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L’etiopathogenese et l’epidemiologie des maladies allergiques sont particulierement complexes. Pollution atmospherique, changements climatiques et perte de la biodiversite sont les principaux problemes ecologiques actuels.

Die Atiopathogenese und Epidemiologie allergischer Erkrankungen sind besonders komplex. Luftverschmutzung, Klimawandel und der Verlust der Biodiversitat sind die aktuellen okologischen Hauptprobleme.

Background: Different scoring systems have been developed to determine the severity of atopic dermatitis (AD); the SCORAD (Scoring Atopic Dermatitis) and EASI (Eczema Area and Severity Index) are among the best-validated scoring systems. Objective: The aim of this study was to produce a rational quality control for routine clinical use by using the modern facilities of digital imaging. Methods: 63 AD patients were scored by a single person at each visit using the SCORAD and EASI scoring methods. Images were taken and rated by two non-dermatology physicians trained in the scoring system. In addition, blood samples were taken for the determination of total IgE, eosinophils and eosinophilic cationic protein. Results: The EASI score established from the digital images, hereby named ‘EASIdig’, correlated at all visits with the results of the SCORAD and EASI. Together with immunological parameters, they also reflected changes of disease severity during the 3 time points. Conclusion: The digital evaluation of the EASI is a reliable tool for the digital assessment of severity and extent of AD.

Clemens von Pirquet (1874 – 1929) pragt den Begriff „Allergie“ nun seit mehr als 100 Jahren. Das Konzept der Allergie war das Resultat von Forschungen im Bereich von Impfung und Serumkrankheit. Pirquet waren bei wiederholter Impfung schneller auftretende und starkere Reaktionen an der Injektionsstelle aufgefallen. Zur Dokumentation der gesteigerten Reaktion impfte sich Pirquet im Selbstversuch uber 5 Tage wiederholt mit Kuhpocken und lies das Resultat am 27. Juli 1905 durch Dr. Carl Henning (1860 – 1917) in einer Moulage festhalten. Diese Moulage von Pirquets volarem Vorderarm zeigt 12 Stunden nach der Impfung eine Quaddel mit Erythem, eine Nekrose nach 48 Stunden, sowie langsame Abheilung bis zum 5. Tag. Die Moulage wurde auch als Photographie in Pirquets Buch „Klinische Studien uber Vakzination und vakzinale Allergie“ von 1907 und weiteren zeitgenossischen Lehrbuchern abgebildet. Eine Kopie der Moulage wurde zu Unterrichtszwecken von Professor Max Tieche (1878 – 1938), dem Grunder der Stadtischen Poliklinik fur Dermatologie (dem heutigen Dermatologischen Ambulatorium des Stadtspitals Triemli) in Zurich verwendet. Heute stellt die Moulage ein eindrucksvolles Zeitzeugnis aus der Geburtsstunde der Allergologie dar.

Introduction: To examine the relationship between elevated basal serum tryptase levels (BST), a marker of total mast cell mass, and bone mineral density (BMD) in patients with anaphylactic reactions and signs of mastocytosis. Methods: Retrospective evaluation of patient charts at an allergy unit. Patients with BST levels above 20 ng/ml were eligible if clinical and follow-up data and results of dual X-ray absorptiometry (DXA) were available. Patients with previous use of anti-osteoporotic medications and with osteoporosis not caused by mastocytosis were excluded. Spearman’s rank correlation, Mann-Whitney test and receiver operating characteristic curve (ROC) was used for analysis. Results: 24 patients were included. The main presenting symptom (17 of 24 patients) was anaphylactic reactions to insect stings. BST levels ranged between 21 and 158 ng/ml (median 48 ng/ml). Study participants with Z-score values below - 1.0 had a median BST level of 46 ng/ml, the patients with Z-score values above or equal to -1.0 had a median BST level of 27 ng/ml. ROC analysis of the patient group with BST values between 30 and 100 ng/ml revealed a best cut-off value of BST to detect a low BMD when BST level would be at least 27 ng/ml resulting in a sensitivity of 92% and a specificity of 70%. Conclusion: Patients with moderately elevated BST levels seem to be at increased risk for low BMD.

Background The severity of rhinoconjunctivitis is typically monitored by means of nasal provocation tests (NPTs), where the nasally applied allergens trigger symptoms that are recorded using a scoring system. However, NPTs are time-consuming and stressful for patients; therefore, recording of symptoms during natural allergen exposure on visual analog scales (VASs) is increasingly being used in clinical trials. Objectives To evaluate (1) the correlation between VAS symptom recording by patients during natural allergen exposure and symptom scoring by the physician during the NPT and (2) the possibility of replacing the more laborious and distressing allergen provocation tests with the more patient-friendly VAS. Methods A total of 119 patients with allergic rhinitis due to grass pollen were enrolled in the study between June 20, 2001, and January 31, 2002. Patients reported the severity of different seasonal symptoms on a VAS and underwent a NPT. Results No significant correlations between VAS and NPT scores were found. However, all the correlation coefficients between the symptom scores from the NPT and the corresponding symptom scores from the VAS were much higher for the female than the male subgroup. Conclusions The VAS does not correlate with the NPT and, therefore, cannot replace the NPT. However, the result may suggest it worthwhile to explore the role of sex in the perception of allergy symptoms.

Relapsing eosinophilic perimyositis is a rare entity. Only 11 cases have been reported in the literature. We describe a patient with relapsing myopathy, peripheral blood eosinophilia and cutaneous manifestations, who had histopathological features of eosinophilic perimysial inflammation. His disease responded to moderate doses of glucocorticosteroids, and pursued an apparently benign course. Serum levels of eosinophilic cationic protein correlate with disease activity, and may be helpful in monitoring treatment. The features of this case are compared with those of other hypereosinophilic syndromes. It appears to be part of the spectrum of eosinophilic myositis.

