IgE to cyclophilins in pollen-allergic children: Epidemiologic, clinical, and diagnostic relevance of a neglected panallergen.

BACKGROUND: Cyclophilins are ubiquitous panallergens whose epidemiologic, diagnostic, and clinical relevance is largely unknown and whose sensitization is rarely examined in routine allergy practice. OBJECTIVE: We investigated the epidemiologic, diagnostic, and clinical relevance of cyclophilins in seasonal allergic rhinitis and its comorbidities. METHODS: We examined a random sample of 253 (25%) of 1263 Italian children with seasonal allergic rhinitis from the Panallergens in Pediatrics (PAN-PED) cohort with characterized disease phenotypes. Nested studies of sensitization prevalence, correlation, and allergen extract inhibition were performed in patients sensitized to birch pollen extract but lacking IgE to Bet v 1/2/4 (74/1263) or with highest serum level of IgE to Bet v 1 (26/1263); and in patients with sensitization to various extracts (ragweed, mugwort, pellitory, Plantago, and plane tree), but not to their respective major allergenic molecule, profilins, and polcalcins. IgE to cyclophilin was detected with recombinant Bet v 7, and extract inhibition tests were performed with the same rBet v 7. RESULTS: IgE to rBet v 7 was detected in 43 (17%) of 253 patients. It was associated with asthma (P < .028) and oral allergy syndrome (P < .017) in univariate but not multivariate analysis adjusted for IgE to profilins (Phl p 12), PR-10s (Bet v 1), and lipid transfer proteins (Pru p 3). IgE to rBet v 7 was also highly prevalent (47/74, 63%) among patients with unexplained sensitization to birch pollen extract. In patients with unexplained sensitization to ragweed, mugwort, pellitory, Plantago and plane tree pollen, the levels of IgE to those extracts correlated with the levels of IgE to rBet v 7, and they were also significantly inhibited by rBet v 7 (inhibition range 45%-74%). CONCLUSIONS: IgE sensitization to cyclophilin is frequent in pollen-allergic patients living in temperate areas and can produce "false" positive outcomes in skin prick and IgE tests to pollen extracts. Molecular diagnostic guidelines should include this panallergen family.

IgE to cross-reactive carbohydrate determinants (CCD) in childhood: Prevalence, risk factors, putative origins.

BACKGROUND: IgE antibodies to cross-reactive carbohydrate determinants (CCD) are usually clinically irrelevant but they can be a cause of false positive outcomes of allergen-specific IgE tests in vitro. Their prevalence and levels have been so far cross-sectionally examined among adult allergic patients and much less is known about their origins and relevance in childhood. METHODS: We examined CCD with a cross-sectional approach in 1263 Italian pollen allergic children (Panallergen in Paediatrics, PAN-PED), as well as with a longitudinal approach in 612 German children (Multicenter Allergy Study, MAS), whose cutaneous and IgE sensitization profile to a broad panel of allergen extracts and molecules was already known. The presence and levels of IgE to CCD were examined in the sera of both cohorts using bromelain (MUXF3) as reagent and a novel chemiluminescence detection system, operating in a solid phase of fluorescently labelled and streptavidin-coated paramagnetic microparticles (NOVEOS, HYCOR, USA). RESULTS: IgE to CCD was found in 22% of the Italian pollen allergic children, mainly in association with an IgE response to grass pollen. Children with IgE to CCD had higher total IgE levels and were sensitized to more allergenic molecules of Phleum pratense than those with no IgE to CCD. Among participants of the German MAS birth cohort study, IgE to CCD emerged early in life (even at pre-school age), with IgE sensitization to group 1 and 4 allergen molecules of grasses, and almost invariably persisted over the full observation period. CONCLUSIONS: Our results contribute to dissect the immunological origins, onset, evolution and risk factors of CCD-sIgE response in childhood, and raise the hypothesis that group 1 and/or 4 allergen molecules of grass pollen are major inducers of these antibodies through an antigen-specific, T-B cell cognate interaction.

Allergic Conjunctivitis Management: Update on Ophthalmic Solutions.

