The importance of educating subjects entitled to use an adrenaline auto-injector for self-administration.

An educational program, consisting in a clear explanation of the technical aspects and use of the adrenaline auto-injection devices (AAD) and in a practical test utilizing a demonstration kit was given to 350 patients from our outpatient clinic. AAD was also distributed to 50 patients formerly followed by another allergy clinic without training. At practical control test, only 10% of the untrained patients where able to correctly use the AAD versus 80% of trained subjects. Since AAD is a life-saving procedure in severe anaphylactic episodes, this attempt to improve the ability of the patient to comply with the procedure can improve the efficacy of the treatment and eventually the patient's health.

Omalizumab treatment in patient with severe asthma and Eosinophilic Granulomatosis with Polyangiitis . A case report.

Eosinophilic Granulomatosis with Polyangiitis (EGPA), formerly named Churg Strauss Syndrome, is a multisystem disorder characterized by chronic rhinosinusitis, asthma, and prominent peripheral blood eosinophilia; it is classified as a vasculitis of the small and medium sized arteries, although the vasculitis is often not clinically apparent in the initial phases of the disease. We present the case of a woman with EGPA who was frequently treated with high dose steroid therapy during hospital admission for refractory asthma. After December 2008, the date when we started Omalizumab, we observed a significative reduction of circulating eosinophils and IgE serum level, and the patient was no more hospitalized for respiratory failure or asthma attacks.

Time course of ischemic and bleeding burden in consecutive patients undergoing transcatheter aortic valve replacement (FOCUS-ONE Registry).

BACKGROUND AND AIMS: Ischemic or bleeding events might occur after transcatheter aortic valve replacement (TAVR), with the potential to hamper clinical outcomes. This study aimed to characterize the average daily ischemic risks (ADIRs) and the average daily bleeding risks (ADBRs) over 1-year in all consecutive patients undergoing TAVR. METHODS: ADBR included all bleeding events according to VARC-2 definition, and ADIR included cardiovascular deaths, myocardial infarction and ischemic stroke. ADIRs and ADBRs were assessed within different timeframes post TAVR: acute (0-30 days), late (31-180 days), and very late (>181 days). Generalized estimating equations were used to test the least squares mean differences for the pairwise comparison of ADIRs and ADBRs. Our analysis was performed in the overall cohort and according to antithrombotic strategy (LT-OAC vs No LT-OAC). RESULTS: Ischemic burden was higher than bleeding burden, independently from the indication to LT-OAC, and in all timeframes examined. In the overall population, ADIRs were three-fold ADBRs (0.0467 [95% CI, 0.0431-0.0506] vs 0.0179 [95% CI, 0.0174-0.0185]; p < 0.001*). While ADIR was significantly higher in the acute phase, ADBR was relatively stable in all timeframes analysed. Of note, in LT-OAC population, OAC + SAPT group showed lower ischemic risk and higher bleeding events compared with OAC alone (ADIR: 0.0447 [95% CI: 0.0417-0.0477] vs 0.0642 [95% CI: 0.0557-0.0728]; p < 0.001*, ADBR 0.0395 [95% CI: 0.0381-0.0409] vs 0.0147 [95% CI: 0.0138-0.0156]; p < 0.001*). CONCLUSIONS: In patients undergoing TAVR Average daily risk fluctuates over time. However, ADIRs overcome ADBRs in all timeframes, especially in the acute phase and regardless of antithrombotic strategy adopted.

Allergy to beer in LTP-sensitized patients: beers are not all the same.

