Prevalence of positive atopy patch test in an unselected pediatric population.

BACKGROUND: In the latest decades, epidemiological studies on allergic disorders in children, including atopic dermatitis, rhinitis and asthma, demonstrated a continuous increase in prevalence. However, such studies are usually performed by questionnaires and, sometimes, by skin prick test or in vitro IgE tests, while the portion of allergy sustained by the cell-mediated mechanism is neglected, because the essential test, i.e. the atopy patch test is not performed. METHODS: This cross-sectional survey studied by a specific questionnaire, skin prick test and atopy patch test, an unselected population, represented by the entire scholastic population attending a Primary school and a Junior Secondary school in the rural town of San Marco in Lamis, 12.000 inhabitants (Puglia, Italy). RESULTS: Among the 456 subjects included, 78 (17.1 %) had a positive skin prick test and 57 (12.5 %) had a positive atopy patch test. In particular, 13.4 % of subjects were positive only to skin prick test and 8.8 % were positive only to atopy patch test. The allergen most frequently positive was the house dust mite, with 41 positive results to skin prick test and 55 to atopy patch test, while for pollen positive results concerned almost exclusively the skin prick test. CONCLUSIONS: This survey on an unselected population of children detected a prevalence of positive results to atopy patch test not so distant from the positive results to skin prick test, and in 8.8 % of subjects the atopy patch test was the only positive test. This would suggest to add the atopy patch test in future epidemiological studies on allergy, in order to avoid to overlook the not negligible portion of patients with T-cell-mediated allergy.

Erratum: Prevalence of positive atopy patch test in an unselected pediatric population.

[This corrects the article DOI: 10.1186/s12948-015-0011-2.].

Metabolic syndrome is strictly associated with parental obesity beginning from childhood.

OBJECTIVE: We aimed to identify potential correlates or risk factors for metabolic syndrome (MetS) in a cohort of schoolchildren. We quantified the prevalence of MetS, analysed the clustering of MetS components and described the distribution of metabolic parameters not included in MetS definition. DESIGN: Population-based, cross-sectional study. PATIENTS AND MEASUREMENTS: A total of 489 children (6·7-13 years) representing the 92·6% of the whole school population between the 1st year of primary school and the 2nd year of junior high school living in a centre of southern Italy. Weight, height, waist circumference, blood pressure (BP), laboratory parameters (indexes of glucose metabolism, lipid profile and uric acid), anamnestic and parental information, lifestyle and dietary habits were collected. Dietary habits data were available only for 353 children. RESULTS: MetS prevalence was 9·8%. Of 48 children with MetS, 38 (79·2%) were simultaneously positive for abdominal obesity and elevated BP. In children with MetS, the prevalence of insulin resistance, high insulin, high non-HDL(high-density lipoprotein) cholesterol and high uric acid was higher than in children without MetS. In 6·7-10-year-old children, only the presence of parental history of obesity [odds ratio (OR) = 4·3, 95% CI = 1·8-10·2] was higher in those with MetS than in those without. In 10·1-13-year-old children, the presence of parental history of obesity, the habits of no walking/cycling to school, long screen time and no breakfast consumption were higher in children with MetS than in those without, but only parental history of obesity (adjusted OR = 3·8, 95% CI = 1·7-8·4) remained significantly related to MetS in multivariate logistic regression. CONCLUSIONS: Parental obesity was strictly associated with MetS in all children and should be considered in clinical practice. In older children, wrong lifestyle and dietary habits were related to parental obesity.

Dissecting the causes of atopic dermatitis in children: less foods, more mites.

