Tarsitis as an initial manifestation of juvenile spondyloarthropathy.

OBJECTIVE: The aim of this study was to determine the frequency of tarsitis as one of the first symptoms of juvenile spondyloarthropathy (JSpA) and to analyze whether patients with tarsitis at onset differ from those without it. METHODS: A retrospective chart review was performed, from January 1996 to September 2007, at a paediatric rheumatology unit of a tertiary university hospital. RESULTS: Tarsitis was detected in one-third of the children diagnosed with JSpA. They had fever and received antibiotics due to a suspected infection more frequently than those without tarsitis. Inflammatory low back pain was extremely unusual among these patients. CONCLUSION: There were some differences between children diagnosed with JSpA initially affected with tarsitis and those without it. Patients with tarsitis as one of the first symptoms were often misdiagnosed as soft tissue infections.

[Recommendations for the use of methotrexate in patients with juvenile idiopathic arthritis]. / Recomendaciones para el uso de metotrexato en pacientes con artritis idiopática juvenil.

OBJECTIVES: To develop a consensus document of recommendations for the use of methotrexate (MTX) in patients with juvenile idiopathic arthritis (JIA). MATERIAL AND METHOD: A group of eleven experts proposed several clinical questions on the use of MTX in patients with JIA. A systematic review was conducted and the evidence and recommendations for each question were extracted. The results were discussed and validated by the experts in a work session to establish the final recommendations. RESULTS: MTX is recommended as the first drug for inducing remission in JIA, and its indication should be made according to the clinical category of the patient. Prior to treatment, it is recommended to perform a complete blood count, including white cells, levels of liver enzymes, serum creatinine, and other analytical parameters according to specific risk factors. Treatment should be initiated with a dose of 10-15 mg/m(2)/week. In cases of uveitis or polyarthritis, an initial dose of 15 mg/m(2)/week should be considered. For a better bioavailability and tolerability, it is preferable to administer MTX parenterally if the dose is ≥15 mg/m(2)/week. It is necessary to periodically perform an analytical monitoring of the patient and to assess possible alterations in liver enzymes to make changes if necessary. Combinations with biological agents may be necessary, as well as the concomitant addition of folic or folinic acid. CONCLUSIONS: This document describes the main recommendations for the appropriate use of MTX in JIA patients, according to scientific evidence and clinical experience.

The role of T cells in Kawasaki disease.

Kawasaki disease (KD) is the most common pediatric vasculitis and the most frequent cause of acquired heart disease in children in the U.S. Its etiopathogenesis is unknown, although T cell, B cell and monocyte/macrophage populations have all been implicated in the disease. The precise role played by T cells is unclear. Analysis of T-cell activation markers in peripheral blood has demonstrated conflicting data. Study of tissue samples, which could clarify this issue, has been limited. Expansion of T cells bearing V beta 2 and V beta 8 has been reported during the acute phase of the disease, suggesting that exposure to a superantigen may represent one of the etiologies. Other studies, however, have not confirmed V beta expansions of T cells; in fact, indirect evidence that a conventional antigen may be involved has been reported in certain patients. Together, these various studies suggest that the clinical entity of KD may be induced by a variety of etiologic agents.

Safety of adenovirus-mediated transfer of the human cystic fibrosis transmembrane conductance regulator cDNA to the lungs of nonhuman primates.