BACKGROUND: Most cases of beer allergy reported so far have been associated with hypersensitivity to the non-specific lipid transfer protein (LTP). In view of the marked differences in brewing processes we assessed IgE reactivity as well as tolerance to many different beers in an allergic patient. METHODS: A 45 year-old man hypersensitive to grass pollen, cat dander and Alternaria tenuis with a history of urticaria and dyspnoea after drinking beer and a weak skin reactivity to commercial corn extract was studied. The patient underwent SPT with 36 different brands of beer and an open challenge with those scoring negative was performed. An immunoblot analysis was carried out using 2 SPT-positive beers, 2 SPT-negative beers, and barley, wheat, and maize extracts using both patient's serum and a maize LTP-specific in-house developed polyclonal antibody from rabbit. Further, the immune reactive LTP of one beer was separated by HPLC and the chromatogram was compared to that of purified maize LTP. RESULTS: Beer SPT scored positive in 30/36 cases. The immunoblot analysis showed IgE reactivity at about 10 kDa against the two SPT-positive beers and against maize with both patient's serum and the polyclonal anti-LTP rabbit serum, whereas the two SPT-negative beers, and barley extract scored negative. The immunodetected protein co-migrated with maize LTP. CONCLUSION: In beer-allergic patients the diagnostic workup may point to the detection of some tolerated products that can be consumed risk-free.

Prevalence of allergic disorders in Italy: the Cotignola population study.

BACKGROUND: The worldwide prevalence of allergic diseases such as rhinitis, asthma, and atopic dermatitis is continuously increasing, while other allergic disorders such as urticaria and angioedema are less investigated. We performed a population study evaluating the prevalence of any kind of allergic disorders. METHODS: The entire population of 7,201 inhabitants of Cotignola (Ravenna, Italy) was surveyed by a questionnaire assessing symptoms related to rhinitis, asthma, anaphylaxis, skin symptoms and insect sting allergy as well as the features of clinical presentations, diagnosis, and treatment received. RESULTS: Valid questionnaires were obtained by 6,676 inhabitants (92.7%). The sample was formed by 3,266 males and 3,495 females, the mean age was 45.6 years; 1,035 subjects (15.5%) were aged less than 18 years; 404 subjects (6%) had at least one episode of wheezing/breathlessness in their lifetime, and 243 of them (60.1%) had a diagnosis of asthma; 1,002 subjects (14.8%) had nose symptoms in their lifetime, and 375 of them (37.4%) had a diagnosis of allergic rhinitis or rhinoconjunctivitis. For other allergic manifestations, data were obtained from 5,730 subjects; of them, 178 (3.1%) had skin symptoms, 59 (1.1%) had oral symptoms, and 37 (0.6%) had anaphylaxis; 207 (3.6%) had reactions to insect stings. There were no significant differences in prevalence between Italians and immigrants. Only 51.7% of subjects with asthma, 46.5% of those with rhinitis, 22.7% of those with other allergies, but 97.1% of those with insect allergy, received treatment. CONCLUSIONS: These findings confirm recent data on epidemiology of allergic diseases in Europe, particularly in Italy, and add some details on how such diseases are managed.

Fever of unknown origin as unique symptom of an indolent mastocytosis.

A 39-years-old man afferred to our hospital for a fever lasting for more than 6 months, without abnormalities at physical examination (in particular no skin alterations); a recent laboratory and instrumental investigation was ineffective and so a fever of unknown origin (FUO) was diagnosed Since he reported an history of infantile mastocytosis (usually auto-resolving) we evaluated his serum-tryptase levels that resulted of 49 ug/L (normal value 20 ug/L), raising the doubt of the presence of an active mastocytosis. The following bone marrow evaluation showed aggregates of CD117 positive cells and a c-Kit point mutation at codon D 816V confirming the diagnosis of indolent mastocytosis.The present case confirm that FUO can be caused by an otherwise asymptomatic indolent mastocytosis, thus suggesting to include the serum-tryptase level measurement in the diagnostic approach to this pathological condition, at least in selected cases.

Efficacy and safety of sublingual immunotherapy with grass monomeric allergoid: comparison between two different treatment regimens.

