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Cough from an allergological as well as from the ENT aspect Abstract. Cough is a common problem in the allergological, but less so in the rhinological consultation. The differential diagnostic spectrum for cough is extensive and may range from rhinitis and asthma to eosinophilic esophagitis and rarer diseases. In the case of chronic cough (> 2 months), the four most frequent causes must be sought, or be excluded (upper airway cough syndrome, asthma [cough-variant-asthma], non-asthmatic eosinophilic bronchitis, gastroesophageal reflux disease). Aeroallergens such as pollen, house-dust mites or occupational substances play a major role in allergies. Nevertheless, it is not uncommon for cough to be a main symptom of an antibody deficiency or a Sicca symptom complex. The more chronic the cough, the more thoroughly an investigation is indicated - often interdisciplinary. Therapy depends on the cause of the cough. In allergic respiratory diseases, allergy-specific immunotherapy may be indicated.

Zusammenfassung. Betalactamantibiotikaallergien sind die am häufigsten erwähnten Medikamentenallergien. In der Hausarztpraxis oder im Falle einer Hospitalisation äussern Patienten oft, an einer Penicillinallergie zu leiden, weswegen in diesen Fällen meist keine Betalactamantibiotika verwendet werden. Häufig handelt es sich bei einer vermeintlichen Allergie jedoch um Nebenwirkungen wie Diarrhoe, Nausea oder Bauchschmerzen. Der grösste Teil dieser Patienten verträgt Betalactamantibiotika ohne Probleme, weswegen eine allergologische Abklärung wichtig ist. Hierfür ist eine gute Anamnese und Dokumentation zentral, da Hautteste und in vitro Verfahren eine eingeschränkte Sensitivität haben. Ergänzend kann mittels Provokationstest eine fragliche Allergie oder alternative, potentiell kreuzreaktive Betalactamantibiotika in Hinblick auf ihre Verträglichkeit geprüft werden. Die Kreuzreaktivität mit Cephalosporinen, insbesondere der 3. Generation und höher, wird meist überschätzt. Kreuzreaktionen zu Carbapenemen sind selten.

Eine Hypersensitivitat auf endogenes Progesteron kann zu vielfaltigen, zyklisch rezidivierenden Hautveranderungen fuhren. Die klinischen Manifestationen konnen von Urtikaria, Angioodemen, Erythema multiforme und Ekzemen bis hin zur Anaphylaxie reichen. Am haufigsten manifestieren sich Ekzeme und Hautschwellungen (Urtikaria, Angioodeme), die auch kombiniert auftreten konnen. Bei einer zyklischen Hautsymptomatik ist an eine autoimmune Progesterondermatitis zu denken. Mittels einer Hauttestung mit Progesteron kann die Verdachtsdiagnose bekraftigt werden. Je nach Leidensdruck und Symptomatik stehen mehrere Therapieoptionen zur Wahl.

Tierallergien sind nach der Hausstaubmilbenallergie der häufigste Grund allergischer Atemwegsbeschwerden in Innenräumen. Falls eine ständige Allergenexposition besteht werden die Symptome wie Rhinitis, Hautjuckreiz oder Asthma gewöhnlich nicht als heftig empfunden und können daher auch nicht einem Tier oder einer Tierquelle zugeordnet werden. In vielen Fällen basiert die Tierallergie auf einer perenniale Allergenexposition. Auch wenn wahrscheinlich alle Tiere Ursache einer Atemwegsallergie sein können, sind doch Katzen, Hunde und Pferde die häufigsten Auslöser. Die Diagnose einer Allergie auf ein Tier muss mit Sorgfalt gestellt werden, weil sie häufig emotionale Reaktionen, verschiedene Konflikte, aber auch Unverständnis auslöst. Seltener sind Pilzallergien, auch wenn sie als Allergiequellen seit Jahrzehnten zur Differentialdiagnose der Atemwegsallergie gehören, speziell beim Spätsommerasthma. Pilze sind ubiquitär und sind in Wohnräumen wie auch in der Natur stets präsent. Leider ist das Gebiet der Pilzallergie wenig erforscht und die diagnostischen Möglichkeiten sind begrenzt. Die erfolgversprechendste Therapie sowohl bei einer Tier- oder einer Pilzallergie wäre den Kontakt mit der jeweiligen Allergenquelle vollständig zu meiden. Zwar werden diverse präventive Empfehlungen abgegeben, aber oft gelingt die Umsetzung nicht zufriedenstellend. In ausgewählten Fällen kann die spezifische Immuntherapie sowohl bei der Tier- wie auch bei der Pilzallergie eine therapeutische Option sein.

