A regional approach to unmet needs in anaphylaxis.

Allergic diseases are under-diagnosed and undertreated despite their wide prevalence, and particularly anaphylaxis is often under-estimated. Evidence-based anaphylaxis guidelines developed by principal allergy organizations agree on increased prevalence of anaphylaxis, especially in patients younger than 18 years (18-27,30): this trend highlights the need for actions on anaphylaxis management and prevention (3,4). Lack of prompt connection between emergency department and allergy unit after discharge, and of a dedicated ICD-9th identification code (18-26), can delay diagnosis and treatment of anaphylaxis (28,29). Also in the experience of our Allergy Unit, patients reach the allergist office after several attacks treated in ED (17), without a previous evaluation and risk assessment. Keeping in mind unmet needs in anaphylaxis (4), we focused on regional approaches to health care delivery. The key point of our project was to establish an active collaboration between allergist clinicians and their counterparts in emergency medicine, with a system of quick filing report of patients discharged from ED with the suspect of anaphylactic reaction, directed to a central allergy unit, acting in a hub and spoke model with the Ligurian allergy network (31). Aim of the project was to improve epidemiological data collection via direct connection among ED and allergy network; moreover, we tried to provide a quick and proper evaluation of all reported patients, identifying, when possible, the agent responsible for anaphylaxis, to provide instructions on how to minimize future exposure; as all individuals at risk for anaphylaxis should carry and know how to self-administer epinephrine, we managed to provide auto injector and proper training when appropriate. A follow up on readmissions was carried out during the study and four months later. In a 20 months observation period (2013/2014), 205 patients were reported: it was possible to reach a diagnosis and risk assessment in 64.3%. Anaphylaxis diagnosis was considered likely if any 1 of 3 criteria is satisfied within minutes to hours: acute onset of illness with involvement of skin, mucosal surface, or both, and at least 1 of the following: respiratory compromise, hypotension, or end-organ dysfunction; 2 or more of the following occur rapidly after exposure to a likely allergen: involvement of skin or mucosal surface, respiratory compromise, hypotension, or persistent gastrointestinal symptoms; hypotension develops after exposure to a known allergen for that patient: age-specific low blood pressure or decreased systolic blood pressure more than 30% compared with baseline. Of 205 patients reported, 132 were classified as severe anaphylaxis; other 73 cases reported were 12 drugs related angioedema (mostly NSAID related), 9 ACEi related angioedema, 3 ereditary C1inh deficiency angioedema, 24 istaminergic idiopatic angioedema, 14 urticaria angioedema, 6 severe asthma, 2 latex reactions; in three patients a proper diagnosis was not achieved due to refuse / impossibility to perform diagnostic workout. Hymenoptera venom and food proved to be the main triggers, followed by drugs. 100% patients at risk of anaphylaxis received self-injectable adrenaline, pertinent education and individual action plan. In the same period, even though short, there were only two readmissions to ED. First result seems to confirm the usefulness of our approach to address some of unmet needs in anaphylaxis management, as recently pointed out by ICON guidelines (4).

OCCUPATION study (OCCUPationl asthma: a naTIONal based study): a survey on occupational asthma awareness among Italian allergists.

Occupational asthma (OA) is the most common work-related respiratory disease. Case identification still remains underperformed. The present survey aimed at investigating the awareness about OA among Italian allergists. 538 Italian Allergists completed a web anonymous questionnaire concerning: patient profile, occupational history, disease features, diagnostic work-up, causal agents, management after diagnosis. 80 cases were registered by 14 members (2.4%). Patients were mostly between 30 and 62 years old; noteworthy, 19% were between 18 and 30. All the patients had a concomitant rhinitis, usually preceding asthma onset. Bakers, hairdressers and healthcare workers were more frequently involved. Diagnostic process included: skin prick test (85%), stop/resume test (57%), specific IgE dosage for occupational allergens (52.5%), peak expiratory flow monitoring (32.5%). Noteworthy, only 27,5% of patients underwent specific challenge. After the diagnosis 50% of patients did not change job. One third of the subjects were not referred to the national Workers Compensation Authority. Our data show that OA is quite neglected by Italian allergists, despite they have a pivotal role both in early identification and in primary prevention of OA. Thus, it is worth increasing awareness concerning OA and creating an easy-access network involving allergists and referral centers for Occupational respiratory diseases.

