The role of skin tests with polyethylene glycol and polysorbate 80 in the vaccination campaign for COVID-19: results from an Italian multicenter survey.

Summary: Background. International guidelines suggested skin tests with Polyethylene-glycol (PEG) and polysorbate 80 (PS-80), to investigate a possible hypersensitivity to these excipients either to identify subjects at risk of developing allergic reactions to Covid-19 vaccines, or in patients with suspected IgE mediated hypersensitivity reactions (HR) to the Covid-19 vaccine. The main purpose of this study was to investigate the prevalence of PEG and PS sensitization in patients with a clinical history of HR to drugs containing PEG/PS and in patients with a suspected Covid-19 vaccine immediate HR. Methods. This was a multicenter retrospective study conducted by allergists belonging to 20 Italian medical centers. Skin testing was performed in 531 patients with either a clinical history of suspected hypersensitivity reaction (HR) to drugs containing PEG and/or PS-80 (group 1:362 patient) or a suspected HR to Covid-19 vaccines (group 2: 169 patient), as suggested by the AAIITO/SIAAIC guidelines for the "management of patients at risk of allergic reactions to Covid-19 vaccines" [1]. Results. 10/362 (0.02%) had positive skin test to one or both excipients in group 1, 12/169 (7.1%) in group 2 (p less than 0.01). In group 2 HRs to Covid-19 vaccines were immediate in 10/12 of cases and anaphylaxis occurred in 4/12 of patients. Conclusions. The positivity of skin test with PEG and or PS before vaccination is extremely rare and mostly replaceable by an accurate clinical history. Sensitization to PEG and PS has to be investigated in patients with a previous immediate HR to a Covid-19 vaccine, in particular in patients with anaphylaxis.

Use of Dupilumab in 543 Adult Patients With Moderate-to-Severe Atopic Dermatitis: A Multicenter, Retrospective Study.

BACKGROUND: Dupilumab has proven to be an effective treatment for patients with moderate-to-severe atopic dermatitis (AD) in clinical trials. However, real-world experience with dupilumab in a broader population is limited. METHODS: The study population comprised adult patients with moderate-to-severe AD, defined as an Eczema Area Severity Index (EASI) score of 24 or higher, treated with dupilumab at 10 Italian teaching hospitals. We analyzed physician-reported outcome measures (EASI), patient-reported outcome measures (pruritus and sleep score, Dermatology Life Quality Index [DLQI]), and serological markers (IgE and eosinophil count) after 16 weeks. RESULTS: We enrolled 543 patients with moderate-to-severe AD. Two patients (0.4%) discontinued treatment. The median (IQR) change from baseline to 16 weeks of treatment in the EASI score was -87.5 (22.0) (P<.001). The EASI-50, EASI-75, and EASI-90 response rates were 98.1%, 81.5%, and 50.8% after 16 weeks. At 16 weeks, 93.0% of the patients had achieved a 4-point or higher improvement in DLQI from baseline. During treatment with dupilumab, 12.2% of the patients developed conjunctivitis, and total IgE decreased significantly (P<.001). Interestingly, in the multivariate logistic regression model, the risk of developing dupilumab-related conjunctivitis was associated with early onset of AD (OR, 2.25; 95%CI, 1.07-4.70; P=.03) and presence of eosinophilia (OR, 1.91; 95%CI, 1.05-3.39; P=.03). CONCLUSION: This is the broadest real-life study in AD patients treated with dupilumab to date. We observed more significant improvements induced by dupilumab in adult patients with moderate-to-severe AD than those reported in clinical trials.

Focus on the role of substance P in chronic urticaria.

