Radoslaw Gawlik

Clinical contraindications to allergen immunotherapy: An EAACI position paper

Clinical indications for allergen immunotherapy (AIT) in respiratory and Hymenoptera venom allergy are well established; however, clinical contraindications to AIT are not always well documented. There are some discrepancies when classifying clinical contraindications for different forms of AIT as ‘absolute’ or ‘relative’. EAACI Task Force on ‘Contraindications to AIT’ was created to evaluate and review current literature on clinical contraindications, and to update recommendations for both sublingual and subcutaneous AIT for respiratory and venom immunotherapy. An extensive review of the literature was performed on the use of AIT in asthma, autoimmune disorders, malignant neoplasias, cardiovascular diseases, acquired immunodeficiencies and other chronic diseases (including mental disorders), in patients treated with β‐blockers, ACE inhibitors or monoamine oxidase inhibitors, in children under 5 years of age, during pregnancy and in patients with poor compliance. Each topic was addressed by the following three questions: (1) Are there any negative effects of AIT on this concomitant condition/disease? (2) Are more frequent or more severe AIT‐related side‐effects expected? and (3) Is AIT expected to be less efficacious? The evidence, for the evaluation of these clinical conditions as contraindications, was limited, and most of the conclusions were based on case reports. Based on an extended literature research, recommendations for each medical condition assessed are provided. The final decision on the administration of AIT should be based on individual evaluation of any medical condition and a risk/benefit assessment for each patient.

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 Immunologys (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.

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.

Self-medication of anaphylactic reactions due to Hymenoptera stings-an EAACI Task Force Consensus Statement.

An anaphylactic reaction due to a Hymenoptera sting is a clinical emergency, and patients, their caregivers as well as all healthcare professionals should be familiar with its recognition and acute management. This consensus report has been prepared by a European expert panel of the EAACI Interest Group of Insect Venom Hypersensitivity. It is targeted at allergists, clinical immunologists, internal medicine specialists, pediatricians, general practitioners, emergency department doctors, and any other healthcare professional involved. The aim was to report the scientific evidence on self‐medication of anaphylactic reactions due to Hymenoptera stings, to inform healthcare staff about appropriate patient self‐management of sting reactions, to propose indications for the prescription of an adrenaline auto‐injector (AAI), and to discuss other forms of medication. First‐line treatment for Hymenoptera sting anaphylaxis is intramuscular adrenaline. Prescription of AAIs is mandatory in the case of venom‐allergic patients who suffer from mast cell diseases or with an elevated baseline serum tryptase level and in untreated patients with a history of a systemic reaction involving at least two different organ systems. AAI prescription should also be considered in other specific situations before, during, and after stopping venom immunotherapy.

Effect of intranasal azelastine on substance P release in perennial nonallergic rhinitis patients.

Background Rhinitis symptoms can be produced or augmented by neural mechanisms. Azelastine, a pharmacologic agent with potent H1-receptor blocking activity can inhibit the release of various mediators implicated in the pathogenesis of nasal hyperresponsiveness. The therapeutic benefits of topical intranasal azelastine on symptoms of perennial nonallergic rhinitis (NAR) are in part because of an impact on neural mechanisms. Assessment of changes in the concentration of substance P (SP) in nasal lavage fluid before and after saline hypertonic challenge may be a means of assessing the effect of intranasal azelastine on neuropeptide release and severity of rhinitis symptoms. Methods Twenty-three patients with perennial NAR (negative skin-prick tests with inhalant allergens and concentration of total IgE in the normal range) were studied. Thirteen of 23 patients were treated with intranasal azelastine 0.15% spray at a dosage of 2 sprays (137 micrograms/spray) twice daily for 10 days. The control group consisted of 10 untreated patients with rhinitis. Nasal provocation using 4.5% saline solution was after 15 minutes by lavage before and after 10 days of treatment with intranasal azelastine. The concentration of SP in nasal lavage fluid was determined by enzyme immunoassay methods. Results Nasal lavage fluid baseline concentrations of SP were similar in both groups. After azelastine treatment, significantly greater concentrations of SP were seen in nasal lavage fluid 15 minutes after hypertonic saline challenge in the untreated patients (56.8 ± 13.8 pg/mL) in comparison with azelastine-treated patients (44.5 ± 16.5 pg/mL; p < 0.05). Total vasomotor rhinitis symptoms scores were substantially reduced in the azelastine-treated subjects compared with the control group. Conclusion Azelastine intranasal spray reduces SP release into nasal lavage fluid of NAR patients immediately after hypertonic nasal saline challenge. Reduction of neuropeptide release may be an important aspect of the clinical efficacy of topical azelastine in perennial NAR patients.

