Journal of Clinical Medicine

Research

12 pages, 285 KiB

Open AccessArticle

Pediatric Anaphylaxis: A 20-Year Retrospective Analysis

by Maria De Filippo, Martina Votto, Maria Albini, Riccardo Castagnoli, Mara De Amici, Alessia Marseglia, Alessandro Pizzo, Gian Luigi Marseglia and Amelia Licari

J. Clin. Med. 2022, 11(18), 5285; https://doi.org/10.3390/jcm11185285 - 7 Sep 2022

Cited by 4 | Viewed by 2864

Abstract

Background. Anaphylaxis is a steadily increasing global problem defined as an acute hypersensitivity multisystem reaction that is potentially fatal. In the pediatric age, the leading cause is food. In other allergic diseases, intrinsic heterogeneity has been reported in the clinical presentation, severity, and [...] Read more.

Background. Anaphylaxis is a steadily increasing global problem defined as an acute hypersensitivity multisystem reaction that is potentially fatal. In the pediatric age, the leading cause is food. In other allergic diseases, intrinsic heterogeneity has been reported in the clinical presentation, severity, and triggers of anaphylaxis. This study analyzes the features and management approach of the anaphylactic reactions in children evaluated at the pediatric clinic in Pavia. Materials and methods. A retrospective study was conducted on patients with anaphylaxis between 2001 and 2021. Results. A total of 148 patients with a median age of 5 years were enrolled, and 80% of the patients had other atopic comorbidities that were correlated with the severity of anaphylaxis. The main trigger of anaphylaxis was food. Most reactions involved mucocutaneous, respiratory, and gastrointestinal systems, and occurred at home. Adrenaline was administered only in a minority of cases. Conclusions. Considering that anaphylaxis is a potentially life-threatening condition requiring prompt management, the use of adrenaline should be implemented. Our data also suggest the importance of educating and spreading awareness of anaphylactic management within the medical community. Full article

(This article belongs to the Special Issue Latest Advances in Allergic Diseases)

18 pages, 340 KiB

Open AccessArticle

Genetic Variants in Epidermal Differentiation Complex Genes as Predictive Biomarkers for Atopic Eczema, Allergic Sensitization, and Eczema-Associated Asthma in a 6-Year Follow-Up Case–Control Study in Children

by Anna Dębińska, Hanna Danielewicz and Barbara Sozańska

J. Clin. Med. 2022, 11(16), 4865; https://doi.org/10.3390/jcm11164865 - 19 Aug 2022

Cited by 3 | Viewed by 2163

Abstract

Atopic eczema is the most common chronic inflammatory skin disease of early childhood and is often the first manifestation of atopic march. Therefore, one challenge is to identify the risk factors associated with atopic eczema that may also be predictors of atopic disease [...] Read more.

Atopic eczema is the most common chronic inflammatory skin disease of early childhood and is often the first manifestation of atopic march. Therefore, one challenge is to identify the risk factors associated with atopic eczema that may also be predictors of atopic disease progression. The aim of this study was to investigate the association of SNPs in hornerin (HRNR) and filaggrin-2 (FLG2) genes with childhood atopic eczema, as well as other atopic phenotypes. Genotyping for HRNR and FLG2 was performed in 188 children younger than 2 years of age, previously screened for the FLG null mutations, and followed at yearly intervals until the age of 6. We demonstrated that risk variants of HRNR rs877776[C] and FLG2 rs12568784[T] were associated with atopic eczema, allergic sensitization, and susceptibility to the complex phenotype—asthma plus eczema. These effects seem to be supplementary to the well-known associations for FLG mutations and may be modulated by gene–gene interactions. Additionally, in children with eczema, these genetic variants may also be considered, along with FLG mutations, as predictive biomarkers for eczema-associated asthma. In conclusion, our results indicate that genetic variants in the epidermal differentiation complex gene could contribute to the pathogenesis of atopic eczema and progression to subsequent allergic disease. Full article

(This article belongs to the Special Issue Latest Advances in Allergic Diseases)

11 pages, 741 KiB

Open AccessArticle

Component-Resolved Evaluation of the Risk and Success of Immunotherapy in Bee Venom Allergic Patients

by Marta Rosiek-Biegus, Robert Pawłowicz, Agnieszka Kopeć, Magdalena Kosińska, Marta Wrześniak and Marita Nittner-Marszalska

J. Clin. Med. 2022, 11(6), 1677; https://doi.org/10.3390/jcm11061677 - 17 Mar 2022

Cited by 2 | Viewed by 1579

Abstract

Venom immunotherapy (VIT) is the only efficient therapy for the Hymenoptera insect venom allergy. Immunotherapy with bee venom is encumbered with a higher risk of systemic side effects and/or therapeutic failures. The objective of the study was to assess if specific profiles of [...] Read more.

