Real-life experience on effectiveness and safety of dupilumab in adult patients with moderate-to-severe atopic dermatitis.

BACKGROUND: Dupilumab, a fully human monoclonal antibody targeting the alpha subunit of IL-4 was recently approved for the treatment of moderate-to-severe atopic dermatitis (AD) in adult patients. OBJECTIVE: To assess dupilumab effectiveness and safety in adults with moderate-to-severe AD in a real-life Italian multicentre retrospective cohort. METHODS: Adult moderate-to-severe AD patients, referring to 39 Italian centers, received dupilumab in the context of a national patient access program. Disease assessment was performed at baseline, after 4 and 16 weeks of treatment using Eczema-Area-and-Severity-Index (EASI) score, itch and sleep numerical-rating-score (itch-NRS, sleep-NRS) and Dermatology-Life-Quality-Index (DLQI). RESULTS: A total of 109 (71 M/38F) patients was studied. There was a significant reduction in EASI score, itch-NRS, sleep-NRS and DLQI from baseline to week 4 and a further significant decline to week 16. EASI 50, EASI75 and EASI90 were achieved by 59.6%, 28.4% and 9.3% of patients at 4 weeks and by 87.2%, 60.6% and 32.4% of them at 16 weeks, respectively. Adverse events were experienced by 19.2% (21/109) of the patients and they were all mild in intensity, being conjunctivitis the most common side effect. CONCLUSIONS: Dupilumab significantly improved disease severity, pruritus, sleep loss and quality of life with an acceptable safety profile.

Molecular diagnostics improves diagnosis and treatment of respiratory allergy and food allergy with economic optimization and cost saving

Background: Component resolved diagnosis (CRD) allows to precisely identify the sensitization to specific molecules of a given allergenic source, resulting in an important improvement in clinical management, particularly of polysensitized subjects. This will end in the correct prescription of allergen immunotherapy (AIT) for respiratory allergy and in adequate avoidance diets or prescription of self-injectable adrenaline in food allergy. Objective: The aim of this multicenter, real life study is to evaluate the percentage change of the diagnostic-therapeutic choice in polysensitized patients with respiratory allergy and in patients with food allergy, after using CRD compared to a first level diagnosis, along with an economic analysis of the patient's overall management according to the two different approaches. Methods: An overall number of 462 polysensitized patients, as suggested by skin prick tests (SPT), and with clinical symptoms related to a respiratory (275 pts) or food (187 pts) allergy, were recruited. All patients underwent CRD for specific IgE against food or inhalant recombinant molecules, which were chosen according to medical history and positivity to SPT. The first diagnostic-therapeutic hypothesis, based only on medical history and SPT, was recorded for each patient while the final diagnostic-therapeutic choice was based on the results from CRD. The rate of change of the diagnostic-therapeutic choice from the first hypothesis to the final choice was statistically evaluated. The economic impact of CRD on the overall management of the allergic patients was analyzed to evaluate whether the increase in the diagnostic costs would be compensated and eventually exceeded by savings coming from the improved diagnostic-therapeutic appropriateness. Results: An approximate 50% change (k index 0.54) in the prescription of AIT for respiratory allergy as well as a change in the prescription of self-injectable adrenaline (k index 0.56) was measured; an overall saving of financial resources along with a higher diagnostic-therapeutic appropriateness was also detected. Conclusion: There is moderate agreement concerning prescription of AIT and self-injectable adrenaline before and after performing CRD: this highlights the usefulness of CRD, at least in polysensitized patients, in indicating the risk assessment and therefore the correct therapy of respiratory and food allergy, which results in a cost-saving approach

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Hymenoptera Venom Allergy: Management of Children and Adults in Clinical Practice.

