia in whom, after aetiological screening, the diagnosis of catastrophic antiphospholipid syndrome was made.

Crohn's disease in a patient with systemic onset juvenile idiopathic arthritis. Association or associated side effect of treatment?

The progression of systemic-onset juvenile idiopathic arthritis (JIAs) to the different forms of presentation of inflammatory bowel disease is extremely rare. We present the first report of a patient with SJIA that progressed to Crohn's disease in which mutations have been detected in genes responsible for the adequate regulation of the innate immune system.

Adiposity Is Related to Inflammatory Disease Activity in Juvenile Idiopathic Arthritis.

OBJECTIVE: To identify factors associated with the higher proportion of fatty tissue and overweight/obesity observed in patients with juvenile idiopathic arthritis (JIA). PATIENTS AND METHODS: We performed a cross-sectional study of 80 JIA patients aged 4-15 years with 80 age- and sex-matched healthy controls. Body composition was assessed using dual-energy x-ray absorptiometry. The 27-joint Juvenile Arthritis Disease Activity score (JADAS27) was calculated. Two multivariate models were constructed to identify factors associated with overweight/obesity and fat mass index (FMI). RESULTS: No differences were found between cases and controls in body mass index (BMI) or body composition. However, compared with controls, patients with a high inflammatory activity (JADAS27 > 4.2 for oligoarticular JIA or >8.5 for polyarticular disease) had higher values for BMI (p = 0.006); total fat mass (p = 0.003); FMI (p = 0.001); and fat in the legs (p = 0.001), trunk (p = 0.001), and arms (p = 0.002). The factors associated with overweight/obesity in patients were the duration of therapy with biological drugs, measured in months (OR [95% CI] = 1.12 [1.02-1.04]; p = 0.037), and physical activity (OR [95% CI] = 0.214 [0.07-0.68]; p = 0.010), while the factors associated with FMI were age (ß [95% CI] = 0.30 [0.17-1.41]; p = 0.014), JADAS27 (ß [95% CI] = 0.45 [0.16-1.08]; p = 0.009), and physical activity (ß [95% CI] = -0.22 [-5.76 to 0.29]; p = 0.031). CONCLUSION: Our study revealed no differences between JIA patients with well-controlled disease and low disability and the healthy population in BMI or body composition. Furthermore, the association observed between inflammatory activity and adiposity could be responsible for poorer clinical course.

Skin lesions in children during the first wave of the SARS-CoV-2 pandemic.

BACKGROUND: Cutaneous manifestations have been included in COVID-19 patients' clinical spectrum. Our objective was to determine the association between skin lesions in children and SARS-CoV2 infection, analyzing others possible infectious/autoimmune etiologies. MATERIAL AND METHODS: Observational, multicenter, cross-sectional study, about children with skin manifestations from April to May 2020. The diagnosis of SARS-CoV2 was performed by PCR in nasopharyngeal exudate and/or presence of antibodies by serology. RESULTS: Sixty-two children were included, 9 (14.5%) presented positive antibodies to SARS-CoV-2, with no positive PCR to SARS-Cov-2 in those patients in whom it was made. Patients with positive serology to SARS-CoV-2 presented chilblains and/or vesicular-bullous skin lesions more frequently (66.7% vs. 24.5%, p = 0.019). Generalized, urticarial and maculopapular rash was more common in patients with negative antibodies (37.7 vs. 0%, p = 0.047), others pathogens were isolated in 41.5% of these patients. There were no significant differences in the positivity for autoantibodies between both groups. CONCLUSION: In our study, the presence of chilblains-like and/or vesicular lesions were significantly related to SARS-CoV2 previous contact.

INTRODUCCIÓN: Las manifestaciones cutáneas se han incluido en el espectro clínico de los pacientes con COVID-19. Nuestro objetivo fue determinar la asociación entre las lesiones cutáneas observadas en niños durante la primera ola de la pandemia y la infección por SARS-CoV-2, analizando otras posibles etiologías infecciosas o autoinmunes. MATERIAL Y MÉTODOS: Estudio observacional, multicéntrico, de corte transversal, desarrollado en niños con manifestaciones cutáneas desde abril hasta mayo de 2020. La determinación de SARS-CoV-2 se realizó mediante PCR en exudado nasofaríngeo y/o serología. RESULTADOS: Se seleccionó a 62 niños; 9 (14,5%) presentaron serología positiva para SARS-CoV-2, siendo la PCR negativa en todos los casos en los que se realizó. Los pacientes con serología positiva para SARS-CoV-2 presentaron con más frecuencia lesiones pernióticas y/o vesiculosas (66,7 vs. 24,5%; p = 0,019). El exantema generalizado, urticarial y maculopapuloso fue más habitual en el grupo de pacientes con serología negativa (37,7 vs. 0%; p = 0,047); se aislaron otros patógenos en el 41,5%. No hubo diferencias significativas en cuanto a la positividad de autoanticuerpos entre ambos grupos. CONCLUSIÓN: En nuestro estudio, las lesiones de tipo perniosis o vesiculosas se relacionaron significativamente con el contacto previo con SARS-CoV-2.

