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Introduction: Hymenoptera venom immunotherapy (VIT) is the only therapy that protects patients with Hymenoptera venom allergy by preventing systemic reactions after a new sting. Various extracts for VIT are available and used. VIT administration consists of an induction phase and a maintenance phase. Depot preparations of Hymenoptera VIT extracts are typically used for cluster and conventional protocols, and the maintenance phase. Many patients with Hymenoptera allergy need to achieve tolerance quickly because of the high risk of re-sting and possible anaphylaxis. Objective: Our study aimed to show the safety and efficacy of an accelerated regimen with depot preparations on aluminum hydroxide by using relatively high starting doses in a heterogeneous group of patients. Methods: The research focused on a group of patients with a history of severe systemic reactions to Hymenoptera stings, with the necessity of swift immunization due to high occupational risks. Aluminum hydroxide depot extracts either of Vepula species or Apis mellifera extracts were used. Results: The induction protocol was started with the highest concentration of depot venom extract of 100,000 standard quality unit and was well tolerated by 19 of 20 patients. Onne patient presented with a mild systemic reaction during the accelerated induction schedule, which was promptly treated with intravenous steroids and intramuscular H1 antihistamine; when switched to a conventional induction protocol, he had a similar reaction but finally reached maintenance with an H1-antagonist premedication. Conclusion: If validated, the accelerated induction protocol by using depot aluminum adsorbed extracts with the highest concentration of venom from the beginning could offer a streamlined and accessible treatment modality for patients diagnosed with anaphylaxis from bee and wasp venoms in need of rapid desensitization. [ABSTRACT FROM AUTHOR]

Background: Eosinophils have a double-edged role in the human body, being essential in important physiologic functions but whose presence is conspicuous in a variety of diseases characterized by a T2 inflammation phenotype. Eosinophils are exquisitely sensitive to corticosteroids, and the latter have, until recently, represented the cornerstone of treatment of eosinophilic diseases. However, most patients remain dependent on oral corticosteroids, with a notable adverse effect burden and experience a chronic relapsing disease that leads to high morbidity and mortality. Treatment prospects have changed with the advent of biologic drugs that target the eosinotropic cytokine interleukin (IL) 5 or its receptor. The success of the latter drugs in severe eosinophilic asthma has paved the way for their use in other, rarer, eosinophilic lung diseases. Recently, mepolizumab, a humanized monoclonal anti-body that works against IL-5, was approved for the add-on treatment of relapsing-remitting or refractory eosinophilic granulomatosis with polyangiitis (EGPA) in patients ages ( 6 years. Benralizumab, a humanized antibody that binds to the a portion of the IL-5 receptor, is also being tested for its efficacy in EGPA in two clinical trials, after a growing number of case reports and case series supported its use as a steroid-sparing agent in the treatment of EGPA. Methods: In this review, we summarized the scientific literature evaluating the efficacy of benralizumab treatment in patients afflicted with rare primary eosinophilic lung diseases. Results: The literature we found, largely case reports, reported that the use of benralizumab in EGPA, chronic eosinophilic pneumonia (CEP) and allergic bronchopulmonary aspergillosis (ABPA) often led to a depletion of eosinophils, less exacerba)tions and a decreased systemic corticosteroid burden. No adverse effects were reported. Conclusion: Benralizumab has a prospective role in the treatment of rare eosinophilic lung diseases, which needs to be fur)ther elucidated in randomized controlled trials. [ABSTRACT FROM AUTHOR]

Background: Recent studies demonstrated that, in the past few years, the number of jellyfish species is increasing worldwide; this increase can be explained by environmental and climatic reasons. Contacts with jellyfish can cause acute and chronic effects, including allergic reactions. Although anaphylaxis caused by jellyfish is a rare event, repetitive stings during bathing as well as marine sports and job activities represent important risk factors that can increase the probability of sensitization. Recently, it was also pointed out the possibility of anaphylaxis caused by jellyfish ingestion. In these cases, the sensitization could also be related to previous stings. In cases in which there is no history of jellyfish contact or ingestion, it has been hypothesized that there is a sensitization to an unknown cross-reactive antigen. Objective: The purpose of this work was to collect and review published studies and cases of anaphylaxis associated with jellyfish. Methods: We performed a medical literature data base search, which included English language articles published until September 2019, by using the key words "jellyfish" associated with "anaphylaxis" or "anaphylactic shock.". Results: The results of our research showed that dangerous reactions can be caused both by contact and ingestion. Moreover, the latest changes in food habits, life style, and globalization could lead to a more frequent exposure to jellyfish both by contact and ingestion, and, consequently, to a higher probability of sensitization. Conclusion: Prospective studies and well-structured research are needed to better understand all the potential immunologic elements of jellyfish, to clarify its role in sensitization, and to avoid possible dangerous allergic reactions caused by crossreactivity. [ABSTRACT FROM AUTHOR]