Die Stellungnahme der SGAI beschaftigt sich mit den alternativmedizinischen Verfahren der „Bioresonanz“ und „Multiresonanz“ sowie der Elektroakupunktur nach Dr. Voll und der „bioelektrischen Funktionsdiagnostik“. Sie ist deshalb notig, da — obwohl negative Stellungnahmen von Seiten verschiedener europaischer Fachgesellschaften fur Allergologie und klinische Immunologie vorliegen — immer noch intensiv, vor allem im Internet, fur den Einsatz dieser „modernen Heilmethoden“ zur Diagnose und Therapie allergischer Erkrankungen geworben wird. Diese Leistungen werden zudem in der Schweiz — auch in Zeiten beschrankter Ressourcen — von Krankenkassen in der Zusatzversicherung abgegolten. Eine medizinische Methode — ob schul- oder komplementarmedizinischer Art — muss den Nachweis der Effektivitat erbringen und auf naturwissenschaftlichen Grundlagen beruhen, die dem aktuellen Stand des Wissens entsprechen. Nun sind die physikalischen Grundlagen dieser Verfahren nach der Uberprufung von Physikern und Ingenieuren falsch, gemessen wird nicht das, was postuliert wird, die gestellten Diagnosen sind zufallig und ofter allergologisch nicht nachvollziehbar, die abgeleiteten Diatempfehlungen irrational, und die vermeintlichen Therapieerfolge liesen sich in kontrollierten Studien nicht feststellen. Auch ein eminenter Vertreter der Komplementarmedizin hat am Beispiel der Bioresonanz dargelegt, wie pseudowissenschaftliche Sprache benutzt wird, um Unsinn als Wissenschaft zu prasentieren, den Patienten in die Irre zu fuhren und so unter Umstanden auch seine Gesundheit zu gefahrden. Die Verbreitung dieser Verfahren bedeutet einen Ruckschlag fur die in den letzten Jahren stark verbesserte Diagnostik und Therapie allergischer Erkrankungen. Man sollte Wege finden, dieses Problem zu minimieren. Die Krankenkassen sollten dem Begehren der Anbieter um Anerkennung dieser Methoden nicht stattgeben.

Die Stellungnahme der SGAI beschaftigt sich mit den alternativmedizinischen Verfahren der „Bioresonanz“ und „Multiresonanz“ sowie der Elektroakupunktur nach Dr. Voll und der „bioelektrischen Funktionsdiagnostik“. Sie ist deshalb notig, da – obwohl negative Stellungnahmen von Seiten verschiedener europaischer Fachgesellschaften fur Allergologie und klinische Immunologie vorliegen – weiterhin immer noch intensiv, vor allem im Internet, fur den Einsatz dieser „modernen Heilmethoden“ fur die Diagnose und Therapie allergischer Erkrankungen geworben wird. Diese Leistungen werden zudem in der Schweiz – auch in Zeiten beschrankter Ressourcen – von Krankenkassen in der Zusatzversicherung abgegolten. Eine medizinische Methode – ob schul oder komplementarmedizinischer Art – muss den Nachweis der Effektivitat erbringen und muss auf naturwissenschaftliche Grundlagen beruhen, die dem aktuellen Stand des Wissens entsprechen. Nun sind die physikalischen Grundlagen dieser Verfahren nach der uberprufung von Physikern und Ingenieuren falsch, gemessen wird nicht das, was postuliert wird, die gestellten Diagnosen sind zufallig und ofters allergologisch nicht nachfuhlbar, die abgeleiteten Diatempfehlungen irrational und die vermeintlichen Therapieerfolge liessen sich in kontrollierten Studien nicht feststellen. Auch ein eminenter Vertreter der Komplementarmedizin hat am Beispiel der Bioresonanz dargelegt, wie pseudowissenschaftliche Sprache benutzt wird, Unsinn als Wissenschaft zu prasentieren, den Patienten in die Irre zu fuhren und so unter Umstanden auch seine Gesundheit zu gefahrden. Die Verbreitung dieser Verfahren bedeutet einen Ruckschlag fur die in den letzten Jahren stark verbesserte Diagnostik und Therapie allergischer Erkrankungen. Man sollte Wege finden, dieses Problem zu minimieren. Die Krankenkassen sollten dem Begehren dieser Anbieter um Anerkennung dieser Methoden nicht stattgeben.

Since antigen-persistence plays a role for induction of immunity, we investigated the in vivo pharmacokinetic of a naked DNA vaccine at the site of its action, i.e., in the lymph node. After direct intralymphatic injection, naked DNA vaccine degraded within a few hours. In correlation with the short persistence of the DNA vaccine we found that the frequency of vaccination critically influenced the strength of the immune response. In mice vaccinated every 3 days, cytotoxic T-cell responses were enhanced compared to immunization in 6 or 9 days intervals. The results suggest that the so far disappointing efficiency of naked DNA vaccines in humans may be overcome by more frequent vaccination.

Background: Despite the well-documented efficacy of Hymenoptera specific immunotherapy (SIT), there is no safe method to reliably characterise the patient level of protection. Only poor correlations between protection and allergen-specific serum immunoglobulins have been found, and a sting challenge is the only means to evaluate the efficacy of immunotherapy. Therefore, we aimed to develop a cutaneous test that measures in vivo neutralisation of the Hymenoptera venom. Materials and Methods: Twenty-four patients with wasp venom allergy were included in the study. Wasp-specific serum IgE, IgG and IgG4 were measured by ImmunoCAP. Dilutions of the individual patient sera were intradermally injected into the forearm. Then, wasp venom extract was injected into these sites to quantitatively assess the formation of wheals and flares. Results: The results show that during the course of SIT, patient sera gained the capacity to neutralise skin reactions to wasp venom extracts in vivo. The test correlated with the duration of SIT as well as with the concentration of IgG and IgG4. Conclusion: The in vivo neutralisation test may become a promising tool in allergy diagnostics as well as in monitoring the success of SIT in patients undergoing allergen SIT.

Background: Controlled studies established the efficacy and good tolerability of pimecrolimus cream 1% for the treatment of atopic dermatitis but they may not reflect real-life use. Objective: To evaluate the efficacy, tolerability and cosmetic acceptance of a pimecrolimus-based regimen in daily practice in Switzerland. Methods: This was a 6-month, open-label, multicentre study in 109 patients (55% ≧18 years) with atopic dermatitis. Pimecrolimus cream 1% was incorporated into patients’ standard treatment protocols. Results: The pimecrolimus-based treatment was well tolerated and produced disease improvement in 65.7% of patients. It was particularly effective on the face (improvement rate: 75.0%). Mean pimecrolimus consumption decreased from 6.4 g/day (months 1–3) to 4.0 g/day (months 3–6) as disease improved. Most patients (74.1%) rated their disease control as ‘complete’ or ‘good’ and 90% were highly satisfied with the cream formulation. Conclusion: The use of a pimecrolimus-based regimen in everyday practice was effective, well tolerated and well accepted by patients.