Successful desensitization to natalizumab in a skin test--positive patient: a case report.

Relevant interest has been focused on rapid desensitization for drug hypersensitivity and on its use for reactions to monoclonal antibodies. Natalizumab is a highly effective therapy for multiple sclerosis but its use can be limited by hypersensitivity reactions. Herein we present a case of a 36-year-old male patient with multiple sclerosis who started natalizumab therapy due to rapid neurological deterioration. During the second infusion he developed a reaction involving urticaria, erythema and angioedema. Natalizumab sensitization was demonstrated by a positive result on the intradermal test. The anti-natalizumab IgG neutralizing antibody assay was negative. Lacking any alternative, equally effective treatment, he underwent a rapid intravenous desensitization protocol. Desensitization was successfully repeated eleven times and the patient's neurological conditions improved and remained stable after one year. This case demonstrates that rapid desensitization is a safe and effective procedure in the treatment of natalizumab hypersensitivity.

Long-lasting effect of a monophosphoryl lipid-adjuvanted immunotherapy to parietaria. A controlled field study.

BACKGROUND: The clinical efficacy of Monophosphoryl lipid A-adjuvanted immunotherapy (MPLA-SCIT) is ascertained, but there are no data on its possible long-lasting effect. We assessed in a real-life setting the persistence of the clinical effect five years after discontinuation. METHODS: Patients with parietaria-induced respiratory allergy and fulfilling the criteria for immunotherapy prescription were evaluated at baseline, after the third year of MPLA-SCIT and five years after discontinuation. Visual analog scores, severity of the disease, pulmonary function and skin reactivity were assessed. Matched subjects who refused immunotherapy served as controls. RESULTS: Twenty nine patients received MPLA-SCIT and 28 were the control group. There was a significant clinical improvement, as assessed by VAS only in the active group after 3 years that remained significant at 5 years versus baseline and controls. The distribution of severity of rhinitis was overall decreased at 3 and 8years as well. The number of patients with conjunctivitis in the active group decreased from 19 to 6 at the end of the treatment and to 9 after 5 years. There was also a decrease in the number of patients with asthma symptoms (from 6 to 2 to 4), which doubled in the control group. A significant reduction in the wheal of the Parietaria skin test was seen in the active group at the end of the treatment (9.5 +/- 2.1 mm vs. 6.4 +/- 2.6 mm; p = .01), but this reduction was lost at the 5-year. No relevant change was overall detected in pulmonary function. CONCLUSION: MPLA-SCIT is effective, and the clinical efficacy is maintained after 5 years of discontinuation.

Phenobarbital-induced DiHS and ceftriaxone hypersensitivity reaction: a case of multiple drug allergy.

Patients with DiHS show an increased risk of sensitization to multiple drugs. We report a case of a young woman who developed cutaneous rash, lymphoadenopathy, malaise and fever after the introduction of phenobarbitale. Because of these symptoms, she was treated with ceftriaxone and she experienced a severe flare-up of the cutaneous and general reaction. Allergological work-up, by cutaneous and lymphocyte transformation test, confirmed a double sensitization to phenobarbital and ceftriaxone. In conclusion, the high risk of DiHS during anticonvulsive therapy should suggest caution in using additional drugs, because of an increased risk of multiple reactions.

Caldera unrest driven by CO2-induced drying of the deep hydrothermal system.

Interpreting volcanic unrest is a highly challenging and non-unique problem at calderas, since large hydrothermal systems may either hide or amplify the dynamics of buried magma(s). Here we use the exceptional ground displacement and geochemical datasets from the actively degassing Campi Flegrei caldera (Southern Italy) to show that ambiguities disappear when the thermal evolution of the deep hydrothermal system is accurately tracked. By using temperatures from the CO2-CH4 exchange of 13C and thermodynamic analysis of gas ascending in the crust, we demonstrate that after the last 1982-84 crisis the deep hydrothermal system evolved through supercritical conditions under the continuous isenthalpic inflow of hot CO2-rich gases released from the deep (~8 km) magma reservoir of regional size. This resulted in the drying of the base of the hot hydrothermal system, no more buffered along the liquid-vapour equilibrium, and excludes any shallow arrival of new magma, whose abundant steam degassing due to decompression would have restored liquid-vapour equilibrium. The consequent CO2-infiltration and progressive heating of the surrounding deforming rock volume cause the build-up of pore pressure in aquifers, and generate the striking temporal symmetry that characterizes the ongoing uplift and the post-1984 subsidence, both originated by the same but reversed deformation mechanism.