Key Clinical Message “Flare-up” reactions are late manifestations of severe T-cell-mediated drug hypersensitivity reactions. Management is anti-inflammatory treatment and avoiding unnecessary medicines. Symptoms like fever, lymph node swelling, and blood count abnormalities may lead to confusion with bacterial infections. For prompt recognition it is important to keep the differential diagnosis in mind.

For decades airborne fungal spores have been implicated as causative factors in respiratory allergy. Exposure to high atmospheric spore counts and sensitization to specific fungal allergens have been associated with severe asthma, mainly in young adults. Although the prevalence of sensitization to commercial fungal extracts is approximately 3% in epidemiologic studies, in selected patients, particularly with asthma, the sensitization rate might increase to 30%. Of the estimated number of more than 1 million of different fungal species, approximately 80 fungi have been connected with respiratory allergy. Currently, diagnosis and specific therapy of fungal allergy is hampered by the poor quality of most of the commercially available extracts. Clinical efficacy of specific immunotherapy with fungal extracts has been shown in 79 actively treated patients in four controlled trials, with only two fungal species, namely Alternaria alternata and Cladosporium herbarum. The use of recombinant fungal allergens might create new prospects in diagnosis and specific immunotherapy for fungal allergy.

Background Leukotriene receptor antagonists have shown some efficacy in the treatment of asthma. Injection of LTC 4 , LTD 4 and LTE 4 into the skin leads to a weal-and-flare reaction, suggesting an involvement of leukotrienes in the pathogenesis of urticaria. Indeed, various reports have indicated a beneficial effect for leukotriene receptor antagonists in patients with chronic urticaria. Objective To determine the therapeutic effect of the leukotriene receptor antagonist zafirlukast in patients with chronic urticaria. Methods The study was a double-blind, placebo-controlled, cross-over study lasting for 12 weeks. Fifty-two patients with chronic urticaria were investigated at a university hospital. The patients were randomized to receive 20 mg zafirlukast b.i.d. or placebo and cross-over was scheduled after 6 weeks. The efficacy of the treatment was evaluated by a daily symptom score, six physical examinations, the requirement of rescue antihistamines (acrivastine) and an overall assessment by the patient and the investigating physician. Results Forty-six patients completed the study: zafirlukast was well tolerated without alteration of the investigated laboratory parameters. In comparison with placebo, treatment with zafirlukast resulted in no significant positive effect for any of the efficacy measures. Moreover, we were unable to identify any subgroup of patients with chronic urticaria responding with a therapeutic benefit. Conclusions The leukotriene receptor antagonist zafirlukast does not provide a significant therapeutic benefit at a dose of 20 mg b.i.d. in patients with chronic urticaria.