Background: The association between parasites and urticaria was first suggested in the last century. A wide range, 0-75.4%, of the prevalence of parasitic infection has been reported with chronic urticaria (CU). Moreover, urticaria may be detected in patients with parasitosis. Nematodes are a type of helminth that infect hundreds of millions of people throughout the world. Objective: The aim of this work was to collect and review the published studies and cases of urticaria associated with nematode infections. Methods: A search of scientific literature data bases from January 1960 until May 2017 was carried out. Results: Numerous nematode infections have been associated with urticaria and/or angioedema: Anisakis simplex, Ascaris species (spp.), Dirofilaria spp., Enterobius vermicularis, Gnathostoma spp., Loa loa, Mansonella streptocerca; Necator americanus, Onchocerca volvulus, Strongyloides stercoralis, Toxocara spp., Trichinella spp., and Wuchereria bancrofti. The pathogenesis of urticaria in these infections generally remains unexplained. In some cases, skin manifestations were caused by the presence of the worm in the skin (Filaria, Gnathostoma); in other cases, such as A. simplex and S. stercoralis infections, there was a clear immunoglobulin E-mediated mechanism that led to allergic reactions, and infection and allergy coexisted; for other nematodes, the association was anecdotal and only a few cases were reported. Conclusion: It is difficult to detect a certain causal effect, except when urticaria improves or disappears after infection treatment. Cases of isolated urticaria not associated with other symptoms rarely may be caused by helminths. In the current guideline for urticaria, parasitosis is considered to be a rare possible cause of CU in developed industrial countries, Therefore, although a routine screening of parasitic infection in CU is not recommended, in our opinion, testing a patient with urticaria for parasites is a physician's choice based on the characteristics of the patient, such as associated symptoms, dietary habit, provenance country and previous travel. [ABSTRACT FROM AUTHOR]

Background: Although the pathophysiology of pruritus has been extensively studied in recent years, with many resultant advancements, management of pruritus is still enigmatic, particularly in chronic cutaneous diseases, such as atopic dermatitis, chronic urticaria, allergic contact dermatitis, cutaneous T-cell lymphoma, and uremic pruritus. The recent finding of the involvement of interleukin (IL) 31 in the pathogenesis of chronic pruritus has provided a novel approach to the management of chronic inflammatory skin disorders. The present report provided an in-depth overview of the role of IL-31 in chronic skin diseases and the possible diagnostic and therapeutic applications in the management of these diseases. Methods: A systematic review of IL-31 was conducted by using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: A review of a total of 45 published research articles revealed that the majority of these articles focused on the role of IL-31 in causation of pruritus and in the worsening of the disease in atopic dermatitis. Other publications examined interleukin in other pruritic diseases (cutaneous T-cell lymphoma, uremic pruritus, allergic contact dermatitis, chronic urticaria). In almost every disease, IL-31 levels were reported to be correlated with the pathology and often with pruritus. The cutaneous injection of IL-31 resulted in a long-lasting itching sensation, and the use of monoclonal antibodies that targeted IL-31 led to a reduction in pruritus. Conclusion: The use of monoclonal antibodies against mediators involved in the pathogenesis of chronic skin diseases has shown promising results. Antibodies that target IL-31, in particular, its receptor A, showed interesting results in atopic dermatitis and decreased pruritus. In subsequent years, the use of these new therapeutic strategies could change the scenario of pruritic skin diseases. However, further studies are needed to more rigorously examine the effects of IL-31 cascade blockage in different chronic skin diseases and to confirm efficacy and the safety of these new therapeutic approaches. [ABSTRACT FROM AUTHOR]

Background: miRNAs are a class of noncoding RNA molecules that modulate gene expression after transcription. It is known that miRNAs are involved in various cellular processes of both normal and diseased skin. Recently, differential expressions of miRNAs have been reported and associated with several immunologic and inflammatory disorders, which indicate a common role in fundamental biologic processes. Objective: To collect and review data from the literature on involvement o/miRNA in inflammatory skin disorders. Methods: A bibliographic search of scientific literature was carried out independently by two researchers in scientific data bases and search engines. The MeSH terms used were the following: "microRNAs" combined with "skin," "dermatitis," "urticaria," "eczema," "hypersensitivity." All research articles from inception until April 2016 were considered. Results: A total of 11 research articles on the study of miRNAs in inflammatory skin disorders (atopic dermatitis, delayed-type hypersensitivity, eczema, toxic epidermal necrolysis) were identified. All the studies confirmed the main role of endogenous noncoding RNAs in diseases such as atopic dermatitis, allergic contact dermatitis, eczema, and toxic epidermal necrolysis. Conclusion: The miRNAs seem to influence regulatory mechanisms of inflammation in both inducing and contrasting acute and chronic skin inflammation. They also seem to be useful instruments in identifying and staging diseases such as dermatitis and other inflammatory skin diseases. Also, the potential application of miRNAs in genetic therapies demonstrated its efficacy on animal models. [ABSTRACT FROM AUTHOR]

