EAACI guidelines on allergen immunotherapy: Hymenoptera venom allergy.

Hymenoptera venom allergy is a potentially life-threatening allergic reaction following a honeybee, vespid, or ant sting. Systemic-allergic sting reactions have been reported in up to 7.5% of adults and up to 3.4% of children. They can be mild and restricted to the skin or moderate to severe with a risk of life-threatening anaphylaxis. Patients should carry an emergency kit containing an adrenaline autoinjector, H1 -antihistamines, and corticosteroids depending on the severity of their previous sting reaction(s). The only treatment to prevent further systemic sting reactions is venom immunotherapy. This guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on Venom Immunotherapy as part of the EAACI Guidelines on Allergen Immunotherapy initiative. The guideline aims to provide evidence-based recommendations for the use of venom immunotherapy, has been informed by a formal systematic review and meta-analysis and produced using the Appraisal of Guidelines for Research and Evaluation (AGREE II) approach. The process included representation from a range of stakeholders. Venom immunotherapy is indicated in venom-allergic children and adults to prevent further moderate-to-severe systemic sting reactions. Venom immunotherapy is also recommended in adults with only generalized skin reactions as it results in significant improvements in quality of life compared to carrying an adrenaline autoinjector. This guideline aims to give practical advice on performing venom immunotherapy. Key sections cover general considerations before initiating venom immunotherapy, evidence-based clinical recommendations, risk factors for adverse events and for relapse of systemic sting reaction, and a summary of gaps in the evidence.

Allergen immunotherapy for insect venom allergy: a systematic review and meta-analysis.

BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines on Allergen Immunotherapy (AIT) for the management of insect venom allergy. To inform this process, we sought to assess the effectiveness, cost-effectiveness and safety of AIT in the management of insect venom allergy. METHODS: We undertook a systematic review, which involved searching 15 international biomedical databases for published and unpublished evidence. Studies were independently screened and critically appraised using established instruments. Data were descriptively summarized and, where possible, meta-analysed. RESULTS: Our searches identified a total of 16 950 potentially eligible studies; of which, 17 satisfied our inclusion criteria. The available evidence was limited both in volume and in quality, but suggested that venom immunotherapy (VIT) could substantially reduce the risk of subsequent severe systemic sting reactions (OR = 0.08, 95% CI 0.03-0.26); meta-analysis showed that it also improved disease-specific quality of life (risk difference = 1.41, 95% CI 1.04-1.79). Adverse effects were experienced in both the build-up and maintenance phases, but most were mild with no fatalities being reported. The very limited evidence found on modelling cost-effectiveness suggested that VIT was likely to be cost-effective in those at high risk of repeated systemic sting reactions and/or impaired quality of life. CONCLUSIONS: The limited available evidence suggested that VIT is effective in reducing severe subsequent systemic sting reactions and in improving disease-specific quality of life. VIT proved to be safe and no fatalities were recorded in the studies included in this review. The cost-effectiveness of VIT needs to be established.

Episodic hemorrhage during honeybee venom anaphylaxis: potential mechanisms.

Episodic hemorrhage is not a typical symptom of anaphylactic reaction to insect stings. Cases of reactions to honeybee (HB) sting or venom immunotherapy in which the uterus is the main target organ are very rare. Hemorrhage can be induced by HB venom components, especially melittin, which interfere with complement cleavage and bradykinin release. Both mechanisms are directly or indirectly associated with coagulation, thrombolysis, hemolysis, and smooth muscle tone. Induction of episodic hemorrhage through pathway destabilization in a defective bradykinin system or vulnerable organ may not be compensated by appropriate regulatory mechanisms. The pathological role of effectors is generally offset by the interaction of various regulatory systems, and the probability of hemorrhage is minimized thanks to this compensatory capability. In endometrial bleeding, the uterus becomes more vulnerable as a result of postmenstrual vascular fragility and additional induction of anaphylaxis-related uterine contractions. Episodic hemorrhage, especially metrorrhagia, as a consequence of HB venom activity may be suspected by an allergologist, but not by a physician. Melittin-free or recombinant allergens of HB venom, as well as modulators of the biochemical systems involved, could help to reduce the likelihood of hemorrhage. However, further investigation is required before these strategies can be introduced in clinical practice.

Prevalence of a family history of atopic disease among 3 generations of atopic respiratory patients in Tirana, Albania.

BACKGROUND AND OBJECTIVE: Having relatives with allergic disease is associated with an increased risk of such disease, but children without a significant genetic predisposition account for much of the increase in asthma prevalence. The aim of this study was to investigate whether the prevalence of a reported family history of allergy has increased among atopic respiratory patients diagnosed in Outpatient Service No. 3 in Tirana in recent decades. METHODS: We evaluated the records of 693 atopic respiratory patients sensitized to mites (n = 480) or pollen (n = 218) or both (n = 5) to detect reports of allergic disease among their close relatives. Patients were classified in 3 groups: those born in 1959 or earlier, those born between 1960 and 1979, and those born between 1980 and 2003. The chi2 test was used for statistical comparisons. RESULTS: The prevalence of a family history of allergy among those born before 1960 (42.7%) was nearly 2-fold greater than the prevalence among those born between 1960 and 1979 (25.3%) or between 1980 and 2003 (23.1%) (P < .001). CONCLUSIONS: Younger generations of atopic respiratory patients report a family history of allergic disease about half as frequently as older ones. It is possible that massive introduction of antibiotics such as penicillin and streptomycin in the late 1960s and early 1970s for use against respiratory or gastrointestinal infections has increased survival for a considerable number of young children, switching the gene thesaurus of successive adult populations to an allergy-predisposing genotype.