PURPOSE OF REVIEW: The aim of this review, is to present an updated revision of topical management of SAC and PAC, based on the available scientific evidence and focused on the impact of ophthalmic solution formulations on eye surface. RECENT FINDINGS: Physicians treating ocular allergy should be aware of tear film and tear film disruption in SAC and PAC, and how eye drop composition and additives affect the physiology of the allergic eye. Seasonal and perennial allergic conjunctivitis (SAC and PAC) are the most frequent causes of ocular allergy (OA), and both conditions are underdiagnosed and undertreated. SAC and PAC are immunoglobulin E (IgE)-mediated hypersensitivity reactions. The additional tear film disruption caused by the release of inflammatory mediators increases and exacerbates the impact of signs and symptoms and may trigger damage of the ocular surface. Comorbidities are frequent, and dry eye disease in particular must be considered. Clinical guidelines for the management of SAC and PAC recommend topical therapy with antihistamines, mast cells stabilizers or dualaction agents as first-line treatment, but care should be taken, as many medications contain other compounds that may contribute to ocular surface damage.

Urticaria exacerbations and adverse reactions in patients with chronic urticaria receiving COVID-19 vaccination: Results of the UCARE COVAC-CU study.

BACKGROUND: Concern about disease exacerbations and fear of reactions after coronavirus disease 2019 (COVID-19) vaccinations are common in chronic urticaria (CU) patients and may lead to vaccine hesitancy. OBJECTIVE: We assessed the frequency and risk factors of CU exacerbation and adverse reactions in CU patients after COVID-19 vaccination. METHODS: COVAC-CU is an international multicenter study of Urticaria Centers of Reference and Excellence (UCAREs) that retrospectively evaluated the effects of COVID-19 vaccination in CU patients aged ≥18 years and vaccinated with ≥1 dose of any COVID-19 vaccine. We evaluated CU exacerbations and severe allergic reactions as well as other adverse events associated with COVID-19 vaccinations and their association with various CU parameters. RESULTS: Across 2769 COVID-19-vaccinated CU patients, most (90%) received at least 2 COVID-19 vaccine doses, and most patients received CU treatment and had well-controlled disease. The rate of COVID-19 vaccination-induced CU exacerbation was 9%. Of 223 patients with CU exacerbation after the first dose, 53.4% experienced recurrence of CU exacerbation after the second dose. CU exacerbation most often started <48 hours after vaccination (59.2%), lasted for a few weeks or less (70%), and was treated mainly with antihistamines (70.3%). Factors that increased the risk for COVID-19 vaccination-induced CU exacerbation included female sex, disease duration shorter than 24 months, having chronic spontaneous versus inducible urticaria, receipt of adenovirus viral vector vaccine, having nonsteroidal anti-inflammatory drug/aspirin intolerance, and having concerns about getting vaccinated; receiving omalizumab treatment and Latino/Hispanic ethnicity lowered the risk. First-dose vaccine-related adverse effects, most commonly local reactions, fever, fatigue, and muscle pain, were reported by 43.5% of CU patients. Seven patients reported severe allergic reactions. CONCLUSIONS: COVID-19 vaccination leads to disease exacerbation in only a small number of CU patients and is generally well tolerated.

EAACI Molecular Allergology User's Guide 2.0.

Since the discovery of immunoglobulin E (IgE) as a mediator of allergic diseases in 1967, our knowledge about the immunological mechanisms of IgE-mediated allergies has remarkably increased. In addition to understanding the immune response and clinical symptoms, allergy diagnosis and management depend strongly on the precise identification of the elicitors of the IgE-mediated allergic reaction. In the past four decades, innovations in bioscience and technology have facilitated the identification and production of well-defined, highly pure molecules for component-resolved diagnosis (CRD), allowing a personalized diagnosis and management of the allergic disease for individual patients. The first edition of the "EAACI Molecular Allergology User's Guide" (MAUG) in 2016 rapidly became a key reference for clinicians, scientists, and interested readers with a background in allergology, immunology, biology, and medicine. Nevertheless, the field of molecular allergology is moving fast, and after 6 years, a new EAACI Taskforce was established to provide an updated document. The Molecular Allergology User's Guide 2.0 summarizes state-of-the-art information on allergen molecules, their clinical relevance, and their application in diagnostic algorithms for clinical practice. It is designed for both, clinicians and scientists, guiding health care professionals through the overwhelming list of different allergen molecules available for testing. Further, it provides diagnostic algorithms on the clinical relevance of allergenic molecules and gives an overview of their biology, the basic mechanisms of test formats, and the application of tests to measure allergen exposure.

