Alessandra Marchesi

Oxidative stress and defective platelet apoptosis in naïve patients with Kawasaki disease

Kawasaki disease (KD) is a rare and often undiagnosed disease, at least in the western countries. It is characterized by an inflammatory acute febrile vasculitis of medium sized arteries with a propensity to damage the coronary arteries. It normally occurs in the early childhood and the diagnosis is based on clinical symptoms. During the progression of the disease thrombocytosis is usually detected. This can exert a pathogenetic role in the cardiovascular complications occurring in KD. In the present work peripheral blood plasma and platelets from twelve naïve patients with KD were analyzed in order to detect possible pathogenetic determinants or progression markers. Morphological, biochemical and flow cytometrical methods have been used. With respect to age-matched healthy donors, we found an increase of platelet activation markers, i.e. degranulation, phosphatidylserine (PS) externalization and leukocyte-red cell-platelet aggregates. Some significant alterations that could represent suitable diagnostic determinants have also been detected in patient plasma: (i) decreased antioxidant power, (ii) decreased levels of asymmetric dymethylarginine (ADMA), a naturally occurring chemical interfering with the production of nitric oxide, and (iii) increased levels of soluble P-Selectin and soluble annexin V. Since PS externalizing platelets are known to exert a pro-coagulant activity, our data suggest the hypothesis that increased risk of vascular complications in KD could depend on platelet stimulation and defective apoptosis probably related to nitrosative stress.

Does Oxidative Stress Play a Critical Role in Cardiovascular Complications of Kawasaki Disease

The aim of the present work was to evaluate the contribution of the different reactive oxidizing species to systemic oxidative stress in the whole blood of patients with Kawasaki disease (KD). This is a rare generalized systemic vasculitis typical of the early childhood characterized by inflammation and endothelial dysfunction with a high risk for cardiovascular fatal events. We found that, compared to age-matched healthy donors, blood from KD patients showed increased production of oxygen- and nitrogen-derived species as detected by electron paramagnetic resonance (EPR) spin probing with the cyclic hydroxylamine 1-hydroxy-3-carboxy-pyrrolidine. The (•)NO pathway involvement was also confirmed by the decreased concentrations of the endogenous (•)NO synthase inhibitor asymmetric dimethyl-arginine and the increased amounts of 3-nitrotyrosine in plasma. Further, increased plasma yields of the proinflammatory enzyme myeloperoxidase were also observed. The appearance of circulating red blood cell alterations typically associated with oxidative imbalance and premature aging (e.g., decrease of total thiol content, glycophorin A, and CD47 expression, as well as increase of phosphatidylserine externalization) has also been detected. Collectively, our observations lead to hypothesize that the simultaneous oxidative and nitrative stress occurrence in the blood of KD patients may play a pathogenetic role in the cardiovascular complications often associated with this rare disease.

Increased frequency of immunoglobulin (Ig)A-secreting cells following Toll-like receptor (TLR)-9 engagement in patients with Kawasaki disease

Kawasaki disease (KD) is an acute vasculitis affecting mainly infants and children. Human B cells express Toll‐like receptor (TLR)‐9, whose natural ligands are unmethylated cytosine–guanine dinucleotide (CpG) motifs characteristic of bacterial DNA. The aim of this study was to clarify the pathogenesis of KD analysing the activation status of peripheral blood mononuclear cells (PBMC), focusing on B lymphocyte activation and functions. Ten patients and 10 age‐matched healthy donors were recruited from the Bambino Gesù Hospital of Rome, Italy and enrolled into this study. We determined phenotype profile and immunoglobulin (Ig) production of PBMC from KD patients and age‐matched controls. We found that the frequency of CD19+ B lymphocytes and CD19+/CD86+ activated B lymphocytes from KD patients during the acute phase before therapy was increased significantly. Moreover, B lymphocytes of acute‐phase KD patients were more prone to CpG oligodeoxynucleotide (ODN) activation compared with the age‐matched controls, as assessed by a significant increase of the number of IgA‐secreting cells (SC). In the same patients we found a marked increase of IgM, IgG, interleukin (IL)‐6 and tumour necrosis factor (TNF)‐α production compared with the control group. In addition, in two convalescent KD patients, conventional treatment with intravenous immunoglobulin (IVIG) restored the normal frequency of CD19+ B cells, the number of IgA‐, IgM‐ and IgG‐SC and the production of IL‐6 and TNF‐α. Our findings indicate that the percentages of peripheral B lymphocytes of acute‐phase KD patients are increased and are prone to bacterial activation in terms of increased numbers of IgA‐SC and increased production of IL‐6 and TNF‐α inflammatory cytokines. Thus, our data support the hypothesis of an infectious triggering in KD.