Summary Background Fungal components can cause allergic symptoms either through inhalation, ingestion or contact. Whereas respiratory allergy is thought to be induced by spores, allergic reactions following ingestion are attributed to other parts of the mushroom. Reports of food-related allergic reactions due to the edible mushroom Boletus edulis have occasionally been reported. Objective The aim of the study was to investigate whether separate allergens may be detected in alimentary allergy to Boletus edulis. Methods Sera of two subjects, one with recurrent anaphylaxis and the other with a predominantly oral allergy syndrome following ingestion of Boletus edulis, have been analysed by a time-course digestion assay using simulated gastric fluid and by SDS-PAGE immunoblotting. Sera of four Boletus edulis skin prick test-negative subjects and all without clinical symptoms to ingested Boletus edulis served as controls. Results In lyophilized Boletus edulis extract, at least four water-soluble proteins were detected, the most reactive at 55 kDa and at 80 kDa. Following the time-course digestion assay, IgE binding was found to a 75-kDa protein, but only if the sera of the subject with recurrent anaphylaxis was used. Conclusion The data indicate that Boletus edulis can cause an IgE-mediated food allergy due to a digestion-stabile protein at 75 kDa. No IgE immune response to this protein was detected in the serum of a subject with respiratory allergy and oral allergy syndrome to Boletus edulis nor in control sera.

We describe a patient who suffered from intestinal perforation after abdominal trauma. Perioperatively, he was treated with a single dose of piperacillin and 9 doses of imipenem/cilastatin over 3 days. The patient was discharged 5 days after surgery in good clinical condition and with normal liver values except for a marginal elevation of alanine aminotransferase. Two weeks after discharge, he developed fatigue, fever and pruritus, necessitating rehospitalization. He was jaundiced and had elevated alkaline phosphatase and transaminases. After exclusion of an intra-abdominal fluid collection, a vascular problem, and infectious or autoimmune liver disease, a liver biopsy was performed. The biopsy revealed centrizonal bilirubinostasis, a portal infiltrate rich in eosinophils and cholangitis. Lymphocyte transformation tests for piperacillin and imipenem/cilastatin were positive, suggesting an immunological mechanism for the observed hepatopathy. Cholestasis gradually decreased but was detectable for several weeks. The patient had a full clinical and biochemical recovery after 3 months. We conclude that short-term therapy with piperacillin, imipenem/cilastatin or the combination of these drugs can lead to the same type of hepatopathy as described for amoxycillin/clavulanic acid or antistaphylococcal penicillins. Liver biopsy and positive lymphocyte transformation are compatible with an immunological mechanism.

Background Local anaesthetics are known to elicit T-cell reactions after epicutaneous application, namely contact dermatitis. In addition, adverse reactions like urticaria and angioedema are rather common after submucosal or subcutaneous injection. The pathogenesis of these side-effects, which appear frequently hours after application, is unknown, but thought to be not immunoglobulin E-mediated, since immediate skin tests are mostly negative. Objectives We investigated whether patients who developed urticaria and angioedema after subcutaneous application have a T-cell sensitization to local anaesthetics, which might be responsible for the symptoms. Methods Twenty patients with generalized and/or local cutaneous reactions after LA were examined with intradermal testing using a standard panel of six LAs and patch testing using between seven and nine LAs in vaseline and four LAs in PBS. In 10 patients, a lymphocyte transformation test (LTT) was performed. Results Only 2/20 patients had an immediate skin reaction (positive intradermal test), whereas 6/20 patients had a positive delayed skin reaction (positive patch test). In 6/10 subjects the LTT was positive. Conclusions Delayed appearance of urticaria and angioedema after subcutaneous application of local anaesthetics may be related to a T cell- mediated sensitization, which might be detected by patch testing or LTT.