There is a belief among some members of the public that the consumption of milk and dairy products increases the production of mucus in the respiratory system. Therefore, some who believe in this effect renounce drinking milk. According to Australian studies, subjects perceived some parameters of mucus production to change after consumption of milk and soy-based beverages, but these effects were not specific to cows' milk because the soy-based milk drink with similar sensory characteristics produced the same changes. In individuals inoculated with the common cold virus, milk intake was not associated with increased nasal secretions, symptoms of cough, nose symptoms or congestion. Nevertheless, individuals who believe in the mucus and milk theory report more respiratory symptoms after drinking milk. In some types of alternative medicine, people with bronchial asthma, a chronic inflammatory disease of the lower respiratory tract, are advised not to eat so-called mucus-forming foods, especially all kinds of dairy products. According to different investigations the consumption of milk does not seem to exacerbate the symptoms of asthma and a relationship between milk consumption and the occurrence of asthma cannot be established. However, there are a few cases documented in which people with a cow's milk allergy presented with asthma-like symptoms.

Allergen-specific immunotherapy (SIT) leads to a long-term amelioration of IgE- and Th2-mediated allergic diseases. However, SIT efficiency is low, with years of treatment along with frequent allergic side effects. The goal of this study was to reduce the side effects by destroying IgE-binding epitopes, i.e. by heat-denaturation, while preserving the therapeutic effect. Mice were immunised with bee venom, birch pollen, grass pollen or cat hair allergens, or with ovalbumin. Heat-denatured allergens bound less IgE but enhanced Th1-dependent IgG2a production as measured by ELISA. The strong IgG2a antibody responses also prevented allergic anaphylaxis in mice, as measured by body temperature drop after a challenge with a high allergen dose. We found that optimal heat-denaturation of allergens left a small proportion in the native conformation to sufficiently stimulate B cells, while non-B cell-mediated effects were probably amplified. The enhanced immunogenicity of heat-denatured allergens is likely explained by enhanced antigen presentation to T cells due to the particulate nature of heat-denatured proteins. This enables Th1 skewing of the immune response with strong production of IgG2a in mice. Therefore, heat-denaturation represents probably the simplest way to enhance the efficiency of SIT while reducing its side effects.

Background Autoreactivity of patients with atopic dermatitis (AD) to human proteins has been postulated as a decisive pathogenetic factor for AD. Objective In this study, it was investigated whether the stress-inducible enzyme manganese superoxide dismutase (MnSOD) of human and fungal origin might act as an autoallergen in atopic dermatitis. Methods Patients with AD (n=69; mean SCORAD [SCORing Atopic Dermatitis], 27) and other inflammatory skin diseases as well as with inhalant allergies were investigated. The presence of specific IgE against recombinant MnSOD of fungal and human origin and the fungal extracts of Aspergillus fumigatus and Malassezia sympodialis was measured by CAP, ELISA, skin prick test, and in subset of patients also by atopy patch tests (APTs) and PBMC proliferation assays. Cross-reactivity between allergens was determined by CAP inhibition. The presence of MnSOD in human skin in various inflammatory skin conditions was investigated by immunohistochemistry. Results Specific IgE antibodies against human MnSOD correlating with the disease activity were found in 29 out of 67 patients with AD. The human protein was able to induce in vitro T-cell reactivity and eczematous reactions in APT in MnSOD-sensitized patients with AD. MnSOD was upregulated in various inflammatory skin reactions and APT skin specimens. Cosensitization to structurally related and cross-reacting fungal MnSOD and the skin-colonizing yeast M sympodialis was observed in all patients sensitized against human MnSOD. Conclusion Human MnSOD may play a role as an autoallergen in a subset of patients with AD, including nonatopic eczema. By molecular mimicry leading to cross-reactivity such sensitization might be induced primarily by exposure to environmental fungal MnSOD of M sympodialis .

Atopic dermatitis (AD) or atopic eczema (AE) is a multifactorial skin disease caused by a variety of factors such as genetic conditions, alterated skin structure, immunologic deviations and environmental factors, among others. According to the new WAO nomenclature, the term "eczema" should be used as the "umbrella" term to cover all different subtypes of atopic dermatitis, i.e. the IgE-associated ("atopic eczema") and the non-IgE-associated type ("non-atopic eczema"). Besides some comments on the new nomenclature and the so-called "atopy march", we provide an overview of the diagnostic importance of atopy patch tests, especially in the formerly called "intrinsic" type of AE and the role of Staphylococcus aureus-enterotoxins with superantigenic activity, and of fungi (Coprinus comatus and Malassezia furfur sive sympodialis) as illness-specific allergens in AD/AE. The use of antiinfectious and antifungal drugs (topic or systemic) may be of notable benefit in some AD/AE patients. Especially in children with AD/AE, eczema is easily aggravated by contact with irritating factors (e.g. aggressive detergents, synthetic and woolen clothes). Also, skin colonization with Staphylococcus aureus is known as a major trigger of the disease. Silver-coated textiles and a silk fabric coated with AEGIS AEM 5772/5, an antimicrobial substance, efficiently reduce Staphylococcus aureus colonization in patients with AD/AE. Some new studies even have shown a superior improvement by treatment with silver-coated textiles or specially manufactured silk clothes compared to cotton textiles or mild topical corticosteroids. Finally, the development of a new class of steroid-free, topic immunomodulatory drugs (tacrolimus and pimecrolimus) has substantially improved the treatment of AD/AE. Nevertheless, patient education is still very important in the management of the disease since it often follows an unpredictable course.

Background: Drug allergy is an increasingly important clinical problem. About 5-10% of patients consulting allergy centers have some form of drug allergy or pseudo allergy. At present there is no consensus concerning the best way to study and diagnose hypersensitivity reactions to drugs. This leads both to practical difficulties in diagnosing individual patients and to more general problems in comparing protocols and results from different centers. Methods/Data base: The European Network for Drug Allergy (ENDA) Drug Ambassador Project aimed to collect information on the ways that different European centers approach these patients. Results: The present report summarizes data collected during this project, focussing on the organization of drug allergy consultations, diagnostic protocols and the various in vitro and in vivo investigation procedures in current use. The study revealed wide variation in the diagnostic procedures used for drug allergy in clinical practice, despite the apparent consensus achieved in recommendations and position papers. Conclusion: Reciprocal exchange of information and discussions based on these observations may help to achieve standardization and harmonization in this sector with significant potential benefits for patients with drug allergies.

