Bernhardt Sachs

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.

Guideline for the diagnosis of drug hypersensitivity reactions

Drug hypersensitivity reactions are unpredictable adverse drug reactions. They manifest either within 1–6 h following drug intake (immediate reactions) with mild to life-threatening symptoms of anaphylaxis, or several hours to days later (delayed reactions), primarily as exanthematous eruptions. It is not always possible to detect involvement of the immune system (allergy). Waiving diagnostic tests can result in severe reactions on renewed exposure on the one hand, and to unjustified treatment restrictions on the other. With this guideline, experts from various specialist societies and institutions have formulated recommendations and an algorithm for the diagnosis of allergies. The key principles of diagnosing allergic/hypersensitivity drug reactions are presented. Where possible, the objective is to perform allergy diagnostics within 4 weeks–6 months following the reaction. A clinical classification of symptoms based on the morphology and time course of the reaction is required in order to plan a diagnostic work-up. In the case of typical symptoms of a drug hypersensitivity reaction and unequivocal findings from validated skin and/or laboratory tests, a reaction can be attributed to a trigger with sufficient confidence. However, skin and laboratory tests are often negative or insufficiently reliable. In such cases, controlled provocation testing is required to clarify drug reactions. This method is reliable and safe when attention is paid to indications and contraindications and performed under appropriate medical supervision. The results of the overall assessment are discussed with the patient and documented in an „allergy passport“ in order to ensure targeted avoidance in the future and allow the use of alternative drugs where possible.

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.

Allergological approach to drug hypersensitivity reactions

Drug hypersensitivity reactions have to be tested to identify the culprit substance. The history includes the general information and specific data concerning used drugs, the classification and circumstances of the reaction. Skin tests are performed in all hypersensitivity reactions with allergic symptoms. Tests should be done between four weeks and six months after clearance of the symptoms by performing skin prick test, intradermal test, patch test or photopatch test. Validated tests for the detection of specific IgE antibodies in the serum are available for only few drugs, especially betalactam antibiotics. Other laboratory tests, e.g., the basophil activation test are done only in special cases. Provocation tests are indicated, if the culprit drug cannot be identified by the above mentioned tests. If possible, the evaluation of provocation tests should rely on objective parameters. The concluding assessment will be discussed with the patient and will be documented in an allergy pass.

Reporting rates for severe hypersensitivity reactions associated with prescription-only drugs in outpatient treatment in Germany

To determine which 10 prescription‐only drugs used in outpatient treatment in Germany are most frequently reported to induce severe drug hypersensitivity reactions taking into account their prescription numbers. In addition, the reader should be made aware of respective databases available to the public and their limitations.

S1-Leitlinie zur Diagnostik und Therapie der Skabies - Kurzfassung.

(1) Abteilung für Translationale Dermatoinfektiologie und Klinik für Hautkrankheiten, Münster (2) Institut für Mikrobiologie und Hygiene, Charité – Universitätsmedizin Berlin (3) Universitätshautklinik Kiel, Universitätsklinikum Schleswig-Holstein, Kiel (4) Landesgesundheitsamt Baden-Württemberg im Regierungspräsidium Stuttgart (5) Fachbereich Soziales und Gesundheit, Ennepe-Ruhr-Kreis (6) Division of Evidence based Medicine (dEBM), Klinik für Dermatologie, Venerologie und Allergologie, Charité – Universitätsmedizin Berlin (7) Klinik für Dermatologie, Venerologie und Allergologie, Charité – Universitätsmedizin Berlin (8) Bundesinstitut für Arzneimittel und Medizinprodukte, Bonn (9) Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Würzburg

Leitlinie Allergologische Diagnostik von Überempfindlichkeitsreaktionen auf Arzneimittel

ZusammenfassungArzneimittelüberempfindlichkeitsreaktionen sind unvorhersehbare, durch Arzneimittel hervorgerufene Reaktionen. Sie manifestieren sich entweder innerhalb von ein bis sechs Stunden nach Arzneimittelzufuhr („Sofortreaktionen“) mit geringgradigen bis lebensbedrohlichen Symptomen der Anaphylaxie oder mehrere Stunden bis Tage später („Spätreaktionen“) vorwiegend als Exantheme. Eine Beteiligung des Immunsystems (Allergie) ist nicht immer nachweisbar. Der Verzicht auf eine Diagnostik kann einerseits schwere Reaktionen bei erneuter Exposition zur Folge haben, andererseits zu ungerechtfertigter Einschränkung der Therapiemöglichkeiten führen. Experten verschiedener Fachgesellschaften und Institutionen haben in dieser Leitlinie Empfehlungen und einen Algorithmus zur Allergiediagnostik erarbeitet. Wesentliche Prinzipien der allergologischen Diagnostik von Überempfindlichkeitsreaktionen auf Arzneimittel werden dargelegt. Die allergologische Klärung möglichst innerhalb von vier Wochen bis sechs Monaten nach der Reaktion ist anzustreben. Eine klinische Zuordnung des Krankheitsbildes anhand von Morphologie und Zeitablauf der Reaktion ist für die Planung der Diagnostik notwendig. Bei typischer Symptomatik einer Arzneimittelüberempfindlichkeitsreaktion und eindeutigen Befunden validierter Haut- und/oder Labortests kann die Zuordnung zu einem Auslöser als ausreichend angesehen werden. Häufig sind jedoch Haut- und Labortests negativ oder nicht sicher aussagekräftig. In diesen Fällen ist eine kontrollierte Provokationstestung zur Aufklärung der Reaktion erforderlich. Bei Beachtung von Indikationen und Kontraindikationen sowie angemessener ärztlicher Überwachung ist sie eine aussagekräftige und sichere Methode. Das Ergebnis der Gesamtbeurteilung wird mit dem Patienten besprochen und in einem Allergiepass dokumentiert, sodass zukünftig eine gezielte Karenz eingehalten werden kann und gegebenenfalls Ausweichmedikamente zur Verfügung stehen.

