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. Acute urticaria or a short episode of angioedema is not an indication for exhaustive evaluation. If basic diagnostic screening is negative in chronic urticaria, a low-pseudoallergen diet can be considered. Skin and serological tests are not objective diagnostic parameters for pseudoallergic reactions. The severity of symptoms should be documented while the patient is on a low-pseudoaller-gen diet. Oral provocation with additives leads to reproducible symptoms only in a few cases. Therefore, if a low-pseudoallergen diet brings improvement, the patient is then exposed to a pseudoallergen-rich "super meal". After a positive reaction to the "super meal" the challenge with additives takes place in the form of collective group exposition. When the patient has asthma or a history of anaphylac-toid reactions, testing with individual substances in carefully increasing dosages is required. The suspicion of adverse reactions against histamine can be confirmed by a challenge with histamine dihydrochloride. In the case of respiratory symptoms, provocation by inhalation should be considered. Objectifying symptoms especially in gastrointestinal diseases is mandatory and should include double-blind placebo-controlled food challenge, if possible.

Approach to suspected food allergy in atopic dermatitis. Guideline of the Task Force on Food Allergy of the German Society of Allergology and Clinical Immunology (DGAKI) and the Medical Association of German Allergologists (ADA) and the German Society of Pediatric Allergology (GPA).

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 ADA ("Arzteverband 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.

Skin testing with food allergens. Guideline of the German Society of Allergology and Clinical Immunology (DGAKI), the Physicians' Association of German Allergologists (ADA) and the Society of Pediatric Allergology (GPA) together with the Swiss Society of Allergology.

Skin testing has a central role in the diagnosis of food allergy. Prick testing is well- established as a routine diagnostic tool. Nonetheless, unstable allergens and the lack of standardized extracts create difficulties in the identification of sensitization to foods in patients with suspected food allergy. Therefore prick-to-prick tests with native (raw, fresh) foods are still recommended. The indications and contraindications are the same as those of routine skin testing in clinical allergology. We recommend a careful and restricted application of skin tests in patients with a history of severe anaphylaxis to foods.

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

BACKGROUND: The 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. OBJECTIVE: To 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. METHODS: All 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. RESULTS: In 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. CONCLUSIONS: Anaphylaxis 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.

The "strip" patch test: results of a multicentre study towards a standardization.

BACKGROUND: The "strip" patch test (SPT) is a variant of patch testing which is used for substances with a poor percutaneous penetration. Penetration of the substances is enhanced by repeated applications of adhesive tape prior to their application to the skin. However, no guidelines exist for standardized performance of the SPT. OBJECTIVES: The aim of this multicentre study was to obtain a first practical approach towards a standardized SPT procedure. METHODS: Intact noninflamed skin of the upper back of 83 healthy volunteers was tape-stripped. For sequential strips, a 25-mm diameter 3M Blenderm surgical tape was vertically applied and gently pressed downward using the fingertips for about 2 s. The tape was removed in one quick movement at an angle of 45 degrees in the direction of adherence. Each strip was performed with a new piece of tape on exactly the same skin area. RESULTS. In each subject, we first determined the number of strips (A) until the skin surface started to glisten and calculated the median number of strips (A) in the sample (A=26 strips). We then ascertained the median number of strips (a) in the sample that was necessary to achieve a statistically significant and twofold increase in TEWL (a=11 strips), revealing a "critical" stratum corneum strip depth. The unknown number of strips (a) for each subject was finally calculated from the formula a/A=a/A, i.e. the individual number of strips (A) until the skin surface started to glisten was multiplied by a derived tape-specific correction factor (cf=a/A=11/26=0.4). The increase in percutaneous penetration in strip patch testing by performing "a" strips versus conventional patch testing was shown by scoring of clinical and subjective SLS irritant reactions. CONCLUSIONS: The present multicentre study outlines an experimentally derived approach for a uniform SPT procedure, which does not require the use of complex technical equipment. This first approach now requires validation by a study involving the application of allergens to obtain evidence of enhancement in the sensitivity of patch testing.

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-FcepsilonRIalpha 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.

Anaphylaxis induced by glucocorticoids.

Glucocorticoids are frequently used to treat allergic reactions. Therefore, allergic reactions to systemic glucocorticoids in particular are considered most unlikely and are not well known. We report on a 23-year-old woman with atopic dermatitis who had an anaphylactic reaction after oral administration of prednisolone. On treatment with epinephrine, antihistamines and volume symptoms resolved. Skin testing with a panel of glucocorticoids showed immediate type reactions to prednisolone, prednisolone hydrogen succinate, prednisone, and betamethasone dihydrogen phosphate. In challenge testing the patient tolerated methyl prednisolone and dexamethasone. There is increasing evidence that true allergic immediate type reactions to glucocorticoids exist. The severity of the reaction can vary from a rash to anaphylaxis. However, a patient sensitized to one or a group of glucocorticoids does not have to refrain from all types of glucocorticoids. Careful challenge testing is by far the best way to select glucocorticoids that are safe for future treatment. Clinicians should be aware that allergic reactions to glucocorticoids can occur and that worsening of symptoms does not always mean treatment failure.

Allergic contact dermatitis from phenylephrine in eyedrops.

Phenylephrine is widely used as an ophthalmic drug. However, there are only very few reports on allergic contact dermatitis induced by phenylephrine. In addition, little is known on cross reactivity patterns between the sympathomimetics phenylephrine, epinephrine and ephedrine which share a similar chemical structure. We report on a man who developed allergic contact dermatitis to Neosynerphin POS eyedrops containing phenylephrine hydrochloride. Cross reactivity between phenylephrine, epinephrine and ephedrine was studied by patch testing. Patch tests were performed with the European standard, an ophthalmics and preservatives series, Neosynerphin POS eyedrops, phenylephrine hydrochloride 10% aq., epinephrine and ephedrine (both 1.0 % aq.). Test sites were read after 48, 72 and 168 hours according to the recommendations of the ICDRG. Neosynerphin POS and phenylephrine hydrochloride 10 % aq. gave positive reactions, whereas epinephrine and ephedrine tested negative. Although phenylephrine is an epinephrine analog delayed type hypersensitivity to phenylephrine did not result in cross reactivity with chemically related epinephrine and ephedrine.