Local Allergic Rhinitis to Pollens is Underdiagnosed in Young Patients

Background Local allergic rhinitis (LAR) has been observed in patients without atopy. However, LAR is still underdiagnosed in patients with perennial or seasonal nasal symptoms. Objective The aim of this study was to determine the prevalence of LAR in young patients with a previous diagnosis of nonallergic rhinitis or suspicion of allergy. Methods A total of 121 patients, ages 12–18 years old, with confirmed nonallergic rhinitis and typical seasonal nasal symptoms were examined. Skin-prick tests; serum and nasal specific immunoglobulin E (IgE) measurements; and nasal provocation tests by using grass (Phleum partense), Artemisia, and birch pollens were performed. A control group of age-matched patients with a diagnosis of seasonal allergic rhinitis underwent the same procedures as the test group. Results LAR to grass pollen (P. partense), Artemisia, and birch was confirmed in 17 (16.6%), 6 (5.9%), and 9 (8.9%) of patients, respectively. Polyvalent allergy was established in 21 subjects (20.8%): grass and Artemisia, 11 patients (10.9%); and grass and birch, 10 patients (9.9%). The remaining 48 patients (47.5%) were diagnosed with nonallergic rhinitis. The results of the nasal provocation tests and the concentrations of nasal IgE were similar among the analyzed groups. Furthermore, the concentration of nasal IgE increased faster in patients with LAR than in patients with allergic rhinitis; however, this difference was not statistically significant. Conclusion LAR is a serious problem in young patients; however, its significance is still unappreciated.

Sublingual immunotherapy (SLIT)--indications, mechanism, and efficacy: Position paper prepared by the Section of Immunotherapy, Polish Society of Allergy.

SLIT (sublingual immunotherapy,) induces allergen-specific immune tolerance by sublingual administration of a gradually increasing dose of an allergen. The mechanism of SLIT is comparable to those during SCIT (subcutaneous immunotherapy), with the exception of local oral dendritic cells, pre-programmed to elicit tolerance. In the SLIT dose, to achieve the same efficacy as in SCIT, it should be 50-100 times higher with better safety profile. The highest quality evidence supporting the efficacy of SLIT lasting 1-3 years has been provided by the large scale double-blind, placebo-controlled (DBPC) trials for grass pollen extracts, both in children and adults with allergic rhinitis. Current indications for SLIT are allergic rhinitis (and conjunctivitis) in both children and adults sensitized to pollen allergens (trees, grass, Parietaria), house dust mites (Dermatophagoides pteronyssinus, Dermatophagoides farinae), cat fur, as well as mild to moderate controlled atopic asthma in children sensitized to house dust mites. There are positive findings for both asthma and new sensitization prevention. Severe adverse events, including anaphylaxis, are very rare, and no fatalities have been reported. Local adverse reactions develop in up to 70 - 80% of patients. Risk factors for SLIT adverse events have not been clearly identified. Risk factors of non-adherence to treatment might be dependent on the patient, disease treatment, physician-patient relationship, and variables in the health care system organization.

Allergen immunotherapy for insect venom allergy: protocol for a systematic review

AbstractBackground The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines for Allergen Immunotherapy (AIT) for the Management of Insect Venom Allergy. We seek to critically assess the effectiveness, cost-effectiveness and safety of AIT in the management of insect venom allergy. MethodsWe will undertake a systematic review, which will involve searching international biomedical databases for published, in progress and unpublished evidence. Studies will be independently screened against pre-defined eligibility criteria and critically appraised using established instruments. Data will be descriptively and, if possible and appropriate, quantitatively synthesised. Discussion The findings from this review will be used to inform the development of recomendations for EAACI’s Guidelines on AIT.

Mediator release of neuropeptides after nasal provocation in perennial allergic rhinitis patients.

BACKGROUND Neuropeptides may play a role in allergic rhinitis including development of vasodilation and vascular leakage, which may result in rhinorrhea and congestion. While neuropeptide release during the immediate allergic response is well known, the role of neuropeptides in the late phase of allergic responses is less well defined. METHODS Eleven subjects with dust mite allergy induced allergic rhinitis were compared to 5 healthy control subjects using nasal allergen provocation. Nasal lavage fluid was analyzed for Substance P, bradykinin, and total protein. RESULTS Both bradykinin and substance P levels increased in nasal lavage fluid immediately after dust mite allergen challenge of dust mite allergic subjects, the magnitude of increase of both neuropeptides being significantly correlated. There was a greater increase in substance P versus bradykinin 4 to 6 hours after allergen challenge, with a lack of correlation between the late phase increases of these two neuropeptides. The bradykinin increases correlated with the increase in total protein in the nasal lavages of the allergic subjects, whereas the increases in substance P did not correlate with the total protein in the nasal lavages. An increase in nasal eosinophils was only seen in the allergic subjects after allergen provocation. CONCLUSION Both bradykinin and substance P appear in nasal lavage fluid 4 to 6 hours after allergen challenge of dust mite allergic subjects, suggesting a role for the neuropeptides in late phase allergic events.

Anaphylaxis as a Manifestation of Horse Allergy

Allergic disease induced by animal exposure is a common phenomenon worldwide. Whereas cat and dog dander exposure are well recognized as causative of allergic rhinitis, allergic asthma, and contact urticaria, horse allergy can present with anaphylaxis. Horse allergy is induced by exposure to the major horse allergens Equ 1 through 5. The severity of the symptoms may be related to the level of exposure. Greatest risk of anaphylaxis occurs in those sensitized patients who have large amounts of animal allergen exposure, such as when in a barn, or when an animal bite occurs exposing sensitized persons to large quantities of the animal allergen that resides in the saliva. Horse allergy may be successfully treated with allergen specific immunotherapy.