BACKGROUND: Sublingual immunotherapy (SLIT) with monomeric carbamylated allergoid proved to be well tolerated, safe and effective in patients with respiratory allergy. Standard administration regimens are expected to require a long time before clinical benefit can be appreciated. We investigated whether pre-seasonal and perennial regimens differently affect the clinical efficacy of grass pollen SLIT. METHODS: Adult patients with allergic rhino-conjunctivitis with/without mild intermittent asthma due to grass pollen were included into this open prospective study and randomised to receive SLIT with a continuous regimen (Group 1: 1,000 AU/week for the entire study period) or a pre-seasonal regimen (Group 2: 5,000 AU/week for 10 weeks/year for 2 years), or on demand drug therapy alone (Group 3) for two years. At entry (November 2005), at the end of the first and second pollen season, a Visual Analogue Scale (VAS) was used to assess patients' well-being. Symptom score and drug consumption were evaluated during the seasons. Methacholine challenge was performed at study entry and conclusion. Adverse events were recorded along the whole study duration. RESULTS: Thirty-two patients were divided into Group 1 (n = 10), Group 2 (n = 11) and Group 3 (n = 11). A significant VAS improvement was observed in both SLIT groups, after the first and second pollen season, compared to baseline and to Group 3 (p < 0.05). Less symptoms and need for medications resulted during the second season (p < 0.05). No relevant variations in bronchial hyper-reactivity have been observed between the three groups. Only 2 patients experienced local or mild reactions in SLIT groups. CONCLUSION: Both pre-seasonal and continuous regimen of SLIT with monomeric allergoid turned out effective and safe, suggesting that a pre-seasonal course with 5,000 AU/week for 10 weeks may represent a convenient option in patients with grass pollen allergic rhinitis with/without mild intermittent asthma. Further research is urgently needed to consolidate these preliminary evidences.

Patients monosensitised to Hev b 8 (Hevea brasiliensis latex profilin) may safely undergo major surgery in a normal (non-latex safe) environment.

BACKGROUND: Natural rubber latex allergy is a condition at high risk of anaphylaxis during surgery. However, latex contains several protein allergens and not all of them may show the same clinical relevance. OBJECTIVE: To investigate the clinical relevance of Hey b 8, the natural rubber latex profilin. METHODS: Seven patients without a clinical history of latex allergy but identified as being latex hypersensitive by positive SPT (3/7) and or positive latex-specific IgE during routine pre-surgery allergy investigations were studied. All patients were monosensitized to Hev b 8 (Hevea brasiliensis latex profilin) as shown by the detection of specific IgE to recombinant latex allergen components. Ten subjects with a history of latex allergy (urticaria, asthma, and/or rhinitis), sensitised to latex allergens other than profilin were enrolled as controls. Both patients and controls underwent a latex glove-wearing test; in case of a negative test, patients underwent surgery in a normal surgical setting. RESULTS: All 7 patients scored negative on latex glove wearing test and underwent major surgery (orthopaedic, Caesarean section, pilonidal sinus, vascular, tonsillectomy, uterine revision, and uretral surgery) in a normal (non-latex safe) surgical setting without any consequence. In contrast, 9/10 (90%) controls showed a positive latex glove-wearing test (p < 0.01). CONCLUSION: Latex profilin is either clinically irrelevant or is no longer present in latex products. This study highlights the importance of a component-resolved diagnosis of latex sensitisation as a tool to get a more precise assessment of the risk and to reduce the costs of healthcare.

A case of anaphylaxis: horse-fly or hymenoptera sting?

In literature it has been described a high risk of systemic reaction after blood-sucking Dyptera bites, like mosquitoes and horsefly, in people sensitive to hymenoptera. A 51 year old man, allergic to hymenoptera venom and with a history of i.v. reaction after Mueller, who has been treated with Vespula sp. ITS for the last 3 years, was stung by a yellow, black and green insect on the neck. Five minutes after the bite, he suffered generalized hitching and urticaria, oral cavity and lower limbs paresthesia, followed by lost of consciousness. At the Emergency Room he was successfully treated with adrenaline, intravenous antihistamines and corticosteroid. The description of the insect as well as the lack of the sting on the site suggested a wasp as the culprit. By studying one of these insect that has been captured by the patient, it turned out it wasn't a Vespula, but a horsefly, the Tabanus bovinus, which resembles Hymenoptera. Skin prick test and RAST for Tabanus confirmed the allergology diagnosis. In conclusion, also Tabanus bovines can cause systemic reaction up to anaphylactic shock.