Venom immunotherapy (VIT) is the only efficient therapy for the Hymenoptera insect venom allergy. Immunotherapy with bee venom is encumbered with a higher risk of systemic side effects and/or therapeutic failures. The objective of the study was to assess if specific profiles of molecular IgE (Immunoglobulin E) responses are associated with an increased risk of systemic side effects and/or the treatment’s inefficacy. The study group numbered 64 bee venom allergic patients (BVA) who received venom immunotherapy modo ultra-rush (VIT-UR), (f/m: 32/32, mean age 43.4 ± 17.2). In total, 54.84% of them manifested allergic reactions of grades I-III (acc. to Mueller’s scale), while 48.66% manifested reactions of grade IV. In all the patients, IgE against bee venom extract, rApi m 1 and tryptase (sBT) were assessed. In 46 patients, assessments of IgE against rApi m 2, 3, 5, 10 were also performed. BVA patients manifesting cardiovascular symptoms (SYS IV⁰) showed higher levels of both sIgE-rApi m 5 (p = 0.03) and tryptase (p = 0.07) than patients with SYS I–III. Systemic adverse events during VIT with bee venom were more frequent in the induction phase than in the maintenance phase: 15.22% vs. 8.7%. In BVA patients who experienced systemic adverse events during VIT, higher concentrations of sIgE-rApi m 5 (p < 0.05), rApi m 1 (p = 0.009), and sBT (p = 0.019) were demonstrated. We conclude that higher levels of sIgE against rApi m 1, rApi m 5, and tryptase many constitute a potential marker of the severity of allergic reactions and therapeutic complications that can occur during VIT with bee venom. Full article

(This article belongs to the Special Issue Latest Advances in Allergic Diseases)

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10 pages, 2107 KiB

Open AccessArticle

Metal Allergy Mediates the Development of Oral Lichen Planus via TSLP-TSLPR Signaling

by Mohammad Fadyl Yunizar, Megumi Watanabe, Lipei Liu, Norikazu Minami and Tetsuo Ichikawa

J. Clin. Med. 2022, 11(3), 519; https://doi.org/10.3390/jcm11030519 - 20 Jan 2022

Cited by 3 | Viewed by 1897

Abstract

Metal allergy is a T-cell-mediated delayed type of hypersensitive reaction. The pathogenetic mechanisms underlying the allergy are unclear, although the condition has been reported to be related to oral lichen planus (OLP), despite an absence of immunological studies to support this relationship. In [...] Read more.

Metal allergy is a T-cell-mediated delayed type of hypersensitive reaction. The pathogenetic mechanisms underlying the allergy are unclear, although the condition has been reported to be related to oral lichen planus (OLP), despite an absence of immunological studies to support this relationship. In this study, histopathological samples of OLP patients were examined to compare the metal allergy-positive and -negative groups, with a focus on the network of epidermal keratinocytes and T cells induced by thymic stromal lymphopoietin (TSLP) and its receptor, TSLPR. Infiltration of T cells into the epithelium was revealed to be higher in the OLP lesions of metal allergy-positive patients than in those of metal allergy-negative patients. Moreover, TSLP-TSLPR signaling and TNF-α production were higher in the epithelial tissue samples of the metal allergy-positive patients than in the metal allergy-negative patients. Metal allergy is associated with both increased expressions of TSLP in keratinocytes and increased TNF-α levels in the epithelium. We propose that this would promote the accumulation of T cells at the lesion site, contributing to the formation of the disease. These results suggest that metal allergy may be an aggravating factor in the pathogenesis of OLP. Full article

(This article belongs to the Special Issue Latest Advances in Allergic Diseases)

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9 pages, 255 KiB

Open AccessArticle

Are Markers of Allergic Inflammation in Grass Pollen Allergy Influenced by H1 Antihistamines?

by Ioana Corina Bocsan, Ioana Adriana Muntean, Nicolae Miron, Irena Pintea, Carmen Teodora Dobrican, Corina Ureche, Anca Dana Buzoianu and Diana Deleanu

J. Clin. Med. 2022, 11(1), 113; https://doi.org/10.3390/jcm11010113 - 26 Dec 2021

Cited by 4 | Viewed by 2411

Abstract

Soluble intercellular adhesion molecule-1 (ICAM-1) and soluble vascular adhesion molecule-1 (VCAM-1) play important roles in allergic rhinitis (AR). Treatment with H1 antihistamines improves AR symptoms and in vitro reduces the levels of adhesion molecules. The aim of the study was to evaluate serum [...] Read more.