[Skin lesions in children during the first wave of the SARS-CoV-2 pandemic]. / Lesiones cutáneas en niños durante la primera ola de la pandemia por SARS-CoV-2.

BACKGROUND: Cutaneous manifestations have been included in COVID-19 patients' clinical spectrum. Our objective was to determine the association between skin lesions in children and SARS-CoV-2 infection, analyzing others possible infectious/autoimmune etiologies. MATERIAL AND METHODS: Observational, multicenter, cross-sectional study, about children with skin manifestations from April to May 2020. The diagnosis of SARS-CoV-2 was performed by PCR in nasopharyngeal exudate and/or presence of antibodies by serology. RESULTS: Sixty-two children were included, 9 (14.5%) presented positive antibodies to SARS-CoV-2, with no positive PCR to SARS-Cov-2 in those patients in whom it was made. Patients with positive serology to SARS-CoV-2 presented chilblains and/or vesicular-bullous skin lesions more frequently (66.7% vs. 24.5%, p=0.019). Generalized, urticarial and maculopapular rash was more common in patients with negative antibodies (37.7 vs. 0%, p=0.047), others pathogens were isolated in 41.5% of these patients. There were no significant differences in the positivity for autoantibodies between both groups. CONCLUSION: In our study, the presence of chilblains-like and/or vesicular lesions were significantly related to SARS-CoV-2 previous contact.

Skin manifestations during the COVID-19 pandemic in the pediatric emergency department.

BACKGROUND: The role of SARS-CoV-2 as the cause of chilblains in children remains a matter of debate but it is important to elucidate it for patient isolation and contact tracing. We sought to define the etiology, clinical presentation, time course, and outcomes of children presenting to the emergency department (ED) with cutaneous manifestations shortly after the first pandemic peak of COVID-19 in Spain. METHODS: A prospective, observational study in children <15 years of age evaluated for skin lesions in the EDs of three pediatric hospitals. Children underwent a comprehensive work-up including tests for SARS-CoV-2 antibodies and polymerase chain reaction (PCR), and serology and PCR tests for other viruses and bacteria. A 1 month follow-up visit was conducted. RESULTS: From April 14 through May 8, 2020, we enrolled 62 children. Of those, 34 had acro-ischemic skin lesions and 28 had a variety of skin rashes. Overall, 40% of children had mild systemic symptoms. Children with chilblains were older, had pain more frequently and a more prolonged duration of skin lesions, while those with non-specific rashes had fever more frequently. Lesions were resolved in 75% of children at follow up. Five patients demonstrated SARS-CoV-2 antibodies, and none tested positive with PCR. Three additional patients tested positive with PCR for rhinovirus, Mycoplasma pneumoniae and Chlamydia pneumoniae. CONCLUSIONS: The number of ED visits for chilblains, which are rare in pediatrics, was high soon after the first peak of COVID-19 in Spain. The disease course was self-limited, outcomes were favorable, and the possibility of viral transmission was negligible as all patients tested negative for SARS-CoV-2 by PCR.

Digital Ischemia as the Initial Presentation of Catastrophic Antiphospholipid Syndrome. / Isquemia digital como forma de presentación de síndrome antifosfolípido catastrófico pediátrico.

Catastrophic antiphospholipid syndrome is an infrequent disease in children, but of major relevance because of its high morbidity and mortality. We report the case of a child with digital ischaemia in whom, after aetiological screening, the diagnosis of catastrophic antiphospholipid syndrome was made.

Expert panel consensus recommendations for diagnosis and treatment of secondary osteoporosis in children.