To define the toxicity of cystic fibrosis transmembrane conductance regulator gene (CFTR) gene therapy with a replication-deficient recombinant adenovirus (Av1Cf2) in a nonhuman primate model, 10(10) plaque forming units (pfu) were instilled directly through a bronchoscope into the right lung of 5 macaques, and a lower dose of 4 x 10(6) pfu was administered to the right lung of 1 macaque. One sham-treated control received phosphate-buffered saline (PBS). The macaques were evaluated sequentially by clinical examination, vital signs, weight, hematology, blood chemistry, chest radiography, pulse oximetry, and bronchoalveolar lavage (BAL) at baseline and 3-28 days post-treatment. After the period of observation, macaques were sacrificed for autopsy and histological examination. The macaques tolerated the experimental therapy clinically with no changes in body temperature, oxygen saturation, heart rate, body weight, or blood pressure. However, 1 macaque with visible evidence of aspiration at the time of initial bronchoscopy developed tachypnea with right lower lobe (RLL) pneumonia on chest radiograph and by histology. There were no changes in Hgb, Wbc, BUN, plasma electrolytes, bilirubin, or hepatic transaminases. In the macaques that received 10(10) pfu, there was a progressive increase in the number of CD8+ lymphocytes in BAL that was maximal at 28 days. Histological examination of the treated lungs of the high-dose macaques at 3 days showed marked peribronchial and perivascular cuffing by inflammatory cells and alveolar accumulation of neutrophils and macrophages. The alveolitis appeared to be resolving at 28 days, although the perivascular and peribronchial aggregates of mononuclear cells were still present. In the high-dose macaques, BAL interleukin-8 (IL-8) was increased at all time points (256-388 pg/ml versus 1-84 pg/ml at baseline and in control), whereas IL-1 beta was increased only at days 21 and 28 (341-852 pg/ml versus 30-92 pg/ml at baseline and in control). There were no increases in BAL cell counts, IL-1 beta or IL-8, and histological changes were mild in the macaque that received 4 x 10(6) pfu. Evaluation for Av1Cf2-derived human CFTR expression using RS-PCR demonstrated expression at 3, 10, and 21, but not 28 days in macaques treated with 10(10) pfu of Av1Cf2. In situ hybridization analysis demonstrated human CFTR mRNA in the alveolar regions of the lobes that received the vector at 10 and 21 days. There was no evidence of expression after treatment with 4 x 10(6) pfu. This study showed that high-dose adenoviral vector administration to the lung achieved CFTR gene transfer and expression but was associated with increased concentrations of cytokines in BAL and alveolar inflammation. A low dose, equivalent to the maximum clinical dose currently proposed for phase I trials in human subjects, was not associated with cellular or cytokine evidence of inflammation, and histological abnormalities were mild.

Lymphoproliferative disorders in paediatric rheumatic diseases. A report of two cases.

Lymphoproliferative disorders (LPD) are reported with a much lower frequency in children with rheumatic diseases than in their adult counterparts. We describe 2 patients who developed a lymphoma during the course of the disease. The first is a 16-year-old girl diagnosed with systemic juvenile idiopathic arthritis 6 years before who developed a mucosa-associated lymphoid tissue (MALT) lymphoma. The second report involves a boy diagnosed with systemic lupus erythematosus at 9 years of age who developed a Hodgkin's lymphoma 9 years after the disease onset. In spite of the low frequency of LPD in children with rheumatic diseases, these processes do occur.

The European Spanish version of the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ).

We report herein the results of the cross-cultural adaptation and validation of 2 health related quality of life instruments into the European Spanish language. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific health instrument that measures functional ability in daily living activities in children with Juvenile Idiopathic Arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health instrument designed to capture the physical and psychosocial well-being of children independently from an underlying disease. The Spanish CHQ was fully validated with 3 forward and 3 backward translations, while the Spanish CHAQ, already published, was revalidated. A total of 149 subjects were enrolled: 80 patients with JIA (28% systemic arthritis, 34% polyarthritis, 17% extended oligoarthritis, and 21% persistent oligoarthritis) and 69 healthy children. The CHAQ appropriately distinguished healthy subjects from JIA patients, with those classified in the systemic arthritis, polyarthritis and extended oligoarthritis categories having a higher degree of disability and pain, as well as a lower overall well-being than their healthy peers. The CHQ was also able to discriminate healthy subjects from JIA patients, with those allocated in the systemic arthritis, polyarthritis and extended oligoarthritis categories having a lower physical and psychosocial well-being than their healthy counterparts. In conclusion, the European Spanish version of the CHAQ-CHQ is a reliable and valid tool for the functional, physical and psychosocial assessment of children with JIA.

The Argentinian version of the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ).

We report herein the results of the cross-cultural adaptation and validation into the Argentinian language of the parent's version of two health related quality of life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific health instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health instrument designed to capture the physical and psychosocial well-being of children independently from the underlying disease. The Argentinian CHAQ was already published and therefore it was revalidated while the Argentinian CHQ was derived from the European Spanish version by changing few words which use is different in the 2 countries. A total of 124 subjects were enrolled: 61 patients with JIA (29% systemic onset, 38% polyarticular onset, 7% extended oligoarticular subtype, and 26% persistent oligoarticular subtype) and 63 healthy children. The CHAQ clinically discriminated between healthy subjects and JIA patients, with the systemic onset, and polyarticular having a higher degree of disability, pain, and a lower overall well-being when compared to their healthy peers. Also the CHQ clinically discriminated between healthy subjects and JIA patients, with the systemic onset, polyarticular onset and extended oligoarticular subtypes having a lower physical and psychosocial well-being when compared to their healthy peers. In conclusion the Argentinian version of the CHAQ-CHQ is a reliable, and valid tool for the functional, physical and psychosocial assessment of children with JIA.

