[Show abstract][Hide abstract] ABSTRACT: Background:
Little is known about the prevalence and clinical relevance of hypersensitivity to the plant panallergen profilin in children.
The present study aimed to investigate prevalence, risk factors and clinical relevance of profilin sensitization in a large cohort of Italian children of different ages living in different geographic areas.
Children with pollen allergy enrolled by 16 pediatric outpatient clinics sited in three main geographic areas of Italy were studied. SPT were carried out with commercial pollen extracts and a commercial purified date palm pollen profilin. IgE specific for allergenic pollen molecules, Phl p 12 (grass profilin) and Pru p 3 (peach lipid transfer protein) were tested by ImmunoCAP FEIA.
IgE to Phl p 12 (≥0.35 kU/l) was observed in 296 of the 1,271 participants (23%), including 17 of the 108 (16%) preschool children. Profilin SPT was positive (≥3 mm) in 320/1,271 (25%) participants. The two diagnostic methods were concordant in 1,151 (91%, p < 0.0001) cases. Phl p 12 IgE prevalence declined from northern to southern Italy and was directly associated with IgE to Phl p 1 and/or Phl p 5 and Ole e 1. Among children with IgE to Phl p 12, OAS was provoked by kiwi, melon, watermelon, banana, apricot and cucumber.
Profilin sensitization is very frequent among pollen-allergic children, occurs at a very young age and contributes to the development of childhood OAS with a typical pattern of offending foods. Pediatricians should always consider IgE sensitization to profilin while examining pollen-allergic children, even if they are at preschool age.
International Archives of Allergy and Immunology 11/2015; 168(1):25-31. DOI:10.1159/000441222 · 2.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Chronic spontaneous urticaria (CSU) is characterized by the recurrence of itchy wheals for at least 6 weeks, affects up to 1% of the general population and may severely impair quality of life. H1-antihistamines are the cornerstones of treatment, but in about 10% of cases they fail to control the disease even at higher than licensed doses. In these patients, short courses of oral steroids may induce a remission in about 50% of cases. Omalizumab, a monoclonal anti-IgE, is effective in antihistamine-unresponsive patients although optimal treatment duration needs to be defined. Immunosuppressive treatment with cyclosporine is also effective in the majority of antihistamine-resistant chronic spontaneous urticaria (CSU) patients, but its use is limited by potential side effects. In refractory patients, other approaches include intravenous immunoglobulin, rituximab, dapsone and anticoagulants. The present review looks with particular interest at the prevalence of treatment failures with the main third-level treatments (corticosteroids, omalizumab and cyclosporine) and discusses them in light of the possible different pathogenic mechanisms underlying chronic spontaneous urticaria.
[Show abstract][Hide abstract] ABSTRACT: In older children, adolescents and adults, a substantial part of all IgE-mediated food allergies is caused by cross-reacting allergenic structures shared by inhalants and foods. IgE stimulated by a cross-reactive inhalant allergen can result in diverse patterns of allergic reactions to various foods. Local, mild or severe systemic reactions may occur already after the first consumption of a food containing a cross-reactive allergen. In clinical practice clinically relevant sensitizations are elucidated by skin prick testing or by the determination of specific IgE in vitro. Component resolved diagnosis may help to reach a diagnosis and may predict the risk of a systemic reaction. Allergy needs to be confirmed in cases of unclear history by oral challenge tests. The therapeutic potential of allergen immunotherapy with inhalant allergens in pollen-related food allergy is not clear, and more placebo-controlled studies are needed. As we are facing an increase of pollen allergies, a shift in sensitization patterns and changes in nutritional habits, the occurrence of new, so far unknown allergies due to cross-reactions is expected. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: Coagulation activation has been demonstrated in two prototypic autoimmune skin diseases, chronic autoimmune urticaria and bullous pemphigoid, but only the latter is associated with increased thrombotic risk. Two markers of coagulation activation (prothrombin fragment F1+2 and fibrin fragment D-dimer) were measured by immunoenzymatic methods in plasma samples from 30 patients with active chronic autoimmune urticaria, positive for autologous serum skin test, 30 patients with active bullous pemphigoid and 30 healthy subjects. In skin biopsies, tissue factor expression was evaluated by both immunohistochemistry and in situ hybridization. F1+2 and D-dimer levels were higher in active chronic autoimmune urticaria (276.5±89.8 pmol/L and 5.56±4.40 nmol/L, respectively) than in controls (145.2±38.0 pmol/L and 1.06±0.25 nmol/L; P=0.029 and P=0.011) and were much higher in active bullous pemphigoid (691.7±318.7 pmol/L and 15.24±9.09 nmol/L, respectively) (P<0.0001). Tissue factor positivity was evident in skin biopsies of both disorders with higher intensity in bullous pemphigoid. F1+2 and D-dimer, during remission, were markedly reduced in both disorders. These findings support the involvement of coagulation activation in the pathophysiology of both diseases. The strong systemic activation of coagulation in bullous pemphigoid may contribute to increase the thrombotic risk and provides the rationale for clinical trials on anticoagulant treatments in this disease.