CD30 serum levels and response to hymenoptera venom immunotherapy.

BACKGROUND: The glycoprotein CD30 is expressed and released by T lymphocytes that secrete type 2 helper cytokines of (T(H)2). These molecules play a role in the pathogenesis of allergic diseases. Venom immunotherapy has proven to be very effective in hymenoptera venom allergy through a shift in cytokine production from T(H)2-type cytokines to T(H)1-type cytokines. OBJECTIVE: To evaluate the relationship between the soluble form of CD30 (sCD30) and venom immunotherapy in patients with hymenoptera venom allergy. MATERIALS AND METHODS: sCD30 levels were assayed by enzyme-linked immunosorbent assay in the sera of 61 healthy controls and 14 patients with hymenoptera venom allergy who had undergone immunotherapy before treatment and 1,3, and 12 months after treatment started. Nine patients were allergic to Apis venom, 4 to Vespula venom, and 1 to Polistes venom. RESULTS: CD30 serum levels (median, interquartile range) were significantly higher in venom-allergic patients before treatment (33.6 U/mL; 14.8-61.6) than in controls (9.7 U/mL, 1.9-21.3) (P < .000). These levels decreased progressively during treatment in all patients except 2 (P < .000). At the third month of therapy, the levels reached statistical significance in comparison with baseline. CONCLUSIONS: This study shows that sCD30 levels are significantly higher in patients with hymenoptera venom allergy and indirectly confirms a preferential T(H)2-type cytokine production in these patients. sCD30 expression decreases during immunotherapy, thus confirming the immunomodulatory role of this treatment in promoting a shift to T(H)1-type cytokines.

Safety of etoricoxib in patients with reactions to NSAIDs.

BACKGROUND: Adverse reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) are a frequently reported problem due to the fact that these molecules are often used for control of pain and inflammation. Although the use of selective inhibitors of cyclooxygenase (COX) 2 helps to prevent some of these adverse reactions, they can have cardiac side effects when taken for prolonged periods. Here we report the safety and tolerability of etoricoxib, a selective COX-2 inhibitor with fewer cardiovascular effects, in patients with adverse reactions to NSAIDs. PATIENTS AND METHODS: We performed placebo-controlled oral challenge with etoricoxib in 65 patients with previous adverse reactions to NSAIDs: 13 to salicylates, 18 to arylpropionic acids, 10 to arylacetic acid, 12 to oxicam and derivates, 8 to pyrazolones, and 4 to acetaminophen (paracetamol). The reported symptoms were urticaria or angioedema in 69%, rhinitis in 3%, and 1 case of anaphylactic shock (1.5%). The challenge was done using the placebo on the first day, half dosage of etoricoxib (45 mg) on the second day, and the therapeutic dose of 90 mg on the third day. The challenge was done in the outpatient department of the hospital and the subjects were monitored for a further 4 to 6 hours after challenge. RESULTS: Oral challenge with etoricoxib was well tolerated in 97% of the patients. Only 2 systemic reactions were reported during the challenge test. CONCLUSION: Etoricoxib can be considered a safe molecule for those patients with previous adverse reactions to NSAIDs.

The wasp-horsefly syndrome.

Here are two cases of two male patients of 57 and 62 years of age, already known as allergic to stinging hymenoptera venom, who after a horsefly bite have presented a serious 3-4 degree-type Mueller classification systemic reaction. The diagnosis has been carried out clinically and after an accurate environmental anamnesis and along with prick tests and RAST, further specific entomological confirm. In literature the so called wasp-mosquito-syndrome has been indicated where hyaluronidase has been referred to as the cross allergen, between the hymenoptera venom and the mosquito saliva, which likely triggers the reaction. We believe that it is also possible to take into consideration a wasp-horsefly-syndrome as well, supposing the increased risk of anaphylactic reactions to Tabanidae bites, relatively frequent in areas with animals and streams, in subjects sensitized to stinging hymenoptera. We also suggest the possibility that in these subjects some systemic reactions are due in fact to Tabanidae bites and not so much for the failure of a possible active ITS of stinging hymenoptera.