Lupine (Lupinus albus) belongs to the family of the legumes (Leguminosae) and, therefore, demonstrates strong cross-reactivity with peanuts, chickpeas and white beans. Due to the high protein and lipid content, lupine flour is extensively used in food industry. It is added to cereal flours and used as emulsifier. Concomitant with the increasing intake of lupine, a rising prevalence of allergic reactions after ingestion as well as inhalation of lupine flour has been observed. We here present a patient with known severe peanut allergy who reacted after eating a pizza with severe respiratory symptoms, which required an intubation in the emergency room. Our investigations revealed that the pizza dough used in this "take-away" pizza was enriched with lupine flour. The sensitization to lupine could be proven by means of the skin prick test (SPT) with native lupine flour and also serologically as 44.30 kU/l (class 4) of specific IgE antibodies were measured by means of CAP-FEIA to lupine seed (f335, Pharmacia Diagnostics). A peanut contamination of the pizza was excluded by the manufacturer as well as by analysis in an immunoassay. IgE binding to major proteins at 20, 34, 60 and 62 kDa was detected by means of immunoblotting. In inhibition experiments, IgE-binding to lupine proteins was partially inhibited by peanut extract. Shortly after that first observation of a lupine allergy, a patient was admitted to our clinic who experienced allergic reactions including edema in the face and abdominal pain after ingestion of gingerbread that was declared to contain lupine flour. Apart from a slight pollinosis in childhood, the patient had no history of allergic reactions and no history of food allergy at all. She revealed a positive reaction to lupine flour in skin prick test and was positive for specific IgE against lupine flour in CAP-FEIA (class 3; 7.59 kU/l). Contrary to the first case, the IgE binding to lupine flour was not inhibited by peanut extract. On the basis of our observations in the two patients and further cases described in the literature, we conclude that allergic reactions to lupine can be mediated by cross-reacting IgE antibodies to peanut, chickpea and white beans or may occur due to an isolated sensitization as well. Because of the increasing use of lupine flour in the food industry and its high allergenic properties, lupine flour should be regarded as a highly allergenic food. Similar to peanut and soy, lupine should be added to the list of allergenic foods of the EU and Swiss Food Regulation that have to be mandatory declared.

Resume Ce compte-rendu a ete prepare par un groupe de l’Academie Europeenne d’Allergologie et d’Immunologie Clinique (European Academy of Allergology and Clinical Immunology, EAACI) representant les cinq sections de l’EAACI ainsi que le Comite directeur de l’EAACI compose de specialistes refletant l’opinion consensuelle sur l’allergie exprimee par differentes specialites cliniques et fondamentales ayant trait a l’allergie. L’objectif de ce compte rendu est de proposer une revision de la nomenclature des reactions allergiques et apparentees pouvant etre utilisee independamment de l’organe cible ou de la tranche d’âge des patients. La nomenclature est fondee sur les connaissances actuelles des mecanismes responsables de l’initiation et de la mediation des reactions allergiques. Cependant, l’intention n’a pas ete de reviser la nomenclature de l’hypersensibilite non allergique.

Prevalence rates of childhood asthma and allergy have been on the increase for several decades. The present study investigated whether this trend continued during the 1990s in adolescents living in Switzerland. Between 1992 and 2000, the change in prevalence of specific immunoglobulin E to aeroallergens, asthma symptoms and hay fever symptoms assessed by parents' and students' answers to the International Study of Asthma and Allergies in Childhood questions was investigated using three cross-sectional surveys. In total 1,324 (74.9%), 1,668 (80.6%) and 1,250 (73.9%) adolescents participated. Prevalence rates of asthma and current asthmatic symptoms remained constant, irrespective of whether the assessment was based on parental questionnaires or the student's self-completed written or video questionnaires (students' report of current wheeze 8.8, 7.3, and 8.3%). Similarly, no further increase was observed for reported hay fever rates and allergic sensitisation rates (positive multiscreen allergy test, SX1-test: 34.6, 38.9, and 35.6%, respectively). Although time trends in the occurrence of a series of known risk factors were recorded, none of these factors had a significant impact on asthma and allergy prevalence over time. No further increase in asthma and allergy rates occurred during the 1990s in adolescents living in Switzerland. However, to adequately assess the trend a longer period of observation is needed.

The opportunistic yeast Malassezia belongs to the normal cutaneous flora but can also cause IgE-mediated sensitization in patients suffering from atopic dermatitis (AD). We investigated the prevalence of sensitization to M sympodialis serologically and by skin test in various allergic conditions. Furthermore, a purpose of this study was to identify the causing allergenic structures of the yeast by using different recombinant allergens of M. sympodialis. Totally, 613 patients with allergic rhinoconjunctivitis to seasonal or perennial allergens (378), allergic asthma (83), AD (55), urticaria (31), food allergy (24), insect sting allergy (42) and 38 healthy controls were investigated. As natural allergen, a crude extract prepared from the M. sympodialis strain ATCC 42132 was used. Specific serum IgE was analyzed by ImmunoCAP ("m70, Pharmacia Diagnostics, Uppsala, Sweden); for the recombinant allergens an ELISA assay was established. Recombinant M. sympodilialis allergens (rMal sl, rMal s5, rMal s6, rMal s7, rMal s8, and rMal s9) were cloned and expressed in the E. coli M15 system and used for detection of allergen-specific IgE in the serum measured by ELISA. In 34 of 55 patients with AD, specific IgE against M. sympodialis was detected. The ELISA assay with recombinant allergens showed differential recognition patterns against the different molecular structures with a predominance of sensitization to rMal s5, rMal f6 and rMal f9. No reactivity to rMal s allergens was seen in other patients or healthy controls. In conclusion, sensitization to M. sympodialis occurs almost exclusively in patients with AD. The use of antifungals may therefore be highly beneficial in some AD patients. Recombinant allergens are an excellent tool to determine the immunologic relevance of fungi in AD.

