Immediate-Type Hypersensitivity Skin Reactions

There are two main sensitization reactions-immedi-ate and delayed hypersensitivity. Immediate type hypersensitivity is the result of antibody-allergen interaction occurring in the skin the reaction that develops is known as allergic contact urticaria. Delayed type hypersensitivity is the result of cell-mediated immunity and is the most frequently reported side effect of topical drugs. Both epidermal and dermal cells play pivotal roles in irritation and sensitization. Keratinocytes... 

If a patient has a mild, delayed allergy to penicillin, first-generation cephalosporins (such as cefazolin) are effective alternatives, but they should be avoided in patients with a history of immediate-type hypersensitivity reactions to penicillins (see Table 109-6). The potential for a true immediate-type allergy should be assessed carefully, and a penicillin skin test should be conducted before giving antibiotic treatment to any patient claiming an allergy. 

Antihistamines prevent wheal and flare reactions of the immediate type of skin hypersensitivity reaction. 

Toxicology. NRL causes allergic skin reactions of type I (immediate-type) and type IV [delayed-type hypersensitivity (DTH)]. 

When injected into the skin, local anesthetics often cause pseudo-allergic reactions, with similar symptoms to immediate type allergy (42). However, true immediate hypersensitivity to local anesthetics is extremely rare. 

NRL is an irritant because of the protein allergens and can cause allergic skin reactions associated with type I (immediate effect) hypersensitivities of hand dermotoses and immunologic contact urticaria . It is also possible to have type IV (delayed effect) hypersensitivities of NRL, due to the chemicals added during its processing (such as accelerators of the thiuram/carbamate/mercaptobenzothiazole types needed for vulcanisation, a number of different antioxidants/antiozonants, emulsifiers, extenders, colorants, retarders, stiffeners, biocides). Either of these types can be serious and even life threatening in some cases [75]. 

Guinea pigs were immunized repeatedly with rifampicin in complete Freund s adjuvant and skin reactions after challenge were studied (Dukor et al. 1973). There was evidence of allergic reactions of the immediate as well as of the delayed type. However, antibodies were not measured by passive cutaneous anaphylaxis or any other immunologic method. Therefore, the skin reactions observed 4 h after challenge could well have masked an incipient type of delayed hypersensitivity reaction (Dewdney 1977). Hence, these experiments do not establish unequivocally the im-munogenicity of rifampicin. 

Type I reactions are those in which antibody is attached to the surface of a mast cell. Contact with antigen in solution results in release of the soluble mediators of anaphylaxis, producing in the skin the typical immediate weal and flare reaction. This commences within minutes of antigen administration, is maximal after 15-20 min, and is usually no longer detectable macroscopically after 1 hour. In humans, most immediate hypersensitivity is produced by antibodies of the IgE-class. However, in many animal species, similar reactions are commonly produced by IgG subclass antibodies. There is also some evidence that immediate-type reactions also can be produced occasionally in humans by non-reaginic IgG subclass antibodies (Parish, 1970). 

The chemically similar teicoplanin, not approved in the USA, is not inferior to vancomycin with regard to efficiency of treating grampositive infections. It shows a lower rate of adverse reactions, particularly nephrotoxicity and, as already discussed, is used as a substitute for vancomycin in red man syndrome. When hypersensitivity reactions do occur with teicoplanin they are generally of the delayed type, but there are a few documented cases of apparent IgE antibody-mediated reactions implicated, for example, by an immediate wheal and flare skin reaction to the drug or by teicoplanin-induced histamine release from a patient s basophils. Despite the chemical and pharmacological... 

Immunologic Two patients with worsening injection site reactions to adalimumab have been described [102 ]. Skin tests suggested immediate type I hypersensitivity reactions. Exposure of peripheral blood leukocytes to adalimumab caused significant histamine release and passive transfer of serum from one of the allergic patients to basophils from a non-atopic, healthy donor sensitized those cells to release significant amounts of histamine after exposure to adalimumab. 