Autoimmune chronic spontaneous urticaria.

Chronic spontaneous urticaria (CSU) is a debilitating mast cell-driven disease characterized by recurrent wheals and/or angioedema. Substantial progress has been made in dissecting the 2 main autoimmune mechanisms that drive the pathogenesis of CSU. Type I autoimmune (autoallergic) CSU is associated with IgE antibodies against autoantigens, for example, thyroid peroxidase and IL-24. Type IIb autoimmune CSU is mediated by autoantibodies that activate mast cells, for example, via IgE and FcεRI, and is present in less than 10% of patients with CSU when strict criteria are used, that is, triple positivity of autologous serum skin test, immunoassays for IgG autoantibodies, and basophil activation tests. A subpopulation of patients with CSU has both types. Type IIb autoimmune CSU is characterized by higher disease severity, concomitant autoimmune diseases, low levels of total IgE, elevated levels of IgG-anti-thyroid peroxidase, basopenia, eosinopenia, poor response to antihistamines and to omalizumab, and a good response to cyclosporine. Novel targeted therapies for CSU are under development such as ligelizumab, an anti-IgE, fenebrutinib and remibrutinib, Bruton's tyrosine kinase inhibitors, and dupilumab, an anti-IL-4Rα. Further studies should investigate the overlap between autoallergic and type IIb autoimmune CSU, optimize the diagnosis of both autoimmune endotypes using easy-to-perform, noninvasive, and inexpensive markers, and assess differences in response to therapy.

Urticarial vasculitis: Clinical and laboratory findings with a particular emphasis on differential diagnosis.

Urticarial vasculitis (UV) is a rare cutaneous vasculitis of small vessels characterized by recurrent episodes of wheal-like lesions that tend to last more than 24 hours, healing with a residual ecchymotic postinflammatory hyperpigmentation. The histopathologic pattern of UV is that of leukocytoclastic vasculitis, consisting of fibrinoid necrosis of dermal vessels' walls and neutrophil-rich perivascular inflammatory infiltrates. Although its etiopahogenesis remains still undefined, UV is now regarded as an immune complex-driven disease with activation of the complement cascade, leading to exaggerated production of anaphylatoxins that are responsible for neutrophil recruitment and activation. This condition can be categorized into 2 main entities according to serum complement levels: normocomplementemic UV and hypocomplementemic UV, the latter being associated with circulating anti-C1q autoantibodies and possible extracutaneous manifestations. Systemic multiorgan involvement may be seen particularly in syndromic hypocomplementemic UV, also known as McDuffie syndrome. This review summarizes the clinicopathological and laboratory features as well as the underlying pathophysiological mechanisms of UV. A focus on its main differential diagnoses is provided, that is, chronic spontaneous urticaria, bullous pemphigoid, IgA (Henoch-Schönlein purpura) and IgM/IgG immune complex vasculitis, lupus erythematous tumidus, Wells syndrome, erythema multiforme, cutaneous mastocytosis, cryopyrin-associated periodic syndromes, and coronavirus disease 2019-associated and anti-severe acute respiratory syndrome coronavirus 2-vaccine-associated urticarial eruptions.

Thyroid Autoimmunity in CSU: A Potential Marker of Omalizumab Response?

The response of severe chronic spontaneous urticaria (CSU) to omalizumab largely depends on the autoimmune or autoallergic endotype of the disease. Whether thyroid autoimmunity may predict omalizumab response along with total IgE in CSU is still unclear. Three hundred and eighty-five patients (M/F 123/262; mean age 49.5 years; range 12-87 years) with severe CSU were studied. Total IgE levels and thyroid autoimmunity (levels of anti-thyroid peroxidase [TPO] IgG) were measured before omalizumab treatment. Based on the clinical response, patients were divided into early (ER), late (LR), partial (PR) and non (NR) responders to omalizumab. Thyroid autoimmunity was detected in 92/385 (24%) patients. Altogether, 52%, 22%, 16% and 10% of patients were ER, LR, PR and NR to omalizumab, respectively. Response to omalizumab was not associated with thyroid autoimmunity (p = 0.77). Conversely, we found a strongly positive association between IgE levels and omalizumab response (p < 0.0001); this association was largely driven by early response (OR = 5.46; 95% CI: 2.23-13.3). Moreover, the predicted probabilities of early response strongly increased with increasing IgE levels. Thyroid autoimmunity alone cannot be used as a clinical predictor of omalizumab response. Total IgE levels remain the only and most reliable prognostic marker for omalizumab response in patients with severe CSU.

