Hypersensitivity type I

Baldo and N.H. Pham, Drug Allergy Clinical Aspects, Diagnosis, Mechanisms, Structure-Activity Relationships, DOI 10.1007/978-l-4614-7261-2 2, Springer Sdence+Business Media, LLC 2013 

1 Hypersensitivity The Early Years—From Koch to Cell and Coombs 

It seems that every new drug administered to humans has the potential to provoke an anaphylactic response, and the likelihood of such a response therefore increases with inaeased administration. Unformnately, while the signs and symptoms of what is commonly termed anaphylactic shock seem clear enough, incidences of anaphylaxis in different countries and to different drugs, as well as the terminology used for reactions is often far from consistent. 

For many years, two terms, anaphylaxis and anaphylactoid, have been used to describe relatively rare reactions that have features commonly associated with severe immediate, often life-threatening, allergic reactions. These two terms are distinguished by the underlying mechanisms of the reactions. The term anaphylaxis is used by many for an immune IgE antibody-mediated, systemic immediate type I hypersensitivity reaction, often occurring within seconds or minutes. 

The incidence of all causes of anaphylaxis in Western countries is estimated to be from about 8 to 50 per 100,000 persons per year with 3-4 % hospitalized and a lifetime prevalence of 0.05-2 %. In one retrospective Danish study of anaphylaxis over a 13-year period outside hospital in a catchment area of 48,000 subjects, an incidence of 3.2 cases per 100,000 persons per year was found. Of the 20 cases of anaphylaxis identified, seven were provoked by oral penicillin and three by oral aspirin, indicating that anaphylaxis to penicillin in the non-hospital environment was more common than thought. A retrospective population-based cohort study of 1,255 US residents in one county over a 5-year period revealed an incidence of anaphylaxis of 30 per 100,000 persons per year with an average annual incidence rate of 21 per 100,000 person-years. Drugs, along with foods and insect stings, were the main causes. In a prospective study of 432 Australian patients, medication was the cause in 8.3 % of cases. Minimum occurrence and incidence of new cases were estimated to be 12.6 and 9.9 episodes per 100,000 patient-years, 

---

FIGURE 69-3. Treatment algorithm3 for acute bacterial rhinosinusitis in patients with mild disease without recent antibiotic exposure.31 aAntibiotics are listed in order of predicted efficacy based on predicted clinical and bacteriologic efficacy rates, clinical studies, safety, and tolerability. Doses can be found in Table 69-4. 6Cephalosporins should be considered for patients with non-type I hypersensitivity to penicillins they are more likely to be effective than the alternative agents. cHigh doses (90 mg/kg per day) are recommended for most children, especially those with day-care contacts or frequent infections. 

Atopy A genetic predisposition to develop type I hypersensitivity reactions against common environmental antigens commonly seen in patients with allergic rhinitis, asthma, and atopic dermatitis. 

Fungal diseases include type I hypersensitivity, the most prevalent disease caused by molds, and a large number of other illnesses, including allergic... 

Type I hypersensitivity reactions (immediate hypersensitivity or anaphylaxis) are immunologic responses to a foreign antigen to which a patient has been previously sensitized. Anaphylactoid reactions are not immunoogically mediated however, symptoms and treatment are similar. 

The incidence of nonallergic ampicillin eruptions is 40 to 100% in patients with concomitant Epstein-Barr virus (mononucleosis), cytomegalovirus, acute lymphocytic leukemia, lymphoma, or reticulosarcoma. Nonallergic penicillin-associated rashes are characteristically morbilliform (symmetrical, erythematous, confluent, maculopapular) eruptions on the extremities. The onset of typical nonallergic eruptions is more than 72 hours after (3-lactam exposure. The mechanism for the nonurticarial ampicillin rash is not known and is not related to IgE or type I hypersensitivity. Penicillin skin tests are not useful in the evaluation of nonurticarial ampicillin rashes. Patients with a history of nonurticarial ampicillin rashes may receive other (3-lactam antibiotics without greater risk of subsequent serious allergic reactions. 