Atopic dermatitis (AD) is a common, chronic or chronically relapsing, multifactorial skin disease that mainly occurs in children but affects also adults. AD usually begins early in life and often concerns people with a personal or family history of asthma and allergic rhinitis. AD is characterized by eczematous changes in the epidermis and originates from a late, T-cell mediated reaction associated to the formation and production of memory T-cell of TH2 type, occurrence of homing receptor at skin level and cutaneous lymphocyte-associated (CLA) antigens. Extrinsic or allergic AD, but not intrinsic AD, shows high total serum IgE levels and the presence of specific IgE for environmental and food allergens. A pivotal role in the pathogenesis of AD is played by filaggrin, a protein contained in the granular layer of the epidermis regulating the aggregation of keratin filaments. Mutation in the filaggrin gene causes decreased barrier function of the corny layers of the epidermis. This favours the enter through the skin of environmental allergens, especially the house dust mite, that further facilitates such entering by the proteolytic activity of its major allergen Der p 1. In fact, recent advances suggest that the dust mite, more than foods, is the major cause of allergic AD. As far as the causal diagnosis of AD is concerned, there is notable evidence supporting the capacity of the atopy patch test (APT) to reproduce the pathophysiologic events of AD. This makes APT a valuable diagnostic tool for AD.

The atopy patch test: is it time to redefine its significance?

OBJECTIVE: The atopy patch test (APT) was recently defined as an important tool in the diagnosis of atopic eczema/dermatitis syndrome (AEDS). Recent data showed that the APT may be positive also in patients with rhinitis or asthma. We examined the mechanisms that could underlie such findings. DATA SOURCE: To locate relevant articles pertaining to the use of APT, MEDLINE databases from 1989 (when the APT was first introduced) to the present were searched. STUDY SELECTION: Articles concerning the results of APT in patients with AEDS and with rhinitis or asthma attributable to sensitization to inhalant allergens were examined. RESULTS: Recent data show that APT to dust mites is frequently positive, and it may be the only positive test, not only in subjects with AEDS but also in subjects with only respiratory symptoms (rhinitis, asthma) and a history of AEDS. Instead, positive skin prick tests and in vitro immunoglobulin (Ig) E tests prevail in patients with a negative history for AEDS. CONCLUSION: Based on the pathophysiology of AEDS, in which the mechanisms of delayed hypersensitivity are predominant, the APT seems to have a greater significance than skin prick tests or in vitro IgE tests in patients with current or past history of AEDS. That different sensitization mechanisms underlie these different clinical expressions seems conceivable. In particular, if mite allergens enter the skin in the presence of a filaggrin-dependent skin barrier dysfunction, the sensitization mechanism seems to be ultimately revealed by a positive APT.

House dust mite-related allergic diseases: role of skin prick test, atopy patch test, and RAST in the diagnosis of different manifestations of allergy.

The atopy patch test (APT) was recently defined as an important tool in diagnosis of atopic dermatitis (AD) and also of rhinitis and asthma caused by hypersensitivity to the house dust mites. We evaluated 465 children (279 males and 186 females) aged 0.4-17.6 years (mean 6.6 +/- 3.8 years), by dividing them into four groups: group A, current AD (40 patients); group B, current AD with respiratory symptoms (156 patients); group C, past AD with respiratory symptoms (203 patients); and the control group, respiratory symptoms with no history of AD (66 patients). The APT was significantly more frequently positive in groups with current AD (groups A and B) or past AD (group C) than in the control group, while skin prick test (SPT) and radioallergosorbent test (RAST) were significantly more frequently positive in the control group. With multivariate analysis, for APT, significant differences were found in the comparison between group A vs group B (odds ratio (OR) 1.55) and between group A vs group C (OR 1.81). The mean age was significantly lower in group A than in groups B, C, and the control group and with less significance in groups C vs D. Children sensitized to mites with current or past AD, with or without respiratory symptoms, have a different response to diagnostic tests, which is characterized by a highly significantly more frequent positive APT in comparison with subjects who have respiratory symptoms but a negative history for AD, who show the common response to SPT and RAST.

[Update on eosinophilic airway disorders]. / Aggiornamento sulle eosinofilie dell'apparato respiratorio.