Summary Background Diagnostic procedures using natural extracts show only limited quantitative correlation between in vivo and in vitro results. Highly pure recombinant allergens might show more predictive findings. Objective The aim of this study was to compare natural birch pollen extract (BPE) and recombinant Betula verrucosa (rBet v 1) for their diagnostic value comparing skin prick tests (SPTS) and nasal provocation tests (NPTS) with specific IgE in the serum. Methods Thirty-four patients allergic to birch pollen and five healthy controls were investigated. SPT and NPT were performed with BPE and rBet v 1 at different concentrations. Specific serum IgE was measured by the Pharmacia CAP system. Results Commercial BPE and rBet v 1 (10mg/mL) were able to elicit similar allergenic reactions in vivo and IgE binding in vitro. SPT reflects immediate-type allergy as determined by NPT to a higher degree than specific IgE, for both reagents. To cause allergic reactions in NPT, higher amounts of rBet v 1 were needed than for skin tests and the sensitivity was lower than with BPE. Conclusion rBet v 1 alone is sufficient for a reliable diagnosis of birch pollen allergy in most patients and induces comparable skin test reactivity as BPE, but less allergic reactions in nasal provocations.

Dieser Bericht ist von einer Arbeitsgruppe der Europaischen Akademie fur Allergologie und klinische Immunologie (EAACI) verfasst worden, die die funf Sektionen und den Vorstand der EAACI vertritt und die sich zusammensetzt aus Spezialisten, die das breite Meinungsspektrum verschiedener klinischer und wissenschaftlicher Disziplinen der Allergologie widerspiegeln. Ziel dieses Berichtes ist es, eine revidierte Nomenklatur fur allergische und verwandte Reaktionen vorzuschlagen, die unabhangig vom betroffenen Organ oder vom Patientenalter verwendet werden kann. Die Nomenklatur basiert auf dem gegenwartigen Wissen uber die Pathomechanismen, die allergische Reaktionen auslosen und vermitteln. Es war nicht die Absicht der Arbeitsgruppe, auch die Nomenklatur der nicht allergischen Hypersensitivitat zu revidieren.

Background: Allergy to hazelnuts is a common example of birch pollen related food allergy. Symptoms upon ingestion are often confined to the mouth and throat, but severe systemic reactions have been described in some patients. The aim of the study was to evaluate the reduction in allergenicity by roasting of the nuts. Methods: Double-blind, placebo-controlled food challenges (DBPCFC) with roasted hazelnuts (140°C, 40 min) were performed in 17 birch pollen allergic patients with DBPCFC-confirmed food allergy to raw hazelnuts. The effect of roasting was further evaluated by skin prick test (SPT), histamine release (HR), measurement of specific IgE, and IgE-inhibition experiments. Results: In 5/17 patients the DBPCFC with the roasted nuts were positive. The symptoms were generally mild and included OAS (oral allergy syndrome) in all patients. Roasting of the nuts significantly reduced the allergenic activity evaluated by SPT, HR, specific IgE, and IgE-inhibition. Immunoblotting experiments with recombinant hazelnut allergens showed sensitization against Cor a 1.04 in 16/17 patients and against Cor a 2 in 7/17 patients. None of the patients were sensitized to Cor a 8. Challenge-positive patients did not differ from the rest in IgE-binding pattern. Conclusions: All the applied methods indicated that roasting of hazelnuts reduces the allergenicity, but since 5/17 birch pollen allergic patients were DBPCFC-positive to the roasted nuts, ingestion of roasted hazelnuts or products containing roasted hazelnuts can not be considered safe for a number of hazelnut allergic consumers. For patients with a history of severe allergic symptoms upon ingestion of hazelnuts, thorough and conscientious food labelling of hazelnuts and hazelnut residues is essential.

Background: Profilins are recognised by IgE of about 20% of patients allergic to birch pollen and plant foods. They are ubiquitous intracellular proteins highly cross-reactive among plant species. Therefore, they were called panallergens and are made responsible for cross-sensitisation between plant pollen and food. Objectives: The aim of the present study was to clone the cDNAs encoding profilins from bell pepper and tomato, to produce and purify the recombinant proteins and to compare their IgE-binding capacities to those of the natural proteins. Methods: cDNA clones coding for profilin were obtained by RT-PCR from total RNA of tomato and bell pepper fruits, sequenced and expressed as non-fusion proteins in Escherichia coli. The recombinant profilins were subsequently purified and tested for IgE-binding and inhibition capacity with sera from 34 food-allergic patients. Possible oligomerisation of recombinant profilins was investigated by HPLC analysis and its influence on IgE binding assayed by ELISA. Results: The open reading frame from both profilins encompasses 393 bp with a predicted molecular mass of 14,184 kD and a pI of 4.44 for bell pepper profilin (Cap a 2) and 14,257 kD and a pI of 4.46 for the profilin from tomato (Lyc e 1). The two protein sequences display 91% identity, whereas tomato profilin from pollen shares only 75% identity with tomato fruit profilin. Eleven out of 34 food-allergic patients (32%) display IgE binding to both purified profilins. Preincubation of a serum pool with either purified rCap a 2 or rLyc e 1 nearly abolished IgE binding to natural Cap a 2 and Lyc e 1, respectively. In addition, purified recombinant Cap a 2 was able to inhibit IgE-binding to rLyc e 1 by approximately 50%, whereas rLyc e 1 completely blocked IgE-binding to rCap a 2 in cross-inhibition assays. HPLC analysis showed that in solution Cap a 2 and Lyc e 1 can be found predominantly as dimers, which can be partially reduced to monomers by addition of dithiothreitol (DTT). In ELISA DTT-treated Lyc e 1 displayed a clearly lower IgE-binding capacity than untreated profilin. Conclusions: Purified rCap a 2 and rLyc e 1 proved to be valuable tools for studying cross-reactivity to profilins in patients allergic to pollen and food.