Hymenoptera venom allergy is an epidemiologically underestimated condition and a major cause of morbidity worldwide. Preventing future allergic reactions in patients who experience a systemic reaction is based on the correct management of the emergency followed by an accurate diagnosis, prescription of adrenaline autoinjectors, and, where indicated, specific venom immunotherapy. Some epidemiological studies highlight our poor knowledge of this disease and the frequent inadequacy of its management. Moreover, they emphasize the importance of such a life-saving treatment as specific immunotherapy. The availability of high-quality hymenoptera venom extracts for diagnostic and therapeutic use has dramatically improved the prognosis and quality of life of allergic patients. Subcutaneous venom immunotherapy is currently the most effective form of allergen-based immunotherapy, with a carry-over effect lasting up to several years after its interruption. This report on the management of hymenoptera venom-allergic children and adults was prepared by a panel of Italian experts. The main objective of this consensus document is to review the scientific evidence related to diagnosis, therapy, and management of patients allergic to hymenoptera venom. Thus, we can improve our knowledge of the disease and promote good clinical practices. The present document provides practical suggestions for correct diagnosis, prescription of emergency therapy and immunotherapy, and strategies for patient care.

Molecular diagnostics improves diagnosis and treatment of respiratory allergy and food allergy with economic optimization and cost saving.

BACKGROUND: Component resolved diagnosis (CRD) allows to precisely identify the sensitization to specific molecules of a given allergenic source, resulting in an important improvement in clinical management, particularly of polysensitized subjects. This will end in the correct prescription of allergen immunotherapy (AIT) for respiratory allergy and in adequate avoidance diets or prescription of self-injectable adrenaline in food allergy. OBJECTIVE: The aim of this multicenter, real life study is to evaluate the percentage change of the diagnostic-therapeutic choice in polysensitized patients with respiratory allergy and in patients with food allergy, after using CRD compared to a first level diagnosis, along with an economic analysis of the patient's overall management according to the two different approaches. METHODS: An overall number of 462 polysensitized patients, as suggested by skin prick tests (SPT), and with clinical symptoms related to a respiratory (275 pts) or food (187 pts) allergy, were recruited. All patients underwent CRD for specific IgE against food or inhalant recombinant molecules, which were chosen according to medical history and positivity to SPT. The first diagnostic-therapeutic hypothesis, based only on medical history and SPT, was recorded for each patient while the final diagnostic-therapeutic choice was based on the results from CRD. The rate of change of the diagnostic-therapeutic choice from the first hypothesis to the final choice was statistically evaluated. The economic impact of CRD on the overall management of the allergic patients was analyzed to evaluate whether the increase in the diagnostic costs would be compensated and eventually exceeded by savings coming from the improved diagnostic-therapeutic appropriateness. RESULTS: An approximate 50% change (k index 0.54) in the prescription of AIT for respiratory allergy as well as a change in the prescription of self-injectable adrenaline (k index 0.56) was measured; an overall saving of financial resources along with a higher diagnostic-therapeutic appropriateness was also detected. CONCLUSION: There is moderate agreement concerning prescription of AIT and self-injectable adrenaline before and after performing CRD: this highlights the usefulness of CRD, at least in polysensitized patients, in indicating the risk assessment and therefore the correct therapy of respiratory and food allergy, which results in a cost-saving approach.

Concomitant celiac disease and wheat allergy: 2 case reports

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Hymenoptera venom allergy: management of children and adults in clinical practice

Hymenoptera venom allergy is an epidemiologically underestimated condition and a major cause of morbidity worldwide. Preventing future allergic reactions in patients who experience a systemic reaction is based on the correct management of the emergency followed by an accurate diagnosis, prescription of adrenaline autoinjectors, and, where indicated, specific venom immunotherapy. Some epidemiological studies highlight our poor knowledge of this disease and the frequent inadequacy of its management. Moreover, they emphasize the importance of such a life-saving treatment as specific immunotherapy. The availability of high-quality hymenoptera venom extracts for diagnostic and therapeutic use has dramatically improved the prognosis and quality of life of allergic patients. Subcutaneous venom immunotherapy is currently the most effective form of allergen-based immunotherapy, with a carry-over effect lasting up to several years after its interruption. This report on the management of hymenoptera venom-allergic children and adults was prepared by a panel of Italian experts. The main objective of this consensus document is to review the scientific evidence related to diagnosis, therapy, and management of patients allergic to hymenoptera venom. Thus, we can improve our knowledge of the disease and promote good clinical practices. The present document provides practical suggestions for correct diagnosis, prescription of emergency therapy and immunotherapy, and strategies for patient care