PLoS ONE 06/2015; 10(6):e0129456. DOI:10.1371/journal.pone.0129456 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Allergen-specific immunotherapy is the only treatment able to change the natural history of either respiratory or hymenoptera venom allergy. From an immunological point of view, there is no reason to believe that its clinical effects should be different in food allergies. However, due to the high prevalence of adverse events that accompanied the first attempts of injection immunotherapy with food extracts some 20 years ago, such treatment is presently non-available although a thoroughly standardized food extract for injection immunotherapy should theoretically not expose the patients to higher risks than airborne allergen extracts or venoms. Allergen-specific immunotherapy with birch pollen extract is an interesting model to investigate the effects of the treatment on plant-food allergies that occur as a consequence of cross-reactivity with the major allergen, Bet v 1. Although the interest for this field has partly settled during the last years, the available data suggest that an adequate dose of the birch pollen major allergen, Bet v 1, particularly if administered subcutaneously, is able reduce secondary plant food allergy also, although doses needed to exert such effect are probably higher than those required to reduce respiratory symptoms. The administration of higher doses of the major allergen without an increase of the risk of adverse reactions should be possible if modified hypoallergenic molecules obtained either by genetic engineering or chemical treatments are used.
[Show abstract][Hide abstract] ABSTRACT: Non-specific lipid transfer proteins (nsLTPs) represent a major cause of systemic food allergic reactions in the Mediterranean area. This study investigate hierarchical patterns and cluster relationships of IgE sensitization to different nsLTPs, and the relationship to clinical allergy in a large Italian cohort.
568 nsLTPs positive subjects after IgE ImmunoCAP ISAC microarray analysis with Ara h 9, Art v 3, Cor a 8, Jug r 3, Pla a 3, Pru p 3 and Tri a 14 allergens, were studied. IgE inhibition experiments were carried out with mugwort and plane tree pollen extracts.
82% of nsLTP positive participants (94% if <6 years old) were Pru p 3(pos) and 71% were Jug r 3(pos) . Participants who reacted to >5 nsLTPs reported a higher incidence of food-induced systemic reactions. Only Art v 3 and Pla a 3 (mugwort and plane tree nsLTPs, respectively) were associated with respiratory symptoms, and a correlation was observed between sensitization to pollen and plant food nsLTPs, particularly between Pla a 3 and tree nut/peanut nsLTPs. Co-sensitization to Par j 2 and PR-10 or profilin pan-allergens was associated with a lower prior prevalence of severe food-induced reactions. In inhibition assays, plane and mugwort pollen extracts inhibited 50%-100% of IgE binding to food nsLTPs in microarrays.
Testing IgE reactivity to a panel of nsLTP allergens unveils important associations between nsLTP sensitization profiles and clinical presentation, and allows the identification of novel cluster patterns indicating likely cross-reactivities and highlighting potential allergens for nsLTP immunotherapy. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: Niniejsze wytyczne są wynikiem systematycznego przeglądu piśmiennictwa dokonanego w oparciu o metodologię GRADE (Grading Recommendations Assessment, Development and Evaluation) oraz dyskusji przeprowadzonych w trakcie konferencji dotyczącej pokrzywki, która odbyła się 28 i 29 listopada 2012 roku w Berlinie. Konferencja ta była wspólną inicjatywą kilku organizacji (Dermatology Section of the European Academy of Allergy and Clinical Immunology [EAACI], EU-funded network of excellence, Global Allergy and Asthma European Network [GA2LEN], European Dermatology Forum [EDF], World Allergy Organization [WAO]) i wzięli w niej udział delegaci z 21 towarzystw zarówno krajowych, jak i międzynarodowych. Pokrzywka jest często rozpoznawaną jednostką chorobową rozwijającą się przy dominującym udziale komórek tucznych, która klinicznie objawia się występowaniem bąbli pokrzywkowych, obrzęku naczynioruchowego lub współistnieniem obu typów objawów skórnych. Ryzyko wystąpienia klinicznych objawów pokrzywki ostrej w ciągu życia w populacji ogólnej szacuje się na około 20%. Przewlekła pokrzywka spontaniczna oraz inne odmiany pokrzywki przewlekłej nie tylko obniżają jakość życia pacjenta, ale wpływają także na poziom funkcjonowania w pracy czy szkole i z tego powodu należy je zaliczyć do grupy ciężkich chorób alergicznych. Niniejsze wytyczne zawierają definicję oraz klasyfikację pokrzywek, uwzględniając postęp, który się ostatnio dokonał w zakresie identyfikacji przyczyn, czynników wyzwalających oraz patomechanizmów zaangażowanych w rozwój objawów klinicznych choroby. Dodatkowo przedstawiają oparte na wiarygodnych dowodach naukowo-badawczych zasady postępowania diagnostycznego i terapeutycznego w różnych podtypach pokrzywek. Niniejsze wytyczne zostały uznane zaakceptowane przez Europejską Unię Lekarzy Specjalistów (European Union of Medical Specialists; UEMS).