BACKGROUND: Emerging data have strengthened the importance of substance P (SP) as a proinflammatory mediator in human pathology. A role for SP in the pathogenesis of urticaria has long been hypothesized. METHODS: Literature data regarding the possible role of SP in chronic urticaria/chronic spontaneous urticaria (CSU) have been reviewed and summarized in this manuscript. This review is based on pertinent articles that were retrieved by a selective literature search in the PubMed database. Articles in English published up to July 2018 were taken into consideration. RESULTS: Recent studies in patients with CSU have demonstrated that circulating levels of SP are significantly elevated, in correlation with disease severity, and that SP-positive basophils are upregulated. SP has been shown to trigger degranulation in basophils derived from CSU patients. Moreover, SP can be involved in pseudoallergic reactions and may act as a histamine-releasing factor in a subset of patients with CSU. Current evidence suggests that the biological activity of SP can be exerted not only through the conventional NK-1 receptor but also through the recently identified Mas-related G protein-coupled receptors. MRGPRX2 can cause mast cell activation and has been found to be upregulated in the skin of patients with severe chronic urticaria. CONCLUSIONS: Many findings seem to support the pathogenic involvement of SP in chronic urticaria/CSU. However, further studies are necessary to elucidate the role of SP as a mediator in CSU pathogenesis and a potential new therapeutic target.

Focus on the agents most frequently responsible for perioperative anaphylaxis.

Adverse reactions (ARs) to drugs administered during general anesthesia may be very severe and life-threatening, with a mortality rate ranging from 3 to 9%. The adverse reactions to drugs may be IgE and non-IgE-mediated. Neuromuscular blocking agents (NMBA) represent the first cause of perioperative reactions during general anesthesia followed by latex, antibiotics, hypnotic agents, opioids, colloids, dyes and antiseptics (chlorhexidine). All these substances (i.e. NMBA, anesthetics, antibiotics, latex devices) may cause severe systemic non-IgE-mediated reactions or fatal anaphylactic events even in the absence of any evident risk factor in the patient's anamnesis. For this reason, in order to minimize perioperative anaphylactic reactions, it is important to have rapid, specific, sensitive in vitro diagnostic tests able to confirm the clinical diagnosis of acute anaphylaxis.

Allergic contact dermatitis to acrylates.

Acrylates and methacrylates are a large group of chemically reactive monomers that are polymerized into acrylic plastics. These have very broad applications in glues, coatings and various plastic materials. Allergic contact dermatitis (ACD) caused by acrylates can be occupational, mainly in dentistry workers during the manufacturing and implantation of dental prosthesis, and in nail technicians during the sculpturing and application of artificial nails. The clinical manifestations vary according to the location of the contact. In non-occupational ACD, hand eczema, pulpitis and stomatitis are more frequent. We conducted a study to investigate the frequency of sensitization to acrylates, determining the most frequently sensitizing acrylates and assessing the possible role of 2-hydroxyethyl methacrylate (2-HEMA) as a screening allergen. From January 2013 to December 2014, 217 patients with a personal history and symptoms suggestive of contact dermatitis were patch tested with an extended series of acrylates at the Dermatology and Allergology Units of the University Hospital of Bari. Seven patients (3.2%) had positive reactions. The reactions were related to artificial nails in 2 patients (28.6%), both beauticians, and dental material in 5 patients (71.4%) with dental prosthesis. 2-HEMA detected 100%of sensitized patients to acrylates.

Probiotics and refractory chronic spontaneous urticaria.

Background. In chronic spontaneous urticaria (CSU) first-line therapy with an antihistamine-based regimen may not achieve satisfactory control in patients. Thus, a continuing need exists for effective and safe treatments for refractory CSU. Aim. To evaluate the clinical efficacy and safety of an intake of a combination of 2 probiotics (Lactobacillus salivarius LS01 and Bifidobacterium breve BR03) in patients with CSU who remain symptomatic despite concomitant H1-antihistamine therapy. Methods. This report analyzes the effects of therapy with two probiotic strains on the clinical progress of 52 unselected patients with difficulty to treat CSU underwent to medical examination in two Italian specialist urticaria Clinics between September 2013 and September 2014. A mixture of Lactobacillus LS01 and Bifidobacterium BR03 were administered in each patient twice daily for 8 weeks. To evaluate patients' improvement with probiotics, urticaria activity score over 7 days (UAS7) was used at baseline and at week 8 in addition to a 5-question urticaria quality of life questionnaire. Results. Fifty-two patients with CSU were included in this study (10 male and 42 female, age range 19-72 years). Mean disease duration was 1.5 years. Fourteen patients discontinued treatment, so evaluable population consisted of 38 patients. Nine of the 38 patients experienced mild clinical improvement during probiotic treatment (23.7%); one patient reported significant clinical improvement (2.6%) and one patient had complete remission of urticaria (2.6%). Twenty-seven patients did not have improvement in symptoms (71.1%). No side effects during the course of therapy were reported. Conclusions. A combination of Lactobacillus salivarius LS01 and Bifidobacterium breve BR03 administered twice daily for 8 weeks might reduce the symptoms scores and improve quality of life scores in a part of patients with CSU who remained symptomatic despite treatment with H1 antihistamine mostly in subjects with allergic rhinitis.