La alergia al veneno de himenópteros es una condición subestimada epidemiológicamente que representa una causa importante de morbilidad en todo el mundo. La prevención de reacciones alérgicas futuras en pacientes que han desarrollado una reacción sistémica se basa en el manejo correcto de la emergencia, seguido de un diagnóstico correcto, la prescripción de autoinyectores de adrenalina y, en el caso de estar indicada, la prescripción de inmunoterapia específica con veneno (VIT). Varios estudios epidemiológicos destacan el escaso conocimiento de esta enfermedad y un frecuente tratamiento insuficiente. Además, enfatizan la importancia de la inmunoterapia específica, un tratamiento que puede salvar la vida del paciente. La disponibilidad de extractos de veneno de himenóptera de alta calidad para uso diagnóstico y terapéutico ha mejorado drásticamente el pronóstico y la calidad de vida de estos enfermos. La VIT subcutánea representa la forma más efectiva de inmunoterapia con alérgeno actualmente disponible, con una eficacia persistente que dura hasta varios años después de su interrupción. Este consenso sobre la evaluación clínica tanto de niños como de adultos alérgicos al veneno de himenópteros ha sido elaborado por un panel de expertos italianos. Su objetivo principal es revisar la evidencia científica disponible en el diagnóstico, la terapia y la evaluación clínica de los pacientes alérgicos al veneno de himenópteros con el propósito de mejorar el conocimiento sobre esta enfermedad y promover buenas prácticas clínicas. Se incluyen sugerencias prácticas para un diagnóstico correcto, la prescripción de terapia de emergencia e inmunoterapia, así como estrategias para el manejo de los pacientes

Laboratory tests for allergy diagnosis.

The introduction of highly purified natural and recombinant single allergenic molecules represented an important improvement in the diagnosis of IgE sensitization. The identification of specific IgE against cross-reacting molecules such as profilin, lipid transfer proteins, calcium binding proteins or against “genuine molecules”, represents an added value and allows to distinguish between true and false polysensitization. In vitro tests add information to recognize patients with sensitization to genuine molecules that cause allergic diseases and to evaluate in childhood the spreading of sensitization for each molecule in order to choose the best treatment and to identify the ideal patient for allergen immunotherapy. Also, in order to detect patients with sensitization to pan-allergens it is important to manage the risk of anaphylaxis for patients allergic to latex and to identify IgE to particular molecules involved in occupational allergy. In patients with negative skin prick tests (SPT), that results in a lower sensitivity compared with in vitro tests, the negative test may be caused by the lack of some important allergenic molecules in the extract used for SPT.

An unusual case of wheat dependent exercise induced anaphylaxis (WDEIA) triggered by Tri a 14 in a pediatric patient: a case report.

Summary: Anakinra, one of the novel biological agents, is a recombinant human IL-1 receptor antagonist. It is preferred as an alternative drug for familial Mediterranean fever cases where colchicine is not sufficient or cannot be used due to its side effects. Like all other biologics, hypersensitivity reactions to anakinra are quite rare. This is the first case which was successfully desensitized with anakinra after a severe immediate-type hypersensitivity reaction. We report a case of WDEIA in an asthmatic boy admitted to our Unit with suspected mushroom acute toxicity. The symptoms occurred during a gym session, approximately 2 hours after the ingestion of a meal based on pasta and cooked mushroom found in the family's garden. Acute toxicity due to mushroom ingestion was then excluded. Triptase serum levels resulted elevated in acute phase and normal after 24 hours. Food specific IgE showed a sensitization to lipid transfer protein Pru p 3 and to Tri a 14. This case highlights that WDEIA is underdiagnosed, especially when patients are firstly visited in Emergency Unit. Moreover, Tri a 14 is seldom described as responsible for WDEIA, compared to omega 5 gliadin.

Scoliid wasp sting: a new cause of anaphylaxis

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Investigation into photostability of soybean oils by thermal lens spectroscopy.