Soluble intercellular adhesion molecule-1 (ICAM-1) and soluble vascular adhesion molecule-1 (VCAM-1) play important roles in allergic rhinitis (AR). Treatment with H1 antihistamines improves AR symptoms and in vitro reduces the levels of adhesion molecules. The aim of the study was to evaluate serum levels of ICAM-1 and VCAM-1 in patients with AR to grass pollen and their response to different H1 antihistamines. Material and methods: A total of 50 patients with grass pollen AR were clinically and biologically evaluated. ICAM-1 and VCAM-1 serum levels were evaluated during pollen season before and after treatment with levocetirizine and desloratadine through the ELISA method. Results: ICAM-1, VCAM-1, eosinophils, and total IgE were elevated in patients with AR, compared with healthy subjects. Both antihistamines improved specific symptoms of AR and increased patients’ quality of life during pollen season after one month of treatment. H1 antihistamines reduced VCAM-1, ICAM-1, and total IgE after one-month treatment but not significantly. Patients with increased baseline values tend to remain with increased values after one-month AH1 treatment. Conclusions: ICAM-1 and sVCAM-1 levels are higher in patients with grass pollen-induced AR than healthy controls during pollen exposure. Their serum levels tend to remain at high values during pollen season despite antihistaminic therapy. Full article

(This article belongs to the Special Issue Latest Advances in Allergic Diseases)

11 pages, 672 KiB

Open AccessArticle

Filaggrin Loss-of-Function Mutations Are Risk Factors for Severe Food Allergy in Children with Atopic Dermatitis

by Annalisa Astolfi, Francesca Cipriani, Daria Messelodi, Matilde De Luca, Valentina Indio, Costanza Di Chiara, Arianna Giannetti, Lorenza Ricci, Iria Neri, Annalisa Patrizi, Giampaolo Ricci and Andrea Pession

J. Clin. Med. 2021, 10(2), 233; https://doi.org/10.3390/jcm10020233 - 11 Jan 2021

Cited by 18 | Viewed by 3596

Abstract

Atopic dermatitis is frequently associated with the onset of other allergic conditions, such as asthma, rhino-conjunctivitis and food allergy. The etiology of atopic dermatitis is marginally understood in spite of the number of predisposing factors, above all, mutations in the Filaggrin gene (FLG [...] Read more.

Atopic dermatitis is frequently associated with the onset of other allergic conditions, such as asthma, rhino-conjunctivitis and food allergy. The etiology of atopic dermatitis is marginally understood in spite of the number of predisposing factors, above all, mutations in the Filaggrin gene (FLG). In this study, the association between loss-of-function variants in the FLG gene and other allergic manifestations, in particular food allergy, was evaluated in an Italian pediatric population affected by atopic dermatitis. The 10 more frequently mutated loci in the FLG gene were genotyped in 238 children affected by atopic dermatitis and tested for association with clinical features of allergic disorders by a multivariate logistic regression model. R501X and 2282del4 were the only two mutations identified; 12.2% of children carry one of these variants, corresponding to an allelic frequency of 6.5%. According to multivariate statistical analysis, loss-of-function variants in the FLG gene represent a risk factor for the onset of severe manifestations of food allergy (OR = 8.9; CI: 3.1–28.3). Peanut and hazelnut were identified as high-risk foods in patients with FLG mutations. This study demonstrates that atopic children carrying FLG mutations represent a high-risk population due to their predisposition to develop severe food allergy reactions, such as anaphylaxis. Full article

(This article belongs to the Special Issue Latest Advances in Allergic Diseases)

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Review

Jump to: Research, Other

13 pages, 1101 KiB

Open AccessReview

An Overview on the Primary Factors That Contribute to Non-Allergic Asthma in Children

by Angela Klain, Giulio Dinardo, Alessandra Salvatori, Cristiana Indolfi, Marcella Contieri, Giulia Brindisi, Fabio Decimo, Anna Maria Zicari and Michele Miraglia del Giudice

J. Clin. Med. 2022, 11(21), 6567; https://doi.org/10.3390/jcm11216567 - 5 Nov 2022

Cited by 7 | Viewed by 5076

Abstract

The prevalence of non-allergic asthma in childhood is low, peaking in late adulthood. It is triggered by factors other than allergens, like cold and dry air, respiratory infections, hormonal changes, smoke and air pollution. In the literature, there are few studies that describe [...] Read more.