Lipid transfer protein allergy: A review of current controversies.

Sensitization to lipid transfer protein (LTP), the most frequent cause of food allergy in southern Europe, still shows several controversial, but also intriguing, aspects. Some of these include the degree of cross-reactivity between LTPs from botanically distant sources, the definition of risk factors, the role of some cofactors, clinical outcomes, geographical differences and the identification of the primary sensitizer in different areas. This review article tries to analyse and comment on these aspects point by point suggesting some explanatory hypotheses with the final scope to stimulate critical thoughts and elicit the scientific discussion about this issue in the readership.

Real-life evaluation of molecular multiplex IgE test methods in the diagnosis of pollen associated food allergy.

BACKGROUND: Diagnosis of food allergies is challenging, as combining information from specific IgE (sIgE)-sensitization pattern and skin prick tests (SPTs) with clinical history is necessary for a personalized management of allergic patients. The aim of this study was to compare two molecular tests, the ImmunoCAP ISAC (ISAC) and the Allergy Explorer, version 2 (ALEX2 ) in the context of pollen food syndrome (PFS) diagnosis in a real-life scenario, to assess the benefit of multiplex testing in PFS patients. METHODS: Diagnosis of food allergy was performed in 53 patients. Allergen-sIgE concentrations were measured with ISAC and ALEX2 . Results for sIgE were statistically compared with each other, with SPT results and with clinical presentation of the patients. RESULTS: Using ISAC as reference test for sIgE measurements, the average sensitivity of ALEX2 for PR-10 allergens was 83.2% and the average specificity 88.0%. If only low sIgE concentrations were included, the sensitivity was 60.8% and the specificity 91.1%. Apple and hazelnut sensitizations were confirmed in most patients by concordance of sIgE and SPT results. Significant correlations were shown between clinical symptoms and Mal d 1- and Gly m 4-sIgE levels measured by both tests and for Cor a 1-sIgE levels measured by ALEX2 . In eight patients, profilin related symptoms were supported by Hev b 8-sensitization. CONCLUSION: Multiplex testing is beneficial to understand patient-specific individual sensitization profiles and to providing personalized management recommendations. In the future, custom-designed test kits might enable reducing costs of multiplex testing for specific patient groups without compromising the diagnostic value.

Development and validation of the food allergy severity score.

BACKGROUND: The heterogeneity and lack of validation of existing severity scores for food allergic reactions limit standardization of case management and research advances. We aimed to develop and validate a severity score for food allergic reactions. METHODS: Following a multidisciplinary experts consensus, it was decided to develop a food allergy severity score (FASS) with ordinal (oFASS) and numerical (nFASS) formats. oFASS with 3 and 5 grades were generated through expert consensus, and nFASS by mathematical modeling. Evaluation was performed in the EuroPrevall outpatient clinic cohort (8232 food reactions) by logistic regression with request of emergency care and medications used as outcomes. Discrimination, classification, and calibration were calculated. Bootstrapping internal validation was followed by external validation (logistic regression) in 5 cohorts (3622 food reactions). Correlation of nFASS with the severity classification done by expert allergy clinicians by Best-Worst Scaling of 32 food reactions was calculated. RESULTS: oFASS and nFASS map consistently, with nFASS having greater granularity. With the outcomes emergency care, adrenaline and critical medical treatment, oFASS and nFASS had a good discrimination (receiver operating characteristic area under the curve [ROC-AUC]>0.80), classification (sensitivity 0.87-0.92, specificity 0.73-0.78), and calibration. Bootstrapping over ROC-AUC showed negligible biases (1.0 × 10-6 -1.23 × 10-3 ). In external validation, nFASS performed best with higher ROC-AUC. nFASS was strongly correlated (R 0.89) to best-worst scoring of 334 expert clinicians. CONCLUSION: FASS is a validated and reliable method to measure severity of food allergic reactions. The ordinal and numerical versions that map onto each other are suitable for use by different stakeholders in different settings.