Use of biomarkers to investigate toxicological effects of produced water treated with conventional and innovative methods.

The aim of this study was to develop and apply a multi-biomarker system to assess the toxicological effects of produced water (PW) from a Mediterranean off-shore oil platform. The selected bioindicator organism, mosquitofish (Gambusia affinis), was exposed in the laboratory to high concentrations of different PW: PW before treatment (BT), after conventional treatment (ACT) and after innovative treatment with zeolites in a prototype system (AIT). A set of biomarkers (benzo(alpha)pyrene monooxygenase, ethoxyresorufin-o-deethylase, vitellogenin, porphyrins, PAH bile metabolites, esterases, catalase, micronuclei) and PAH concentrations were measured in the experimental organism. The methodology proved to be appropriate and biomarker responses (CYP 1A1, PAH bile metabolites, micronuclei, esterases, porphyrins) affected by BT were less affected by ACT. PW treated with zeolites (AIT) had the lowest toxicological impact. The results obtained applying this multi-biomarker approach suggest that the system using zeolites is effective for treating produced water.

Focal nodular hyperplasia after busulfan treatment.

The case of a 48-year-old woman in whom focal nodular hyperplasia of the liver developed after busulfan therapy was administered for essential thrombocytosis is described. Focal nodular hyperplasia is a reactive disorder related to a circulation disorder. The close temporal relation between the haematological disease, busulfan treatment and the appearance of hyperplastic diseases of the liver in our patient supports the possibility that the association of the events might not be casual.

Anaphylactic shock to Argas reflexus bite.

Anaphylaxis is a severe, life-threatening allergic reaction, affecting both children and adults. The occurrence of anaphylaxis is not as rare as generally believed (1.21% to 15.04% of the US population). Often the cause of this reaction remain unknown, mainly due to the difficulty in defining the outbreaking causes. Herein, we describe an interesting case of a patient, who developed an anaphylactic reaction after the bite of a pigeon tick. During the last 2 years, in wintertime, the patient often came to the emergency room for general rash and swelling, hypotension and tachycardia preceded by itching and general distress. Notably, the symptoms manifested themselves as night fell. In two particular occasions the patient reached the hospital in a state of shock. After another episode of general swelling, the patient was invited to examine her domestic environment. She brought us some parasites, collected at home, particularly on the bed. A morphological examination by entomologists proved these parasites to belong to Argas reflexus (Arg.r.), one of the 31 species of soft ticks. The presence of specific IgE to a protein secreted by the Arg.r. salivary glands was in favour of immediate-type systemic reaction, as supposed by the clinical history.

Serum total tryptase level confirms itself as a more reliable marker of mast cells burden in mast cell leukaemia (aleukaemic variant).

Mast cell leukemia (MCL) is a very rare form of systemic mastocytosis (SM) with a short median survival of 6 months. We describe a case of a 65-year-old woman with aleukaemic variant of MCL with a very high serum total tryptase level of 2255 µg/L at diagnosis, which occurred following an episode of hypotensive shock. She fulfilled the diagnostic criteria of SM, with a bone marrow smear infiltration of 50-60% of atypical mast cells (MCs). She tested negative for the KIT D816V mutation, without any sign of organ damage (no B- or C-findings) and only few mediator-related symptoms. She was treated with antihistamine alone and then with imatinib for the appearance of anemia. She maintained stable tryptase level and a very indolent clinical course for twenty-two months; then, she suddenly progressed to acute MCL with a serum tryptase level up to 12960 µg/L. The patient died due to haemorrhagic diathesis twenty-four months after diagnosis. This clinical case maybe represents an example of the chronic form of mast cell leukemia, described as unpredictable disease, in which the serum total tryptase level has confirmed itself as a reliable marker of mast cells burden regardless of the presence of other signs or symptoms.

Influence of chronic ethanol consumption on the inositol phospholipid fatty acid composition of human peripheral blood lymphocytes.