Assessment of photochemical stability is essential for evaluating quality and the shelf life of vegetable oils, which are very important aspects of marketing and human health. Most of conventional methods used to investigate oxidative stability requires long time experimental procedures with high consumption of chemical inputs for the preparation or extraction of sample compounds. In this work we propose a time-resolved thermal lens method to analyze photostability of edible oils by quantitative measurement of photoreaction cross-section. An all-numerical routine is employed to solve a complex theoretical problem involving photochemical reaction, thermal lens effect, and mass diffusion during local laser excitation. The photostability of pure oil and oils with natural and synthetic antioxidants is investigated. The thermal lens results are compared with those obtained by conventional methods, and a complete set of physical properties of the samples is presented.

Role of photophysics processes in thermal lens spectroscopy of fluids: a theoretical study.

Photophysics processes are ubiquitous in nature and difficult to be quantitatively characterized by conventional spectroscopy. Alternatively, pump-probe methods have been widely applied to study these complex processes. In this context, the thermal lens technique is a precise spectroscopic tool for material characterization and presents a wide range of applications in chemical analysis. Here, we present an all numerical approach to analyze the dynamics of photophysics processes and to identify the role of individual contributions of photoreaction and mass diffusion in the thermal lens experiments. The results are essential for a proper understanding of the dominant physical mechanisms in laser-induced photodegradation, which allow precise data analysis of the effects in photosensitive fluids.

Component resolved diagnosis (CRD): how much is it presently used by Italian allergists?

Component resolved diagnosis (CRD) represents an innovative and revolutionary tool in allergy diagnosis. At the same time, some criticisms can be outlined. The present web survey aimed at investigating the role of CRD in daily clinical practice, according to a sample of Italian specialists who manage allergic patients. 127 physicians, mostly allergists, completed the questionnaire, mainly coming from North and Center of Italy. Most of them (80%) were allergists. One physician out of three regularly takes into consideration CRD, that is currently available about in a half of the hospitals where the specialists work. CRD is mostly prescribed in the diagnostic work-up of suspected food allergy, as it can drive risk assessment, epinephrine prescription and dietary advice. Concerning respiratory allergy, CRD is considered useful in investigating cross-reactivity and in defining the best treatment option, even if only 32% of patients treated with immunotherapy had been previously studied with CRD. The present survey points out the need for the specialists to develop a more practical know-how about CRD. Its diagnostic accuracy and its real impact on the clinical management need to be better defined. The lacking of CRD technology in many hospitals limits the possibility for many allergists to directly experience molecular diagnosis.

Heterogenity of IgE response to walnut and hazelnut in Italian allergic patients.

BACKGROUND: The prevalence of IgE reactivity against genuine walnut and hazelnut allergens is poorly defined. OBJECTIVE: The IgE response to walnut and hazelnut was investigated in Italian patients with primary allergy to these nuts. METHODS: Sera from 36 patients allergic to hazelnut and/or walnut, not reactive to PR-10, profilin, and LTP, underwent immunoblot analysis with extracts of both nuts. RESULTS: Most patients had a history of systemic symptoms following the ingestion of the offending food(s). Twelve patients were sensitized to both walnut and hazelnut, and 13 were sensitized to other nuts and seeds (cashew, peanut, sesame, pine nut, almond, Brazil nut, and pistachio). On walnut immunoblot, the 7 sera which scored positive showed much variability in their IgE profile. Two reacted uniquely at 10 kDa, and the others at 35 , 40, 45, 50, 67, and > 67 kDa. The profiles obtained under reducing and non-reducing conditions showed several differences. The 7 sera positive on hazelnut immunoblot under reducing conditions recognized sera at 10 kDa and at <10 kDa (n=1), 20 kDa (n=4), at about 22, 24, 30, 40, 43, 58, 60, and 90 kDa, and higher m.w. in other cases. Under non-reducing conditions IgE reactivity at 20, 28, 35, 40, 45, 60, 90, and 100 kDa, was detected. Only two sera scored positive under both conditions and showed an IgE profile that partly changed from one assay to another. CONCLUSION: The current list of walnut and hazelnut allergens is far from being complete. Both reducing and non-reducing conditions are needed to detect IgE reactivity in individual patients.