The international EAACI/GA²LEN/EuroGuiDerm/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria.

This update and revision of the international guideline for urticaria was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GA²LEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), the European Dermatology Forum (EDF; EuroGuiDerm), and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology with the participation of 64 delegates of 50 national and international societies and from 31 countries. The consensus conference was held on 3 December 2020. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease that presents with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous or inducible urticaria is disabling, impairs quality of life, and affects performance at work and school. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.

Allergenicity at component level of sub-pollen particles from different sources obtained by osmolar shock: A molecular approach to thunderstorm-related asthma outbreaks.

BACKGROUND: The so-called "thunderstorm asthma" (TA) is an uncommon but dramatic outbreak of asthma attacks occurring during a thunderstorm in the pollen and moulds season. Mechanisms which make the pollen able to enter the deeper airways and provoke severe asthma symptoms are still unclear. OBJECTIVE: To test the hypothesis that sub-pollen particles (SPPs) originated from the rupture by an osmotic shock of pollen associated with TA contain allergens. METHODS: After hydration, SPPs released from pollen grains of grass, pellitory, olive, cypress, ragweed and birch were isolated and determined by microscopy. Allergens were determined by in vitro ELISA inhibition tests indirectly using the sera from 10 polyreactive patients. An inhibition <50% was considered as negative, 50%-75% moderate and > 75% complete. RESULTS: The inhibition experiments showed that the SPPs from birch and cypress were unable to inhibit serum IgE reactivity to Bet v 1 and Cup a 1, respectively. Ragweed SPPs inhibited ragweed pollen extract and Amb a 1 by 75.8 ± 0.11% and 81.2 ± 0.15%, respectively. Olive and pellitory SPPs retained almost the whole IgE-binding capability in all cases tested. Grass SPPs inhibited 32 ± 0.06% of Lolium perenne Lol p 1 and 65% of Phleum pratense extracts, but results were highly variable for individual allergens (97.5%-0.03% for Phl p 2, 45.3 ± 0.12% for Phl p 5, 24.7 ± 0.22% for Phl p 6, and 38.3 ± 0.2% for Phl p 1). CONCLUSIONS: Inhibition experiments confirm the hypothesis that SSPs obtained after the osmotic shock of pollen involved in TA, namely grass, pellitory and olive tree pollen, contain allergens and therefore they can induce severe asthma attacks during thunderstorms.

A qualitative and quantitative comparison of IgE antibody profiles with two multiplex platforms for component-resolved diagnostics in allergic patients.

BACKGROUND: Clinically complex phenotypes require more and more sophisticated and comprehensive diagnostic approaches, able to discriminate genuine sensitizations from cross-reactivity. Interpretative complexity of multiplex diagnostic arrays has somewhat limited their diffusion. This study compares two currently available methods, namely ISAC® test and ALEX2® test. METHODS: In total, 140 allergic individuals, with a history of atopic dermatitis, adverse food reactions, allergic rhinitis and/or bronchial asthma were studied by Allergy Explorer-ALEX2® macroarray and ImmunoCAP ISAC112® . Lin's concordance correlation coefficient, intraclass correlation coefficient and Bland-Altman plots were used to verify the agreement between continuous values. Cohen's kappa coefficient (k) was assessed for the molecules available in both tests. The degree of relationship was analysed using Spearman's correlation (quantitative variables) and Pearson's χ2 or Fisher's exact test (categorical variables). RESULTS: A substantial agreement (κ = 0.795) was observed between the two methods with 94,3% concordant results when results were dichotomized as negative or positive, but if double-negative results were discarded, the agreement dropped to 71%. Conversely, little or no concordance was observed comparing raw data. Considering the 102 molecules shared by both systems, 28/102 (27%) showed an almost perfect agreement (k > 0.81), and concordance was good (k > 0.61) in a further 32 (31%) cases. A perfect to substantial agreement was observed by comparing species-specific aeroallergens. Heterogeneous results emerged comparing panallergens (co-recognition ranging from 30% for tropomyosin/serum albumins to 70% for PR-10/profilin). The correlation among LTP, profilin and PR-10 assayed with ISAC® was better than ALEX2® , but the latter identified more positive cases due to the wider number of molecules available. The CCD blocker provided by ALEX® test abolishes the carbohydrate determinants signal in 60% of the 33 cases reactive to MUXF3 on the ISAC® test. CONCLUSION: Despite the excellent concordance of the species-specific markers, the analysis of the panallergens provided in both methods suggests a better performance of the ISAC® test on those components, while the ALEX2® test, which includes a larger number of allergens, allowing a broader molecular detection.