Immediate-type hypersensitivity reaction to Mannitol as drug excipient (E421): a case report.

Allergic reactions to mannitol have been reported rarely, despite its widespread use as a drug and as a food excipient. This is the first case report in which oral mannitol induces an immediate type hypersensitivity as a drug excipient, in a 42 year old man affected by rhinitis to olive tree pollen. Unusual and undervalued risk factors for mannitol hypersensitivity are examined.

Molecular diagnosis and the Italian Board for ISAC.

The Component Resolved Diagnostic (CRD) approach has been developed when highly purified or recombinant allergen molecules have become available. These molecules are the allergenic proteins toward which the specific and clinically relevant IgE immune response is directed. So, the identification of protein families and cross-reactivity patterns of importance in allergy have been possible. The Italian advisory BOARD for ISAC was born: to evaluate the advantages, disadvantages and placement in diagnosis of CRD studying its application in allergic patients; to facilitate the interpretation of molecular diagnostics for clinical allergists; to evaluate the effectiveness of CRD in improving diagnostic risk assessment and early preventive treatment of allergic diseases. In the last years, its fields of interest have been: the evaluation of the performance of CRD on multi-sensitized allergic patients with respiratory symptoms and on poly-sensitized athletes; the evolution of IgE repertoire directed to single allergenic components by evaluating allergic patients with different age at a molecular level; the relevance of results obtained using allergen microarray technique for describing the IgE repertoire in allergic patients by reviewing the main articles focused on CRD published in the last 2 years; the need for an educational program focused on this new diagnostic tool also through the creation of an exhaustive and interactive explanation of the laboratory report molecular allergy; the investigation of the performance and potential additional diagnostic values of the ISAC microarray in a real-life clinical setting, taking into account also the economic values.

Short-term tolerability of morniflumate in patients with cutaneous hypersensitivity reactions to non-steroidal anti-inflammatory drugs.

Morniflumate is the morpholinoethyl ester of niflumic acid, a non-steroidal anti-inflammatory drug, derived from nicotinic acid. We studied 112 patients who had experienced cutaneous reactions after using non-steroidal anti-inflammatory drugs. Only two of all the patients who underwent an oral challenge with morniflumate had a positive result to the test. By demonstrating the low incidence of reactions to morniflumate through oral challenges, we suggest that patients with non-steroidal anti-inflammatory drug hypersensitivity may tolerate this drug which would therefore be a useful alternative.

Diagnosis of latex allergy: the importance of hev B 11.

We present the cases of 5 patients with a positive clinical history of cutaneous symptoms due to contact with latex products. A latex allergological assessment was made through skin prick tests (SPTs) both with commercial latex extracts and extemporaneous glove extracts, and serum-specific IgE to latex and glove-use tests. In addition, serum-specific IgE to recombinant allergens for Hevea brasiliensis was dosed. Molecular diagnostics in association with the glove-use test and, to a lesser extent, the SPTs with glove eluate are useful diagnostic tests to confirm the diagnosis of latex allergy in patients with mucocutaneous symptoms.

Cyclosporin-A efficacy in chronic idiopathic urticaria.

