Debate around infection-dependent hemophagocytic syndrome in paediatrics.

BACKGROUND: Hemophagocytic syndrome (HPS) is clinically defined as a combination of fever, liver dysfunction, coagulation abnormalities, pancytopenia, progressive macrophage proliferation throughout the reticuloendothelial system, and cytokine over-production, and may be primary or secondary to infectious, auto-immune, and tumoral diseases. The most consistent association is with viral infections but, as it is still debated whether any micro-organisms are involved in its pathogenesis, we critically appraised the literature concerning HPS and its relationship with infections. DISCUSSION: Infection-dependent HPS has been widely observed, but there are no data concerning its incidence in children. A better understanding of the pathophysiology of HPS may clarify the interactions between the immune system and the variously implicated potential infectious agents. Epstein-Barr virus (EBV) infection has been prominently associated with HPS, with clonal proliferation and the hyperactivation of EBV-infected T cells. However, a number of other viral, bacterial, fungal, and parasitic infections have been reported in association with HPS. In the case of low-risk HPS, corticosteroids and/or intravenous immunoglobulin or cyclosporine A may be sufficient to control the biological process, but etoposide is recommended as a means of reversing infection-dependent lymphohistiocytic dysregulation in high-risk cases. SUMMARY: HPS is a potential complication of various infections. A polymerase chain reaction search for infectious agents including EBV, cytomegalovirus and Leishmania is recommended in clinical settings characterised by non-remitting fever, organomegaly, cytopenia and hyperferritinemia.

Gastrointestinal Involvement in Children with Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disorder. When it presents before the age of 18 years (childhood-onset systemic lupus erythematosus, cSLE), the disease course tends to be more severe with a higher rate of organ involvement and requires an early diagnosis. Gastrointestinal involvement in cSLE is rare and scarcely reported in the literature. Any organ of the gastrointestinal system may be affected, either as a direct consequence of the disease, as a subsequent complication, or as an adverse drug event. Abdominal pain is the most common GI symptom, it can be diffuse or well localized, and can underline different conditions such as hepatitis, pancreatitis, appendicitis, peritonitis, or enteritis. cSLE may have an alteration of the intestinal barrier with features of protein-losing enteropathy or, in genetically predisposed patients, may develop associated autoimmune disorders such as Coeliac Disease or Autoimmune Hepatitis. The aim of this manuscript is to provide a narrative review of gastrointestinal manifestations in cSLE focused on hepatic, pancreatic, and intestinal involvement. A comprehensive literature search based on the PubMed database was performed.

Determinants of bone mineral density, bone mineral content, and body composition in a cohort of healthy children: influence of sex, age, puberty, and physical activity.

Interventions directed to the recognition of abnormal bone mineral density, bone mineral content, and body composition in the pediatric age require the definition of factors influencing bone mass acquisition during growth. We have evaluated in a cross-sectional manner by dual-energy X-ray absorptiometry the impact of sex, age, puberty, and physical activity on total body areal bone mineral density, regional (lumbar and femoral) bone mineral densities, bone mineral content, and body composition (fat mass and lean mass) in a cohort of 359 healthy Italian children aged 3-14 years and investigated their specific contribution to bone mass accrual. Statistical multiple regression analysis was performed dividing the population in pre- and post-pubertal groups. Bone mineral density at the lumbar spine has resulted equally distributed in both sexes before puberty while has resulted higher at the femoral necks in males at whatever age. A significant effect on bone mass acquisition was exerted by male sex and lean mass. In the areas where the cortical bone is prevalent, males of the pre-pubertal group have presented the highest values; in the areas where the cancellous bone is prevalent, both sexes were equivalent until the age of 9 years, but after this age, females have presented higher increases, probably related to the inferior dimensional development of lumbar vertebrae. Conclusively, male sex and lean mass seem to represent independent predictors of bone mass accrual in the cortical bone of the examined children, while female sex and pubertal maturation are independent predictors of bone mass accrual in the trabecular bone.

Recurrent pericarditis in a patient with Bardet-Biedl syndrome: A case report.

Bardet-Biedl syndrome is a rare autosomal recessive disorder characterized by rod-cone dystrophy, renal dysfunction, obesity, learning difficulties, hypogonadism, polydactyl, and many other minor features that can affect the cardiovascular, locomotive, neurological, and endocrine systems. We report the case of a 16-year-old boy affected by Bardet-Biedl syndrome who presented with recurrent pericarditis with an optimal response to treatment with Anakinra. To our knowledge, this is the first description of an association between Bardet-Biedl syndrome and recurrent pericarditis.