The diagnosis and management of allergic reactions in patients sensitized to non-specific lipid transfer proteins.

Sensitization to one or more non-specific lipid transfer proteins (nsLTPs), initially thought to exist mainly in southern Europe, is becoming accepted as a cause of allergic reactions to plant foods across Europe and beyond. The peach nsLTP allergen Pru p 3 is a dominant sensitizing allergen and peaches a common food trigger, although multiple foods can be involved. A frequent feature of reactions is the requirement for a cofactor (exercise, alcohol, non-steroidal anti-inflammatory drugs, Cannabis sativa) to be present for a food to elicit a reaction. The variability in the food and cofactor triggers makes it essential to include an allergy-focused diet and clinical history in the diagnostic workup. Testing on suspected food triggers should also establish whether sensitization to nsLTP is present, using purified or recombinant nsLTP allergens such as Pru p 3. The avoidance of known trigger foods and advice on cofactors is currently the main management for this condition. Studies on immunotherapy are promising, but it is unknown whether such treatments will be useful in populations where Pru p 3 is not the primary sensitizing allergen. Future research should focus on the mechanisms of cofactors, improving diagnostic accuracy and establishing the efficacy of immunotherapy.

Systemic allergic reactions induced by labile plant-food allergens: Seeking potential cofactors. A multicenter study.

BACKGROUND: Heat-and-pepsin-sensitive plant food allergens (PR-10 and profilin) sometimes cause systemic reaction. OBJECTIVE: To detect the risk factors for systemic reactions induced by labile food allergens. METHODS: A retrospective multicenter study was performed on patients with a documented history of systemic allergic reaction to labile plant food allergens and on age-matched controls with a history of oral allergy syndrome (OAS) induced by the same foods. Offending foods, their amount, and state (solid or liquid), and potential cofactors (nonsteroidal anti-inflammatory drugs, protonic pump inhibitors, exercise, alcohol, and fasting) were considered. RESULTS: We studied 89 patients and 81 controls. Sensitization to PR-10 or profilin, IgE to Bet v 1 and/or Bet v 2, and foods causing OAS were similar in the two groups. Twenty patients experienced >1 systemic allergic reaction. Tree nuts, Rosaceae, Apiaceae, and soymilk were the main offending foods. Seventeen (19%) patients were taking a PPI when the systemic reaction occurred (vs 5% in controls; P < .025). The ingestion of the offending food in liquid form (soymilk) was frequent among patients (15%) but unusual among controls (2%; P < .025). Soy milk-induced systemic reactions were independent of PPI treatment. Fasting and excess of allergen, but not NSAID and exercise, were other relevant cofactors for systemic reactions. Systemic reactions occurred without any identifiable cofactor in 39 (44%) cases. CONCLUSION: PR-10- and profilin-induced systemic reactions are facilitated by PPI, ingestion of large amounts of unprocessed foods, and fasting. Soybean beverages represent a risk for PR-10 hypersensitive patients and should be avoided.

The global impact of the COVID-19 pandemic on the management and course of chronic urticaria.

INTRODUCTION: The COVID-19 pandemic dramatically disrupts health care around the globe. The impact of the pandemic on chronic urticaria (CU) and its management are largely unknown. AIM: To understand how CU patients are affected by the COVID-19 pandemic; how specialists alter CU patient management; and the course of CU in patients with COVID-19. MATERIALS AND METHODS: Our cross-sectional, international, questionnaire-based, multicenter UCARE COVID-CU study assessed the impact of the pandemic on patient consultations, remote treatment, changes in medications, and clinical consequences. RESULTS: The COVID-19 pandemic severely impairs CU patient care, with less than 50% of the weekly numbers of patients treated as compared to before the pandemic. Reduced patient referrals and clinic hours were the major reasons. Almost half of responding UCARE physicians were involved in COVID-19 patient care, which negatively impacted on the care of urticaria patients. The rate of face-to-face consultations decreased by 62%, from 90% to less than half, whereas the rate of remote consultations increased by more than 600%, from one in 10 to more than two thirds. Cyclosporine and systemic corticosteroids, but not antihistamines or omalizumab, are used less during the pandemic. CU does not affect the course of COVID-19, but COVID-19 results in CU exacerbation in one of three patients, with higher rates in patients with severe COVID-19. CONCLUSIONS: The COVID-19 pandemic brings major changes and challenges for CU patients and their physicians. The long-term consequences of these changes, especially the increased use of remote consultations, require careful evaluation.