Common drugs in the therapy of chronic idiopathic urticaria (CIU) include antihistamines alone or combined with corticosteroids, but severe unresponsive patients require alternative treatments. This retrospective study aims to evaluate clinical response and safety of low-dose and long-term oral Cyclosporin-A (CyA) in unresponsive patients. One hundred and ten CIU patients, unresponsive to a previous treatment (antihistamines plus prednisone 0.2 mg/kg/day), received additional oral CyA 1–3 mg/kg/day for 6 months. The patients were subdivided into three groups (A, B, C) according to the different CyA doses. Parameters of clinical efficacy including pruritus, and size and number of wheals were evaluated at baseline, after three and six months. All adverse events were recorded. The mean total symptom severity score decreased by 63% in Group A, 76% in Group B, and 85% in Group C after 6 months. Total disappearance of the symptoms was recorded in 43 patients (39.1%): 7 (28%) of Group A; 12 (37.5%) of Group B and 24 (45%) of Group C. After a mean of 2 months from CyA suspension, 14 patients (11%) had recurrence of symptoms. Minor side effects were noted in 8 patients (7%). Our study indicates that low-dose, long-term CyA therapy is efficacious and safe in severe unresponsive CIU.

Acquired angioedema with C1 inhibitor deficiency associated with anticardiolipin antibodies.

Acquired angioedema (AAE) with C1 inhibitor deficiency is often associated to B cell lymphoproliferative disorders or autoimmune diseases. We report a case of AAE associated with IgM anti-cardiolipin antibodies, with frequent edematous attacks, that disappeared completely after a slight immunosuppression and danazol therapy.

[The occupational physician and communication to workers]. / Il medico del lavoro e la comunicazione con i lavoratori.

Communication ability is essential for the Physician to the proper management of ambulatory activity and corporate training. The aim of this work is describe the communication strategies to be adopted in everyday healthcare practice. When the occupational physician relates with an employee his message must act both verbal both non-verbal. The medical history should be collected carefully and during the physical examination is important to put the employee at ease by adopting a discreet and attentive attitude. The clinical findings and the capacity to work with any limitations will be discussed at the end of health surveillance using understandable terminology to the worker. During the training-information process is important to define the primary objectives, organize the program and bring the display materials. The worker should be actively involved and encouraged to learn throughout the course information. In the text will also be shown the main aspects of information on line.

Tomato atopy patch test in adult atopic dermatitis: diagnostic value and comparison among different methods.

Tomato atopy patch test in adult atopic dermatitis.

Sensitization, asthma and allergic disease in young soccer players.

BACKGROUND: The aim of this study was to identify the prevalence of allergic disease in young soccer players compared to age-matched students and to evaluate if this prevalence changes as the intensity of training increases. METHODS: A modified ECRHS questionnaire was administered to 194 soccer players divided by age as Beginners (8-11 years), Juniors (12-16 years) and Under 21 (17-20 years) to evaluate the prevalence of allergic diseases and symptoms as well as drug consumption. Subjects with a positive personal history of allergic diseases underwent skin prick and/or patch tests. Age-matched students (n = 136) were used as a control group. RESULTS: The prevalence of allergic diseases was 34.5% in soccer players and 31.6% in control subjects (n.s.). Skin sensitization to inhalant allergens was detected in 14.4% of symptomatic soccer players and in 19.2% of control students (n.s.). Patch tests were positive in 35.7% of soccer players and 23.0% of controls with allergic dermatitis (n.s.). The prevalence of allergic diseases did not significantly change in relation to the intensity of training. Although the relative prevalence of sensitization to perennial allergens and asthma was less frequent in soccer players than in controls, and the occurrence of exercise-induced bronchoconstriction was similar in the two groups, soccer players used twice as many anti-allergic and anti-asthmatic drugs as control students. CONCLUSIONS: An increasingly intensive training programme is not associated with greater risk of allergic disease in soccer players. Therapy regimens of allergic athletes and exercisers should be monitored more closely to guarantee adequate treatment yet avoid inappropriate drug use and doping practices.

Long-term tolerability of etoricoxib in patients with previous reactions to non-steroidal anti-inflammatory drugs.

Non-steroidal anti-inflammatory drugs frequently cause adverse reactions. This retrospective study was based on analysis of the data obtained from interviews conducted with 173 patients, who underwent and tolerated a challenge test with etoricoxib (a selective cyclooxigenase 2 enzyme inhibitor). Only one of 82 patients who were treated with etoricoxib reported reactions. We can conclude that etoricoxib shows a high long-term tolerability in patients with non-steroidal anti-inflammatory drug hypersensitivity.