Charles Harrison Blackley was the first to carry out a scratch test on his own skin with timothy pollen in 1873. In 1912, the American pediatrician Oscar Menderson Castle was able to confirm the alimentary pathogenesis of certain allergies by means of scarification tests. In 1907, Clemens von Pirquet pricked his forearm skin with a skin scarifier (Pirquet drill) through a drop of a tuberculin solution and scarified the skin. In 1908, Felix Mendel recommended the intracutaneous application of tuberculin; a few months later, Charles Mantoux published the tuberculin test named after him. To be fair, the tuberculin test should therefore be called the Mendel-Mantoux test. In 1915, Robert Anderson Cooke published the method of intracutaneous or intradermal testing with pollen extracts to detect pollen sensitization. In 1924, Lewis and Grant were the first to publish the procedure of prick testing. In 1959, Helmtraud Ebruster presented a modified prick test, a combination of an intracutaneous procedure and a scarification test, in which not only is the skin scarifier punctured through the dripped test solution, but it is also lifted and rotated. Jack Pepys, apparently unaware of Ebruster's publication, published recommendations for carrying out the modified prick test. The prick test subsequently became the first step in allergy workup. Since skin tests with commercial extracts from fruits and vegetables often turn out to be false negative, the prick-to-prick test method was increasingly used to test these allergens in addition to scratch tests with native material. Alberto Oehling described a new test in Bad Lippspringe in 1961, the nib test. In this simple test, the native allergens (wood, coffee dust, apple, etc.) are rubbed on the volar surface of the forearm. The allergens are absorbed via the hair follicles: a positive reaction leads to follicular wheal formation.

After the Second World War, the various fields of medicine recovered from the crisis at different paces; allergy and immunology were not among the first disciplines to be firmly established very soon. In fact, this field was newly emerging out of many different disciplines hying to find its shape and structure both in experimental research as well as in clinical practice. This was reflected by the foundation of several national and international associations which called themselves Society for "Allergy", "Allergology", "Allergy and Clinical Immunology" or "Allergy and Immunity Research", and so on. The 1st European Congress on Allergy was held in Paris from May 31 to June 1, 1950, and was organized by L.P. Vallery Radot, B.N. Halpern, and P. Blamoutier. On that occasion, the idea of a closer collaboration on a European level was suggested. The representatives of the European Allergy Societies created a European Council with the task to organize the next European Congress. A milestone for the development of allergology in Europe was the First International Congress for Allergy, September 23 - 29, 1951, in Ztirich. The president was Prof. Fred W. Wittich, Minnesota (USA), and it was organized by Prof. Ch.W. Loftier and Prof. A.S. Grumbach, Zurich (Switzerland). Thirteen European National Society Members were present at the 1951 Congress: the Societe Beige de l'Allergie, the British Association of Allergists, the Danish Society for All-crgological Research, the Deutsche Gesellschaft fur Allergie-Forschung, the Sociedad Espanola de Alergia, the Finnish Allergy Society, the Hungarian Society of Allergists, the Societe Francaise d'Allergie, the Associazione Italiana per lo Studio dell'Allergia, the Nederlandse Vereiniging voor Allergie the Sociedade Portuguesa de Alergia, the Swedish Association of Allergists, and the Schweizerische Allergie-Gesellschaft. This article contains a short description of these societies according to the years of their foundation. The discovery of IgE 1966/67 opened a new acra for allergology.