The Mexican version of the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ).

We report herein the results of the cross-cultural adaptation and validation into the Mexican language of the parent's version of two health related quality of life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific health instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health instrument designed to capture the physical and psychosocial well-being of children independently from the underlying disease. The Mexican CHAQ was already published and therefore it was revalidated while the Mexican CHQ was derived from the European Spanish version with changing of the few words whose use is different in the 2 countries. A total of 182 subjects were enrolled: 89 patients with JIA (26% systemic onset, 47% polyarticular onset, 13.5% extended oligoarticular subtype, and 13.5% persistent oligoarticular subtype) and 93 healthy children. The CHAQ clinically discriminated between healthy subjects and JIA patients, with the systemic onset, and polyarticular onset subtypes having a higher degree of disability, pain, and a lower overall well-being when compared to their healthy peers. Also the CHQ clinically discriminated between healthy subjects and JIA patients, with the systemic onset, and polyarticular onset having a lower physical and psychosocial well-being when compared to their healthy peers. In conclusion the Mexican version of the CHAQ-CHQ is a reliable, and valid tool for the functional, physical and psychosocial assessment of children with JIA.

The Chilean version of the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ).

We report herein the results of the cross-cultural adaptation and validation into the Chilean language of the parent's version of two health related quality of life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific health instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health instrument designed to capture the physical and psychosocial well-being of children independently from the underlying disease. The Chilean CHAQ-CHQ were derived from the European Spanish version with changing of the few words whose use is different in the 2 countries. A total of 126 subjects were enrolled: 72 patients with JIA (29% systemic onset, 39% polyarticular onset, 4% extended oligoarticular subtype, and 28% persistent oligoarticular subtype) and 54 healthy children. The CHAQ clinically discriminated between healthy subjects and JIA patients, with the JIA patients having a higher degree of disability, pain, and a lower overall well-being when compared to their healthy peers. Also the CHQ clinically discriminated between healthy subjects and JIA patients, with the JIA patients having a lower physical and psychosocial well-being when compared to their healthy peers. In conclusion the Chilean version of the CHAQ-CHQ is a reliable, and valid tool for the functional, physical and psychosocial assessment of children with JIA.

Kawasaki disease.

This article is an up-to-date review of issues surrounding Kawasaki disease, with particular emphasis on the immunologic aspects. Kawasaki disease is now the leading cause of acquired heart disease in children in most developed countries.

[Differentiation between transient synovitis and septic arthritis of the hip with clinical and ultrasound criteria]. / Diferenciación de sinovitis transitoria y artritis séptica de cadera con criterios clínicos y ecográficos.

INTRODUCTION: Ultrasound does not distinguish between different types of synovitis. The aim of this study was to evaluate its contribution, together with several clinical data, in the diagnosis of septic arthritis (SA) and transient synovitis (TS) of the hip. METHODS: Prospective study of patients diagnosed with unilateral SA or TS of the hip carried out between December 2006 and July 2009. A set of clinical variables and ultrasound measurements were analysed. The ultrasound examinations were performed using a standardised procedure. RESULTS: The sample included 26 children, 22 diagnosed with TS and 4 with SA. A difference was found in the history of fever (P=0.002). On the other hand, no differences were detected in the age of the children, although mean and median in the TS group were 6 years vs a mean of 4.3 with a median of 2.3 years in the SA group. There were no differences in the ultrasound measurements either. The positive predictive value of the criterion "older than 4 years of age and no history of fever" for the diagnosis of transient synovitis was 100%, while "younger than 4 years and history of fever" for the diagnosis of septic arthritis was 75%, once radiology had excluded orthopaedic processes and ultrasound showed an effusion. CONCLUSIONS: In spite of the study limitations (sample size and low prevalence) the combination of age and history of fever appears to be useful in distinguishing transient synovitis from septic arthritis. The contribution of ultrasound was to confirm the presence of joint effusion.

PRINTO/PRES international website for families of children with rheumatic diseases: www.pediatric-rheumatology.printo.it.

