Skin reaction to COVID-19 vaccine: A report of 4 cases.

Since the beginning of the covid-vaccine campaign, a lot of local and systemic dermatologic reactions happening after the administration of Coronavirus disease 2019 (COVID-19) vaccines have been described, even if their exact biological mechanism is still debated. In this paper we report 4 cases of cutaneous manifestations arose within ten days after the first dose of messenger RNA (mRNA)-based COVID-19 vaccination: one case of giant urticaria, one case of head and neck redness and two cases of Erythema Multiforme (EM). In our experience these reactions were mild, transient and all of them resolved, not recurring after the second dose, so these manifestations shouldn't be considered as an absolute contraindication to the second dose of vaccine, that to date is fundamental.

Lipid transfer protein syndrome: How to save a life through careful education.

Introduction: Lipid transfer proteins (nsLTPs) are ubiquitous allergens. Patients affected by nsLTP syndrome experience symptoms to various plant-derived foods, ranging from local manifestations to anaphylaxis, the critical treatment of which is represented by self-administration of adrenaline. The principle aim of this study is to assess how dietary recommendations influence the occurrence of new and severe cases and if poly-sensitization to different nsLTPs may play a role. We also investigated about the appropriate use of adrenaline auto-injector during the episodes of anaphylaxis. Moreover, we examinated how other features (ie, co-sensitization to profilin and PR-10 and the presence of risk co-factors) affect these events. Materials and methods: We evaluated 78 patients allergic to nsLTPs, investigating adherence to diet and ability to use the adrenaline auto-injector. Number of sensitization to nsLTPs, co-sensitization to other panallergens, and presence of risk factors for new reactions were also assessed. Diagnosis was based on clinical history and positivity to in vivo and in vitro tests. During the follow-up, compliance, diet modifications, and new reactions were noted, and re-training for the use of epinephrine auto-injector was performed. At the last visit we evaluated the patients' ability to use the self-injector. Results: The whole of fruits belonging to the Rosaceae family emerged as the most frequent culprit foods (28%), followed by walnut (17%), peanut (17%), and hazelnut (10%). At the baseline visit 23% of the patients described the presence of a risk factor during the allergic reaction (mainly nonsteroidal anti-inflammatory drugs [NSAIDs] and exercise). Forty-five percent of the patients reported anaphylactic reactions; no association between the type of food and the severity of the reactions was found. The presence of sensitization to 4 or more nsLTPs was associated to more severe reactions (p < .05; OR 1.67). During the follow-up 38% of the patients experienced at least 1 new allergic reaction: in 79% of them the culprit food was previously tolerated, and in 69% the reaction was an anaphylaxis. Only 47% of the patients showed a proper use of adrenaline auto-injector during the final evaluation, but a significant correlation between periodic education and reduction of the probability of mistakes in the use was reported (p < .05; OR 0.34). Furthermore, an association between co-sensitization to PR-10 (in particular Bet v1) and profilin and less severe symptoms was found, but without a significant odds ratio. Conclusion: A careful education aimed to the prevention of new reactions, through dietary restrictions and avoidance of risk co-factors, and to the management of anaphylaxis, through the training for the correct use of adrenaline auto-injector, should be a routine practice in nsLTP syndrome.

Current treatment strategies for seasonal allergic rhinitis: where are we heading?

INTRODUCTION: Allergic rhinitis (AR) is very commonly caused by pollens. The symptoms of AR consist of sneezing, nasal congestion, rhinorrhea, nasal itching and airflow obstruction. The diagnosis has long been based on clinical history, skin prick tests and in vitro measurement of specific IgE, but the innovative approach of precision medicine has made diagnostic tools of much greater accuracy available. AREAS COVERED: This review covers the advances in the treatment of seasonal AR concerning the drugs to be used according to the grade of disease and the characteristics of the patients, and the role of allergen immunotherapy (AIT), which is the only treatment capable of acting, in addition to the symptoms, on the cause of AR and therefore to modify its natural history. EXPERT OPINION: Drug treatment of AR include a large number of agents, the choice of which depends on the severity of the disease. AIT has high evidence of efficacy demonstrated by meta-analyses, and further improvement is currently apparent, as for diagnosis, applying the means of precision medicine. However, when AIT is performed in current practice, without the strict rules of controlled trials, long-term low adherence is a major problem to be solved.