Joseph Jadassohn (1863-1936) is considered to be the researcher who first described patch testing or "Lappchentest" as he named it in German. This has to be questioned however, because at the Dermatology Conference in Graz, Austria in 1885, Jadassohn did not present a method for the diagnosis of hypersensitivity. Instead he described the relationships of triggering substances with external or internal forms of application. Bruno Bloch (1878 1933) has to be given credit when it comes to the first real description of a patch-test. Besides a detailed description of the test method, Bloch also recommended the first model of a "standard test" based on his observations. The controversy between Moritz Oppenheim (1876 1949) and his assistant Karl Steiner (at the Department of Dermatology and Venereology at the Wilhelminenspital in Vienna) on the one side and Hans Stauffer (Bloch'sche Klinik) on the other will be explained in this article. Oppenheim and Steiner had a very sceptical view towards the patch test, which they referred to as "functional skin test according to Jadassohn-Bloch", and only acknowledged its diagnostic value in cases of congenital hypersensitivity (idiosyncrasy). Guido Miescher (1887-1961) and his coworker Walter Burkhardt (1905-1971), who later became head of the Municipal Outpatient Clinic in Zurich, Switzerland, focused on patch testing in hypersensitivity to turpentine oil and nickel as well as in patients with cement eczema. In 1950, chromates in cement were first described as the reason for this frequent type of eczema in construction workers (H. Jager und E. Pelloni at the Dermatology Clinic, Lausanne, Switzerland). The term "patch test" as such was introduced into the English language literature by Marion Baldur Sulzberger (1895-1983) and Fred Wise (1895-1983) in 1931; however, they did not even mention the name Bloch and only referred to Jadassohn. The book "Die Epicutantestung" by Bandmann and Dohn (1967) became the standard work for an entire generation of German dermatologists.

The following article presents some milestones and tidbits of the findings in the area of food allergy and food allergens made in the past 100 years. In 1912, the American pediatrician Oscar Menderson Schloss (1882 - 1952) was the first to demonstrate an allergy to food using scratch testing. He also described the procedure of oral desensitization using food (albumen and milk). The phenomenon of "catamnestic skin reactions", the identification of celery allergy, unusual pathways of food allergy induction (e.g., "derivative allergy"), allergies induced by kissing, and "connubial allergy" will also be presented. Finally, the phenomenon of fatal food allergies, which is known since the 1980s, will be pointed out.

The co-saisonal desensitization of pollinosis with the scarification method (so-called "quadrillages cutanes") after the French allergologists Pierre and Jean Blamoutier was an useful treatment at the time where non-sedating antihistamines were not already at the market. Recently, the epicutaneous allergen administration is presented as as a novel method of allergen-specific immunotherapy.

Clemens von Pirquet (1874 1929) coined the term "allergy" now more as 100 years ago. The concept of allergy was the result of research in the field of serum sickness and vaccination. Pirquet had noted faster and stronger reactions at the site of injection after repeated vaccination. As a documentation of these reactions Pirquet repeatedly vaccinated himself with cow pox during 5 days and took readings of the reaction. On July 27, 1905 a wax model (moulage) of the reactions on Pirquet's arm was done by Dr. Carl Henning (1860 1917). This wax model shows a papule and a flare in the reading after 12 hours. During the readings up to 48 hours the papules become necrotic. The readings up to 5 days show a gradual healing. The moulage has been shown as a coloured photograph in Pirquet's book Klinische Studien uber Vakzination und vakzinale Allergie" published in 1907 and other contemporary textbooks. A copy of the original wax model was used for teaching purposes by Professor Max Tieche in the Stadtische Poliklinik fur Haut- und Geschlechtskrankheiten (today's Dermatologisches Ambulatorium Stadtspital Triemli Zurich) in Zurich. Today this moulage is an impressive lifelike testimony of the research at the outset of allergology.

Potential und limitations of allergologic in-vitro diagnosis of food and histamine intolerance Food intolerances are non-immunologically mediated hypersensitivity reactions to food and food additives. Pathogenesis differentiates between enzymatic, pharmacologic and unknown intolerance-inducing mechanisms. Thus, the diagnostic work-up for food intolerances cannot be carried out using immunologic in-vitro methods. Lactose intolerance as well as hereditary fructose intolerance can nowadays be diagnosed by genetic testing. For everyday practice the most useful method to diagnose lactose intolerance or fructose malabsorption is the 112 breath test after lactose or fructose provocation. For the diagnosis of histamine intolerance syndrome there are no established parameters: the diagnostic impact of the determination of serum DAO is being discussed controversially. Lately, a genetic test has become available. This test shows whether a person has a normally functioning gene variant of histamine N-methyltransferase (HNMT) or another gene variant (mutation, genetic defect, polymorphisms). Gluten intolerance (celiac disease) is an immunologically mediated intestinal disease (autoimmunity) that affects only genetically predisposed persons. For diagnostic work-up IgA antibodies against endomysium and transglutaminase (ELISA) as well as the IgA level are determined. In cases of IgA deficiency (frequently associated with celiac disease) IgG against native gliadin and gluten are determined. Most intolerances caused by food additives are based on unknown mechanisms that lead to the release of mediators from blood basophils or mucosal mast cells. Skin tests or validated in-vitro tests for diagnosis are not yet available. The determination of IgG/IG4 against food or food additives as well as cytotoxic tests have not been scientifically validated so far.