Pathogenetic determinants in Kawasaki disease: the haematological point of view.

Kawasaki disease is a multisystemic vasculitis that can result in coronary artery lesions. It predominantly affects young children and is characterized by prolonged fever, diffuse mucosal inflammation, indurative oedema of the hands and feet, a polymorphous skin rash and non‐suppurative lymphadenopathy. Coronary artery involvement is the most important complication of Kawasaki disease and may cause significant coronary stenosis resulting in ischemic heart disease. The introduction of intravenous immunoglobulin decreases the incidence of coronary artery lesions to less than 5%. The etiopathogenesis of this disease remains unclear. Several lines of evidence suggest that an interplay between a microbial infection and a genetic predisposition could take place in the development of the disease. In this review, we summarize the state of the art of pathogenetic mechanisms of Kawasaki disease underscoring the relevance of haematological features as a novel field of investigation.

Red blood cells as bioindicators of cardiovascular risk in Kawasaki disease: A case report

Kawasaki disease (KD) is a rare systemic vasculitis typical of theearly childhood. It is characterized by small- and medium-sized bloodvessel inflammation that can also lead to coronary artery weakening,aneurysmformation,andmyocardialinfarction.Therapywithimmuno-globulinandaspirinaimstoreducecoronaryarteryinflammation.How-ever, it has been hypothesized that, notwithstanding the efficacy of thepharmacological therapy, patients with regressed KD are at increasedrisk to develop atherosclerosis after the acute illness.In this work, the case of a 17-month-old child with KD was studied.The patient was recruited from the Bambino Gesu Hospital of Rome(Italy). Diagnosis of KD was based on the standard clinical criteria [1].The study was conducted at admission of the patient (naive patient)and at follow-up. Five age-matched healthy donors (HD) were usedforeachtimepointascontrols.Informedconsentbyparentswasobtain-ed.This study was approved from theInstitutional Review Board of the“Bambino Gesu” Hospital of Rome, Italy.At admission, the patient reported fever since 5 days, and hadurticar-ial, a non-purulent conjunctivitis, cheilitis and a hyper-echogenicity ofcoronary arteries without dilatation. Laboratory analyses showed: redblood cell (RBC) and platelet counts in the normal range (4.26 · 10

Kawasaki disease: guidelines of Italian Society of Pediatrics, part II - treatment of resistant forms and cardiovascular complications, follow-up, lifestyle and prevention of cardiovascular risks

This second part of practical Guidelines related to Kawasaki disease (KD) has the goal of contributing to prompt diagnosis and most appropriate treatment of KD resistant forms and cardiovascular complications, including non-pharmacologic treatments, follow-up, lifestyle and prevention of cardiovascular risks in the long-term through a set of 17 recommendations.Guidelines, however, should not be considered a norm that limits the treatment options of pediatricians and practitioners, as treatment modalities other than those recommended may be required as a result of peculiar medical circumstances, patient’s condition, and disease severity or individual complications.