Eosinophilic disorders of the airways affect the nose and paranasal sinuses, the bronchi and the lungs. Involvement of the nose includes the well known non allergic rhinitis with eosinophilia syndrome and new disorders characterized by co-participation of mast cells and neutrophils. Eosinophilic bronchitis must be distinguished from asthma, on the basis of some functional findings and a different cytokine profile. Eosinophilic pneumonia comprises acute and chronic forms, Churg-Strauss syndrome, hypereosinophilic syndrome, and eosinophilic granuloma, as well as secondary pneumonia such as Loeffler's syndrome.The treatment is mainly based on corticosteroids and the prognosis is variable, depending upon the development of acute respiratory failure (acute eosinophilic pneumonia, eosinophilic granuloma) or of vasculitis with multi-organ organ involvement in Churg-Strauss syndrome.

The invisible fat.

Childhood and adolescence are decisive periods in human life. Body composition and psychological changes determine nutritional requirements as well as eating and physical activity behavior variability. Aims of the present paper are to discuss recent advances in measurements for quantifying total body and regional adiposity, and for mapping adipose tissue distribution in order to evaluate metabolic risk factors in children. Among the new methods available for assessing pediatric body composition, magnetic resonance imaging (MRI) can serve as a reference method for measuring tissue and organ volumes because estimates is reliable independent of age. MRI is the method of choice for calibrating field methods designed to measure adipose tissue and skeletal muscle in vivo and is the only method available for measurement of internal tissues and organs. MRI can be used to validate measures of important molecular level components such as fat measured by dual energy X-ray absorptiometry and bioimpedance analysis. Moreover, the large gap in available information for certain topics makes MRI measurement a dynamic and growing scientific area of body composition investigation.

Local allergic rhinitis: evolution of concepts.

The discovery of an exclusive local production of IgE antibodies dates back to the 1970s, but only recently the pathophysiology of such phenomenon was deeply investigated, leading to the concept of local allergic rhinitis (LAR). Currently, LAR is defined by the occurrence, in patients with symptoms clearly suggesting allergic rhinitis but with negative results to common allergy testing, of allergen specific IgE in the nasal mucosa. Most studies investigating LAR were based on the development of rhinitis symptoms following nasal provocation test (NPT) with the suspected allergens, but such test may be performed by a number of options, none of them being as yet acknowledged and recommended in consensus document. On the other hand, also the mere detection of IgE in the nasal mucosa indicates, as for IgE measurement in blood or other tissues, allergic sensitization but cannot give the certainty of clinical allergy. Therefore, the combination of IgE detection in nasal mucosa and a positive result of NPT should be used to diagnose LAR. Recent data on the use for in vitro testing of molecular allergy diagnostics in place of whole allergen extracts suggest that this method could improve the sensitivity and specificity of laboratory tests, and an appraisal of the basophil activation test as a third level technique, to be implemented when the results of local IgE testing and NPT are uncertain, is currently ongoing.

Utility of the Atopy Patch Test in the Diagnosis of Allergic Rhinitis.

INTRODUCTION: The diagnostic work-up of allergic rhinitis (AR) is first and foremost based on the combination of clinical history data and results of skin prick tests (SPT). Other tests, including specific IgE measurement, nasal challenge, and, as a third option, component resolved diagnosis or basophil activation test, may be useful when the diagnosis is difficult because of polysensitization or when negative results of SPT are observed despite a suggestive history for allergy. The atopy patch test (APT) that assesses the type 4 delayed hypersensitivity allergy is currently not sufficiently used. The data obtained in recent studies on the diagnostic utility of the APT in patients with AR was reviewed. DATA SOURCES: Review of the literature. CONCLUSION: The data from available studies show that the APT is frequently positive in patients with AR, especially when there is a positive history for atopic dermatitis. Very often, APT is the only positive test and therefore performing only SPT or in vitro IgE measurement may lead to an erroneous diagnosis of nonallergic rhinitis. Recent data suggest a role for APT not only for diagnosis but also in epidemiological investigation on respiratory allergy.

High Discrepancy in Abdominal Obesity Prevalence According to Different Waist Circumference Cut-Offs and Measurement Methods in Children: Need for Age-Risk-Weighted Standardized Cut-Offs?