Allergies in elderly patients Data on the prevalence and incidence of atopy and allergic diseases in the age group of over 60 years are sparse. Based on existing data an atopy prevalence (defined as the presence of specific serum IgE, positive Phadiatop test) of 15 - 20% has to be assumed. The prevalence of allergic rhinitis is suggested to be approximately 10 - 15%. One study found the rate of first manifestation of pollen allergies in patients over 60 to be 5.5%. In Northern Italy the age of first manifestation of ragweed allergy was over 50 in 30% of cases and over 60 in 9.5% of cases. Almost nothing is known about the occurrence of food allergies in this elderly population. Furthermore, there are only few (prospective) studies on the efficacy and tolerability of specific subcutaneous immunotherapy (SCIT) in elderly patients with atopic allergic rhinitis and asthma and no studies on sublingual immunotherapy (SLIT). Generally, even elderly high-risk patients with insect venom allergy should not be denied SIT; an increased tryptase level in old age predisposes to severe reactions, also under SIT. The use of beta-blockers under SCIT increases the risk of adverse airway reactions (bronchial obstruction) and carries the danger that an adrenalin therapy, that might me necessary in case of emergency, is less effective. The discontinuation of angiotensin receptor antagonists is being discussed controversially. Further research on the incidence and prevalence of atopic sensitization and allergic diseases in elderly patients is essential. In elderly patients with respiratory symptoms a thorough allergy work-up is of major importance.

A 47-year-old female patient without pre-existing manifest atopic diseases experienced 5 episodes of severe anaphylactoid reactions within I year. All events occurred subsequently to physical activities (nordic walking, cycling, dancing). Before these activities the patient had eaten pasta or bread and in at least 3 cases also shrimps. Thus, the clinical picture of food-dependent, exercise-induced anaphylaxis (FDEIA) was present. Allergologic work-up was carried out in two steps and demonstrated a strong sensitization against flour proteins, particularly against gluten (mainly rTri a19-Omega 5 gliadin), a strong sensitization against house dust mite and a weak sensitization against crustaceans. Skin prick testing with a commercially available extract had initially been negative for flour allergens so that in the beginning shrimps intake was considered to be the only reason for FDEIA. After a cereal- (and initially also crustacean-)free diet before physical exercise, no further anaphylactic reactions occurre

Acute allergic reaction due to occupational exposure to a proteolytic enzyme preparation with high peptidase and high proteinase activity We report the case of a skilled worker in the fragrance and flavour industry - without previous atopic manifestations such as asthma, hay fever or atopic eczema - who developed acute asthma, rhinoconjunctivitis and swelling of the tongue after the first exposure with a powdered enzyme preparation with high peptidase and high proteinase activity (Umamizyme). Skin prick test and IgE CAP were clearly positive for the enzyme preparation. A probably previous, latent sensitization to other proteolytic enzymes, which the patient had handled during his work, may explain the fact that he reacted after the first contact with this enzyme. Specific IgE to enzymes used in the detergent industry (Maxatase, Alkalase, Savinase) or to proteases of plant origin (Bromelain, Papain) were negative. To our knowledge, serum IgE antibodies against this proteolytic enzyme with high peptidase activity and without cross-reactivity to other proteases have been demonstrated for the first time. This case illustrated again that the handling with pulverized enzymes can lead to sensitization and allergy also in non-atopic persons.