Correction to: Guideline for the diagnosis of drug hypersensitivity reactions

Correction to:Allergo J Int 2015https://doi.org/10.1007/s40629-015-0052-6 Suspected drug hypersensitivity reactions require allergological investigation in order, firstly, to prevent severe reactions upon renewed exposure or, secondly, to avoid unnecessary drug restrictions. Skin tests are …

Allergologische Diagnostik von Überempfindlichkeitsreaktionen auf Arzneimittel / Allergological approach to drug hypersensitivity reactions Leitlinie der Deutschen Dermatologischen Gesellschaft (DDG) und der Deutschen Gesellschaft für Allergologie und klinische Immunologie (DGAKI) in Zusammenarbeit mit dem Ärzteverband Deutscher Allergologen (ÄDA) und dem Berufsverband Deutscher Dermatologen (BVDD)Entwicklungsstufe 1 (S 1) Erstellungsdatum: 30.09.2007Nächste Überprüfung geplant: 1.10.2011

Zusammenfassung Überempfindlichkeitsreaktionen auf Arzneimittel müssen ausreichend geklärt werden mit dem Ziel, den Auslöser zu identifizieren. Die Anamnese umfasst neben der allgemeinen Anamnese auch Informationen zu angewandten Arzneimitteln, zur Klassifikation und zu den Umständen der Reaktion. Hauttests erfolgen bei allen Reaktionen mit Symptomen allergischer Überempfindlichkeiten mit geeigneten Testkonzentrationen, möglichst zwischen 4 Wochen und 6 Monate nach Abheilung der Reaktion durch Pricktest, Intrakutantest, Epikutantest oder Photopatchtest. Validierte Tests zum Nachweis spezifischer IgE-Antikörper im Serum sind nur für wenige Arzneistoffe (vor allem Betalaktamantibiotika) verfügbar; andere immunologische Labormethoden, z.B. der Basophilen-Aktivierungstest, werden nur in ausgewählten Fällen angewendet. Provokationstests sind indiziert, wenn der Auslöser durch bisherige Untersuchungen nicht mit Sicherheit identifiziert werden kann. Die Bewertung der Ergebnisse von Provokationstests sollte möglichst anhand objektiver Parameter erfolgen. Das Ergebnis der abschließenden Gesamtbeurteilung wird mit dem Patienten ausführlich besprochen und in einem Allergiepass niedergelegt. Abstract Drug hypersensitivity reactions have to be tested to identify the culprit substance. The history includes the general information and specific data concerning used drugs, the classification and circumstances of the reaction. Skin tests are performed in all hypersensitivity reactions with allergic symptoms. Tests should be done between four weeks and six months after clearance of the symptoms by performing skin prick test, intradermal test, patch test or photopatch test. Validated tests for the detection of specific IgE antibodies in the serum are available for only few drugs, especially betalactam antibiotics. Other laboratory tests, e.g., the basophil activation test are done only in special cases. Provocation tests are indicated, if the culprit drug cannot be identified by the above mentioned tests. If possible, the evaluation of provocation tests should rely on objective parameters. The concluding assessment will be discussed with the patient and will be documented in an allergy pass.

Food allergy in adulthood

We have read with great interest the review article entitled Food allergy in adulthood , recently published by Crespo and Rodriguez in Allergy (2003;58:98–113). We wish to make the following comments on the diagnostic evaluation of food allergy. We agree with Crespo and Rodriguez that in a stepwise approach to confirming food allergy in vitro tests are only one part of the diagnostic procedure. Proof of allergen specific serum immunoglobulin (Ig)E has played a key role in in vitro diagnosis for many decades. However, we would like to stress that in vitro testing is not purely confined to measuring specific IgE. Over the past years there have been a number of publications showing that allergen induced basophil activation is associated with an increased expression of the cell surface marker CD63 (1, 2). The CD63 based basophil activation test (BAT) comprises stimulation of the basophils with the putative allergen including a positive and negative control and labeling with a fluorescent antibody recognizing basophils (usually anti-IgE) and another one recognizing activated basophils (usually antiCD63). Finally, analysis by flow cytometry yields the percentage of activated CD63+ basophils. This method has been evaluated in different fields of allergy such as allergy to hymenoptera venom, drug, latex and inhalation allergens (3). The CD63 based BAT has proofed to increase overall sensitivity of in vitro diagnosis. Although this test has the potential to become a routine method many questions remain yet to be answered, for instance the optimal cut-off for a range of common allergens using receiver operating characteristics (ROC) curves (3). ROC curves are used to assess the optimal cut-off for a positive test. A ROC is a plot of a test’s sensitivity (on the y-axis) versus its false positive rate (that is, 1-specificity, plotted on the x-axis) for different decision thresholds for defining positive and negative results. To date studies evaluating the CD63 based BAT in food allergy are yet confined to only very few publications (4, 5). Moneret et al. showed for the first time that this method is feasible in children with allergy to different foods (4). We could demonstrate that in adults with pollen associated food allergy to carrot, celery and hazelnut the BAT was more sensitive than measurement of specific IgE by the CAP method (5). We concluded that this test is particularly helpful in cases with a suggestive history of food allergy, however lacking proof of allergen specific serum IgE. Although this method needs further evaluation in food allergy in particular we among others see a role for the CD63 based BAT in supplementing routine tests for in vitro diagnosis of IgE-mediated allergy in the future.