Chronic urticaria: importance of a medical-psychological approach.

Chronic urticaria is often associated with psychological factors, such as depression, anxiety and stress, which may play a role not only in the genesis of the disease but also in its evolution. Aims of this study were to evaluate the utility of psychological assessments (presence of depression, impact on the quality of life and incidence of "life events" before the beginning of urticaria) in conjunction with the allergological evaluation and to provide appropriate treatment to the patients selected. Thirty subjects diagnosed as Chronic Urticaria patients were submitted to psychological assessments (semi structured interview, Beck Depression Inventory, Nottingham health Profile and Dermatology Life Quality Index). The results of the evaluation show that most of the patients experienced a "stressor" event within the six months before the onset of the cutaneous manifestation. The incidence of depression resulted very high in comparison with the general population and in three cases at a severe level. The impact on the quality of life results to be moderate, but involving different fields of life (physical image, social life, quality of sleeping and eating, etc). Despite these results, only six patients accepted to be assigned to an appropriate treatment. In conclusion, we demonstrate the usefulness of a medical- psychological approach in chronic urticaria and we confirmed the resistance of psychosomatic patients to undergo psychological treatment.

Psychological aspects of drug intolerance.

A consecutive unselected series of 50 patients suffering from drug intolerance was evaluated by allergological and psychological tests. We wanted to verify the existence of a correlation between some psychological characteristics (hysteria, depression and Ego Integrity), and some clinical aspects (number and type of episodes, severity and probability of the reactions). We confirmed the prevalence of female sex in these disorders, particularly in middle-aged married women. The mean score of hysteria in the whole sample was lightly higher than normal. Moreover a relevant number of subjects (24%) scored higher than the cut off for clinical depression, with a significant difference in comparison to the overall prevalence of depression in the general population. Finally, the analysis of clinical variables considered in our patients showed that subjects with a history of less serious reactions and unlikely reactions scored higher in depression and hysteria scales. The importance of psychological evaluation of drug intolerance patients is discussed and confirmed.

Allergy to pollens from Betulaceae and Corylaceae in a Mediterranean area (Genoa, Italy)--a ten-year retrospective study.

Allergy to pollens from Betulaceae and Corylaceae is becoming a leading problem in Genoa, a northern Mediterranean area in Italy. The results of a 10-year retrospective study on combined observations both on the aerobiological presence of Betulaceae and Corylaceae pollens (Alnus, Corylus, Ostrya) and on the incidence of positive SPT in the allergic population living in the same area are reported. Among 3473 patients suffering from seasonal respiratory allergy with positive SPT to one or more pollens, 558 (16.06%) showed SPT positivity to Betulaceae and/or Corylaceae pollens, both isolated and associated with other allergens. These patients suffered from winter or early spring hay fever, with a high incidence of bronchial asthma. A statistically significant increase (0.02 < p < 0.05) in the number of these sensitizations from 1981 to 1990 has been observed. Some possible explanations for this phenomenon, including an increase in the total amount of local airborne pollens, are suggested. About 24% of the patients with positive SPT to these pollens referred oral allergic syndrome associated with the ingestion of some foods, especially apples and nuts, with or without other additional clinical symptoms.

Sublingual immunotherapy in Parietaria pollen-induced rhinitis: a double-blind study.