Causes of SLIT discontinuation and strategies to improve the adherence: a pragmatic approach.

Sublingual immunotherapy (SLIT) is often discontinued, and many patients do not renew the prescription. We evaluated the reasons for discontinuation and set up an educational/follow-up plan to improve the adherence. In a first phase, the adherence at 4 months was directly assessed. Based on those results, an action plan (education, frequent contacts, and strictly scheduled visits) was developed and tested in other patients. A group of matched patients did not undergo the follow-up plan (controls). In the first phase, involving 252 subjects, at 4 months, there were 30% dropouts, mainly due to side-effects. In the second phase, 149 patients underwent education/follow-up and 90 received no intervention. In the first group, discontinuations at 4 months were 5%, vs 18% in the controls (P = 0.01). After one year, 12% of patients were lost in the first group and 35% in the control group (P < 0.001). An adequate education and a strict follow-up can significantly reduce SLIT's discontinuations.

Operative procedure for the monitoring of anaphylactic reactions and the prevention of recurrence.

Prevention of anaphylaxis depends on optimal management of patient-related risk factors, an educational programme to teach how to avoid confirmed relevant allergens. We observed in our routine practice several patients who underwent allergological evaluation months or years after the occurrence of anaphylactic reaction or a relapse. The main issues of this proposal are to identify all patients arrived to Emergency Unit with anaphylactic reactions ranging from Mueller classification grade II-IV and to refer them to an Allergy Unit with the intent to promote, within 48 hours, a diagnostic and therapeutic programme, set the anaphylactic risk for each patient and deliver Fast Jeckt (Epinephrine autoinjectors). The programme is evaluated by Quality Unit of Piacenza's AUSL that suggests two monitoring indicators: "Efficacy" of the plan is checked measuring recurrence rate in a year,"Quickness" of Allergological consultation is monitored recording time of consultation request from Emergency Unit and time of first allergological visit. We observe an increase in the number of patients referred to the Allergy Unit within 48 hours to receive a diagnostic and therapeutic programme to prevent recurrence of anaphylaxis: 6 patients in 2007 and 31 in 2010 and a decrease in the number of patients arrived after anaphylaxis sent by practitioner: 7 in 2007 and 1 in 2010 (p < 0.05). All quarterly reports have reported an Efficacy less than 15% of recurrences and a Quickness more than 90%. The procedure has received an institutional accreditation by Emilia Romagna Health Agency. These observations underline the importance of an operative procedure for the monitoring of anaphylactic reactions, in order to provide an effective and immediate medical examination and also avoid the risk of recurrence.

Wellbeing, illness perception and coping strategies in Italian Celiac patients.

The clinical features of Celiac Disease (CD) are heterogeneous and both severity and extent of villous atrophy do not correlate with clinical presentation. This study aims to evaluate the psychological wellbeing of CD patients with a similar clinical pattern and to explore whether patients with different levels of wellbeing differed in illness perception and coping strategies. CD outpatients with proven diagnosis filled in validated questionnaires to investigate wellbeing (PGWBI), illness perception (IPQ-R) and coping style (COPE). One hundred and four patients underwent data analysis. Compared to Italian reference sample, CD patients reported a significantly reduced PGWBI total score (p<0.001), self-control (p<0.001), general health (p=0.002) and vitality (p<0.001) and increased anxiety (p=0.009). 7.7% of patients reported a positive wellbeing, 40.4% distress absence, 28.8% a moderate distress and 23.1% a severe distress. Patients with distress showed a different illness perception and reported more frequently two dysfunctional strategies: focus on and venting emotions (p= 0.009) and substance abuse (p= 0.01) compared to those having a positive wellbeing. A high percentage of CD patients experience distress and differ from those who reach wellbeing in illness perception and use of coping strategies. Assessing subjective viewpoint with standardized methods can provide useful information for a better management of CD patients.