OBJECTIVE: To prepare a website for families and health professionals containing up to date information about paediatric rheumatic diseases (PRD). METHODS: Firstly, paediatric rheumatology centres and family self help associations were surveyed to characterise current clinical practice of physicians providing care for children with PRD, research activities, and training facilities of each centre. Secondly, international consensus was reached on the content of the website. Finally, the website was developed and the texts translated. RESULTS: The web page contains three main sections: (a) description for families of the characteristics of 15 PRD; (b) list of paediatric rheumatology centres; (c) contact information for family self help associations. A version for 45 countries in 52 languages (with another three in progress) is now available on the web. 291 surveys from 171 centres and 102 family associations were received from 42 countries. The median proportion of time spent in paediatric practice in the centres examined was 100%, with 70% of this time dedicated to paediatric rheumatology. 90% of the centres were willing to perform clinical trials in the future. CONCLUSIONS: The PRINTO/PRES website provides a well defined and competent set of information about PRD, with appropriate multiple translated versions and easy web navigational direction.

Epidemiology of musculoskeletal pain in primary care.

AIMS: (1) To determine the proportion of children evaluated for musculoskeletal pain in a paediatric primary care clinic over a three year period; (2) to describe the number of office visits due to musculoskeletal pain; (3) to categorise the more common presenting complaints; and (4) to characterise the aetiology of musculoskeletal pain in a paediatric primary care clinic. METHODS: Retrospective chart review of all children > or =3 and <15 years of age evaluated in an urban paediatric primary care clinic in Madrid between 1 January 1997 and 31 December 1999. RESULTS: (1) A total of 317 children were evaluated for musculoskeletal pain throughout the study. The prevalence of musculoskeletal pain increased as children grew older, from 2.4-5.7% at age 3 to 27.5-36% at age 14. Regression analysis showed that age (OR 1.20) and gender (OR 0.75) were associated with MSP. (2) Musculoskeletal pain was reported in 397 of 6500 office visits (6.1%; 95% CI 5.5 to 6.7%). (3) Arthralgias and soft tissue pain represented 65% of the presenting musculoskeletal complaints. (4) Trauma was the most common aetiology, responsible for 44% of all musculoskeletal pain related office visits. Mechanical/overuse pathology (23.9%) and osteochondroses (10.3%) represented the second and third leading aetiologies. CONCLUSIONS: Musculoskeletal pain is a common presenting complaint in primary care. The number of children presenting with musculoskeletal pain increases as they grow older, being particularly frequent among the adolescent population. The spectrum of aetiologies involved is limited, to the extent that three are responsible for almost 80% of cases.

Musculoskeletal pain in primary pediatric care: analysis of 1000 consecutive general pediatric clinic visits.

OBJECTIVES: 1) To determine the number of primary care clinic visits attributable to musculoskeletal pain (MSP) in children >/=3 and <15 years of age. 2) To describe the demographic characteristics of this population assessed for limb/back pain. 3) To characterize the etiology of musculoskeletal pain in an urban general pediatric clinic in Madrid, Spain. METHODS: Prospective evaluation of 1000 consecutive clinic visits to an urban general pediatric clinic. Inclusion criteria were 1) age >/=3 and <15 years and 2) musculoskeletal evaluation requested by the family or patient. All consultations related to MSP were recorded via standard protocol and data record form. RESULTS: During the study period, 61 of 1000 (6.1%; confidence interval: 4.6-7.5) clinic visits for children >/=3 and <15 years were related to MSP. Patients' age, mean +/- SD, was 9.7 +/- 3.3 years. Musculoskeletal complaints were more frequent in boys (57.4%), although there was no statistical difference. The presenting complaints included knee arthralgias in 33%; other joint (eg, ankles, wrists, elbows) arthralgias in 28%; soft tissue pain in 18%; heel pain in 8%; hip pain in 6%; and back pain in 6%. Symptoms were attributable to trauma in 30%; overuse syndromes in 28% (eg, chondromalacia patellae, mechanical plantar fasciitis, overuse muscle pain); and normal skeletal growth variants (eg, Osgood-Schlatter syndrome, hypermobility, Sever's disease) in 18% of patients. CONCLUSION: MSP represents a frequent presenting complaint in general pediatric practice. A new heightened awareness of the frequent occurrence of MSP should be adopted when designing pediatrics continuing medical education and training programs. musculoskeletal pain, limb pain, arthralgia, children, general pediatrics, pediatric primary care.

