Diagnostic relevance of IgE sensitization profiles to eight recombinant Phleum pratense molecules.

BACKGROUND: Grass pollen-related seasonal allergic rhinoconjunctivitis (SARg) is clinically heterogeneous in severity, comorbidities, and response to treatment. The component-resolved diagnostics disclosed also a high heterogeneity at molecular level. Our study aimed at analyzing the characteristics of the IgE sensitization to Phleum pratense molecules and investigating the diagnostic relevance of such molecules in childhood. METHODS: We examined 1120 children (age 4-18 years) with SARg. Standardized questionnaires on atopy were acquired through informatics platform (AllergyCARD™). Skin prick tests were performed with pollen extracts. Serum IgE to airborne allergens and eight P. pratense molecules (rPhl p 1, rPhl p 2, rPhl p 4, rPhl p 5b, rPhl p 6, rPhl p 7, rPhl p 11, rPhl p 12) were tested by ImmunoCAP FEIA. RESULTS: The analysis of IgE responses against eight P. pratense molecules showed 87 profiles. According to the number of molecules recognized by IgE, the more complex profiles were characterized by higher serum total IgE, higher grass-specific serum IgE, and higher number and degree of sensitization to pollens. The most frequent IgE sensitization profile was the monomolecular Phl p 1. Sensitization to Phl p 7 was a reliable biomarker of asthma, whereas Phl p 12 of oral allergy syndrome. Sensitization to Phl p 7 was associated with a higher severity of SARg, and complex profiles were associated with longer disease duration. CONCLUSIONS: In a large pediatric population, the complexity of IgE sensitization profiles against P. pratense molecules is related to high atopic features although useless for predicting the clinical severity. The detection of serum IgE to Phl p 1, Phl p 7, and Phl p 12 can be used as clinical biomarkers of SARg and comorbidities. Further studies in different areas are required to test the impact of different IgE molecular profiles on AIT response.

Endotypes of pollen-food syndrome in children with seasonal allergic rhinoconjunctivitis: a molecular classification.

BACKGROUND: Pollen-food syndrome (PFS) is heterogeneous with regard to triggers, severity, natural history, comorbidities, and response to treatment. Our study aimed to classify different endotypes of PFS based on IgE sensitization to panallergens. METHODS: We examined 1271 Italian children (age 4-18 years) with seasonal allergic rhinoconjunctivitis (SAR). Foods triggering PFS were acquired by questionnaire. Skin prick tests were performed with commercial pollen extracts. IgE to panallergens Phl p 12 (profilin), Bet v 1 (PR-10), and Pru p 3 (nsLTP) were tested by ImmunoCAP FEIA. An unsupervised hierarchical agglomerative clustering method was applied within PFS population. RESULTS: PFS was observed in 300/1271 children (24%). Cluster analysis identified five PFS endotypes linked to panallergen IgE sensitization: (i) cosensitization to ≥2 panallergens ('multi-panallergen PFS'); (ii-iv) sensitization to either profilin, or nsLTP, or PR-10 ('mono-panallergen PFS'); (v) no sensitization to panallergens ('no-panallergen PFS'). These endotypes showed peculiar characteristics: (i) 'multi-panallergen PFS': severe disease with frequent allergic comorbidities and multiple offending foods; (ii) 'profilin PFS': oral allergy syndrome (OAS) triggered by Cucurbitaceae; (iii) 'LTP PFS': living in Southern Italy, OAS triggered by hazelnut and peanut; (iv) 'PR-10 PFS': OAS triggered by Rosaceae; and (v) 'no-panallergen PFS': mild disease and OAS triggered by kiwifruit. CONCLUSIONS: In a Mediterranean country characterized by multiple pollen exposures, PFS is a complex and frequent complication of childhood SAR, with five distinct endotypes marked by peculiar profiles of IgE sensitization to panallergens. Prospective studies in cohorts of patients with PFS are now required to test whether this novel classification may be useful for diagnostic and therapeutic purposes in the clinical practice.

Association of halo nevus/i and vitiligo in childhood: a retrospective observational study.

BACKGROUND: Although halo nevus (HN) is frequently observed, the relationship between vitiligo and HN in children has rarely been investigated. OBJECTIVES: To investigate the association between HN and vitiligo in children and understand if HN/HNi might be a risk factor for vitiligo. METHODS: Ninety-eight patients with only HN/HNi and 27 with HN/HNi and vitiligo were investigated for number and localization of HN/HNi, family history for HN/HNi and vitiligo and personal and family history for autoimmune or other diseases. A follow-up telephone interview was performed to investigate the evolution of HN/HNi and the possible onset of vitiligo and/or other diseases. RESULTS: In the HN/HNi and vitiligo group, HN/HNi and vitiligo had started almost simultaneously in 11 children; in nine, the onset of HN/HNi was followed by vitiligo after 6 months to 5 years; seven patients presented vitiligo first and HN/HNi after 3-9 years. Patients with associated vitiligo had, significantly more often, multiple HNi and a positive personal and/or family history of autoimmune thyroiditis compared with those with only HN/HNi. Follow-up longer than 5 years was available in 54/98 patients with only HN/HNi; two of them, both with multiple HNi, developed vitiligo. After follow-up, multiple HNi were noticed in 18/52 patients without vitiligo and in 9/11 of those in whom HN/HNi heralded vitiligo (s.s.). CONCLUSIONS: In patients with multiple HNi, the risk of vitiligo and other autoimmune diseases seems to be higher than in pediatric patients with a single HN; clinicians should pay particular attention to children with multiple HNi and personal or family history of autoimmune diseases.