Background: An intolerance to food might be induced by an impaired enzymatic histamine degradation due to a deficiency of diamine oxidase (DAO) activity (Histamine intolerance [HIT]. Objective: The aim of the Study was to investigate if patients histories, that are suggestive to HIT have a significant reduced serum DAO activity compared to patients Without history of HIT. Methods: 6 1 patients and 20 controls were studied. 26 patients (strong HIT) had a history of at least two typical symptoms of HIT with relation to the intake of at least two histamine rich foods. 35 patients (moderate HIT) had a history of at least one symptom after the intake of at least one histamine rich food (but not both). 20 healthy volunteers (control) did not have any symptoms of HIT. Patients were interviewed on type of clinical symptoms and the relation of symptoms to food ingestion. Sera were analysed for DAO activity by an ELISA test. Results: No difference of serum DAO levels could be found between groups of different history of HIT. Conclusion: Based on the patients history with allergy like symptoms occurring with intake of histamine rich food, determination of DAO activity in the serum does not facilitate diagnosis of HIT in routine clinical practice.

BACKGROUND:Patients sensitized to birch pollen frequently suffer from a food allergy to plant foods such as celery, carrots, or hazelnut. One of the main manifestations of birch pollen-related food allergy is the oral allergy syndrome. Skin tests and allergen-specific immunoglobulin (Ig) E determinations are poor predictors of such reactions when assessed by double-blind placebo-controlled food challenge (DBPCFC).OBJECTIVE:To investigate whether a cellular test based on leukotriene release from basophils, the cellular antigen stimulation test in combination with enzyme-linked immunosorbent assay (CAST-ELISA), is predictive of pollen-related food allergy.METHODS:Birch pollen-sensitized patients with positive DBPCFC to celery (n=21), hazelnut (n=15), and carrot (n=7) underwent skin tests along with determination of specific IgE and CAST-ELISA for the respective allergens. The results were compared with those of 24 birch pollen-sensitized patients with negative open food challenge to celery, hazelnut, and carrot.RESULTS:While skin prick tests had a sensitivity of 85%, 80%, and 29% for commercial extracts of celery, hazelnut, and carrot, respectively, prick testing with self-prepared extracts yielded sensitivities of 100%, 80%, and 100%, respectively. For specific IgE determinations, sensitivities were 71%, 73%, and 57%, respectively, and the respective specificities were 67%, 73%, and 60%. For CAST-ELISA with various sources and doses of allergens, the sensitivity varied from 71% to 95% for celery, 73% to 80% for hazelnut, and 43% to 86% for carrot. The respective specificities were 67% to 92%, 75% to 88%, and 77% to 91%. Analysis of the predictive value of CAST-ELISA with receiver operating characteristic curves showed that the results of the tests were more predictive of pollen-related food allergy than quantitative allergen-specific IgE determinations.CONCLUSIONS:CAST-ELISA is more specific than routine diagnostic tests for the diagnosis of pollen-related food allergy to celery, hazelnut, and carrot.

Background: Clinical efficacy has been documented for sublingual immunotherapy (SLIT) in monosensitized patients with seasonal allergic rhinoconjunctivitis (SARC) using extracts containing only 1 allergen; but to our knowledge, no SLIT study has ever been published in polysensitized patients using mixed extracts. Objective: To investigate the clinical efficacy of SLIT with mixed extracts in polysensitized patients of an out-patient clinic and to evaluate the relative clinical efficacy in relation to systemic side effects. Methods: A 3-year prospective open study including 79 polysensitized patients, mean age 3 3, range 7-62, 49% male, 51% female, with SARC receiving sublingual-swallow immunotherapy with mixed pollen extracts. During the pollen season patients recorded symptoms (0 = absent, 1 = mild, 2 = moderate, 3 = severe) for rhinitis, conjunctivitis and asthma and their need for medication (oral antihistaminic, antihistaminic eye drops and nasal spray or corticosteroid nasal spray or inhaled antiasthmatic drugs (beta-agonists and/or inhaled corticosteroids)). If rhinoconjunctivitis was uncontrolled, prednisone tablets were allowed. Clinical efficacy was evaluated separately for clinical symptoms (symptom scores) and for use of rescue drugs (medication scores). Improvement of rhinitis, conjunctivitis and asthma is described by the changes in the individual frequency of symptoms (in 4 stages ranging from less than once per week to several times daily) and in the severity of symptoms (in 5 stages ranging from none to very severe). The frequency of symptoms was classified both at the start of the titration period and the end of the observation phase of the maintenance period into "less than once per week", "several per week", "once per day", or "several per day". To avoid problems with data not being normally distributed, nonparametric statistics were used on an explorative basis. Demographic data were analyzed by chi(2) test or Fishers exact test. Within group comparison Wilcoxon tests were applied for the primary outcome parameter, i.e. clinical efficacy and Mann-Whitney for side effects, p values - 0.05 were considered significant. Results: Clinical efficacy was estimated in 79 patients completing 3 years of treatment by subtracting baseline data and by calculating the ratio third treatment year vs. baseline. The monthly dose of 1,200 IR for 1 allergen extract mixture was 150 times higher than the subcutaneous dose administered typically in the same time period. The total cumulative dose varied between 43,200 IR (I allergen) and 10,800 IR (4 allergen mixtures) for the 3-year treatment period. SLIT diminished the median disease severity of rhinitis, conjunctivitis and asthma at the start to 1/2 of baseline after 3 years and and marked improve the intraindividual frequency of the three main symptoms. Symptom and medication scores showed statistically significant and clinically relevant effectiveness. SLIT treatment only resulted in local mild side-effects. Conclusion: SLIT with mixed extracts is clinically effective in polysensitized patients with SARC.