Patient's Adherence and Compliance and Quality of Life During/After VIT.

Adherence and compliance, respectively considered as a more positive, proactive behavior, resulting in a patient's lifestyle change to follow a daily regimen, and, as a more enforced response to an external command, are a critical aspect of any medical therapy, since it is estimated that less than half of the patients who are prescribed a therapy perform it, respecting the doses and duration. As far as aeroallergen immunotherapy is concerned, current data show that adherence is respected in about 50% of subcutaneous immunotherapy and in percentages even lower than 20% in sublingual immunotherapy treatments. This review analyzes the adherence to venom immunotherapy (VIT), in which, given its purpose of preventing potentially fatal anaphylactic reactions to insect stings, this aspect plays a critical role. In fact, protection from stings already takes place when the maintenance dose is reached, but VIT interruption before the recommended duration of 5 years exposes patients to new sting reactions. The data on adherence to VIT are far less abundant than that for aeroallergen immunotherapy. One of the first studies reported poor adherence in Austria, but the model used, consisting in the estimate of the percentage of patients with systemic reactions who accepted or rejected VIT, does not meet the criteria that define adherence to treatment. As for appropriate adherence studies, rates higher than 70% were reported in the United States and European countries. Studies from Italy found that good adherence were observed also in patients receiving, after 4 years of VIT, 3 months extended maintenance dose, as well as in patients treated during the COVID-19 pandemic, <10% of whom stopped VIT. Instead, only 35% of the patients treated for allergy to imported fire ant remained adherent after 1 year of treatment. However, also concerning honeybees and vespids, although adherence is satisfactory, it is possible to further improve it by increasing information and support for patients. Health-related quality of life (HRQL) is an efficient measure to estimate the effectiveness and safety of medical treatment. Tools designed to make patients aware of its improvement through VIT and, in particular, of the complete prevention of the risk of fatal reactions have an important role in reinforcing adherence. However, aspects not yet evaluated, such as the possible relationship between the efficacy of VIT and HRQL or its particular features in patients with mastocytosis, deserve specific studies.

Effectiveness and safety of dupilumab in patients with chronic rhinosinusitis with nasal polyps and associated comorbidities: a multicentric prospective study in real life.

BACKGROUND: Biologics are currently one of the main treatment options for a number of diseases. The IgG4 monoclonal antibody dupilumab targets the Interleukin-4 receptor alpha chain, thus preventing the biological effects of the cytokines IL-4 and IL-13, that are essential for the Th2 response. Several controlled trials showed that dupilumab is effective and safe in patients with atopic dermatitis (AD), severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP), thus resulting in approval by regulatory agencies. Aim of the study was to evaluate the efficacy and safety of dupilumab in adult patients with CRSwNP stratified by common overlapping comorbid conditions. METHODS: We performed a multicenter, observational, prospective study enrolling adult patients with severe CRSwNP who had started dupilumab treatment in the context of standard care from January 2021 to October 2021. Data were collected from twentynine Italian secondary care centers for allergy and clinical immunology, all of which were part of the Italian Society of Allergy, Asthma and Clinical Immunology (SIAAIC). A number of efficacy parameters were used. Patient data were compared using the Wilcoxon test for paired data. All statistical analyses were performed with SPSS version 20 (IBM, Armonk, NY, USA). RESULTS: In total, 82 patients with nasal polyposis were identified. A significant improvement was detected for all the applied efficacy parameters, i.e. 22-item Sino-Nasal Outcome Test (SNOT-22) and bilateral endoscopic nasal polyp score (NPS) scores for CRSwNP, Rhinitis Control Scoring System (RCSS) and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores for allergic perennial rhinitis, Forced Expiratory Volume in the 1st second (FEV1) and Asthma Quality of Life Questionnaire (AQLQ) scores for asthma, Eczema Area and Severity Index (EASI) and Dermatology Life Quality Index (DLQI) scores for AD. A non-significant improvement was also obtained in the Urticaria Activity Score over 7 days (UAS7) for chronic spontaneous urticaria. Treatment with dupilumab was well tolerated. CONCLUSIONS: These data suggest that dupilumab treatment in patients suffering from CRSwNP and associated comorbidities may be suitable. Such outcome, although confirmation by trials is warranted, suggests the possibility to treat different disorders with a single therapy, with favorable effects especially under the cost-effectiveness aspect.