Kawasaki disease: guidelines of the Italian Society of Pediatrics, part I - definition, epidemiology, etiopathogenesis, clinical expression and management of the acute phase

The primary purpose of these practical guidelines related to Kawasaki disease (KD) is to contribute to prompt diagnosis and appropriate treatment on the basis of different specialists’ contributions in the field. A set of 40 recommendations is provided, divided in two parts: the first describes the definition of KD, its epidemiology, etiopathogenetic hints, presentation, clinical course and general management, including treatment of the acute phase, through specific 23 recommendations.Their application is aimed at improving the rate of treatment with intravenous immunoglobulin and the overall potential development of coronary artery abnormalities in KD. Guidelines, however, should not be considered a norm that limits treatment options of pediatricians and practitioners, as treatment modalities other than those recommended may be required as a result of peculiar medical circumstances, patient’s condition, and disease severity or complications.

Scurvy: still a threat in the well-fed first world?

We report three cases of scurvy in previously healthy children referred to us for leg pain and refusal to walk. All children had no significant medical history, symptoms had started months before and subtly advanced. Two of them presented with gingival hyperplasia and petechiae, another one reported night sweats and gingival bleeding in the past few weeks. Two had vitamin D deficiency, and all had microcytic anaemia (in one case requiring transfusional support). A nutritional screening revealed low or undetectable levels of ascorbic acid. This, along with the clinical and radiological findings, led to a diagnosis of scurvy. Vitamin C supplementation was started with rapid improvement of the children’s clinical condition. Scurvy is a rare disease in the ‘first world’, but there are anecdotal reports of scurvy in children without any of the known risk factors for this condition. In our cases, a selective diet was the only risk factor.

72nd Congress of the Italian Society of Pediatrics

Child and youth migrations are a particularly dramatic and a daily aspect of the more general problem of contemporary migration flows. Behind and within each of the stories of these children accompanied and unaccompanied migrant children, as UN calls them in a bureaucratic jargon school becomes a treasure trove of identity splinters through biographies and fragments of a past that can return visibility to what would be irreparably forgotten otherwise. School has the opportunity to welcome, support, accompany these children and young new citizens towards the inclusion. School has, also, the opportunity to learn an anthropological view of the presence of migrant children from these life stories, thus activating action-research processes. This action-research will develop new teaching strategies, new approaches based on questions, on an open dialogue, on the paradigms of responsibility, commitment and diversity. A unique opportunity to develop diversity education and citizenship skills, too often mentioned but poorly practiced. Above all, thanks to the sharing and revival of significant life stories and emotionally touching, you can develop emotional intelligence skills, so necessary in an often deregulated age of complexity, which always produces more and more “wasted lives”, above all, thanks to the sharing and reintroduction of significant and emotionally touching life stories. Through a generous listening of students’ lives, and dialogic practices, school could generate new narrations of migration processes, thus replacing those narrations made up of stereotypical clichés, believes, petty and selfish believes of an overlapping lawlessness, of cruelty and hypocritical welcome. These new narrations tell of possibilities, of mutual discoveries, of processes of successful inclusion, of present-future to build together. “The dialogical as Arnkil and Seikkula say is not a method or a set of techniques but it is an attitude, a way of seeing, which is based on recognizing and respecting the otherness of the other, and on going to meet them.” Applying the integrated dialogic approach to coaching as a lifestyle means to mobilize psychological resources of both people who are directly involved and the whole community and local social network, it means being able to stimulate dialogue. Stories of wanderings and landings, escapes and refuges, of scared identities and unpredictable cultural metamorphosis, of so much suffering, are intertwined and interdependent to the dreamed and

Redox alterations of platelets and erythrocytes represent progression marker and pathogenetic determinants in Kawasaki disease

Background Kawasaki disease (KD) is a rare generalized systemic vasculitis of unknown etiology in which the main complication is the development of coronary artery abnormalities. Considering that an inflammation-associated systemic pro-oxidant status could play a critical pathogenetic role in KD progression [1], we evaluated some peripheral blood redox-associated parameters, including redox and aging features associated with red blood cells (RBCs) and platelets (PLT) integrity as possible pathogenetic determinants or progression markers in KD disease.