During a general anesthesia a 51-year-old otherwise healthy female patient without past allergic problems developed suddenly and simultaneously the following symptoms during antibiotics infusion with Zinacef (cefuroxim): acute circulary depression, bronchospam and erythema. Clincally a tachycardia of < 130/min was seen, the capnographically measured end-expiratory CO2 sank abruptly to 2.3 kPa and finally no blood pressure could be measured with the cuff and the pulsatile curve vanished from the monitor. After stopping the cefuroxim infusion at once and after and aggressive volume therapy, intravenous adrenaline and steroids (100 mg hydrocortisone) as well as intratracheal bronchodilators, followed by neo-synephrine and then noradrenaline via perfusor (due to the persisting sinus tachycardia) normal circulation and respiration could be achieved within 30 - 40 minutes. Later a practising allergist carried out intracutaneous and skin prick testing with the penicillin series (PenKit) (PPL, MDM, Penicillin) as well as scratch testing with a Zinat tablet (cefuroximaxetil). All tests were negative. A lymphocyte transformation test (LTT) with cefuroximaxetil (pure substance) was also negative. Therefore, the patient was diagnosed as having no allergy against penicillin. One year later her general practitioner prescribed Zinat due to a urinary tract infection. She showed an anaphylactic reaction within 1 hour after the intake of the tablet. The attending allergist now assumed a allergy against cefuroxim and initiated a CASTCOMBI (CAST ELISA and Flow-CAST by flow cytometry) with beta-lactam antibiotics. For unknown reasons cefuroxim was not tested. Stimulation with cephalosporin C was negative for both methods. Stimulation with amoxicillin was negative in the CAST, but in the flow cytometry with 2 amoxicillin concentrations (500 and 250 mu g/ml) it was marginal for a stimulation index of 2.1 and positive for an index of 2.9. The allergist interpreted these results as being negative. For these negative test results despite the clear anamnesis of a cefuroxim allergy the following explanations are possible for the first extensive testing: drugs, as they are haptens, are no complete antigens and would therefore have to be linked to a carrier protein; the activating drug allergen is usually a metabolite which was not available for the testing. There is a known dissociation (heterogeneity) between the reactivity of the cutaneous mast cells, the connective tissue mast cells and the blood basophils so that discrepant test results are possible. During the operation Zinacef (cefuroximum natricum) was applied, while in the in vivo and in vitro testings Zinat (cefuroximmaxetil, cefuroximum axetil) was used, because it was assumed that Zinat was the indentic oral administration form of Zinacef. Subsequently, Zinat caused the second anaphylactic reaction, remarkably only 1 hour after the peroral intake. Cefuroximaxetil, the 1-acetoxyethyl ester of cefuroxim, is a prodrug and has to be metabolized in the body to the metabolite cefuroxim. This explains the negative scratch testing and the delayed reaction after oral intake. Therefore, all allergologic in vivo (skin test) and in vitro (LTT) tests should have been carried out with Zinacef instead of Zinat. The conclusion is: cefuroxim is not the same as cefuroxim!.