Acupuncture has traditionally been used in China in the treatment of bronchial asthma and is being increasingly applied in Western countries. Although there are many published studies on acupuncture and asthma, few meet the scientific criteria necessary to prove the effectiveness of acupuncture.To examine the short- and long-term effects of real versus sham or no acupuncture in patients with bronchial asthma.Randomized partially blinded study with three parallel groups.Sixty-six (66) patients of both genders (mean age, 39 years) with mild-to-moderate persistent bronchial asthma.After 2 weeks of run-in, the patients with asthma were randomized to receive either real (23 patients) or sham acupuncture (23 patients) or no acupuncture (20 patients). Two acupuncture periods (each 4 weeks) within the first 4 months were followed by a 6-month observation.Primary outcome was the change of peak expiratory flow (PEF) variability at the end of the two treatment periods. Secondary outcomes were changes in forced expiratory volume in 1 second (FEV1), airway responsiveness, symptoms of asthma, the use of asthma drugs, and patients' well-being. Moreover, the effect of the intervention on eosinophils and eosinophil cationic protein (ECP) in blood and sputum was assessed.PEF variability decreased in all groups. In a subgroup of patients whose asthma medication remained fairly unchanged, PEF variability decreased significantly after needling of real as well as sham points at month 4 and 5 compared to controls (por = 0.005). However, there was no difference in the decrease of PEF variability between patients who had the blinded treatment with real or sham acupuncture. Most of the other functional and clinical variables did not differ from those obtained in controls. Eosinophils and ECP in blood and sputum decreased in all groups, but the only significant differences were found in blood eosinophil count at 4 months between sham acupuncture and the control group (p0.05) and at 10 months between real and sham acupuncture (p0.05) suggesting a possible effect on eosinophilic inflammation.In view of the fact that the effects after real and sham acupuncture compared to controls who had no needling at all were small, in all likelihood clinically irrelevant, our data do not seem to support the use of acupuncture in the management of pharmacologically well-treated patients with mild-to-moderate persistent asthma.

Background Banana is a frequent cause of food allergy, particularly in latex-sensitized patients. Objective The aim of the study was to get insights in immunoglobulin (Ig)E antibody responses of patients with a history of allergic reaction to banana but not to latex. Methods In four patients who complained about symptoms after banana consumption, skin prick tests (SPTs) with aeroallergens, latex, banana, avocado, and kiwi were performed. Total and specific serum IgE to birch pollen, rBet v 1 and rBet v 2, latex, banana, avocado, and kiwi were determined by the CAP method (Pharmacia Diagnostics, Uppsala, Sweden). Allergens were identified by immunoblotting with banana extract and recombinant banana profilin. Two patients underwent double-blind, placebo-controlled food challenges (DBPCFC) with banana. Results All patients showed a positive SPT to banana, and three were IgE-CAP positive (≥ class 2). Two patients were also sensitized (SPT and CAP) to latex, avocado, kiwi, and birch pollen. In the immunoblot these two patients' sera reacted to 32- to 34-kDa proteins, which had already been described as major banana allergens. In both patients banana allergy was confirmed by DBPCFC. The third patient also had a sensitization to avocado, but not to latex or pollen. Immunoblot analysis detected a single band at 70 kDa. The fourth patient was sensitized to birch pollen, rBet v 1 and rBet v 2, but not to latex. Immunoblot analysis in this patient's serum was positive with recombinant banana profilin. Conclusions The relevance of banana as a source of food allergy was confirmed in two patients by DBPCFC. In 1 of 2 patients, in whom banana allergy was not a consequence of latex sensitization, a 70-kDa protein was identified as a banana allergen, and in the other patient profilin was detected as a putative cross-reactive allergen.

A 24-year-old man was suffering from severe asthma, urticaria and generalized pruritus since the age of 14 after eating all kinds of cow's milk products. Even the ingestion of small amounts of cheese and butter produced the same symptoms. Serologic testing showed a sensitization to casein (CAP class 5, 68.2 kU/L). Prick testing showed a strongly positive reaction to cow's milk and cheese. Prick-to-prick testing with feta cheese was negative so an oral challenge test with feta cheese was done, started with 5 g. 15 minutes after ingestion he presented a conjunctivitis and a running nose, followed by edema and a severe asthma attack. The following examination showed highly elevated specific IgE to casein, especially to the fraction of α 1 -casein to cow's, sheep's and goat's milk. The patient was told to follow a milk-free diet. In case of an accidental ingestion of milk the patient was given emergency medicaments (antihistamines, steroids and adrenaline for subcutaneous injection). Cross reactions can explain allergic reactions to other milk species, so goat's, sheep's and horse's milk is definitely no generalized alternative. In any case testing and if uncertainties remain, double blind oral food challenge is necessary.

In the treatment of allergic disorders, specific immunotherapy (SIT) occupies a central role as the only currently available causal method of treatment. The concept of ‘‘local immunotherapy’’ includes all nonsubcutaneous forms of SIT, which are used to treat allergic disorders such as rhinitis and asthma. Nasal, bronchial, oral and sublingual administration of allergen extracts is regarded as local immunotherapy (LIT). Attempts were made very early to produce tolerance to certain allergens by the oral route. Dakin reported in1829 that North American Indians regularly chewed small amounts of leaves of the ‘‘poison ivy’’ (Rhus toxicodendron) in order to prevent or weaken the severe dermatitides that occur after contact with this plant (Dakin, 1829 quoted after (1)). In 1900, 11 years before the first work on subcutaneous immunotherapy, Curtis published an article about the efficacy of oral allergen-specific immunotherapy (OIT) in hay fever (2). This was followed five years later by other reports about the success of OIT in cow’s milk allergy (3). In the 1920s and 1930s, too, reports of positive experiences with this method appeared again and again. However, a negative, multicentre comparative study of ragweed pollinosis (4) (in which, interestingly, good results were reported in children!) severely limited the use of OIT in adults in the Anglo-Saxon countries. In the early 1950s, Schuppli in Basel, Switzerland took up OIT again. His positive results in children ensured that this method soon became widespread (5–12). New methods of local application were sought, because various studies in recent years showed that OIT is clearly inferior to allergen-specific subcutaneous (injected) immunotherapy (SIT) with regard to both clinical and immunological efficacy. From a clinical aspect however, there is a whole series of arguments to explain the preference for LIT compared to injected IT. Poor compliance can limit the applicability of injected SIT (13). Because LIT can be carried out at home by the patient and the injections in the doctor’s office are no longer necessary, greater compliance is ascribed to LIT than to SIT. However, more precise studies of this subject are lacking, so the effective compliance of LIT patients is not known. Severe systemic side-effects restrict the broad use of SIT, although the risk in hay fever patients is lower compared to asthma patients (14, 15). When SIT is carried out correctly, severe systemic side-effects in patients with allergic rhinitis, who are treated with potent extracts, occur in about 5% of all the SIT injections (16). Based on the published data, on the other hand, systemic side-effects appear to occur only very rarely with LIT. The rapid development of molecular biology and progress not only in general allergen characterization but also in the production of large quantities of recombinant allergens have reawakened interest in recent years in local immunotherapy (LIT), both in science and among the producers of allergen extracts. At present there appears to be a trend away from oral towards sublingual allergen-specific IT (SLIT).

