Wheal and flare reaction

Dynorphin, a-neoendorphin and /1-endorphin each produced a dose-dependent (10 6 M to 10 4 M) release of histamine from rat peritoneal mast cells but not from rat mucosal mast cells which were isolated following collagenase digestion [128]. When administered intradermally to the forearms of human volunteers, dynorphin, /f-endorphin, Leu-enkephalin and morphiceptin each produced a wheal and flare reaction at nM concentrations. Mast cell degranulation was confirmed by electron microscopy of biopsy samples and by its inhibition by hyroxyzine pretreatment [129]. 

The classical example of immediate hypersensitivity in humans is the wheal and flare reaction. Challenging a sensitized individual with an intradermal injection of... 

A 45-year-old man with type 2 diabetes treated with glibenclamide and metformin received combined chemotherapy for non-Hodgkin s lymphoma and was given premixed insulin. He developed local wheal-and-flare reactions immediately after the injections. Skin prick tests were positive for various types of insulin but weakly positive for lispro and negative for insulin aspart. He tolerated aspart insulin without any allergic reactions. 

A 4-week, single-blind, randomized, parallel-groups, dose-response study was conducted to test botanicals for allergy as measured by a skin patch test (wheal-and-flare reaction). The study was approved by an independent review board, informed consent was obtained before any screening or study measures, and the study was... 

Query patient about burning, stinging, itching. Diagnosis by immediate-type testing for wheal-and-flare reaction... 

The authors cited evidence that the kallikrein/kinin system is involved in cold urticaria, that ACE inhibitors increase wheal-and-flare reactions to cutaneously applied bradykinin, and that ACE inhibitor therapy is associated with raised plasma kinin concentrations. They therefore recommended avoidance of ACE inhibitors in patients with cold urticaria. 

A 22-year-old woman with a history of atopy had anaphylaxis 10 minutes after widespread application of an oxybenzone-containing sunscreen (4). Blinded patch tests with the sunscreen and its ingredients yielded wheal and flare reactions after 15 minutes to the sunscreen and to oxybenzone. Some days before skin testing the woman had had contact urticaria on the face after kissing a friend who had applied the same sunscreen. 

A 38-year-old man developed an immediate hypersensitivity reaction, characterized by pruritus, throat constriction, and light-headedness, after topical application of tea tree oil (9). An intradermal test with tea tree oil gave a wheal and flare reaction. Specific IgG and IgE were not detected. 

In allergic conditions, histamine released from mast cells, basophils, and other cells bind to and activate specific H, receptors in the nose, eyes, respiratory tract, and skin, causing characteristic symptoms of edema, wheal and flare reactions, itching, rhinorrhea, and lacrimation. Histamine also stimulates nerve endings, causing pruritus. The action of histamine on H, receptors in the microcirculation... 

In percutaneous testing, a positive control (histamine) and a negative control are essential for correct interpretation. After 15 minutes of the application of the allergen, the site is examined for a positive reaction (defined as a wheal and flare reaction). Because correct testing is done with extremely minute doses, undetectable by nonsen-sitized individuals, this reaction is evidence of the presence of mast cell-bound IgE specific to the allergen tested. Common allergens are available as standardized allergenic extracts. 

Antihistamines and a few other medications interfere with the wheal and flare reaction. First-generation antihistamines should be... 

In a single dose study, administration of itraconazole 200 mg one hour prior to fexofenadine 180 mg increased the AUC of fexofenadine 2.3-fold, and 3-fold in two groups of subjects of different genotypes for the gene encoding P-glycoprotein. Itraconazole pretreatment increased the effect of fexofenadine on histamine-induced wheal and flare reaction. ... 

The polymers isolated from ampicillin and benzylpenicillin solutions have further been shown to give wheal and flare reactions in a number of penicillin allergic patients, all of whom have given skin reactions also to a penicilloyl-polylysine conjugate (JuHLiN et al. 1977). Finally, a limited clinical study by Parker and Richmond (1976) has indicated that the use of so-called polymer-free ampicillin may reduce the incidence of certain exanthematic adverse reactions to ampicillin preparations. 

In 1962 Siegel (1962) observed that benzylpenicillin incubated with the additive carboxymethylcellulose was capable of producing a wheal and flare reaction in sensitive patients. Later, Schneider et al. (1971 a) have shown that the antigenic product produced in the reaction between penicillin and the additive is a penicilloy-lated carboxymethylcellulose conjugate. 

