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CMDT 2008
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Various slow desensitization protocols have been developed for patients suffering from late-appearing morbilliform eruptions (eg, AIDS patients with sulfamethoxazoleinduced dermatitis) These eruptions are not IgE-mediated, and the slow reintroduction of drug allows for less haptenation during sulfonamide metabolism with generation of less immunoreactive drug metabolites This form of desensitization is distinct from rapid desensitization of IgE-mediated drug allergy Desensitization for non IgEmediated drug reactions has been successful for aspirin, nonsteroidal anti-inflammatory drugs, and allopurinol Any history or finding consistent with toxic epidermal necrolysis or Stevens-Johnson syndrome would be an absolute contraindication for drug readministration For any proven food hypersensitivity, strict avoidance is the only rational recommendation Patients should also be provided with an epinephrine autoinjector (Epi-pen) if indicated
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Grammer LC et al Drug allergy and protocols for management of drug allergies, 3rd edition Part II General principles of prevention of allergic drug reactions Allergy Asthma Proc 2004 July August; 25(4):267 272 Nowak-Wegrzyn A et al Adverse reactions to foods Med Clin North Am 2006 Jan; 90(1):97 127 [PMID: 16310526] Sicherer SH et al An expanding evidence base provides food for thought to avoid indigestion in managing difficult dilemmas in food allergy J Clin Allergy Immunol 2006 Jun;117(6): 1419 22 [PMID: 16751007]
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IMMUNE COMPLEX DISEASE (SERUM SICKNESS)
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Fever, pruritus, and arthropathy Reaction is delayed in onset, usually 7 10 days, when specific IgG antibodies are generated against the allergen Immune complexes found circulating in serum or deposited in affected tissues
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For IgE-mediated drug hypersensitivity, acute rapid desensitization may allow administration of a drug if there is no suitable alternative treatment regimen This procedure carries a significant risk and should be undertaken in an intensively monitored setting This is accomplished by a course of oral or parenteral doses starting with extremely low doses (dilutions of 1 10 6 or 1 10 5 units) and increasing to the full dose over a period of hours IgEmediated reactivity diminishes during the course of this desensitization, creating a temporary drug-specific refractory state During the refractory period, skin histamine responsiveness is maintained, and mast cells may be activated by other stimuli but the patient may receive the desired drug with a very low risk of anaphylaxis Acute rapid desensitization may work through cellular mechanisms different from those involved in standard injection immunotherapy, and the refractory period is maintained only throughout the course of uninterrupted therapy
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Serum sickness reactions occur when immune complexes are formed by the binding of antigens (eg, drugs, heterologous serum) to antibodies Deposition of these complexes in tissues or in vascular endothelium can produce immune complex-mediated tissue injury by activation of complement, generation of anaphylatoxins, chemoattraction of polymorphonuclear leukocytes, and tissue injury The commonly affected organs include skin (urticaria, vasculitis), joints (arthritis), and kidney (nephritis)
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Clinical Findings
A Symptoms and Signs
Constitutional symptoms, such as drug fever, are common
CMDT 2008
Tramer MR et al Pharmacological prevention of serious anaphylactic reactions due to iodinated contrast media: systemic review BMJ 2006 Sep 30;333(7570):675 [PMID: 16880193]
B Laboratory Findings
The specific IgG antibody may be present in sufficient quantity in serum to be detected by the precipitin-in-gel method Detection of these precipitating antibodies by gel diffusion can be useful in the diagnosis of allergic bronchopulmonary aspergillosis or hypersensitivity pneumonitis Enzyme-linked immunosorbent assay (ELISA) will detect antibodies present in lesser amounts Circulating antigen-nonspecific immune complexes can be detected in a variety of malignancies and in autoimmune, hypersensitivity, and infectious diseases Immunohistochemical techniques can identify immune complexes or complement fragments deposited in tissue biopsy specimens Depressed serum levels of C3, C4, or CH50 may be sought as nonspecific evidence of immune complex disease with consumption of soluble factors The erythrocyte sedimentation rate is increased, and other nonspecific laboratory findings may include elevated hepatic aminotransferases or reduced complement levels Circulating immune complexes may be found, but current assays are limited in sensitivity Evidence of nephritis may be found by observing red cell casts at urinalysis
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