Immunologic Skin testing of 26 patients clinically diagnosed with immediate (type I) hypersensitivity to infliximab found seven positives (30%) and six of these had infliximab-reactive serum IgE antibo es. One skin test-positive patient had no detectable IgE antibodies to the mAb [155 ]. After multiple infusions with infliximab, a 61-year-old woman with Crohn s disease experienced an acute anaphylactic reaction immediately after the start of an infusion. Although anti-infliximab IgE antibodies were not detected, the concentration of anti-infliximab IgG was high and this remained the case 1 year after the mAb was discontinued. Substitution of adalimumab for infliximab 1 week after the anaphylactic reaction was tolerated until the 12th day when the patient displayed a delayed, type IV hypersensitivity reaction mediated by IgG antibodies specific for adalimumab [ISb ]. In addition to types I and IV hypersensitivities to infliximab, other immune-mediated reactions representing the other hypersensitivity states also occur to infliximab. This is illustrated by a recent report of a case of a 27-year-old woman of infliximab-induced systemic lupus erythematosus [157 ], an autoimmune connective tissue disease which is both a type II and a type III hypersensitivity response. 

Growth factor potential The possibility that epoetin alfa can act as a growth factor for any tumor type, particularly myeloid malignancies, cannot be excluded. Hypersensitivity reactions Skin rashes and urticaria are rare, mild, and transient. If an anaphylactoid reaction occurs, immediately discontinue the drug and initiate appropriate therapy. Refer to Management of Acute Hypersensitivity Reactions. Fertility Impairment In female rats treated IV with epoetin alfa, there was a trend for slightly increased fetal wastage at doses of 100 and 500 units/kg. 

Immunologic reactions to drugs resulting in serum sickness are more common than immediate anaphylactic responses, but type II and type III hypersensitivities often overlap. The clinical features of serum sickness include urticarial and erythematous skin eruptions, arthralgia or arthritis, lymphadenopathy, glomerulonephritis, peripheral edema, and fever. The reactions generally last... 

A 53-year-old woman with Rajmaud s phenomenon developed an urticarial rash, pruritus, and hjrpotension 10 minutes after the parenteral administration of buflomedil. She received corticosteroids and recovered within 6 hours. When she later underwent skin tests with buflomedil, there was an immediate positive reaction, suggesting a type I hypersensitivity mechanism. 

Adverse reactions Overall, the penicillins are well tolerated. The most common adverse effects are due to hypersensitivity reactions. Hypersensitivity reactions can be simply categorized as immediate reactions (type 1) or late reactions. Type 1 reactions are IgE mediated and are often associated with systemic manifestations such as diffuse erythema, pruritus, urticaria, angioedema, and bronchospasm. The most severe yet rare IgE-mediated side effect is anaphylaxis (0.05%). Type 1 reactions usually occur within 72 hr of administration. Late reactions usually occur 72 hr after drug administration. The most common late reactions include skin rashes characterized as maculopapular or morbilliform rashes. Rarely, nafcillin may cause neutropenia. Seizures in high doses, vaginal moniliasis, and Clostridium difficile infection also can occur with all penicillins... 

Generation of a type I reaction can be evident as an immediate hypersensitivity reaction, or anaphylaxis. Immediate reactions may be limited to single organs, typically in the nasal mucosa (rhinitis), respiratory tract (acute asthma), skin, or gastrointestinal tract, or can involve multiple organs simultaneously, termed analphylaxis. 

The most serious hypersensitivity reactions produced by the penicillins are angioedema and anaphylaxis. Acute anaphylactic or anaphylactoid reactions to the penicillins constitute the most important immediate danger connected with their use. Among all drugs, the penicillins are most often responsible for this type of untoward effect. Anaphylactoid reactions to penicillins may occur at any age their incidence is thought to be 0.004-0.04%. About 0.001% of patients treated with these agents die from anaphylaxis. Anaphylaxis most often has followed parenteral use but also has been observed after oral or intradermal administration. The most dramatic reaction is sudden hypotension and death. In other instances, bronchoconstriction with severe asthma abdominal pain, nausea, and vomiting extreme weakness or diarrhea and purpuric skin eruptions have characterized the anaphylactic episodes. 

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