The breakdown of inositol phospholipids is an important event after the binding of antigens to the T-cell antigen receptor. In alcoholics, changes either in early or in late steps of lymphocyte activation have been documented, however no study on the role of phosphoinositide fatty acid composition in signal transduction has been reported. We have analyzed the fatty acid pattern of phosphatidylinositol, phosphatidylinositol-4-phosphate and phosphatidylinositol-4,5-bisphosphate from peripheral blood lymphocytes of alcoholic patients and healthy controls, in order to point out the possible compositional differences which could interfere with the signal transmission responsible for the early events in lymphocyte activation. In alcoholics, the arachidonic acid relative molar content in all the inositol phospholipid (PtdIns) fractions derived from lymphocytes was lower than in controls; all PtdIns classes appeared much more saturated than the corresponding fractions from control lymphocytes. The different fatty acid pattern of PtdIns in alcoholic patients could be responsible for an altered second messenger production, above all the production of a modified diacylglycerol which, in turn, could cause a different activation pattern of protein kinase C, with a consequent alteration in cell proliferation. The decrease in arachidonic acid molar content in the phosphoinositides and particularly in the phosphatidylinositol-4,5-bisphosphate fraction of PBL of alcoholic patients could lead to a reduced synthesis of prostanoids of the (n-6) series, and, as a consequence, to an alteration in the mitogenic response of the cells.

Alpha 1-acid glycoprotein (alpha 1-AGP) on the membrane of human lymphocytes: possible involvement in cellular activation.

A glycoprotein termed alpha 1-acid glycoprotein (alpha 1-AGP) is a component of normal human serum; its concentration is often increased in several pathological disorders, including acute inflammation and cancer. Inhibitory effects of alpha 1-AGP on some in vitro T and B cell function assays have been reported but our recent data indicated that alpha 1-AGP is indeed a T cell mitogen at physiological concentrations. The present study was designed to investigate: (a) the relationship between this glycoprotein and two other glycoproteins of the T and B cell membrane, i.e. the T3 and Ia antigens; (b) the ability of lymphocytes to take up exogenous alpha 1-AGP; (c) the different expression of alpha 1-AGP on the T cell membrane upon different activation pathways, i.e., autologous non-T-cells (B cells and monocytes) phytohemagglutinin and anti-T3 monoclonal antibody (MAb) stimulations. The data reported herein show no competition at the membrane level between anti-alpha 1-AGP and anti-T3 or anti-Ia MAbs. In addition, (1) the lymphocytes were able to absorb alpha 1-AGP from the culture medium and (2) the expression of this glycoprotein was enhanced upon T cell stimulation (all three stimulants employed induced an increase of alpha 1-AGP positive T cells), thus suggesting a possible role of this glycoprotein in in vitro T cell activation.

Phosphatidylinositol metabolism in lymphocytes of chronic alcoholic patients after anti-CD3 stimulation.

The immunological alterations observed in chronic alcoholic patients may be due to alterations of signal transduction across the lymphocyte membrane. Upon binding of mitogens or antigens to specific plasma membrane receptors, the activation of phospholipase C leads to the hydrolysis of inositol phospholipids, producing inositol phosphates and diacylglycerol. One of the early events in lymphocyte activation is an increase of intracellular calcium concentration, due to both an influx from extracellular fluid and a release from intracellular stores mediated by inositol phosphates. In this study we verified whether the diminished mobilization of intracellular calcium, previously observed in alcoholics, is caused by alteration in phosphoinositide turnover. We evaluated total inositol phosphate production in peripheral blood lymphocytes after anti-CD3 stimulation, comparing control subjects and alcoholic patients. Lymphocyte activation generated inositol phosphates in both controls and alcoholics, but to a different extent, inositol phosphate production being significantly higher in controls than in alcoholics. This reduction in inositol phosphate production could be accounted either to an inhibition of PLC activity or to a modified affinity of phospholipase C for its own substrates, i.e., phosphoinositides, which fatty acid composition has been previously demonstrated to be greatly different in alcoholics in comparison to healthy subjects.