Stephan Erdmann

Diagnostic Tests Based on Human Basophils: Potentials, Pitfalls and Perspectives

Human basophils are important tools for studying immediate-type hypersensitivity reactions since they release a variety of mediators (e.g., histamine, leukotriene C4, IL-4 and IL-13) following allergen triggering. Several diagnostic tools have been introduced that measure either leukotriene production or the upregulation of surface markers (CD63 and CD203c) from these cells after antigen stimulation. However, a broad variability in basophil activity exists between different basophil donors and different antigens within one donor. This manifests itself in terms of their reactivity (maximum secretory response), based on the intracellular signaling of the basophils studied, and in terms of their sensitivity. The latter is governed by the number of IgE receptors per basophil, the ratio of antigen-specific IgE to total IgE, and by the number of cell surface antigen-specific IgE molecules for half-maximal responses, termed ‘intrinsic sensitivity’. These variables give rise to shifts in the dose-response curves which, in a diagnostic setting where only a single antigen concentration is employed, may produce false-negative data. Thus, in order to meaningfully utilize the current basophil activation tests for diagnostic purposes, each allergen should be pre-evaluated separately in order to determine a suitable stimulation range. Additionally, anti-IgE or anti-FcΕRIα antibodies should serve as positive controls, bearing in mind that 10–20% of basophil donors are not responsive to IgE-mediated stimulation. Diagnostic studies using CD63 or CD203c in hymenoptera, food and drug allergy are critically discussed. Basophil-based tests are indicated for allergy testing in selected cases but should only be performed by experienced laboratories.

Allergic contact dermatitis from povidone-iodine.

A patient developed an erythematous papular, vesicular rash after application of povidone-iodine 10% solution used as a surgical antiseptic. Patch testing revealed positive responses to povidone iodine 10 and 5% in water; 25 controls were negative. Patch testing with iodine, 0.5% in ethanol gave negative results.

Fluoroquinolone-associated anaphylaxis in spontaneous adverse drug reaction reports in Germany: differences in reporting rates between individual fluoroquinolones and occurrence after first-ever use.

BackgroundThe frequency of fluoroquinolone-associated anaphylaxis has been estimated to be 1.8–23 per 10 million days of treatment based on spontaneous reports. It is unknown whether there are differences between the reporting rates of anaphylaxis with individual fluoroquinolones. According to pathophysiology, anaphylaxis may be immune mediated (anaphylactic) or not (anaphylactoid). The latter may occur after first-ever intake since no sensitisation phase is necessary.ObjectiveTo analyse spontaneous reports of fluoroquinolone-associated anaphylaxis contained in the spontaneous adverse drug reaction database of the Federal Institute for Drugs and Medical Devices in Germany with regard to differences in reporting rates between various fluoroquinolones, the previous intake and the time to onset of the reaction.MethodsAll fluoroquinolone-associated cases of anaphylaxis, anaphylactic shock, and anaphylactic/anaphylactoid reaction spontaneously reported to the Federal Institute for Drugs and Medical Devices between 1 January 1993 and 31 December 2004 were identified and assessed with regard to the correctness of the diagnosis of anaphylaxis, the causal relationship with the drug, the previous intake of fluoroquinolones and the time to onset of the reaction.ResultsIn 166 of 204 cases identified, the diagnosis of anaphylaxis and a causal relationship with the drug were considered at least possible. Moxifloxacin, levofloxacin, ciprofloxacin and ofloxacin accounted for 90 (54%), 25 (15%), 21 (13%) and 16 (10%) of the 166 cases, respectively. The corresponding reporting rates per 1 million defined daily doses based on crude estimates of exposure were 3.3, 0.6, 0.2 and 0.2 for moxifloxacin, levofloxacin, ciprofloxacin and ofloxacin, respectively. The occurrence of anaphylaxis after the first dose or within the first three days was reported in 71 of 166 (43%) cases, but no information on prior exposure with this or any other fluoroquinolone was provided with these reports. In 21 of 166 (13%) cases, the reaction occurred within the first 3 days and it was stated that the particular fluoroquinolone had never been taken before.ConclusionsAnaphylaxis appears to be associated with the fluoroquinolone class of antibacterials. Observed differences in reporting rates should be further investigated. Fluoroquinolone-associated anaphylaxis may occur after first-ever intake of the agent.