[Show abstract][Hide abstract] ABSTRACT: The relationship between hypersensitivity to NSAID and atopic status is still incompletely defined. Previous studies found a high prevalence of atopic diseases in multiple NSAID reactors. The present study aimed to investigate whether this is the case also in Italian adults hypersensitive to NSAIDs.
Skin tests with a large panel of seasonal and perennial airborne allergens were carried out in 252 patients with a clear-cut history of acute urticaria induced by nonsteroidal anti-inflammatory drugs. Patients were classified as single or multiple NSAID reactors based on clinical history, presence/absence of chronic urticaria, re-challenge with the reported offending drug in case of doubt history, and oral challenges with aspirin or propionic acid derivatives.
Single NSAID reactors showed a much higher prevalence of atopic diseases than multiple NSAID reactors either with or without chronic urticaria (61% vs 19% and 19%, respectively; p < 0.001).
As a difference from previous reports, in Italian patients hypersensitive to NSAID atopy is much more prevalent among single reactors, a finding that indirectly supports the possible IgE-mediated origin of this type of adverse drug reaction.
European annals of allergy and clinical immunology 03/2015; 47(2):48-53.
[Show abstract][Hide abstract] ABSTRACT: Chronic urticaria (CU) is a skin disorder characterized by transient, pruritic wheals persisting longer than 6 weeks. According to European Academy of Allergy and Clinical Immunology (EAACI) guidelines, CU can be categorized into two main types: chronic spontaneous urticaria (CSU), in which the wheals appear spontaneously, and inducible urticaria, that is triggered by physical agents. CSU may be due to triggering factors such as food allergens or infections, but is in at least 40% of cases autoimmune in origin, caused by circulating autoantibodies anti--FcεR1 or anti--IgE, or autoreactive. In the present paper, re--evaluating the EAACI guidelines, we have developed a document containing some practical indications which are useful for diagnosis and management of CSU in the context of the Italian reality. Concerning CSU treatment, second generation antihistamines are the first line treatment; these drugs can be used, as second line treatment, at higher than licensed dose in patients who don't respond adequately at licensed doses. The third line treatment include leukotriene receptor antagonists which, however, don't have a specific indication for the treatment of CSU, cyclosporine, whose use in this disease is still off--label, and omalizumab. The latter is a recombinant monoclonal IgG antibody that binds free IgE, down regulates mast cell function and induces eosinophil apoptosis. Recently, it has emerged as an effective and safe treatment for antihistamine--unresponsive CSU of both autoimmune/autoreactive and non--autoimmune/non--autoreactive, and has been officially approved for the use in this disease.
Giornale italiano di dermatologia e venereologia: organo ufficiale, Societa italiana di dermatologia e sifilografia 02/2015; 150(2). · 0.86 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The EuroPrevall project aimed to develop effective management strategies in food allergy through a suite of interconnected studies and a multidisciplinary integrated approach. To address some of the gaps in food allergy diagnosis, allergen risk management and socioeconomic impact, and to complement the EuroPrevall population based surveys, a cross-sectional study in 12 outpatient clinics across Europe was conducted. We describe the study protocol.
Patients referred for immediate food adverse reactions underwent a consistent and standardised allergy work-up that comprised collection of medical history, assessment of sensitisation to 24 foods, 14 inhalant allergens, and 55 allergenic molecules, and confirmation of clinical reactivity and food thresholds by standardised double-blind placebo-controlled food challenges (DBPCFC) to milk, egg, fish, shrimp, peanut, hazelnut, celeriac, apple and peach.
A standardized methodology for a comprehensive evaluation of food allergy was developed, and implemented in 12 outpatient clinics across Europe. A total of 2121 patients (22.6% <14 years) reporting 8257 reactions to foods were studied, and 516 DBPCFC were performed.