Venom Immunotherapy and Aeroallergen Immunotherapy: How Do Their Outcomes Differ?

Allergen immunotherapy (AIT) and venom immunotherapy (VIT) are meant to work on the causes of allergies, respectively, to respiratory allergens and Hymenoptera venom, inducing tolerance to the allergens and modifying the natural history of allergy. Both types of immunotherapies have evidence of efficacy, but actually they present wide differences in both effectiveness and safety. Indeed, as far as the effectiveness of VIT is concerned, if the protection against fatal reactions to stings is considered as the primary objective, more than 40 years of clinical practice demonstrate complete success. The clinical success of AIT is measurable on the basis of reduction or disappearance of allergic symptoms. The difference between the two treatments is even higher as regards safety: AIT has been concerned in the past by a series of fatal reactions caused, which underwent a progressive decrease when it was understood that they were related to the presence of uncontrolled asthma. However, fatal reactions related to failure to recognize the presence of risk factors or administration errors are still reported. Similarly to what has been observed for efficacy, VIT has never been affected by fatal reactions to the administration of venom, and the most important risk of anaphylaxis, which is the concomitance of mastocytosis, is now identified by measuring its marker serum tryptase. To date, mechanisms of hypersensitivity reactions that differentiate respiratory allergy from Hymenoptera venom allergy have not been successfully demonstrated. We have examined the past and present literature in order to propose reasonable hypotheses about the mechanisms actually involved.

Diagnostic performance of nasal cytology.

PURPOSE: Nasal pathologies are characterized by a symptomatology that hardly allows to distinguish allergic rhinitis (AR), non-allergic rhinitis (NAR), and chronic rhinosinusitis (CRS). Nasal cytology (NC) has shown increasing importance in helping the clinician to differentiate the various phenotypes of rhinitis. NC allows us to evaluate nasal cellularity by distinguishing AR and various types of NAR. The objective of the study is to assess the diagnostic performance of the NC by evaluating its sensitivity, specificity, and predictive value. METHODS: We recruited 387 patients with persistent rhinitis symptoms, and nasal cytology was performed. The rhinocytogram was obtained by reading for fields and the cellular count was made using quantitative and semi-quantitative grading together. RESULTS: Two hundred and fifteen patients (55.5%; 38 had acute rhinitis, 24 acute sinusitis, 153 chronic rhinosinusitis) out of 387 referred nasal symptoms. Cytological specimen showed a mean of 94 ± 4% ciliated cells, 29 ± 0.2% mucinous cells, 16 ± 0.1% neutrophils, 11 ± 0.08% eosinophils, 4 ± 0.03 lymphocytes, 4 ± 0.03% mast cells, and 4 ± 0.01% other cells. NC was positive in 271 cases (70%). After revision of medical history, 153 patients (39%) were considered positive for NAR. Test sensibility was 100% (95% CI 97-100), specificity was 49.6% (95% CI 43-56%). Positive predictive value (PPV) was 56% (95% CI 50-62%), and negative predictive value (NPV) was 100% (95% CI 96-100%). The positive likelihood ratio was 1.98 (95% CI 1.75-2.25). Accuracy of the test was 69.5% (95% CI 64.6-74.0%). CONCLUSION: Our data showed ability to identify the true-positive patients with NAR but a low ability to identify the true-negative patients, with a global accuracy of 69.5%.

The quest for improving general and in hospital health care during COVID-19 pandemic.

Since January 2020 the COVID-19 pandemic has emerged as a serious public health problem (1), which -according to the 13 August 2021 WHO update- is burdened by 205.338.151 cases and 4.333.094 deaths (2). [...].

Dermatological manifestations during COVID-19 infection: a case series and discussion on the problem of differential diagnosis.