BACKGROUND: Osteoporosis incidence in children is increasing due to the increased survival rate of patients suffering from chronic diseases and the increased use of drugs that can damage bones. Recent changes made to the definition of childhood osteoporosis, along with the lack of guidelines or national consensuses regarding its diagnosis and treatment, have resulted in a wide variability in the approaches used to treat this disease. For these reasons, the Osteogenesis Imperfecta and Childhood Osteoporosis Working Group of the Spanish Society of Pediatric Rheumatology has sounded the need for developing guidelines to standardize clinical practice with regard to this pathology. METHODS: An expert panel comprised of 6 pediatricians and 5 rheumatologists carried out a qualitative literature review and provided recommendations based on evidence, when that was available, or on their own experience. The level of evidence was determined for each section using the Oxford Centre for Evidence-based Medicine (CEBM) system. A Delphi survey was conducted for those recommendations with an evidence level of IV or V. This survey was sent to all members of the SERPE. All recommendations that had a level of agreement higher or equal to 70% were included. RESULTS: Fifty-one recommendations, categorized into eight sections, were obtained. Twenty-four of them presented an evidence level 4 or 5, and therefore a Delphi survey was conducted. This was submitted electronically and received a response rate of 40%. All recommendations submitted to the Delphi round obtained a level of agreement of 70% or higher and were therefore accepted. CONCLUSION: In summary, we present herein guidelines for the prevention, diagnosis and treatment of secondary childhood osteoporosis based on the available evidence and expert clinical experience. We believe it can serve as a useful tool that will contribute to the standardization of clinical practice for this pathology. Prophylactic measures, early diagnosis and a proper therapeutic approach are essential to improving bone health, not only in children and adolescents, but also in the adults they will become in the future.

Recurrent multifocal osteomyelitis in children: Experience in a tertiary care center. / Osteomielitis multifocal recurrente en niños: experiencia de un centro de tercer nivel.

INTRODUCTION: Chronic recurrent multifocal osteomyelitis is a rare aseptic bone inflammation that affects pediatric patients. Its management and treatment have not yet been standardized. METHODS: Retrospective, descriptive study of patients under 14 years of age diagnosed with chronic nonbacterial osteomyelitis (CNBO) in a tertiary hospital. We included patients diagnosed over the last 6 years (2010-2015) who met the Jansson criteria. The clinical and radiological characteristics of CNBO were analyzed, as was the outcome after different therapeutic options. RESULTS: We report 12 patients, with a mean age of 11 years (±1.6 standard deviation [SD]) and female predominance (10:2). The mean number of foci was 3.5 (±2.2 SD). The most common locations were ankle (58%), clavicle (50%), sternum (33%) and hip (25%). The mean disease duration was 10.5 months (±10.3 SD), and the median time to diagnosis was 2.38 months (range 0.17-16). Bone scintigraphy detected asymptomatic foci in 33% and we detected lytic lesions in 50% through magnetic resonance imaging. Biopsy was performed in 60%; 2/12 (16%) were associated with inflammatory disease and 1/12 (8.3%) later developed lymphoma. In all, 58% received antibiotic therapy with little response, 100% anti-inflammatory agents, 50% systemic corticosteroids, 41.6% methotrexate/pamidronate and 16% anti-tumor necrosis factor (TNF) α. The mean duration of treatment was 14.8 months (±12.4 SD) and 66% had recurrences. Currently, 83% are in clinical remission without treatment. CONCLUSIONS: When CNBO is refractory to treatment with anti-inflammatory drugs, intravenous pamidronate can be an alternative. Anti-TNF drugs can be considered in patients who fail with pamidronate, as can agents associated with other autoimmune conditions.

[Low bone mineral density in juvenile idiopathic arthritis: Prevalence and related factors]. / Baja densidad mineral ósea en artritis idiopática juvenil: prevalencia y factores relacionados.

INTRODUCTION: Height adjustment is currently recommended for Z-score bone mineral density (BMD) assessed by dual energy X-ray absorptiometry. At present there are no studies that evaluate the prevalence of low BMD in paediatric patients with Juvenile Idiopathic Arthritis (JIA) in Spain following current recommendations. OBJECTIVES: To evaluate low BMD in JIA in paediatric patients with JIA in Spain following the latest recommendations, as well as to assess associated factors. METHODS: Observational cross-sectional study of Spanish JIA patients from 5 to 16 years-old, followed-up in a Paediatric Rheumatology Unit between July 2014 and July 2015. Anthropometric, clinical and treatment data were recorded. Dual energy X-ray absorptiometry, and bone metabolism parameters were collected, and a completed diet and exercise questionnaire was obtained. RESULTS: A total of 92 children participated. The population prevalence estimation of low BMD was less than 5% (95% CI). A significant positive correlation was found in the multiple linear regression analysis between the body mass index percentile (B: 0.021; P<.001) and lean mass index (B: 0.0002; P=.012), and BMD Z-score adjusted for height (Z-SAH). A significant negative correlation was found between fat mass index (B: -0.0001; P=.018) and serum type I collagen N-propeptide (B: -0,0006; P=.036) and Z-SAH. CONCLUSIONS: Low BMD prevalence in JIA patients in our population is low. An adequate nutritional status and the prevalence of lean over fat mass seem to promote the acquisition of bone mass. Those JIA patients with lower BMD could be subjected to an increase of bone turnover.