Delayed reaction sensitization

When the signs and symptoms of a hemolytic transfusion reaction occur more than 24 hours after transfusion, the reaction is classified as a delayed reaction (60-62). It is estimated that up to 0.025% of recipients may well be at risk of delayed transfusion reactions (1) however, in one study only 1 in 10 668 transfused units cause delayed hemolysis. The severity of this type of reaction varies widely. Many of these reactions are so mild that they remain unnoticed only a few are severe or fatal. Almost all patients with this type of complication have a history of previous transfusion and/or pregnancy, which has made sensitization possible. The symptoms comprise fever, chills, anemia, hemoglobinemia, hemoglobinuria, and reticulocytosis. Renal insufficiency can occur and the direct antiglobulin test is positive. 

Simple molecular substances, as for example metal ions, amines, and epoxy monomers, primarily sensitize through skin contact. The reaction of these allergens to the body s own proteins leads to the formation of specific sensitized immune cells. Repeated skin contact can lead to an allergic contact eczema with a time delay. The sensitization is dependent on the intensity of the contact and the sensitizing potency of the substance. In the case of existing sensitization, mostly very small amounts of the corresponding substances can activate these skin reactions. 

Laubstein and Niedergesass (1970) report on 24 patients with nitrofurazone sensitization. Except in one case continuation of the sensitization for 4 years could be demonstrated. The latency periods up to the manifestation of a contact allergy, were between a few weeks and 4 years. In epicutaneous tests with Nifucin, delayed reactions were seen relatively often. Group reactions against other nitrofuranes were not observed in patients sensitized by Nifucin. 

In Ippen s (1978) case of contact eczema, the epicutaneous test, with isoniazid as substance or as pulverized tablets (from several manufacturers), showed in all instances definite eczema reactions which exceeded the test areas and required local treatment with corticosteroids. Wang and Schmeo (1974) report the case of a patient with occupational allergy to isoniazid. Beside the allergic reaction of the immediate type (asthma bronchiale) there was a latent sensitization of the delayed reaction type (eczema reaction). This latent sensitization was manifested in a circumscribed area by the epicutaneous test. Reexposure to the allergen led to an asthmatic spasm of the bronchi and to recrudescence of the eczematous cutaneous efflorescences when it was inhaled. 

Citraconic anhydride provokes specific reactions in sensitized guinea pigs (Jacobs Jacobs and coll., 1940) an immediate urticarial reaction after 30 minutes, then a delayed reaction after 6 to 8 hours which subsequently disappears in a few days. The immediate reactions were occasionally accompanied by a generalized rash. 

Ten to thirty minutes after the scratch-test and even after the patch test, an urticarial papule appears. This urticarial lesion appears in a much shorter time if the guinea pig is strongly sensitized. When the immediate urticarial reaction is at its maximum, there is occasionally a generalization of the reaction in the form of papules and there is sometimes even an erythrodermia. This reminds one of the generalized toxicodermal reactions in man (Jacobs, 1940). After about 7 hours, the urticarial lesion at the site of the test undergoes a progressive transformation into a delayed type of reaction, which is well defined, less papular, and less red. Unlike Jacobs (1940), we were unable to determine the moment at which the immediate reaction disappears and the delayed reaction appears. 

However, we must report that in sensitized guinea pigs we have not always observed an immediate urticarial reaction whereas, a delayed reaction appearing 7 hours after the test, has always been present, with one exception. 

From guinea pigs sensitised to CA, we were able to transmit the sensitisation to normal animals, bj a modification of the Praunsnits-Kustner method" (N. Hunziker, 1964). It has been known for a long time that an immediate type of sensitization can be transmitted with serum. Indeed, in guinea pigs sensitized to CA, we have seen that the delayed reaction is preceded by an urticarial reaction. Thus, it is not surprising that we were able to transmit a reaction of the immediate type by serum, which is visible after 30 minutes (as Chase 1947 described with this same substance). 

This relationship is not confirmed by a patch test in guinea pigs sensitized to CA and treated by hydrocortisone. The case of Hofer and Golay was a matter of an immediate reaction in man, while we examined a delayed reaction in the guinea pig. 

Wahlberg and Wennersten (1977) found that patients showed a more intense reaction when sites were irradiated with short-wavelength ultraviolet light and, recently, Manciet et al. (1995) were able to demonstrate that patch tests - when subsequently irradiated with ultraviolet light - showed both immediate and delayed reactions. However, White and Rycroft (personal communication) were unable to find an increased incidence of chromate sensitivity in patients with photosensitivity. It seems that, while in very rare cases one can find a certain element of photosensitivity, this is unusual and rare. 

Penicillins can induce both contact dermatitis and urticaria or severe anaphylactic reactions. Sensitivity to penicillins often concerns healthcare workers and mainly nurses, but also workers in the pharmaceutical industry. Those antibiotics are also used by veterinarians and cattle breeders as medications and animal-feed antibiotics. All penicillin contain the 6-aminopenicillanic acid moiety. Penicillins of the G, V, A, and M groups are characterized by a specific 7-side-chain. Cross reactivity is possible between several penicillins but is not systematic since both immediate-and delayed-type sensitivity can implicate the 6-aminopenicillanic acid moiety, or be specific of the 7-side-chain. 

Presentation of current knowledge of the mechanisms underlying the various systemic and cutaneous drug reactions including mechanisms of immediate, late, and delayed reactions, type II and type III hypersensitivities, and some important drug-induced sensitivities lacking an immune basis. 

Cell-mediated immunity (CMI) is the result of the activity of many leukocyte actions, reactions, and interactions that range from simple to complex. This type of immunity is dependent on the actions of the T lymphocytes, which are responsible for a delayed type of immune response The T lymphocyte becomes sensitized... 

During the development of these criteria the Semenov analysis was extended to systems with heat-exchanger reservoir temperatures different from feed temperatures (Tr < Tq) and with delayed runaway (larger value of e), which resulted In significant concentration drift prior to runaway. Since values of e for chain-addition polymerizations are not nearly as small as those for the gaseous explosions Investigated by Semenov, R-A Is not as sensitive nor Is It as early In terms of extent of reaction. 

Numerous positive delayed skin tests in patients with contrast medium-induced non-immediate skin reactions have been reported when the patients were tested with the culprit contrast medium [summarized in 1]. In a large European multicenter study, 37% of patients with non-immediate reactions were positive in delayed IDEs and/or patch tests [13]. The majority of the patients also reacted to the culprit contrast medium and also to other, structurally similar RCM. Notably, in more than 30% of those skin test-positive patients a RCM had been administered for the first time. Thus, there is a lack of a sensitization phase. Again it may be hypothesized that these previously non-exposed patients may have already been sensitized. Different patterns of RCM cross-reactivity indicate that several chemical entities could be involved. No positive skin tests have been obtained with other contrast medium excipients, such as ethylenediaminetetraacetic acid (EDTA), and only rarely patients have been found to react to inorganic iodide. 

The further allergologic workup is recommended should be performed within 6 months after the reaction [13]. Both delayed IDTs and patch tests are frequently positive, when read after 48 and 72 h (in case of local pruritus or erythematous plaques optionally at other time points, e.g. 24 h, 96 h). Since some patients tested positive with only one of these tests, it is recommended to use both tests in parallel to enhance test sensitivity (table 3). Patch tests should be conducted with undiluted RCM, whereas 10-fold diluted products in physiologic saline had been recommended when performing delayed IDTs. IDTs and late readings with undiluted RCM may be discussed in non-severe reactions to increase sensitivity, however this has not been evaluated in a sufficient number of controls. A panel of several different RCM should be tested to identify skin test-negative substances. 

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