The association of PTPN22 rs2476601 with juvenile idiopathic arthritis is specific to females.

A preponderance of females develop autoimmune disease, including juvenile idiopathic arthritis (JIA), yet the reason for this bias remains elusive. Evidence suggests that genetic risk of disease may be influenced by sex. PTPN22 rs2476601 is associated with JIA and numerous other autoimmune diseases, and has been reported to show female-specific association with type 1 diabetes. We performed main effect and sex-stratified association analyses to determine whether a sex-specific association exists in JIA. As expected, rs2476601 was associated with JIA in our discovery (413 cases and 690 controls) and replication (1008 cases and 9284 controls) samples. Discovery sample sex-stratified analyses demonstrated an association specifically in females (odds ratio (OR)=2.35, 95% confidence interval (CI)=1.52-3.63, P=0.00011) but not males (OR=0.91, 95% CI=0.52-1.60, P=0.75). This was similarly observed in the replication sample. There was evidence for genotype-by-sex interaction (Pinteraction=0.009). The association between rs2476601 and JIA appears restricted to females, partly accounting for the predominance of females with this disease.

Clinical features and outcome of pediatric Wegener's granulomatosis.

OBJECTIVE: Wegener's granulomatosis (WG) is a predominantly small-vessel vasculitis associated with antineutrophil cytoplasmic antibodies (ANCAs). There are few reports describing its clinical features and outcome in children. We report on the experience at a single tertiary referral center over 21 years. METHODS: We conducted a retrospective chart review of all patients diagnosed with WG at The Hospital for Sick Children between 1984 and 2005. RESULTS: Twenty-five patients were identified. Median age at diagnosis and median followup were 14.5 years and 32.7 months, respectively. Male-to-female ratio was 1:4. Median duration of symptoms before diagnosis was 2 months. Of 22 patients, 21 were ANCA positive during their disease course (classic ANCA 78.9%). Constitutional symptoms were the most common clinical feature at presentation (24 of 25). Glomerulonephritis was present in 22 patients at presentation. Only 1 of 11 patients who presented with or developed renal impairment had normalization of serum creatinine. Upper airway involvement occurred in 21 patients at presentation and 24 over followup; only 1 had subglottic stenosis. Twenty patients had initial pulmonary involvement, most commonly nodules (44%) and pulmonary hemorrhage (44%). Five patients required ventilation for pulmonary hemorrhage. Four patients (16%) had venous thrombotic events (VTEs). Treatment included prednisone (100%), cyclophosphamide (76%), azathioprine (40%), and methotrexate (32%). CONCLUSION: Pediatric WG typically presents in adolescence and has a female predominance. Glomerulonephritis and pulmonary disease are common at diagnosis and frequently present as a pulmonary-renal syndrome. Loss of renal function is common and rarely completely reversible. As in adults, children with WG are at risk of VTEs.

Scurvy: forgotten but not gone.

Scurvy is still seen sporadically in the developed world. At a time when subclinical vitamin C deficiency in the general population is being recognized increasingly, the need for clinicians to be aware of this disease remains. We present the case of a 9-year-old boy admitted to hospital with musculoskeletal pain, weakness and changes in the skin and gums. After extensive investigation, he was found to have vitamin C deficiency resulting from a restricted eating pattern. Musculoskeletal complaints are a common mode of presentation of scurvy in children. Failure to appreciate this fact and the risk factors for poor vitamin C intake in the paediatric age group can result in unnecessary and invasive investigations for apparent 'multisystem' disease.

Reducing the impact of rheumatic diseases in childhood.

Reducing the impact of rheumatic diseases in childhood is the fundamental objective of every member of the multi-disciplinary team involved in the care of affected children and families. The means by which this objective may be achieved are broad and include the implementation of a range of non-pharmacological therapies to address the effects of rheumatic diseases on the physical development of the child. In addition, the treating team must be aware of the psychosocial impact that these diseases may have and the ways in which this may be minimized. This chapter is devoted to an examination of some of the non-pharmacological issues that arise in the management of the commonest rheumatic disease found in children, juvenile idiopathic arthritis (JIA). Aspects of physical rehabilitation, schooling, medication compliance, pain management and family dynamics are discussed, as are interventions to reduce the impact of this disease and its sequelae, utilizing, where possible, evidence-based principles from the literature. Although specific issues applicable to children with arthritis will be discussed, the broad principles of much of what follows applies to all of the rheumatic diseases in childhood.

Clinical correlates of response to pneumococcal immunization.

OBJECTIVE: The inability to form antibodies to polysaccharide antigens may occur as a part of a more significant immunodeficiency or as an isolated defect. The latter has been reported in some children with recurrent upper and lower respiratory tract infections and evaluation of the responsiveness of such patients to polysaccharide antigens is indicated as part of their assessment. The present study evaluated the pattern of antibody responses of patients immunized with pneumococcal vaccine as part of the investigation of recurrent upper and lower respiratory tract infections to determine if any correlation exists between these responses and clinical presentation. METHODOLOGY: An analysis was performed of antibody responses to pneumococcal serotypes 3, 4 and 6 following immunization with a 23-valent vaccine in 42 children with normal IgG levels who were evaluated for recurrent infections. Antibody responses were assessed in relation to clinical features and the results of other immunological investigations. RESULTS: Of the 42 patients evaluated, 25 (59%) were responders to all serotypes tested. Failure to respond to serotype 3 alone was the least common pattern of non-response. Recurrent pneumonia, but not otitis media with discharge or chronic productive cough, was significantly associated with a lack of response to two or three serotypes. Failure to respond to serotype 3 alone or in combination with other serotypes was associated with more significant immune abnormalities. CONCLUSION: In a selected population of children with recurrent bacterial infections, pneumococcal serotype 3 is a strong immunogen. In this clinical group recurrent pneumonia is associated with a defect in response to multiple pneumococcal serotypes.