The aim of this study was to produce the Bet v 1-related major hazelnut allergen Cor a 1.0401 and variants thereof as recombinant allergens, and to compare their immuno-reactivity with the major hazel pollen allergen using sera of patients whose hazelnut allergy recently was confirmed by double-blind placebo-controlled food challenges (DBPCFC) in a multicenter study. Total RNA was isolated from immature hazelnuts and transcribed into cDNA. Full length coding DNA obtained by PCR-strategy was subcloned into pTYB11 vector and expressed in E. coli ER2566 cells. Native non-fusion target proteins were purified by DTT-induced self-cleavage of the intein-tagged N-terminal fusion proteins. IgE reactivity of the recombinant allergens was tested by enzyme allergosorbent test (EAST), EAST-inhibition, immunoblot-inhibition and histamine release assays. Four recombinant allergens were produced showing deduced amino acid sequence identities among each other of 97–99%, and were considered as variants Cor a 1.0401 (GenBank Accession no.: AF136945), Cor a 1.0402 (AF323973), Cor a 1.0403 (AF323974) and Cor a 1.0404 (AF323975). Cor a 1.0402 and 03 only differed in a C4S exchange. Cor a 1.0404 had a unique proline residue in position 99. Surprisingly, only 63% identity was revealed with hazel pollen Cor a 1. EAST with 43 sera of patients with positive DBPCFC to hazelnut indicated IgE reactivity to Cor a 1.0401 in 95% of the sera, to Cor a 1.0402 in 93%, to Cor a 1.0403 in 91%, and in only 74% of the sera to the proline variant Cor a 1.0404. The allergenic activity of the four variants was confirmed by histamine release assays in 15 hazelnut-allergic patients stimulated with the four variants and controls. Eleven sera were positive with extract from native hazelnut, 13 with rCor a 1.0401, 12 with rCor a 1.0402, 11 with rCor a 1.0403, and only two with rCor a 1.0404 containing the proline exchange. The high IgE binding variant Cor a 1.0401 showed only partial IgE cross-reactivity with pollen Cor a 1. IgE-binding and histamine release capacity led to a concordant ranking of the allergenic activity of the recombinant variants: Cor a 1.0401>Cor a 1.0402 and 03>Cor a 1.0404 (the proline variant). Similar results for Cor a 1.0402 and 03 suggest a minor influence in IgE binding of cysteine in position 4, whereas proline in position 99 appears to be responsible for the decrease in IgE reactivity in Cor a 1.0404. It appears that the epitopes of hazelnut Cor a 1.04 are less related to pollen Cor a 1 than to Bet v 1 from birch pollen. Low IgE binding variants or mutants of Cor a 1.04 are candidate compounds for developing a novel and safe approach of specific immunotherapy of hazelnut allergy.

In this chapter we will first consider whether there is real evidence on the basis of literature for early descriptions in antiquity of pathogenic reactions after food intake that could be comparable to allergy, for instance in the scriptures of Hippocrates or Lucretius. On this topic we are skeptical, which is in agreement with the medical historian Hans Schadewaldt. We also assert that it is unlikely that King Richard III was the first food-allergic individual in medical literature. Most probably it was not a well-planned poisoning ('allergy') with strawberries, but rather a birth defect ('… his harm was ever such since his birth') that allowed the Lord Protector to bring Mylord of Ely to the scaffold in the Tower, as we can read in The History of King Richard III by Thomas More (1478-1535; published by his son-in-law, Rastell, in 1557). In 1912, the American pediatrician Oscar Menderson Schloss (1882-1952) was probably the first to describe scratch tests in the diagnosis of food allergy. Milestones in the practical diagnosis of food allergy are further discussed, including scratch tests, intradermal tests, modified prick tests and prick-to-prick tests. False-negative results can be attributed to the phenomenon of a 'catamnestic reaction' according to Max Werner (1911-1987), or to the fermentative degradation of food products. Prior to the discovery of immunoglobulin E, which marked a turning point in allergy diagnosis, and the introduction of the radioallergosorbent test in 1967, several more or less reliable techniques were used in the diagnosis of food allergy, such as pulse rate increase after food intake according to Coca, the leukopenic index, drop in basophils or drastic platelet decrease. The 'leukocytotoxic test' (Bryan's test), today called the 'ALCAT' test, shows no scientific evidence. The double-blind placebo-controlled food challenge test remains the gold standard in the diagnosis of food allergy. For the future, component-resolved diagnostics with the use of recombinant molecular allergens or chip arrays, such as the ISAC technique, hold a lot of promise. With regard to the clinical situation, a subjective selection is given, touching on the pollen-associated food allergies ('birch-mugwort-celery-spice syndrome'), as well as the new phenomenon of lethal food allergies that have appeared since the 1980s. Finally, rare ways of elicitation of a 'derivative allergy', first described by Erich Fuchs (1921-2008), for example by kissing, as well as 'oral allergy syndrome' and oral hyposensitization are considered.

In this chapter we will first consider whether there is real evidence on the basis of literature for early descriptions in antiquity of pathogenic reactions after food intake that could be comparable to allergy, for instance in the scriptures of Hippocrates or Lucretius. On this topic we are skeptical, which is in agreement with the medical historian Hans Schadewaldt. We also assert that it is unlikely that King Richard III was the first food-allergic individual in medical literature. Most probably it was not a well-planned poisoning ('allergy') with strawberries, but rather a birth defect ('… his harm was ever such since his birth') that allowed the Lord Protector to bring Mylord of Ely to the scaffold in the Tower, as we can read in The History of King Richard III by Thomas More (1478-1535; published by his son-in-law, Rastell, in 1557). In 1912, the American pediatrician Oscar Menderson Schloss (1882-1952) was probably the first to describe scratch tests in the diagnosis of food allergy. Milestones in the practical diagnosis of food allergy are further discussed, including scratch tests, intradermal tests, modified prick tests and prick-to-prick tests. False-negative results can be attributed to the phenomenon of a 'catamnestic reaction' according to Max Werner (1911-1987), or to the fermentative degradation of food products. Prior to the discovery of immunoglobulin E, which marked a turning point in allergy diagnosis, and the introduction of the radioallergosorbent test in 1967, several more or less reliable techniques were used in the diagnosis of food allergy, such as pulse rate increase after food intake according to Coca, the leukopenic index, drop in basophils or drastic platelet decrease. The 'leukocytotoxic test' (Bryan's test), today called the 'ALCAT' test, shows no scientific evidence. The double-blind placebo-controlled food challenge test remains the gold standard in the diagnosis of food allergy. For the future, component-resolved diagnostics with the use of recombinant molecular allergens or chip arrays, such as the ISAC technique, hold a lot of promise. With regard to the clinical situation, a subjective selection is given, touching on the pollen-associated food allergies ('birch-mugwort-celery-spice syndrome'), as well as the new phenomenon of lethal food allergies that have appeared since the 1980s. Finally, rare ways of elicitation of a 'derivative allergy', first described by Erich Fuchs (1921-2008), for example by kissing, as well as 'oral allergy syndrome' and oral hyposensitization are considered.