Background: The association between urticaria and virus infections has rarely been reported in the literature. The lack of reported cases is probably due to the difficulty in establishing a cause-and-effect relationship. It is not possible to challenge the patient with an etiologic agent. Objective: The purpose of this work was to perform a systematic review on the association between urticaria and virus infections. Methods: This systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched for articles from January 1, 2008, through May 2015, by using two key terms related to urticaria and virus diseases, 'urticaria' and one key term related to virus infections, 'virus disease,' then 'urticaria' and the name of each virus family, and of the most representative virus serotypes. Results: We reported cases of patients affected either by acute or chronic urticaria with a concurrent virus infection. Previous other causes of urticaria had to be excluded. Herpesviridae infections and urticaria were the most frequently reported associations in children. However, hepatitis virus infections would appear to be the most-frequent cause of urticaria in adults. Conclusions: Data obtained indicated viral infection as a potential trigger and sometimes as the main etiologic agent in causing acute or chronic urticaria. In every case, urticarial manifestation cleared up after either healing or controlling of the viral infection. However, prospective studies and well-structured research is needed to better clarify the role of viruses in the pathogenesis of urticaria and their relative prevalence. [ABSTRACT FROM AUTHOR]

Oxidative stress occurs in many allergic and immunologic disorders as a result of the imbalance between the endogenous production of free reactive oxygen species (ROS) and/or the reduction of antioxidant defense mechanisms. Advanced glycation end products (AGEs), advanced oxidation protein products (AOPPs), and nitrosylated proteins (NPs) can be used as markers of oxidative stress and inflammation. Our objective was to examine the serum levels of AGEs, AOPPs, and NPs in patients with allergic reactions to hymenoptera venom before and after ultrarush venom immunotherapy (VIT). The study included two groups of patients: 30 patients allergic to yellow jacket or honey bee venom and treated by aqueous preparation of Vespula spp (26 patients) or Apis mellifera (four patients) VIT, and 30 healthy donors as controls. Blood samples were collected to measure serum levels of AGEs, AOPPs, and NPs at baseline (T1), at the end of the incremental phase of the VIT protocol (T2), and after 15 days (T3). Serum AOPP levels at T1 were significantly higher in comparison with controls (p = 0.001), whereas serum levels of NPs at T1 were significantly lower than those in controls (p < 0.0001). No significant difference in circulating levels of AOPPs, AGEs, and NPs was found during immunotherapy. These findings suggest that, although hymenoptera venom allergy (HVA) is characterized by isolated episodes of reactions to stinging insect venom and is not included among chronic inflammatory diseases, an oxidative stress status occurs in patients suffering from this kind of allergy. Furthermore, VIT does not modify serum levels of these oxidative stress biomarkers. [ABSTRACT FROM AUTHOR]

The association between urticaria and infectious diseases has been discussed for >100 years. However, a causal relationship with underlying or precipitating infection is difficult to establish. The purpose of this work was to perform a systematic analysis of the published cases of urticaria associated with bacterial infections. We give an umbrella breakdown of up-to-date systematic reviews and other important publications on the complex association of urticaria and bacterial infections. We did a Medline search, for English language articles published until January 2014, using the key words 'urticaria' and 'bacteria/bacterial disease'; a second analysis was performed in groups of bacteria and using each germ name as a key word. Many bacterial infections have been associated with urticaria manifestation, such as Helicobacter pylori, Streptococcus, Staphylococcus, Mycoplasma pneumonia, Salmonella, Brucella, Mycobacterium leprae, Borrelia, Chlamydia pneumonia, and Yersinia enterocolitica. In some cases the skin manifestations, described as urticaria, could be caused by the presence of the microorganism in the skin, or for the action of their toxins, or to the complement activation mediated by circulating immune complexes. Although only a weak association with urticaria of unclear pathogenesis exists, clinicians should consider these bacterial agents in the workup of the patients with urticaria. The eradication of the infection could, in fact, lead to the resolution of urticaria. Prospective studies and well-structured research are obviously needed to better clarify the real role of bacteria in the pathogenesis of urticaria and their relative prevalence. [ABSTRACT FROM AUTHOR]