BACKGROUND: Waist circumference (WC) is a good proxy measure of central adiposity. Due to the multiplicity of existing WC cut-offs and different measurement methods, the decision to use one rather than another WC chart may lead to different prevalence estimates of abdominal obesity in the same population. Aim of our study was to assess how much the prevalence of abdominal obesity varies in Italian schoolchildren using the different available WC cut-offs. METHODS: We measured WC at just above the uppermost lateral border of the right ilium in 1062 Italian schoolchildren aged 7-14 years, 499 living in Northern Italy and 563 in Southern Italy. Abdominal obesity was defined as WC ≥90th percentile for gender and age according to nine WC charts. RESULTS: We found an extremely high variability in the prevalence of abdominal obesity detected in our study-populations according to the different WC charts, ranging in the overall group from 9.1% to 61.4%. In Northern Italy children it varied from 2.4% to 35.7%, and in Southern ones from 15.1% to 84.2%. CONCLUSIONS: On the basis of the chosen WC cut-offs the prevalence of abdominal obesity varies widely, because percentile-charts are strongly influenced by the population status in a particular moment. A further rate of variability may lay on the site of WC measurement and on the statistical method used to calculate WC cut-offs. Risk-weighted WC cut-offs measured in a standardized anatomic site and calculated by the appropriate method are needed to simply identify by WC measurement those children at high risk of cardio-metabolic complications to whom specific and prompt health interventions should be addressed.

Advances of knowledge on allergic inflammation and the oral mucosa.

Allergic diseases are common worldwide and are prevalently caused by an inflammatory pathophysiology induced by the exposure to the specific allergen(s). The development of inflammation requires the involvement of regulatory cells that include antigen presenting cells and T lymphocytes, respectively orientating and orchestrating the immunological response, and the activity of cells such as mast cells and basophils, that release the typical mediators of allergic reactions, and eosinophils, which sustain the protracted inflammation. Differently from other sites of contact with allergen (s) such as respiratory or gastrointestinal tissues, the oral mucosa, based on the abundance of dendritic cells and their interaction with T cells, apparently works as a tolerogenic site concerning the response to allergen molecules. The other pivotal aspect of the oral mucosa is the minimal presence of inflammatory cells, especially eosinophils and mast cells. These characteristics play a crucial role in the sublingual administration of allergen immunotherapy, which in fact is easier to tolerate than injective immunotherapy, taking into account recent studies highlighting the important role of the Waldeyer's ring in developing tolerance to the sublingually administered allergen. Some patents addressing the identification of therapeutic agents for allergic inflammation are also summarized.

Safety of sublingual immunotherapy in children.

INTRODUCTION: Sublingual immunotherapy (SLIT) was introduced as a safer option to subcutaneous immunotherapy (SCIT) which was associated with the possible occurrence of systemic reactions including anaphylaxis and, though very rarely, fatalities. Some anaphylactic reactions to SLIT are reported, mainly in adults but also in children. It is therefore important to investigate the risk factors related to such reactions. AREAS COVERED: Data from the literature on the safety of SLIT in children were reviewed. The data reviewed concerned the application of this treatment to patients with respiratory allergy and also possible new indications such as food allergy, atopic dermatitis and latex allergy. Reports of anaphylactic reactions were analyzed to identify the potential risk factors. EXPERT OPINION: SLIT is a well tolerated treatment, the common side effect being local reactions in the mouth. Systemic reactions, concerning the skin and the airway, are rare and anaphylactic reactions are extremely rare.

Food allergy as defined by component resolved diagnosis.

The diagnosis of food allergy, as assessed by skin tests or in vitro tests with allergen extracts, has insufficient diagnostic performance and needs to be confirmed by food challenges. However, the availability of molecular allergens (recombinant or highly purified) for laboratory methods has profoundly changed the diagnostic approach to food allergy. In fact, the allergy diagnosis conducted at the molecular level, which is defined internationally as component resolved diagnosis (CRD), allows to characterize more precisely the sensitization profile of the individual patient, distinguishing the sensitizations to allergens that are strongly associated with a given source (genuine sensitizers) from those to molecules that are common to many sources (panallergens) or cross-react with other components from the same family or from other families. This review provides an update on the allergen molecules from foods, including plant foods and animal foods, and on the techniques to detect them, by means of a single reagent (singleplex) or an array of molecules tested at the same time (multiplex). Such testing offers detailed information on the sensitization profile of patients and enables the physician to suitably manage their allergy. Moreover, identifying the real causative allergens will be crucial when allergen immunotherapy for food allergy will be introduced in the near future. We also address patents concerning food allergens in this review.