The prevalence of non-allergic asthma in childhood is low, peaking in late adulthood. It is triggered by factors other than allergens, like cold and dry air, respiratory infections, hormonal changes, smoke and air pollution. In the literature, there are few studies that describe non-allergic asthma in pediatric age. Even though it is a less common disorder in kids, it is crucial to identify the causes in order to keep asthma under control, particularly in patients not responding to conventional treatments. In this review, we discuss non-IgE-mediated forms of asthma, collecting the latest research on etiopathogenesis and treatment. Full article

(This article belongs to the Special Issue Latest Advances in Allergic Diseases)

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11 pages, 276 KiB

Open AccessReview

Hydrolyzed Rice Formula: An Appropriate Choice for the Treatment of Cow’s Milk Allergy

by Caterina Anania, Ivana Martinelli, Giulia Brindisi, Daniela De Canditiis, Giovanna De Castro, Anna Maria Zicari and Francesca Olivero

J. Clin. Med. 2022, 11(16), 4823; https://doi.org/10.3390/jcm11164823 - 17 Aug 2022

Cited by 4 | Viewed by 3683

Abstract

Cow’s milk allergy (CMA) is a common condition in the pediatric population. CMA can induce a diverse range of symptoms of variable intensity. It occurs mainly in the first year of life, and if the child is not breastfed, hypoallergenic formula is the [...] Read more.

Cow’s milk allergy (CMA) is a common condition in the pediatric population. CMA can induce a diverse range of symptoms of variable intensity. It occurs mainly in the first year of life, and if the child is not breastfed, hypoallergenic formula is the dietary treatment. Extensively hydrolyzed cow’s milk formulas (eHF) with documented hypo-allergenicity can be recommended as the first choice, while amino acid-based formulas (AAF) are recommended for patients with more severe symptoms. Hydrolyzed rice-based formulas (HRFs) are a suitable alternative for infants with CMA that cannot tolerate or do not like eHF and in infants with severe forms of CMA. In the present paper, we reviewed the nutritional composition of HRFs as well as studies regarding their efficacy and tolerance in children, and we provided an updated overview of the recent evidence on the use of HRFs in CMA. The available studies provide evidence that HRFs exhibit excellent efficacy and tolerance and seem to be adequate in providing normal growth in healthy children as well as in children with CMA. Full article

(This article belongs to the Special Issue Latest Advances in Allergic Diseases)

34 pages, 767 KiB

Open AccessReview

Monoclonal Antibodies in Treating Chronic Spontaneous Urticaria: New Drugs for an Old Disease

by Sara Manti, Alessandro Giallongo, Maria Papale, Giuseppe Fabio Parisi and Salvatore Leonardi

J. Clin. Med. 2022, 11(15), 4453; https://doi.org/10.3390/jcm11154453 - 30 Jul 2022

Cited by 9 | Viewed by 2681

Abstract

Background: H1-antihistamines (H1AH) represent the current mainstay of treatment for chronic spontaneous urticaria (CSU). However, the response to H1AH is often unsatisfactory, even with increased doses. Therefore, guidelines recommend the use of omalizumab as an add-on treatment in refractory CSU. This paved the [...] Read more.

Background: H1-antihistamines (H1AH) represent the current mainstay of treatment for chronic spontaneous urticaria (CSU). However, the response to H1AH is often unsatisfactory, even with increased doses. Therefore, guidelines recommend the use of omalizumab as an add-on treatment in refractory CSU. This paved the way for the investigation of targeted therapies, such as monoclonal antibodies (mAbs), in CSU. Methods: A literature review was conducted including papers published between 2009 and 2022 and ongoing trials about the efficacy and safety of mAbs as treatment for CSU. Results: Twenty-nine articles, a trial with preliminary results, and seventeen ongoing or completed clinical trials on the use of mAbs in CSU were included. Randomized controlled trials (RCTs), meta-analysis, and real-life studies have proven the effectiveness and safety of omalizumab as a third-line treatment in refractory CSU. However, a percentage of patients remain unresponsive to omalizumab. Therefore, other mAbs, targeting different pathways, have been used off-label in case series and others are under investigation in RCTs. Most of them have showed promising results. Conclusions: Omalizumab remains the best choice to treat refractory CSU. Although results from other mAbs seem to be encouraging to achieve symptom control in refractory CSU, thus improving patients’ QoL, RCTs are needed to confirm their effectiveness and safety. Full article