Polysensitization is quite frequent in allergic children and may cause difficulties for the allergist in prescribing allergen-specific immunotherapy. This study aimed at evaluating the clinical effectiveness of 1 year of sublingual immunotherapy (SLIT) in a cohort of Italian allergic children with polysensitization. This open study was performed on 51 polysensitized children (34 boys; mean age, 11.8 years; range, 5.2-17.7 years) with allergic rhinitis and/or mild to moderate asthma. All of them were treated with SLIT for 1 year. The kind and the number of prescribed allergen extracts, the type of diagnosis, the severity of symptoms, and the use of drugs were evaluated at baseline and after 1 year. The adverse events to SLIT were also evaluated. Forty-two children were treated with a single extract, four with two different extracts and three with a mix of allergens. SLIT treatment induced a significant reduction in the number of sensitizations (p = 0.018); significant improvement of allergic rhinitis classification and severity; significant reduction of ocular, nasal, and bronchial symptoms (p < 0.01 for all); and drugs use (p < 0.01 for all drugs). No systemic reactions to SLIT were observed. This open study provides evidence that polysensitization is not an obstacle for prescribing SLIT in polysensitized children. Indeed, SLIT efficacy on clinical parameters is significant after 1 year and the therapy is safe. [ABSTRACT FROM AUTHOR]

Nickel sensitization can not only induce allergic contact dermatitis (ACD), but also can induce an overlapping disease referred to as “systemic nickel allergy syndrome” (SNAS), characterized by urticaria/angioedema and gastrointestinal symptoms correlated to the ingestion of nickel-containing foods. This study was designed to determine if oxidative stress occurs in patients with nickel allergy. Thirty-one female patients (mean age 31.26 + 13.04 years, range 16-64 years) with confirmed nickel CD underwent oral nickel challenge because of clinically suspected SNAS; serum concentrations of protein carbonyl groups (PCGs) and nitrosylated proteins (NPs; biomarkers of oxidative stress) were measured before and after oral nickel challenge as well as in healthy female controls. Twenty-three of these 31 patients were diagnosed with SNAS because they had a positive reaction to the oral nickel challenge, and 8 patients had no reaction and therefore were classified as patients with contact nickel allergy only. Although both nickel-allergic patients and controls presented similar serum levels of PCGs, NP values in nickel-allergic patients appeared higher than in controls and tended to decrease after the challenge; furthermore, serum levels of NPs in patients affected by SNAS were higher (although not significantly) than in patients with nickel ACD only. The involvement of specific biomarkers of oxidative stress such as NPs and the lack of involvement of other biomarkers such as PCGs may help to better understand the alteration of the redox homeostasis occurring in nickel ACD and particularly in SNAS. [ABSTRACT FROM AUTHOR]

Since the first case reported in 1927, latex allergy has attracted the attention of allergists including its capacity to cross-react with fruits. To evaluate the frequency of sensitivity to some fruit allergens shown to cross-react with latex, we evaluated 82 patients (43 men and 39 women, aged between 18 and 45 years) with latex allergy. All patients underwent skin tests with various fruit extracts that potentially cross-react with latex. Only patients with negative prick tests successively underwent prick-by-prick tests with fresh fruits. Thirty-nine of 82 patients (47.5%) were found to have positive skin tests. Prick tests with fruit extracts were positive in 28 patients (kiwi, 21 patients; banana, 17 patients; avocado, 8 patients; and papaya, 3 patients), and the prick-by-prick test had positive results in 11 patients (kiwi, 7 patients; banana, 4 patients; and avocado, 3 patients). In our experience patients with latex allergy are at a high risk of sensitization to some fruits and they often develop allergic reactions, even severe ones, after eating them; for this reason fruit sensitization should be taken into consideration when investigating patients allergic to natural rubber latex. (Allergy and Asthma Proc 24:193--197, 2003). [ABSTRACT FROM AUTHOR]

To clarify the immunologic changes associated with specific immunotherapy (SIT), we analyzed interleukin (IL)-18 and CD30 serum levels in a group of patients with allergic rhinitis before and after SIT. IL-18 is a proinflammatory cytokine that plays an important role in the Th1 response. CD30 is a marker of Th2 lymphocytes. We selected 16 healthy donors (HDs) and 16 patients affected by allergic rhinitis, matched for sex and age. Serum IL-18 and CD30 levels were assayed by an immunoenzymatic method. IL-18 serum levels in the patients were lower than in the HDs before SIT (200.69 ± 93.48 pg/mL versus 296.50 ± 66.29 pg/mL; p < 0.05). After SIT, patients showed an increase of serum IL-18 levels (288.69 ± 146.69 pg/mL versus 200.69 93.48 pg/mL; p < 0.05). On the contrary, serum CD30 levels were higher in patients before SIT with respect to HDs (14.78 ± 8.30 IU/mL versus <1 IU/mL; p < 0.05). SIT caused a decrease of serum CD30 levels in patients who were allergic (5.95 ±5.70 IU/mL versus 14.78± 8.30 IU/mL; p < 0.05). In conclusion, in this study we showed for the first time the shift of IL-18 and CD30 production after SIT. (Allergy and Asthma Proc 24:179--183, 2003). [ABSTRACT FROM AUTHOR]