Seeking allergy when it hides: which are the best fitting tests?

In the common practice of respiratory allergy, the confirmation by IgE tests of the relationship between the occurrence and duration of symptoms and the exposure to specific inhalant allergens allows an aetiological diagnosis. However, to see patients with suggestive history but negative IgE tests is not rare, and this generally leads to a diagnosis of nonallergic rhinitis or asthma. In many cases, such diagnosis is wrong, because the patient may be revealed as allergic by using additional testing. This is true for local allergic rhinitis, characterized by an exclusive IgE production in the nasal mucosa, that may be correctly diagnosed by performing a nasal IgE measurement or a nasal provocation test with the suspected allergen (s). Another misleading issue is the role of T cell-mediated, delayed hypersensitivity in the pathophysiology of rhinitis and asthma. Recent studies showed that in patients with rhinitis or asthma and negative IgE tests, especially when there is a positive history for current or past atopic dermatitis, the clinical symptoms are actually driven by such mechanism, that may be detected by performing an atopy patch test (APT). The allergen source most frequently responsible for this kind of allergy is the house dust mite, but other allergens may also be involved. Thus, before delivering a diagnosis of nonallergic rhinitis or asthma in patients with negative result to common allergy testing, further tests are needed. To miss the diagnosis of allergy has obvious consequences in terms of management, including allergen avoidance, patient's education, and specific immunotherapy.

Allergen immunotherapy: how to balance the different views from pulmonologists and allergists?

Allergen immunotherapy (AIT) is the treatment characterizing the allergological approach to respiratory allergy. Unfortunately, most available data from the literature and current practice indicate that pulmonologists do no consider AIT when choosing the treatment strategy in patients with asthma. Indeed AIT, from its introduction in 1911 to nowadays, was unceasingly improved and has accumulated clear evidence on its effectiveness. Moreover, AIT has a characteristic not shared by drugs in the capacity to modify the natural history of asthma, due to its immunologic mechanisms of actions, and thus also works after the treatment withdrawal. This also makes AIT a clearly cost-effective treatment over time. It is surprising that pulmonologists, for whom asthma is a major disease to manage, do not consider AIT when choosing the optimal treatment in single patients. The insufficient information on AIT and the availability of allergen extracts with less than good quality are likely to be the most important factors influencing such an attitude. The current development of standardized, pharmaceutical-grade products for AIT seems capable of making allergen extracts comparable to drugs and to stimulate a rethinking of AIT's role in the treatment of asthma in pulmonologists. A reappraisal of the significance of the allergen-specific bronchial challenge could represent a further factor suggesting AIT as a reliable option.

From fatness to leaness: where did we go wrong?

INTRODUCTION: In humans, using adipose tissue to store fat represents the most effective means to 'store' energy. On the whole and over an extended period of time, intake of energy has exceeded energy expenditure and where previously the excess of energy was regularly turned over through physical activity, this crucial circle has now been broken. In this way obesity ascribed to either 'overeating' or 'under-activity'. Central adiposity poses a major risk for chronic diseases such as hypertension, cardiovascular diseases and diabetes, and possibly mortality. Predictors and potential factors underlying the development of excess adiposity were well studied and established with emphasis on fat mass. OBJECTIVE: When studying the development of body composition, bone mass, fat mass and lean mass should be considered together. The purposes of the present paper are to briefly analyze the methodologies used to estimate the lean mass (LM), understanding the interrelationship between fat mass (FM) and LM and underline the importance of LM during growth. RESULTS: As muscle and adipose tissue are closely linked anatomically, biologically and pathologically, the interrelationship between these two tissues is of great importance in understanding the pathogenesis and development of diseases related to obesity and physical activity/inactivity. LM estimation, and LM programming could show several implications for the early origin of obesity. CONCLUSION: Measurements of lean mass may improve the capacity to tailor nutrition, treatment and management to metabolic criteria. This approach could offer a unique opportunity of putting lean mass in the first line keeping in mind that this metabolic active tissue need to be preserved when obesity prevention and treatment are considered.