A double-blind, placebo-controlled study of immunotherapy was conducted in 31 patients with allergic rhinitis due to Parietaria pollen to evaluate the efficacy and safety of high doses of allergen via the sublingual route. The patients were assessed before and after a 10-month period of treatment by clinical (symptom-medication scores and specific nasal reactivity) and immunological (total IgE, specific IgE, IgG and IgG4 antibodies) parameters. High doses of Parietaria extract corresponding to a cumulative dose of 105 BU for each patient were administered with negligible side effects. The actively treated patients had significantly lower medication scores than those on placebo (p < 0.05) when the maximum pollen count was recorded, and at the end of the trial they showed a significant decrease in nasal reactivity (p < 0.02) and a significant increase in serum specific IgG4 (p = 0.02). No differences were detected in any of these parameters in the placebo group. Possible explanations for the mechanisms of sublingual immunotherapy are proposed.

Management of patients at risk for adverse reactions to local anesthetics: analysis of 386 cases.

Local anesthetics are among the most used drugs in clinical practice. Various types of reactions have been reported and many patients are told that they are allergic to caines or are at risk of allergic reactions. We report our experience with 386 patients using skin test and progressive subcutaneous challenge in order to select a local anesthetic that could be safely used. The patients underwent specific protocol including clinical history, prick and intradermal tests, and subcutaneous incremental challenge with a local anesthetic from the amide group which was free of preservatives and vasoconstrictors. Thirteen patients showed a positive skin test: 10 with positive prick test underwent the subsequent challenge with no reactions; the three who were also positive by the intradermal route were carefully evaluated with a different drug. Eight of the patients with negative skin tests complained of various clinical symptoms after the challenge. All the patients found the local anesthetic to be well tolerated and nobody reported reactions after the clinical use. These results show that skin tests and subcutaneous challenge are safe and sufficient to reliably identify a local anesthetic that patients with a prior history of adverse reaction or at higher risk could tolerate.

A double-blind comparative trial of astemizole and terfenadine for the treatment of hay fever.

Astemizole, a new long acting and non sedative antihistamine, and Terfenadine, an H1 antagonist widely used, were compared in a randomized double-blind study over 4 weeks in 55 patients suffering from hay fever. The clinical symptoms were recorded daily from each patient on a 4-point scale from 0 = none to 3 = severe. After 2 weeks of therapy and at the end, the total clinical score was evaluated and both the investigator and the patient made an overall assessment of the therapeutic effect. Both drugs were effective in reducing nasal and ocular symptoms, but the clinical response tended to be better with Astemizole than Terfenadine. The difference between the two drugs, however, was statistically significant (p less than 0.05) only after 2 weeks of treatment. Some side effects, including drowsiness, were observed with similar incidence in both treatment groups. Astemizole appears to be a simple, effective and safe therapy for hay fever.

Preventive symptomatic immunotherapy versus placebo in seasonal rhinitis due to grasses in children and to Parietaria in adult patients.

BACKGROUND: EPD is the only preventive symptomatic immunotherapy available on the market and approved by competent bodies. Recent double-blind placebo controlled (DBPC) studies have demonstrated its efficacy in seasonal and perennial rhinitis. The aim of the study was to confirm the efficacy and safety of a single dose of immunotherapy administered six-eight weeks before the pollen season. METHODS: Two simultaneous DBPC trials were carried out. The first consisted of 20 children with grass-pollen seasonal rhinitis (Bollate-Milano, Italy) and the second included 30 adult patients with Parietaria-pollen seasonal rhinitis (Genova, Italy). EPD was administered only to the active groups. RESULTS: A significant difference in favour of the active treatment groups was seen in oral antihistamine use (p < 0.05) during the peak pollen seasons. Throughout the pollen seasons, rhinoconjunctivitis scores for the two groups in both studies presented no significant difference, even if the values were lower in the active groups. CONCLUSIONS: The oral antihistamine reduction, observed in the active groups during the seasonal period, supports the efficacy of this treatment, although a significant improvement in the rhinoconjunctivitis symptoms was not observed, probably due to the use of oral antihistamine in the placebo groups. The overall profile of the EPD was good. It could be particularly suited for short term therapy to prevent seasonal symptoms in allergic patients.

ELISA in diagnosis of respiratory allergy. A comparison with RAST and skin tests.