Cardiac function in systemic lupus erythematosus.

Cardiovascular disease is one of the main causes of morbidity and mortality in patients with systemic lupus erythematosus (SLE). The observation that the disease may affect all cardiac tissues, although frequently in a subclinical fashion, has come to attention only recently after the introduction of non-invasive sensitive cardiac imaging technology in clinical practice. We review the current perspective of this topic, placing special emphasis on what is known and what is not known regarding cardiac disease in the pediatric population with SLE. Our current lack of information calls for the initiation of collaborative research in this area.

Evaluation of ILAR classification criteria for juvenile idiopathic arthritis in Spanish children.

OBJECTIVE: To evaluate the proposed International League of Associations for Rheumatology (ILAR) classification criteria for juvenile idiopathic arthritis in a cohort of Spanish children. METHODS: One hundred twenty-five patients with chronic arthritis were categorized according to one of the traditional classifications and the proposed ILAR classification system after at least 6 months of disease. The traditional classifications included the European League Against Rheumatism (EULAR) criteria for pauciarticular, polyarticular rheumatoid factor (RF) negative, and systemic juvenile chronic arthritis (JCA), as well as for RF+ polyarthritis; the Vancouver criteria for juvenile psoriatic arthritis (JPsA); and the European Spondylarthropathy Study Group (ESSG) preliminary criteria for juvenile spondyloarthropathy (JSpA). RESULTS: The ILAR criteria classified 106/125 patients (84.8%). All patients with systemic and polyarticular JCA, RF+ polyarthritis, and definite juvenile psoriatic arthritis were reclassified in the corresponding ILAR category. In contrast, only 80% of pauciarticular JCA and 47% of JSpA patients could be allocated to the ILAR oligoarthritis (47/59 patients, 35 persistent and 12 extended) and enthesitis related arthritis (ErA. 8/17 patients) categories. Two children with probable PsA were reclassified in the RF- polyarthritis category. Nineteen patients (15.2%) were allocated to the ILAR "other arthritis" group, 13/19 because they did not fulfill criteria for any of the other categories (12 due to family history of psoriasis and one because of family history of HLA-B27 associated disease). The remaining 6 patients met criteria for 2 categories, RF- polyarthritis and either ErA (n = 5) or PsA (n = 1). No differences other than family history of psoriasis were found in any of the variables studied between pauciarticular JCA patients classified in the oligoarthritis (n = 47) and those in the "other arthritis" (n = 11) ILAR categories. CONCLUSION: The proposed ILAR criteria allocated 84.8% of the patients classified by traditional criteria. Family history of psoriasis (n = 12) and polyarticular onset of disease in patients with ErA (n = 5) were responsible for most of the exclusions from other ILAR categories.

T cell receptor repertoire differences between African Americans and Caucasians associated with polymorphism of the TCRBV3S1 (V beta 3.1) gene.

The generation of TCR diversity occurs primarily through rearrangement of germline DNA. Genetic polymorphism of the TCR chains appears to be a rarer mechanism for generating repertoire differences between races. Flow cytometric analysis of the TCR V beta repertoire in a population of healthy African Americans (n = 30) and Caucasians (n = 30) revealed a significant difference in the frequency of cells bearing V beta 3.1, but not V beta 2, V beta 5.1, V beta 5.2-5.3, V beta 6.7, V beta 8.1-8.2, V beta 12.1, V beta 13.3, or V beta 19. African Americans had a significantly lower frequency of V beta 3.1+ cells, in both the CD4+ (2.55 +/- 0.36% vs 4.85 +/- 0.43%, p = 0.0001) and the CD8+ (3.03 +/- 0.54% vs 5.32 +/- 0.57%, p = 0.004) population than did Caucasians, and this difference was independent of the age of the individuals. Analysis of genomic DNA revealed that the observed difference in frequency of V beta 3.1+ cells correlated with a recently described polymorphism of the recombination signal sequence of the TCRBV3S1 gene. Allele 1, associated with a lower frequency of V beta 3.1+ cells, was more commonly present in African Americans (0.68 vs 0.43), whereas allele 2, associated with a higher frequency of V beta 3.1+ cells, was more commonly present in Caucasians (0.31 vs 0.56). This study demonstrates the potential for TCR repertoire differences, based on genetic polymorphism, between African Americans and Caucasians.