Allergy is not the main trigger of urticaria in children referred to the emergency room.

BACKGROUND: Urticaria is the disease that has the highest impact on quality of life and requires the most visits to the emergency room. OBJECTIVE: To investigate the clinical presentation of acute urticaria in children referred to the paediatric emergency room of our hospital and to define possible related aetiologies. METHODS: We included 814 children consecutively referred to the emergency room between January 2006 and December 2007 with a diagnosis of acute urticaria, isolated or associated with other clinical symptoms. RESULTS: Only 2.0% of the cases studied were associated with severe clinical pictures. In 437 cases (53.7%), the cause of urticaria was not determined. The infections of the respiratory tract were the most frequently suspected aetiological factor. The diagnosis of allergic urticaria is more defined, but belongs to a minority group (10.8%). The first level treatment includes the use of non-sedating oral H1-antihistamine. CONCLUSION: The children with urticaria are frequently referred to the paediatric emergency room, but only in a few cases were associated with severe clinical manifestations or allergy. The evidence of an inverse relationship between the number of accesses and the patients' age may be explained by the higher prevalence of this disease in early childhood and possibly also by a higher concern of the parents of the younger patients.

Role of topical calcineurin inhibitors on atopic dermatitis of children.

Besides the traditional topical treatment of mild and moderate forms of atopic dermatitis (AD), which includes the daily use of emollients and the intermittent use of topical corticosteroids (TCSs) as anti-inflammatory drugs, a new group of drugs has recently been introduced to control the inflammatory phase of the disease: topical calcineurin inhibitors (TCIs). Although the efficacy of TCSs is evident, prolonged unrestricted use is limited by local and systemic side effects. The major risk in children is the hypothalamic-pituitary-adrenal gland suppression, due to the higher percutaneous absorption of the TCSs. TCIs selectively block the activity of calcineurin, a serin/threonine protein phosphatase regulated by cellular calcium first detected in skeletal muscle and brain. Within the past few years, calcineurin has been implicated in a wide range of biological responses including lymphocyte activation, neuronal and muscle development, and morphogenesis of heart valves. TCIs disrupt the intracellular signalling towards NF-AT by forming a complex with macrophilin-12. This complex inhibits the activity of calcineurin, thereby preventing the dephosphorylation of NF-AT and so interfering with the transcription of several genes. The nuclear component of NF-AT, binding to its nuclear counterpart, is essential for the transcription of various genes, including interleukin (IL)-2 and other proinflammatory cytokines. Recent findings about the therapeutic efficacy of TCIs have provided a possible alternative to TCSs in the treatments of mild to severe forms of AD.

[Liver abscess in children]. / L'ascesso epatico nel bambino.

A case of solitary hepatic abscess in an apparently normal 5-year old infant is described. The symptoms in this patient were generally nonspecific and the child were erroneously operated with a presumptive diagnosis of acute appendicitis. Subsequently, because of persistence of isolated abdominal signs, abdominal ultrasonography were performed, and an abscess of the right hepatic lobe was evidenced. The pathogenesis of the hepatic abscess in this child is unclear.

Elevated thrombopoietin in plasma of burned patients without and with sepsis enhances platelet activation.

BACKGROUND: Thrombopoietin (TPO) is a humoral growth factor that does not induce platelet aggregation per se, but enhances platelet activation in response to several agonists. Circulating levels of TPO are increased in patients with sepsis and are mainly related to sepsis severity. OBJECTIVES: To investigate the potential contribution of elevated TPO levels in platelet activation during burn injury complicated or not by sepsis. METHODS: We studied 22 burned patients, 10 without and 12 with sepsis, and 10 healthy subjects. We measured plasma levels of TPO, as well as leukocyte-platelet binding and P-selectin expression. The priming activity of plasma from burned patients or healthy subjects on platelet aggregation and leukocyte-platelet binding, and the role of TPO in these effects were also studied in vitro. RESULTS: Burned patients without and with sepsis showed higher circulating TPO levels and increased monocyte-platelet binding compared with healthy subjects. Moreover, TPO levels, monocyte-platelet binding and P-selectin expression were significantly higher in burned patients with sepsis than in burned patients without sepsis. In vitro, plasma from burned patients without and with sepsis, but not from healthy subjects, primed platelet aggregation, monocyte-platelet binding and platelet P-selectin expression. The effect of plasma from burned patients with sepsis was significantly higher than that of plasma from burned patients without sepsis. An inhibitor of TPO prevented the priming effect of plasma from burned patients. CONCLUSIONS: Increased TPO levels may enhance platelet activation during burn injury and sepsis, potentially participating in the pathogenesis of multi-organ failure in these diseases.

Not all children with under-control asthma are controlled.

Subclinical lung function alterations can sometimes be discovered in asthmatic patients under clinical control. This study aimed to identify the burden of asthmatic children with subclinical airways abnormalities who may benefit from an adjustment in asthma therapy. 134 6-to-17-year-old asthmatic children were enrolled. Of them, 98 presented apparently under clinical control disease and all performed spirometry before and after bronchodilation: 17 (17.3%) had a positive bronchodilation test, in addition to significantly lower lung function indexes as compared to those with under-control asthma who had a negative bronchodilation test. These patients were randomized and re-evaluated: patients (n=8) receiving an adjustment in their therapy showed an improvement in lung function tests and quality of life indexes as compared to 7 without therapy adjustment. In conclusion, a substantial number of apparently-under-control asthmatic children show airways alterations that can be improved by adjusting their therapy, which also seems to enhance their quality of life.