Skin reaction to inhaled tiotropium bromide: a case report.

INTRODUCTION: Systemic reactions to inhaled drugs are rare. To the best of our knowledge, we report the first case of generalized itching related to the use of tiotropium bromide, a long acting inhaled anti-cholinergic agent commonly used to treat chronic obstructive pulmonary disease. CASE PRESENTATION: A 78-year-old Caucasian woman was referred to our facility for allergological evaluation. Our patient had been treated twice with tiotropium for chronic obstructive pulmonary disease and had experienced an allergic reaction with itching. We performed a double-blind placebo-controlled inhalation challenge for our patient with tiotropium and a placebo. Inhalation tests yielded positive results for tiotropium and negative results for the placebo. The results of a skin prick test with tiotropium were negative. CONCLUSIONS: These findings reveal that tiotropium may elicit immediate skin allergic reactions. The negative result from the skin test suggests that such a reaction is not immunoglobulin E-mediated.

Relationship between the atopy patch test and clinical expression of the disease in children with atopic eczema/dermatitis syndrome and respiratory symptoms.

BACKGROUND: The atopy patch test (APT) may be the only positive skin test result in patients with either atopic eczema/ dermatitis syndrome (AEDS) or respiratory abnormalities with or without AEDS. OBJECTIVE: To investigate the possible significance of APT to dust mite by comparing the positive result to this test with that of the skin prick test (SPT) in patients with different characteristics. METHODS: A total of 297 individuals (178 boys and 119 girls) aged 5 to 221 months (mean [SD] age, 64.5 [42.1] months; median age, 58 months) were included in this study. Participants were divided into 4 groups: current AEDS, current AEDS and respiratory symptoms, past AEDS and respiratory symptoms, and respiratory symptoms with neither current nor past AEDS (control group). All the patients underwent SPT and APT using house dust mite extract. RESULTS: In the study groups, the rate of positivity was significantly higher for APT, whereas in the control group, there were significantly more positive results to SPT (P < .001 for both). Multivariate analysis showed that there was a high probability of a positive APT result in patients with AEDS (odds ratio [OR], 17.4), with AEDS and respiratory disease (OR, 21.9), and with past AEDS and respiratory disease (OR, 22.8). CONCLUSIONS: These patients with AEDS showed 2 different patterns of allergic response to allergens, one IgE mediated (as evaluated by positive SPT results) and the other cell mediated (as evaluated by positive APT results). The former seems to follow the so-called atopic march model, and the latter persists even after the disappearance of AEDS and is likely to be implicated in the pathogenesis of respiratory allergy.

Metabolic syndrome: a child is not a small adult.

Obesity is associated with an increased all-cause mortality rate and even small weight losses can be associated with short-term reduction in risk factors for disease. There is strong evidence that weight loss in obese subjects improves risk factors for diabetes and cardiaovascular diseases. Metabolic syndrome (MS) in adults is defined as a cluster of risk factors for cardiovascular disease and type 2 diabetes mellitus, which includes abdominal obesity, dyslipidemia, glucose intolerance and hypertension. Application of the MS concept in children and adolescents is controversial; in fact no consensus exists on a specific definition for pediatric MS. Lack of consensus is in part due to body evolution associated with childhood and puberty that is related to changes in metabolic and clinical characteristics. The aim of this article is to try to clarify the differences between the MS as a concept and the MS as a diagnostic category, as well as to develop a theory related to its pathophysiology. We comment on the relationship between obesity, regional fat distribution and the MS, and finally we offer some insights into MS methodological approaches for estimating metabolic risk-factor clustering in children and adolescents.