Genetic characteristics of Neisseria meningitidis serogroup B strains carried by adolescents living in Milan, Italy: implications for vaccine efficacy.

Before a protein vaccine is introduced into a country, it is essential to evaluate its potential impact and estimate its benefits and costs. The aim of this study was to determine the genetic characteristics of Neisseria meningitidis B (NmB) in the pharyngeal secretions of 1375 healthy adolescents aged 13-19 y living in Milan, Italy, in September 2012, and the possible protection offered by the two currently available NmB protein vaccines. Ninety-one subjects were Nm carriers (6.6%), 29 (31.9%) of whom carried the NmB capsular gene. The 29 identified strains belonged to eight clonal complexes (CCs), the majority of which were in the ST-41/44/Lin.3 CC (n = 11; 37.9%). All of the identified strains harboured ƒHbp alleles representing a total of 15 sub-variants: the gene for NHBA protein was found in all but three of the studied strains (10.3%) with 13 identified sub-variants. There were 15 porA sub-types, seven of which were identified in just one CC. The findings of this study seem to suggest that both of the protein vaccines proposed for the prevention of invasive disease due to NmB (the 4-protein and the 2-protein products) have a composition that can evoke a theoretically effective antibody response against the meningococcal strains currently carried by adolescents living in Northern Italy. The genetic characteristics of NmB strains can be easily evaluated by means of molecular methods, the results of which can provide an albeit approximate estimate of the degree of protection theoretically provided by the available vaccines, and the possible future need to change their composition.

Exposition to chickenpox of two children with autoinflammatory syndromes under treatment with anakinra.

We report two children with autoinflammatory syndromes treated with anakinra who came in contact with the varicella-zoster virus after being exposed accidentally to infected children: both cases were managed prophylactically with specific antichickenpox intravenous immunoglobulins and anakinra temporary suspension; neither adverse events nor complications related to the natural course of chickenpox were experienced by the two patients. The risk of developing infectious events should be closely monitored, because of the absence of data concerning long-term safety of biological agents in the pediatric age, and prevention strategies should be highly encouraged before they are started.

Large pericardial effusion requiring pericardiocentesis as cardinal sign of macrophage activation syndrome in systemic onset-juvenile idiopathic arthritis.

We report a case of large pericardial effusion which has been managed with pericardiocentesis as the main presentation feature of a dramatic clinical picture, only retrospectively framed as referred to macrophage activation syndrome in a child with juvenile idiopathic arthritis at its onset. The risk of developing this rare and severe complication should be recognized in various pathological settings of childhood, above all in children displaying systemic signs of juvenile idiopathic arthritis.

First report of macrophage activation syndrome in hyperimmunoglobulinemia D with periodic fever syndrome.

We describe for the first time a case of macrophage activation syndrome in a child with hyperimmunoglobulinemia D with periodic fever syndrome who required intensive care support. Up-regulated monokine production, high serum levels of triglycerides and ferritin, clotting abnormalities with hypofibrinogenemia, and rapidly evolving pancytopenia should alert the clinician to the possible diagnosis of macrophage activation syndrome, even in autoinflammatory diseases characterized basically by the periodic recurrence of unprovoked inflammatory attacks. Bone marrow aspiration showing well-differentiated macrophages phagocytosing hematopoietic elements remains the main tool for a final diagnosis, and cyclosporine is the best strategy for treatment.

Treatment with anakinra in the hyperimmunoglobulinemia D/periodic fever syndrome.

Hyperimmunoglobulinemia D/periodic fever syndrome is caused by recessively inherited mutations in the mevalonate kinase gene and is characterized by persistently high polyclonal serum IgD titre and recurrent febrile attacks. No conventional therapy exists for preventing the typical recurrent inflammatory picture of patients. A host of studies have evidenced that elevated levels of various cytokines, such as interleukin-1 (IL-1), mark febrile attacks in this disease and that IL-1 might represent a suitable therapeutic target. We describe the case of a 7-year-old female-child with an established diagnosis of hyperimmunoglobulinemia D/periodic fever syndrome in whom anakinra, IL-1 receptor antagonist, was daily administered at the dosage of 1 mg/kg/day by subcutaneous injection for 18 months after numerous disappointing attempts with non-steroidal anti-inflammatory drugs, steroids, colchicine and etanercept through the years. The clinical response under anakinra treatment was recorded through a standardized diary, whilst inflammation parameters were serially measured in comparison with the half-year before starting anakinra. Frequency and severity of fever attacks were totally reduced by anakinra and this is the first child demonstrating that symptoms of hyperimmunoglobulinemia D/periodic fever syndrome might be at least extenuated by anakinra, though not abolished.