Diagnostic tests in patients with Hymenoptera venom allergy are frequently positive to venoms of both honey bee and wasp (Vespula). Component-resolved analysis with recombinant species-specific major allergens (rSSMA) may help to distinguish true double sensitization from crossreactivity.Included were 121 patients with systemic allergic reactions to Hymenoptera stings, 76 with double positivity of serum-specific IgE (sIgE) to both venoms, 45 with single positivity to bee or wasp venom, and 32 controls without history of systemic reactions to Hymenoptera stings and no sIgE to whole venoms. In venom-allergic patients and controls, sIgE to rSSMA Api m 1 of bee venom and to Ves v 1 and Ves v 5 of wasp venom were tested by ImmunoCAP.Only 47% of 76 patients with double positivity to whole venoms reacted also to rSSMA of both species. Specificity of sIgE to the 3 rSSMA was very high, with no sIgE to rSSMA of the other species in single-positive venom-allergic patients and only one control with low sIgE to Ves v 1. All wasp-allergic single-positive patients had sIgE to Ves v 5 and/or Ves v 1, and 78.3% of single-positive bee venom-allergic patients had sIgE to Api m 1.Specificity of sIgE to rSSMA of both species is excellent. Sensitivity of sIgE to rSSMA was optimal for wasp venom. Sensitivity of bee venom Api m 1 could be increased by adding rSSMA of other important bee venom allergens.

Seafood is a common cause of food allergy. Allergic reactions are reported by consumers following ingestion of seafood meat and by processing workers after occupational exposure to seafood by inhalation of vapors generated during cooking. Although seafood allergy is commonly observed in clinical practice, its precise prevalence is not established. Based on our estimates, approximately 100,000 to 250,000 Americans are at risk of developing allergic reactions to seafood products. In this study, skin testing, in vitro assays and double-blind, placebo-controlled food challenge were employed to investigate seafood allergy in shrimp-allergic individuals. As in most food allergy studies only 1/3 of the alleged shrimp-sensitive subjects had a positive shrimp challenge test. The combination of a positive shrimp skin test and shrimp RAST (>11% bound) had the best predictive value (87%) for a positive challenge response. Although occupational seafood allergy is not well-studied, based on a Canadian investigation, it can be estimated that 57,000 American seafood workers are at risk of developing work-related allergic reactions. Since seafood is a major food allergen in consumers and industrial workers, further studies are necessary. Despite developments of new antiallergic therapies, avoidance continues to be the best “treatment”for allergic ingestive, inhalative and occupational disease.

OBJECTIVE: To determine the characteristics of asthma (A) and allergic rhinitis (AR) among asthma patients in primary care practice. RESEARCH DESIGN AND METHODS: Primary care physicians, pulmonologists, and allergologists were asked to recruit consecutive asthma patients with or without allergic rhinitis from their daily practice. Cross-sectional data on symptoms, severity, treatment and impact on quality of life of A and AR were recorded and examined using descriptive statistics. Patients with and without AR were then compared. RESULTS: 1244 asthma patients were included by 211 physicians. Asthma was controlled in 19%, partially controlled in 27% and not controlled in 54%. Asthma treatment was generally based on inhaled corticosteroids (ICS) with or without long acting beta 2 agonists (78%). A leukotriene receptor antagonist (LTRA) was used by 46% of the patients. Overall, 950 (76%) asthma patients had AR (A + AR) and 294 (24%) did not (A - AR). Compared to patients with A - AR, A + AR patients were generally younger (mean age +/- standard deviation: 42 +/- 16 vs. 50 +/- 19 years, p < 0.001) and fewer used ICS (75% vs. 88%, p < 0.001). LTRA usage was similar in both groups (46% vs. 48%). Asthma was uncontrolled in 53% of A + AR and 57% of A - AR patients. Allergic rhinitis was treated with a mean of 1.9 specific AR medications: antihistamines (77%), nasal steroids (66%) and/or vasoconstrictors (38%), and/or LTRA (42%). Rhinorrhoea, nasal obstruction, or nasal itching were the most frequently reported AR symptoms and the greatest reported degree of impairment was in daily activities/sports (55%). CONCLUSIONS: Allergic rhinitis was more common among younger asthma patients, increased the burden of symptoms and the need for additional medication but was associated with improved asthma control. However, most asthma patients remained suboptimally controlled regardl-ess of concomitant AR.