ß-1,3-glucanase rOle e 9 and MnSOD rAsp f 6 IgE reactivity are the signature of atopic dermatitis in the Mediterranean area.

BACKGROUND: Atopic dermatitis (AD) represents a chronic skin disorder seriously affecting patients' QoL and is often associated with immunological imbalance, disorders of the skin barrier function and environmental factors. OBJECTIVE: We extensively studied the proteomic IgE sensitization profile in a large AD Mediterranean cohort. METHODS: A total of 588 individuals with moderate-severe (70.6%) or mild and/or history of (29.4%) AD were evaluated in comparison to 1285 unselected atopic controls (AC) with a history of adverse reactions to foods, allergic rhinitis and/or bronchial asthma by means of ImmunoCAP ISAC112 ® and Allergy Explorer-ALEX® microarray analysis. RESULTS: The olive tree pollen ß-1,3-glucanase rOle e 9 and the manganese superoxide dismutase from Aspergillus rAsp f 6 were the molecules most significantly associated with AD occurrence and allowed to discriminate among the moderate and severe forms of disease. An IgE hyper-reactivity to cypress, grasses, olive tree, house dust mites (including rDer p 11), and to all cross-reactive components except profilin and polcalcin was observed. About 60% of adults with severe AD were sensitized to nsLTPs. Cross-reactive carbohydrate determinants (CCDs) IgE was found in about one-third of AD participants. Hen eggs nGal d 1 IgE sensitization was more prevalent in the paediatric population, whilst rAsp f 6 and rOle e 9 reactivity was found particularly in older patients. Despite the status of widespread IgE sensitization to both environmental and food allergens, a reduced frequency of patient-reported severe reactions to food or of asthma was observed in AD patients compared to AC, particularly in case of concomitant Ole e 9 reactivity. CONCLUSION AND CLINICAL RELEVANCE: Testing IgE reactivity to a large panel of molecular components unveils important associations between IgE reactivity profiles and AD clinical presentation, highlights the allergens useful for a precise AD signature and allows the detection of interesting sensitisations patterns.

Disease-Specific Molecular Profiles Highlighted by Radar Graphic Display.

BACKGROUND: Management of hundreds of analytes obtained from the molecular multiplex techniques currently available may represent a challenge for clinicians in daily clinical practice. OBJECTIVES: The aim of the study was to describe a comprehensive and simple approach to assess such complex molecular results, to display relevant disease-specific signatures at a glance, and to facilitate their interpretation. METHOD: A total of 6,332 consecutive allergic patients, categorized based on clinical symptoms reported at the time of the first visit before IgE testing, were evaluated through ImmunoCAP ISAC112®. RESULTS AND CONCLUSIONS: The occurrence of bronchial asthma is associated with polcalcin, serum albumin, or lipocalin reactivity. Higher risk of severe reaction to food is linked to tropomyosin or nonspecific lipid transfer protein reactivity (in the absence of plant pathogenesis-related proteins [PR-10] or profilin sensitization). We used radar graphic display to highlight, at a glance, the molecular reactivity profiles associated with relevant disease-specific patterns.

House Dust Mite-Shrimp Allergen Interrelationships.

PURPOSE OF REVIEW: Focusing on the strict relationship between house dust mites and crustaceans from the allergenic point of view. RECENT FINDINGS: The well-known tropomyosin was considered for years as the cross-reacting allergen between shrimp and house dust mites. In the last few years, several allergens not only in shrimps but also in house dust mite have been identified and other molecules other than tropomyosin have been shown to cross-react between crustaceans and mites. The present review investigates the very complex allergen sources in shrimp and mites, giving a satisfactorily complete picture of the interrelationships between common allergens. Several minor HDM allergens are homologous to major and minor shrimp allergens; tropomyosin is not the only cross-reactive allergen between shrimp and mites.