Trigeminal nasal-specific neurons respond to nerve growth factor with substance-P biosynthesis.

BACKGROUND: Nerve growth factor (NGF) has been found to induce substance-P biosynthesis in large-diameter A-fibres vagal airway neurons. However, the effect of NGF on trigeminal neurons innervating the nasal mucosa of the mouse has not been investigated so far. OBJECTIVE: NGF has been implicated in allergic diseases by modulating sensory nerves. Therefore, the present study investigated the effect of NGF on neuropeptides expression such as substance-P and glutamate in nasal trigeminal neurons. METHODS: Using neuronal tracing in combination with double labelling immunohistochemistry the expression of substance-P, glutamate and neurofilament protein 68-kDa expression was examined in nasal-specific trigeminal neurons of BALB/c-mice. RESULTS: The numbers of Fast blue-labelled trigeminal neurons expressing substance-P were significantly increased after NGF exposure (NGF-treated ganglia: 16.4 +/- 0.6% vs. control: 7.0 +/- 0.4%, P

Helminths can protect themselves against rejection inhibiting hostile respiratory allergy symptoms.

The ability of common environmental allergens to stimulate IgE responses and thus to produce allergic diseases has tended to overshadow the fact that helminthic parasites are possibly the most potent inducers of this immunoglobulin that exists in nature. Although it has been well established that during these infections there is a stimulation of IgE against their own antigens as well as a strong induction of nonspecific TH2/IL-4 polyclonal IgE, similarly to the allergic processes, many authors debate if the presence of these infections correlates inversely or not with the rate prevalence of atopy or respiratory allergy. Interpreting this relationship, we suggest that sometimes the intensive infections of hosts, especially with soil helminths which migrate in the respiratory ways or use there as entrance, can induce the production of some mediators ('helminth(k)ines'), to reduce the possibility of their reactive expulsion from the host. The ability to suppress hostile allergic symptoms despite the simultaneous induction of IgE response and local inflammation maybe is established due to the selective evolution, to assure for the parasites better chances for an effective life and reproduction within their mammalian hosts.

Allergic airway inflammation induces tachykinin peptides expression in vagal sensory neurons innervating mouse airways.

BACKGROUND: Allergic airway inflammation has been shown to induce pro-inflammatory neuropeptides such as tachykinin peptides substance P (SP) and neurokinin A (NKA) together with related peptide like calcitonin gene-related peptide (CGRP) in nodose sensory neurons innervating guinea-pig airways. OBJECTIVE: The present study was designed to examine the effects of allergen sensitization and challenge on the SP/NKA expression in the jugular-nodose ganglion neurons innervating the murine airways. METHODS: Using retrograde neuronal tracing technique in combination with double-labelling immunohistochemistry, the expression of SP/NKA was investigated in a murine model of allergic airway inflammation. RESULTS: Allergic airway inflammation was found to induce the expression of SP/NKA (13.2+/-1.43% vs. 5.8+/-0.37%, P<0.01) in large-diameter (>20 microm) vagal sensory neurons retrograde labelled with Fast blue dye from the main stem bronchi. CONCLUSION: Based on the induction of tachykinins in airway-specific large-sized jugular-nodose ganglia neurons by allergic airway inflammation, the present study suggests that allergen sensitization and challenge may lead to de novo induction of tachykinins in neurons. This may partly contribute to the pathogenesis of airways diseases such as allergic airway inflammation.

Hymenoptera sting anaphylactic reactions in the Mediterranean population of Albania.

BACKGROUND: Relatively few studies have examined the relation of different hymenoptera sting reactions. OBJECTIVE: To investigate the relation of anaphylactic reactions against stings of different hymenoptera subspecies in the Mediterranean population of Albania. MATERIALS AND METHODS: A retrospective study was conducted using the clinic files of 111 patients who were diagnosed for hymenoptera sting reactions from 1987 to 1996. Antigens used consisted of purified hymenoptera venom (bee, wasp, and paperwasp). The patients were diagnosed by intracutaneous tests in concentrations of 0.001 microgram/ml, 0.01 microgram/ml, 0.1 microgram/ml, and 1 microgram/ml. RESULTS: The median age of the patients was 27 years. 57% of stings occurred between 20 to 40 years of age. The majority of anaphylactic reactions were recorded during the months of June to October, 81% of the patients were admitted to the hospital due to Mueller grade II to III reactions. In 26% of all cases, crossreactions (bee-wasp 16%, bee-wasp-paperwasp 7%, wasp-paperwasp 2%, bee-paperwasp 1%) were found. Of all anaphylactic reactions, 64% were attributed to bees, 24% to wasps, 8% to both bees and wasps, and 2% to paperwasps. CONCLUSIONS: In contrast to industrialized countries such as the United States or Western Europe where urban populations predominate, reactions to bee venom were more prevalent in the present study population.