Several semisynthetic derivatives of curare (e.g., methylcurare, toxiferine and diallylnortoxiferine, alcuronium) have been produced, and have been shown to be less potent as inducers of wheal and flare reactions in the skin, and of histamine release (Foldes et al. 1961 Feldman 1973). Nevertheless, none of them is totally inactive as an inducer of wheal and flare reactions in the skin of everybody. Also, none of them is free from the risk of inducing reactions in susceptible individuals. Furthermore, some of those compounds which have been claimed to be virtually free from histamine releasing activity, such as alcuronium, proved to be relatively more potent in eliciting histamine release from leucocytes (Assem 1977). 

Benzylpenicilloic acid is the main hydrolysis product of benzylpenicillin and is able to elicit wheal and flare reactions when used in skin tests in some patients allergic to penicillins. It has therefore been considered as one of the minor antigenic determinants of penicillin allergy (Siegel and Levine 1964 Voss et al. 1966) although the precise chemical nature of the determinant(s) derived from penicilloic acid has not been elucidated. The proportion of patients responding in skin test to penicilloic acid varies between 21% and 55% (Table 1). 

Wheal and flare reactions in penicillin-sensitized patients can also be elicited by protein conjugates of phenylacetyl glycine and dimethoxybenzyl glycine (SfflBATA et al. 1968). Using conjugates prepared with various penicillins, the side chain specificity of human skin-sensitizing antibodies has also been evaluated by several groups (Parker and Thiel 1963 Van Dellen et al. 1971). Exclusive or predominant side chain specificity of hypersensitivity may be responsible for the tolerance toward other penicillins of some patients who have been sensitized by penicillin G (Luton 1964). 

Wheal and flare reactions to polymyxins are difficult to evaluate owing to the direct mast cell degranulating capacities of these compounds. One report stated that tests had been done with great caution and the occurrence of a positive skin test of the immediate type appears to be relevant (Lakin et al. 1975 b). In patients with stasis ulcers and dermatitis, positive patch tests have been obtained (Moller 1976), but this seems to be rather uncommon. 

Anaphylactic shock reactions claimed to be caused by tartrazine and Sunset Yellow were reported in a patient receiving an enema of liquid castile soap (Trautlein and Mann 1978). Tests with components of the soap showed marked wheal and flare reactions to the dyes. It should be pointed out that positive skin test reactions to azo dyes are not found in patients with urticaria and asthma. 

Contact urticaria usually clears spontaneously repeated exposure may produce dermatitis (eczema). In addition, it may be associated with allergic contact dermatitis (type-IV hypersensitivity), von Krogh and Maibach [4] tested 67 patients for immediate and delayed hypersensitivity, and 22 (33%) developed a positive delayed response subsequent to the initial wheal-and-flare reaction. The responsible agents were food products, rubber latex, cinnamic aldehyde, para-aminodiphenylamine, ethylaminobenzoate, ammonium persulfate, teak, epoxy resin and lemon perfume. They suggested that the term contact dermatitis of immediate and delayed type be used for patients exhibiting both types of reactions in the test situation, whether the initial reaction is uncharacteristic, urticarial or vesicular [4]. 

Nonimmunologic contact urticaria (NICU) occurs in individuals not sensitized to the contactant, i.e., almost any normal subject. The mechanism of action is the result of a direct release of vasoactive substances, which causes a localized response [20]. Prostaglandins are mediators in the reaction to at least benzoic and sorbic acids and to methyl nicotinate, and systemic or topical inhibitors of prostaglandin synthesis inhibit the reaction to these substances [21-23]. Ultraviolet radiation (UVB and UVA) has also been shown to inhibit NICU reactions to some substances [24]. The NICU reaction is often redness without edema rather than a real wheal-and-flare reaction. The appearance of clinical signs depends mainly on the duration of exposure, the concentration of the contactant and other factors, such as rubbing or scratching. The reaction usually remains localized and systemic reactions are probably... 

The anatomical distribution of the dermatitis should be consistent with the exposure, correlating with the occupational gestures and activities. The clinical appearance of contact dermatitis is habitually characterized by eczematous inflammation. A wheal-and-flare reaction is the prototype of immediate contact urticaria. However, it is impossible to make a distinction based exclusively in morphological criteria. Neither allergic nor irritant OCD has definite clinical or histological features that can lead to the diagnosis, and immediate contact reactions are most consistently characterized by a broad spectrum of clinical manifestations. 

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