An enzyme-linked immunosorbent assay (ELISA), employing beta-galactosidase conjugated anti-IgE, was used for the determination of specific IgE antibodies to common inhalant allergens (Dermatophagoides pt. and f., Parietaria and four grass pollens) in serum samples from 82 adult patients with asthma and/or rhinitis. A total of 194 analysis were carried out and the results were compared with those of skin tests and RAST. The correlation coefficient (r) between ELISA and RAST results was high (r = 0.95); the correlation between skin tests and ELISA (r = 0.93) was greater than that between skin tests and RAST (r = 0.90). No significant differences were found among the allergens used. We conclude that the version of ELISA used develops an overall good correlation with skin tests and RAST and seems to provide a satisfactory alternative to RAST for allergy diagnosis.

Long-term hyposensitization and adverse immunologic responses. A laboratory evaluation.

Ninety atopic patients with allergic asthma and/or rhinitis were classified into three groups: group A, consisting of 30 patients never subjected to immunotherapy; group B, 30 patients receiving immunotherapy for various allergies for 3 to 24 months; group C, 30 patients receiving immunotherapy for 5 or more years. The following studies were performed using standard techniques: quantitative determination of serum immunoglobulin concentrations IgA, IgG, IgM, rheumatoid factor, C3 and C4 concentrations, antinuclear antibodies (ANA). Circulating immune complexes were detected by a competitive immuno-enzyme assay. No statistical differences were found in the groups studied for every parameter considered. Although signs and symptoms of autoimmune disease were not present, an elevated incidence of ANA in the entire group (23.3%) was found.

Allergy to Parietaria pollen and month of birth.

It has been suggested that the season of birth is a predisposing factor for allergic sensitization. In the last few years many authors in different countries have found a statistically significant correlation between the month of birth and the subsequent allergy for grasses and birch pollens and house dust mites. Nevertheless, other investigators failed to confirm these results. The aim of the present study is to assess the relationship between the season of birth and the development of respiratory allergy to pollen of Parietaria, an Urticacea plant characteristic of Mediterranean flora, which is the most important hay fever producing one in our country. Among the patients who visited the Servizio Autonomo di Allergologia at the St. Martino Hospital (Genoa, Italy) in the year 1986, 264 subjects (113 F and 151 M, 5-35 years of age, all born and living in Genoa and its suburbs) were selected. The birth month of these patients, affected by rhinitis and/or bronchial asthma and with positive prick-test only toward Parietaria pollen, was recorded and compared with that of the population born in Genoa in the same years. Statistical evaluation made by X2 test showed the absence of a statistically significant relationship between the birth in the pollen season (April-July) and the pollinosis, with the exception of the month of May. The reasons of the discrepances observed between the behaviour of Parietaria pollen and that of the other pollens, grasses and birch, described in the above studies, are discussed.

Sublingual immunotherapy in tree pollen allergy. Double-blind, placebo-controlled study with a biologically standardised extract of three pollens (alder, birch and hazel) administered by a rush schedule.

BACKGROUND: sublingual immunotherapy has been recognised as safe and effective but it is still poorly documented in tree pollen allergy. Allergy to alder, birch and hazel is important in Northern European countries but its clinical relevance is increasing in Southern Europe. METHODS: thirty patients, selected and observed for one pollen season, were randomised to receive placebo (15 patients) or active treatment (15 patients). Twenty-seven patients completed the first year and 24 of them were treated with active therapy during the second year of the study in comparison to a parallel group of ten patients treated only with drugs. Symptom and drug scores during each pollen season, birch-specific IgE, changes in skin test reactivity, changes in specific Nasal Provocation Test and the daily average pollen count for the relevant trees were considered for the assessment of the efficacy of the treatment. RESULTS: both active and placebo group showed a statistically significant improvement in scores in comparison to the previous year, under a lower allergenic pressure. The improvement was higher in the active group (76.04 % reduction of drugs) but not significantly different from that registered in the placebo group (37.05 % reduction). In the open phase of the study, treated patients showed significantly better scores in comparison to the control group. No significant changes in skin reactivity, specific IgE and Nasal Provocation Test were registered. SLIT tolerance was very good. CONCLUSIONS: our data show a better but not statistically significant clinical outcome for patients actively treated with SLIT, but the placebo effect and the year-by-year variability of the environmental allergenic load in our small-size pilot study do not allow for a conclusive statement about the efficacy of this form of therapy.