Approach to suspected food allergy in atopic dermatitis

The following guideline of the “Arbeitsgruppe Nahrungsmittelallergie der DGAKI” (Task Force on Food Allergy of the German Society of Allergology and Clinical Immunology) and the ÄDA (“Ärzteverband Deutscher Allergologen”, Medical Association of German Allergologists) and the GPA (German Society of Pediatric Allergology) summarizes the approach to be taken when food allergy is suspected in patients with atopic dermatitis (neurodermatitis, atopic eczema). The problem is clinically relevant because many patients assume that allergic reactions against foods are responsible for triggering or worsening their eczema. It is important to identify those patients who will benefit from an elimination diet but also to avoid unnecessary diets. Elimination diets (especially in early childhood) are associated with the risk of malnutrition and additional emotional stress for the patients. The gold standard for the diagnosis of food‐dependent reactions is to perform placebo‐controlled, double‐blind oral food challenges because specific IgE, prick tests and history often do not correlate with clinical reactivity. This is particularly true in the case of delayed eczematous skin reactions. Diagnostic elimination diets should be used before an oral provocation test. If multiple sensitizations against foods are discovered in a patient, an oligoallergenic diet and a subsequent stepwise supplementation of the nutrition should be performed. If a specific food is suspected of triggering food allergy, oral provocation should be performed after a diagnostic elimination diet. As eczema‐tous skin reactions may develop slowly (i. e. within one or two day), the skin be inspected the day after the provocation test and that a repetitive test be performed if the patient has not reacted to a given food on the first day of oral provocation. The guideline discusses various clinical situations for patients with atopic dermatitis to facilitate differentiated diagnostic procedures.

In vitro detection and characterization of drug hypersensitivity using flow cytometry

Background:  The lymphocyte transformation test (LTT) is the only in vitro test for detecting drug sensitization at the cellular level irrespective of the reaction’s phenotype. However, the LTT includes working with radioactive substances and is considered impracticable for routine laboratory investigation.

Association between TNFA-308 G/A polymorphism and sensitization to para-phenylenediamine: a case–control study

Background:  Para‐phenylenediamine (PPD) and related chemicals are common contact sensitizers, frequently causing allergic contact dermatitis (ACD). The cytokine tumor necrosis factor‐alpha (TNF‐α) plays a key role in contact sensitization.

Diagnostic approach for suspected pseudoallergic reaction to food ingredients

Chronic urticaria, recurrent angioedema and non‐allergic asthma have all been associated with pseudoallergic reactions to food ingredients. For atopic dermatitis and diseases of the gastrointestinal tract, this association is controversial. Pseudoallergic reactions can be elicited by additives as well as by natural food ingredients. An altered histamine metabolism may be associated with pseudoallergy.

Standardisierung von oralen Provokationstests bei Verdacht auf Nahrungsmittelallergie

1Pädiatrische Allergologie und Pneumologie, Hedwig-von-Rittberg-Zentrum, DRK-Kliniken Westend, Berlin; 2Allergie-Centrum-Charité, Klinik für Pädiatrie mit Schwerpunkt Pneumologie und Immunologie, Charité – Universitätsmedizin Berlin; 3Praxis für Dermatologie, Bergisch-Gladbach; 4Abteilung Dermatologie und Venerologie, Universitätsmedizin Göttingen; 5Allergieund Asthma-Zentrum Westend, Berlin; 6Herz-LungenPraxis Stade; 7Gastroenterologie, Pneumologie und Endokrinologie, Medizinische Klinik 1, Universität Erlangen; 8Ernährungstherapie, München; 9Hautklinik und Poliklinik, Universitätsmedizin der Johannes-Gutenberg-Universität, Mainz; 10Ernährungstherapie, Hamburg; 11Universitätsklinik für Kinderund Jugendheilkunde, Medizinische Universität Wien, Österreich; 12Abteilung Allergologie, Paul-Ehrlich-Institut, Langen; 13AllergieCentrum-Charité, Klinik für Dermatologie, Venerologie und Allergologie, Charité – Universitätsmedizin Berlin; 14Klinik und Poliklinik für Dermatologie und Venerologie, Medizinische Hochschule Hannover

Anaphylaxis and toxic epidermal necrolysis or Stevens-Johnson syndrome after nonmucosal topical drug application : fact or fiction?