This is the largest multicentre European case series in food allergy, in which subjects underwent a comprehensive, uniform and standardised evaluation including DBPCFC, by a methodology which is made available for further studies in food allergy. The analysis of this population will provide information on the different phenotypes of food allergy across Europe, will allow to validate novel in vitro diagnostic tests, to establish threshold values for major allergenic foods, and to analyse the socioeconomic impact of food allergy. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: Although food allergy has universally been found to impair HRQL, studies have found significant differences in HRQL between countries, even when corrected for differences in perceived disease severity. However, little is known about factors other than disease severity which may contribute to HRQL in food-allergic patients. Therefore, The aim of this study was to identify factors which may predict HRQL of food-allergic patients and also to investigate the specific impact of having experienced anaphylaxis and being prescribed an EAI on HRQL.
A total of 648 European food-allergic patients (404 adults, 244 children) completed an age-specific questionnaire-package including descriptive questions. Multivariable regression analyses were performed to develop models for predicting HRQL of these patients.
For adults, the prediction model accounted for 62% of the variance in HRQL and included perceived disease severity, type of symptoms, having a fish or milk allergy and gender. For children, the prediction model accounted for 28% of the variance in HRQL and included perceived disease severity, having a peanut or soy allergy, and country of origin. For both adults and children, neither experiencing anaphylaxis nor being prescribed an epinephrine auto-injector (EAI) contributed to impairment of HRQL.
In this study food allergy-related HRQL may be predicted to a greater extent in adults than in children. Allergy to certain foods may cause greater HRQL impairment than others. Country of origin may affect HRQL, at least in children. Experiencing anaphylaxis or being prescribed an EAI has no impact on HRQL in either adults or children. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: Background
We tested the hypothesis that specific molecular sensitization patterns correlate with the clinical data/manifestation in a European peanut allergic population characterized under a common protocol.Methods68 peanut allergic subjects and 82 tolerant controls from 11 European countries were included. Allergy to peanut and lowest symptom-eliciting-dose were established by double-blind placebo-controlled food-challenge in all but anaphylactic subjects. Information of early or late (before or after 14 years of age) onset of peanut allergy was obtained from standardized questionnaires. IgE to peanut allergens rAra h 1-3, 6, 8-9, profilin and CCD were determined using ImmunoCAP.Results78% of peanut allergics were sensitised to peanut extract and 90% to at least one peanut component. rAra h 2 was the sole major allergen for the peanut allergic population. Geographic differences were observed for rAra h 8 and rAra h 9, which were major allergens for central/western and southern Europeans, respectively. Sensitisation to rAra h 1 and 2 were exclusively observed in early onset peanut allergy. Peanut tolerant subjects were frequently sensitised to rAra h 8 or 9 but not to storage proteins. Sensitisation to Ara h 2 ≥1.0 kUA/L conferred a 97% probability for a systemic reaction (p=0.0002). Logistic regression revealed a significant influence of peanut extract sensitization and region on the occurrence of systemic reactions (p=0.0185 and p=0.0436 respectively).Conclusion
Sensitization to Ara h 1, 2 and 3 is usually acquired in childhood. IgE to Ara h 2 ≥1.0 kUA/L is significantly associated with the development of systemic reactions to peanut.This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: The pathomechanism of chronic spontaneous urticaria (CSU), defined by the recurrence of short-lived wheals for more than 6 weeks without apparent triggers, remained to be mysterious until 1986. In that year, skin reactivity to the injection of autologous serum was reported in about half of patients with CSU; that observation and the subsequent discovery of histamine-releasing autoantibodies against the high-affinity IgE receptor (FcεRI) and against IgE in patients with CSU were major breakthroughs in the pathogenesis of this disorder. A role for complement activation in autoantibody-dependent histamine release was subsequently demonstrated. CSU was hence considered as an autoimmune disorder due to histamine-releasing autoantibodies in a consistent proportion of cases. However, this model does not fit all cases and shows several inconsistencies. Recently, it was shown that sera from most CSU patients are able to degranulate also mast cells lacking FcεRI, suggesting the involvement of other as yet unknown mechanisms. New light on CSU pathogenesis was shed by the demonstration of coagulation activation and eosinophil involvement during active phases of the disease, paralleling urticaria severity. Finally, the efficacy of omalizumab (a recombinant humanized monoclonal IgG anti-IgE antibody) in the treatment of refractory CSU opened a new scenario in the pathophysiology of the disease. Indeed, omalizumab has multiple biological effects relevant in CSU pathogenesis, such as binding of free IgE, downregulation of mast cell function including expression of high affinity IgE receptors, and induction of eosinophil apoptosis.