Twenty-seven patients with allergy to house-dust mite and the clinical symptoms of perennial rhinitis and/or mild asthma were treated with specific immunotherapy (SIT) with standardized extracts of house-dust mite for 3 years. The success of therapy was evaluated in yearly intervals by 1) subjective rhinitis and asthma scores. 2) allergen-specific skin and conjunctival tests. 3) nonspecific bronchial hyperreactivity to methacholine. 4) medication scores of rhinitis and asthma. SIT induced a significant improvement of all parameters already after 1 year, with further improvement in the follow-up measurements at 2 and 3 years. We found a constant improvement of the rhinitis and asthma symptom scores, a reduced reactivity in the skin prick and conjunctival provocation tests, and a constantly increasing reduction of bronchial hyperreactivity to methacholine. Concomitantly, the use of medication (topical corticosteroids, beta2-mimetics, and antihistamines) was reduced. Our data support the concept that SIT with standardized extracts of house-dust mite results in an improvement of allergen-specific parameters in patients with perennial rhinitis and intermittent asthma. This beneficial effect of SIT on allergen-specific immune parameters seems to induce also a diminution of nonspecific bronchial hyperreactivity and enables reduction of symptomatic treatment.

Background: Chronic urticaria is a common disease, though only few data on its natural course are available. In most cases the cause cannot be determined. Recently a relationship of chronic urticaria to infection with Helicobacter pylori (HP) has been postulated, but no controlled study has been performed to prove this association. Methods: In this prospective study the clinical course and rate of HP infection in 46 patients with chronic ‘idiopathic’ urticaria were investigated. Infected patients were treated in a double–blind placebo–controlled crossover study with amoxycillin and lansoprazol. Eradication and clinical course were followed up 2 months after each treatment, respectively, 3 and 6 months after the first consultation. Results: In 19/46 (41%) the chronic ‘idiopathic’ urticaria resolved within 6 months. 12 patients (24%) were infected with HP, which corresponds to the infection rate of the population at comparable ages without urticaria in Switzerland. Eradication of HP was achieved in 3, but only in 1 was the eradication associated with the resolution of urticaria. Conclusions: Our data show that in young patients with a rather short history of chronic urticaria frequently a rather favourable natural course of chronic idiopathic urticaria can be seen. No association between HP infection and chronic urticaria could be demonstrated.

BACKGROUND: H1 antihistamines increase safety during allergen-specific immunotherapy and might influence the outcome because of immunoregulatory effects. OBJECTIVE: We sought to analyze the influence of 5 mg of levocetirizine (LC) on the safety, efficacy, and immunologic effects of ultrarush honeybee venom immunotherapy (BVIT). METHOD: In a double-blind, placebo-controlled study 54 patients with honeybee venom allergy received LC or placebo from 2 days before BVIT to day 21. Side effects during dose increase and systemic allergic reactions (SARs) to a sting challenge after 120 days were analyzed. Allergen-specific immune response was investigated in skin, serum, and allergen-stimulated T-cell cultures. RESULTS: Side effects were significantly more frequent in patients receiving placebo. Four patients receiving placebo dropped out because of side effects. SARs to the sting challenge occurred in 8 patients (6 in the LC group and 2 in the placebo group). Seven SARs were only cutaneous, and 1 in the placebo group was also respiratory. Difference of SARs caused by the sting challenge was insignificant. Specific IgG levels increased significantly in both groups. Major allergen phospholipase A(2)-stimulated T cells from both groups showed a slightly decreased proliferation. The decrease in IFN-gamma and IL-13 levels with placebo was not prominent with LC, whereas IL-10 levels showed a significant increase in the LC group only. Decreased histamine receptor (HR)1/HR2 ratio in allergen-specific T cells on day 21 in the placebo group was prevented by LC. CONCLUSIONS: LC reduces side effects during dose increase without influencing the efficacy of BVIT. LC modulates the natural course of allergen-specific immune response and affects the expression of HRs and cytokine production by allergen-specific T cells.