Background:  Drug‐induced anaphylaxis and toxic epidermal necrolysis (TEN) or Stevens‐Johnson syndrome (SJS) represent severe immediate and delayed‐type adverse drug reactions (ADRs), respectively. Occurrence of such reactions after topical drug application has only rarely been reported. Hence, we compiled a large number of such cases which we systematically analyzed.

Therapiemöglichkeiten bei der IgE-vermittelten Nahrungsmittelallergie

ZusammenfassungNach eindeutigem Nachweis einer Nahrungsmittel-Allergie möglichst mittels doppelblind und plazebo-kontrolliert durchgeführter oraler Provokation stellt sich die Frage der therapeutischen Möglichkeiten. Die Karenz ist die einzige Intervention, deren Effekt geprüft ist. Der Patient muss ausführliche Diätpläne mit Meidungsstrategien und Hinweisen zu sinnvollem Ersatz der Ernährung erhalten und eingehend beraten werden. Die Karenz muss im Fall von Allergenen, die potenziell schwere anaphylaktische Reaktionen auslösen können, mit Notfall-Medikamenten (schnell absorbierbares orales Antihistaminikum, Glukokortikosteroid, Adrenalin) kombiniert werden. Eine Reexposition erscheint nur unter ärztlicher Aufsicht nach ein bis zwei Jahren gerechtfertigt. Die bei anderen allergischen Erkrankungen kausal wirkende Therapie der Hyposensibilisierung (spezifische Immuntherapie) stellt bei der Nahrungsmittel-Allergie die Ausnahme dar.Bei der baumpollenassoziierten Nahrungsmittel-Allergie kann den Patienten in Aussicht gestellt werden, dass sich nach Hyposensibilisierung mit einem Baumpollenextrakt auch die Reaktion auf die Nahrungsmittel bessert. Die subkutane Hyposensibilisierung mit Nahrungsmittelextrakten ist dagegen ausschließlich wissenschaftlichen Untersuchungen vorbehalten. Eine orale Toleranzinduktion mit nativen Nahrungsmitteln kommt nur in Einzelfällen und bei nicht sicher meidbaren Nahrungsmitteln infrage.Haben Patienten vorwiegend gastrointestinale Beschwerden, kann eine zeitlich begrenzte Therapie mit Cromoglykat versucht werden. Bei leichten Symptomen empfiehlt sich zur symptomorientierten Therapie ein modernes, nicht sedierendes, schnell wirksames Antihistaminikum.Abzulehnen sind „alternative Therapieformen“ wie Rotationskost oder so genannte „bioenergetische Verfahren“ wie Elektroakupunktur nach Voll oder Bioresonanz.SummaryOnce the diagnosis of food allergy is established by double-blind, placebo-controlled food challenges, the only proven therapy is a strict elimination diet. Special food exclusion diets exist that allow patients to avoid food allergens while maintaining a good quality of life. If the allergen provokes anaphylactic reactions, the restriction diet has to be combined with the prescription of an emergency medication (antihistamine, corticosteroid, adrenaline). As symptomatic food allergy is often „lost“ over time, food challenges can be repeated at intervals of one to two years under monitored conditions.Immunotherapy with food extracts should only be used in controlled studies for the treatment of food hypersensitivity. Concerning their associated food allergy, patients with tree pollen allergy may profit from a specific immunotherapy with tree pollen extract. An induction of oral tolerance using increasing amounts of raw food is only useful in selected, highly compliant patients and in instances of not reliably avoidable foods. Antihistamines may partially mask symptoms of oral allergy syndrome and IgE-mediated skin symptoms.In allergic reactions with gastrointestinal disorders, Cromoglycate might be used for a short time. Alternative therapies such as rotation diets, electroacupuncture, or bioresonance should be disapproved.