On March 11, 2019 the World Health Organization (WHO) declared Coronavirus disease-2019 (COVID-19), caused by SARS-CoV-2, as a pandemic. As of 15/01/2021, more than ninety million cases of infections have been confirmed, with almost two million related deaths. SARS-CoV-2 causes bilateral interstitial pneumonia, which can responsible of respiratory failure in the most severe cases, but the virus has also a wide range of other manifestations, including gastrointestinal, cardiovascular, neurological, and cutaneous signs and symptoms. Cutaneous manifestations are an important matter of study for allergy specialists, as they can be specific signs of the infection, but also manifestations of adverse reactions to the medical therapy in use. In this case series, we report four different cases of dermatological manifestations in COVID patients, two in hospitalised patients and two in patients with mild disease, treated at home. The first case reported is a woman, who develops urticaria while being treated at home with mild COVID-infection; the second and the third one case reported are drug- hypersensivity reaction to remdesevir and low molecular weight heparin. The last case reported is a man with mild covid with vasculitic sacral lesions. Key words: COVID pandemic, SARS-CoV-2, dermatological manifestation in covid infections, remdesevir hypersensitivity, covid and urticaria, covid and vasculitic lesions.

Allergen immunotherapy for respiratory allergy: to what extent can the risk of systemic reactions be reduced?

INTRODUCTION: Allergen immunotherapy is an effective treatment for respiratory allergy, but the administration to patients of extracts of the causative allergen may elicit systemic reactions, which include, particularly with subcutaneous immunotherapy (SCIT), anaphylaxis. In the past, the occurrence (tough rare) of fatal reactions has represented a serious problem that has limited the prescription of SCIT. AREAS COVERED: The authors analyzed in this review the safety data of SCIT, especially concerning the years following the identification of uncontrolled asthma at the moment of allergen injection as the major risk of life-threatening reactions and fatalities. The safety of SLIT, which is far better than SCIT, was analyzed and its specific risk factors for systemic reactions were highlighted. EXPERT OPINION: Presently, the safety profile of SCIT and SLIT is satisfactory, provided the treatment is administered by physicians experienced in this treatment, who are aware of the known risk factors for severe reactions and who implement all measures to avoid them. For SLIT, which is self-administered by the patient, receiving the first dose under medical control is recommended.

Mabs for treating asthma: omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab.

The introduction of biologics for the treatment of patients with refractory asthma represented a marked therapeutic advance. For more than 10 y, the only biologic available has been the monoclonal anti-IgE antibody omalizumab, reserved for patients with asthma caused by perennial allergen. In recent years, other biologics have been licensed for the treatment of severe eosinophilic asthma. They include monoclonal antibodies that target the Th2-pathway cytokines, such as IL-5 (mepolizumab and reslizumab) or its receptor (benralizumab) and the IL-4 and IL-13 receptor (dupilumab). The effectiveness of these biologics was demonstrated in several placebo controlled trials, the main outcomes being the significant reduction of the rate of asthma exacerbation and the improvement of respiratory function in actively treated patients. Based on the further understanding of the pathogenesis of asthma, new cytokines network and new targets are emerging, such as thymic stromal lymphopoietin, which can activate Th2 cells, innate lymphoid cells, or both, or prostaglandin D2 (PGD2), to develop additional biologics.

Immunotherapy and biologicals for the treatment of allergy to Hymenoptera stings.

Introduction: Venom immunotherapy (VIT) is an effective treatment for Hymenoptera venom allergy. The occurrence of severe reactions (SRs) to VIT, although infrequent, hampers the achievement of tolerance to insect stings. Risk factors for such reactions include allergy to honeybee venom, concomitant mast cell disorders, and the build-up phase of VIT. A role for omalizumab has come forward in recent years. Areas covered: This article reviews the available literature on the efficacy of omalizumab in preventing SRs and allowing the attainment of VIT maintenance doses. Pre- and co-treatments with omalizumab were evaluated, with positive overall results. Adding omalizumab to VIT in patients with SRs generally results in tolerance to VIT, thus restoring its precious preventive value. Expert opinion: VIT is effective for patients with Hymenoptera venom allergy and is recommended to prevent further (possibly fatal) reactions to stings. Omalizumab has shown efficacy in protecting patients from VIT-related SRs, particularly in those at high risk of SRs because of mast cell disorders and/or honeybee venom allergy. Notwithstanding, the accepted dose and time course of omalizumab for achieving tolerability and ensuring safety during VIT are not yet defined. In the future, other biologicals may play a role in preventing SRs during VIT.