(This article belongs to the Special Issue Latest Advances in Allergic Diseases)

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11 pages, 281 KiB

Open AccessReview

Drugs and Vaccines Hypersensitivity in Children with Mastocytosis

by Francesca Mori, Giuseppe Crisafulli, Annamaria Bianchi, Paolo Bottau, Silvia Caimmi, Fabrizio Franceschini, Lucia Liotti, Claudia Paglialunga, Francesca Saretta and Carlo Caffarelli

J. Clin. Med. 2022, 11(11), 3153; https://doi.org/10.3390/jcm11113153 - 1 Jun 2022

Cited by 9 | Viewed by 1859

Abstract

Mastocytosis, a heterogeneous mastcell disease, include three different entities: cutaneous mastocytosis, systemic mastocytosis (SM) and mast-cell sarcoma. Tryptase levels can differentiate cutaneous mastocytosis from SM. In mastocytosis, quick onset drug hypersensitivity reactions (DHRs) that are facilitated by mastcell mediators, are investigated in adults. [...] Read more.

Mastocytosis, a heterogeneous mastcell disease, include three different entities: cutaneous mastocytosis, systemic mastocytosis (SM) and mast-cell sarcoma. Tryptase levels can differentiate cutaneous mastocytosis from SM. In mastocytosis, quick onset drug hypersensitivity reactions (DHRs) that are facilitated by mastcell mediators, are investigated in adults. Due to the limited number of children with mastcell disease and increased serum tryptase levels, the role of drugs in this age group is less studied. In this review, we critically assessed relevant papers related with immediate DHRs in children with mastocytosis and discuss practical issues of the management. In childhood mastocytosis, anaphylaxis is frequently idiopathic, and elevated level of basal tryptase, and high burden of disease may increase the risk. Among drugs, antibiotics, NSAIDs and opioids can potentially induce anaphylaxis, anyway avoidance should be recommended only in case of previous reactions. Moreover, vaccinations are not contraindicated in patients with mastocytosis. The risk of severe systemic reactions after drugs intake seems to be extremely low and in general lower in children than in adults. Anyway, studies on this topic especially focusing on children, are missing to state final recommendations. Full article

(This article belongs to the Special Issue Latest Advances in Allergic Diseases)

Other

Jump to: Research, Review

6 pages, 225 KiB

Open AccessBrief Report

Down Syndrome in FPIES: An Overwhelming and Unexpected Prevalence

by Valentina Pecora, Maurizio Mennini, Rocco Valluzzi, Vincenzo Fierro, Alberto Villani, Diletta Valentini and Alessandro Fiocchi

J. Clin. Med. 2022, 11(14), 4047; https://doi.org/10.3390/jcm11144047 - 13 Jul 2022

Cited by 3 | Viewed by 1692

Abstract

Down syndrome (DS) is one of the most common chromosomal anomalies. Gastrointestinal disorders in DS are predominantly related to anatomical anomalies and celiac disease. In 2015, the first two cases of non-IgE-mediated food allergy in patients with DS were described. However, gastrointestinal symptoms [...] Read more.

Down syndrome (DS) is one of the most common chromosomal anomalies. Gastrointestinal disorders in DS are predominantly related to anatomical anomalies and celiac disease. In 2015, the first two cases of non-IgE-mediated food allergy in patients with DS were described. However, gastrointestinal symptoms experienced by subjects with DS have never been related to a possible non-IgE-mediated food allergy and a Food Protein-induced Enterocolitis syndrome (FPIES). A retrospective descriptive single-center study was conducted. Subjects included were children with acute FPIES who entered our institutional follow-up protocol between January 2013 and January 2020. Among the 85 patients (forty-nine boys—57.6%), ten (11.76%) were children with DS. In our population, the FPIES triggers included different foods (such as milk, egg, fruit, fish, wheat, soy, beef, etc.). Nine patients with DS showed FPIES reactions after ingesting cow’s milk (one even with beef and three with soy), while the last one was affected by FPIES to fish. Considering the subgroup of patients affected by cow’s milk FPIES (40 subjects overall), 22.5% had a diagnosis of DS. Patients with DS experienced acute FPIES reactions with a severity degree slightly higher than that reported in other patients, ranging from mild-moderate to severe or very severe. During the acute reactions, the patients with DS showed increased white blood cell production, absolute neutrophil count and C-reactive protein levels. This series provides a starting point for novel hypothesis-testing clinical research and possible specific immunological alterations in FPIES children with or without DS. Full article

(This article belongs to the Special Issue Latest Advances in Allergic Diseases)

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