Background: Undeclared allergens in foodstuffs represent a major health problem for sensitized persons. Until recently, most food control authorities were not in the position to monitor hidden allergens and to take legal measures against their presence in foodstuffs. Methods: In this study, we employed human sera-based immunoassay techniques, enabling semiquantitative detection and identification of peanut allergens in a variety of foodstuffs. Results: This study showed the presence of undeclared allergens in products belonging to various food categories, such as cereals, cookies, cakes, and snacks. The detection limit for peanut contamination was in most instances less than 50 mg peanut material per kg, i.e., less than about 5 mg peanut allergens per kg. We legally objected to products with more than one part per thousand or 1000 mg/kg of peanut contamination. Conclusions: In most cases, food producers, confronted with our results, were able to detect and eliminate the sources of the contamination. They implemented measures to prevent the presence of hidden peanut allergens in their products, increasing food safety for sensitized persons and overall food quality.

Departmentof Pharmacology, University of Bern, Bern, SwitzerlandKey words: atopic dermatitis; clinical features;constitutional dermatitis; epidemiology; extrinsictype; immunopathology; intrinsic type.Prof. Dr B. Wu¨thrichAllergy Unit, Department of DermatologyUniversity Hospital8091 ZurichSwitzerlandAccepted for publication 22 March 2001

Terbinafin (Lamisil) ist eine weit verbreitete und effiziente Therapie von Dermatomykosen. Wir berichten uber einen 20-jahrigen Patienten, der wegen einer Candidiasis inguinoscrotalis mit oral verabreichtem Terbinafin (Lamisil) behandelt wurde. Er entwickelte 8 Tage nach Beginn der Einnahme disseminierte pustulose Hautveranderungen und febrile Temperaturen. Die Hautbiopsie zeigte subkorneale und spongiforme Pusteln. Aufgrund der Anamnese, des klinischen Bildes und der Laborparameter wurde die Diagnose einer terbinafininduzierten akuten generalisierten exanthematischen Pustulose (AGEP) gestellt. Im Folgenden werden Krankheitsbild, Differenzialdiagnose, Ausloser und Therapie der AGEP diskutiert und eine Zusammenstellung der in der Literatur mitgeteilten Falle terbinafininduzierter AGEP gegeben.

In dieser Übersicht werden die epidemiologischen Daten über das Vorkommen allergischer Erkrankungen in der Schweiz zusammengefasst. Die Schweizer Studie über Luftverschmutzung und Atemwegserkrankungen bei Erwachsenen (SAPALDIA) erfasste in den Jahren 1991 bis 1993 9651 zufällig ausgewählte Probanden (18- bis 60-jährige) in acht Schweizer Regionen (Stadt-, Land- und Berggebiete). Bei 8357 lagen vollständige Allergieteste vor. 32,3% erwiesen sich als Atopiker (positive Prickteste und/oder positiver Phadiatop). (Phadiatop ist ein In-vitro-Screening-Test für inhalative Sensibilisierungen.) 12,7% waren gegen Graspollen, 8,9% gegen Hausstaubmilben, 7,9% gegen Birkenpollen und 3,8% gegen Katzenepithelien sensibilisiert. 11,1% litten an einer allergologisch diagnostizierten aktuellen Rhinitis pollinosa, 6,8% an einem vom Arzt diagnostizierten Asthma bronchiale (kumulative Prävalenz). Die Pollinosis war häufiger in den Städten (z.B. in Basel 18,0%) als in den ländlichen Regionen (z.B. in Payerne 6,4%). Die geometrischen IgE-Mittelwerte der SAPALDIA-Stichprobe betrugen 31,3 kU/l (30.3.–32.3); Raucher wiesen höhere Serum-IgE-Spiegel (39,7 kU/l) auf. Die niedrigsten IgE-Werte zeigten Phadiatop-negative Nicht-Raucher (15,5 kU/l) (p < 0.001). Bei Phadiatop-positiven Probanden lagen die mittleren IgE-Serumspiegel bei 104,3 kU/l. Passivraucher hatten im Vergleich zu nicht-exponierten Nicht-Rauchern ein erhöhtes Risiko für pfeifende Atmung (OR = 1,94), Atemnot (1,45), Asthma (1,39) und chronische Bronchitis (1,50). Gemäß der Schweizer Studie über das Vorkommen von Allergien bei Schulkindern (SCARPOL) (6/7-, 9/11-, 13/15-Jährige) leiden 17,0% der 15-jährigen Schüler an Heuschnupfen, Knaben mit 19,4% häufiger als Mädchen mit 14,8%. Ein vom Arzt diagnostiziertes Asthma bronchiale (jemals) kam mit etwa 9,0% in allen Altersgruppen gleich häufig vor. Die Prävalenz von atopischer Dermatitis betrug durchschnittlich 13% mit einer aktuellen Prävalenz von 8%, ohne signifikante Unterschiede innerhalb der Altersklassen. Ihr Vorkommen ist jedoch stark von sozio-ökonomischen Faktoren und einer Katzenhaltung abhängig. Bauernkinder leiden signifikant seltener an Heuschnupfen und Asthma als gleichaltrige Kinder ohne Tätigkeit in der Landwirtschaft. Sowohl die SAPALDIA- als auch die SCARPOL-Studie belegen die hohe Prävalenz von atopischen Sensibilisierungen und atopischen Erkrankungen in der Schweiz und die gesundheitlichen Auswirkungen der Luftverschmutzung und des «western life-style» auf ihr Vorkommen. Die Beobachtungen an Bauernkindern hingegen lassen den Schluss zu, dass ein traditioneller bäuerlicher Lebensstil ein Schutzfaktor vor Allergien bedeuten könnte.