Aztreonam may be used as a substitute for an aminoglycoside in the treatment of infections caused by susceptible gram-negative organisms. Most of the adverse effects of aztreonam are local reactions at the site of injection. Interestingly, aztreonam rarely causes allergic reactions in patients with a history of type I hypersensitivity to other (3-lactam antibiotics. 

A severe type I hypersensitivity reaction such as systemic anaphylaxis (eg, from insect envenomation, ingestion of certain foods, or drug hypersensitivity) requires immediate medical intervention. 

Mechanism of type I hypersensitivity. Initial exposure to allergen (sensitization phase) leads to production of IgE by plasma cells differentiated from allergen-specific cells (not shown). The secreted IgE binds IgE-specific receptors (FcsR) on blood basophils and... 

Figure 6.31 The basis of type I hypersensitivity reactions. The antigens cross-link with IgE antibodies, which are attached to mast cells.

Formaldehyde, used in a large number of consumer products, resins, and wood products. This agent causes type I hypersensitivity manifested by respiratory symptoms, including rhinitis, bronchial asthma, and asthmatic bronchitis. 

Three mechanisms are implicated in CUS immunologic (ICU), nonimmunologic (NICU), or uncertain mechanism.20 ICU is a type I hypersensitivity reaction that is IgE mediated and is associated with atopy. NICU is the more common variety of CUS. NICU due to cosmetics is most commonly caused by fragrances (e.g., cinnamic aldehyde) and preservatives (e.g., benzoic acid and sorbic acid).2 Parabens have been documented by passive transfer to cause ICU.21... 

In mucosal sheets from porcine ileum, the delta opioid agonist DPDPE inhibits saxitoxin-sensitive elevations in neurogenic ion transport evoked by histamine [142], tryptase-like enzymes [143], serotonin [144], kallidin [145], and type I hypersensitivity [142]. These effects of DPDPE are inhibited by naltrindole. In contrast, elevations in neurogenic ion transport occurring secondary to an immediate hypersensivity reaction in the guinea pig ileal mucosa are augmented by DPDPE, indicating that the neuromodulatory actions of opioids on active mucosal transport evoked by inflammation or anaphylaxis may depend on the species examined [146],... 

Figure 32.9. Schematic representation of Type I hypersensitivity. Induction Resident respiratory tract dendritic cells (DC) take and process antigen, mature, migrate to the draining lymph nodes, and present antigen to T lymphocytes. Activated T-lymphocytes, in turn, activate B-cell differentiation into antibody-producing plasma cells. IL-4 promotes Ig isotype class switching from IgM to IgE and promotes mast cell development. IgE is associated with mast cells. Elicitation Allergen crosslinks the mast-cell-bound IgE, thereby causing the release of preformed mediators and cytokines. (See Table 32.7.) Inflammation and bronchoconstriction occur.

Two cases of cocaine-induced type I hypersensitivity reactions, have been reported (223). 

The difference between a normal immune response and a type I hypersensitive response is that in the latter, plasma cells secrete IgE. This class of antibody binds to Ec receptors on the surface of tissue mast cells and blood basophUs. Mast cells and basophUs coated by IgE are sensitised . Later exposure to the same allergen cross-links the bound IgE on sensitised cells, resulting in degranulation and the secretion of pharmacologically active mediators such as histamine, leukotrienes and prostaglandins. The principal effects of these products are vasodilation and smooth-muscle contraction (Table 15.6). 

Table 15.6 Mediators released by mast cells in type I hypersensitivity...

Aspirin hypersensitivity is also a potential concern and can occur in two ways (1) a respiratory reaction, which is more profitimd in patients with rhinitis, asthma, or nasal polyps, or (2) a typical type I hypersensitivity reaction, including urticaria, wheals, angioedema, itching, rash, bronchospasm, laryngeal edema, hypotension, shock, or syncope. This latter response generally occurs within 1 hour of aspirin ingestion. Such aspirin intolerance may manifest itself in 4% to 19% of patients with asthma and may approach 40% of steroid-dependent asthmatics. 

Type I hypersensitivity reactions usually occur within minutes to hours of exposure to an antigen in sensitized individuals. The immediate allergic response is initiated 5 to 30 minutes after allergen exposure and resolves in 30 to 60 minutes.This may be followed by the late-phase reaction, which is more severe and of greater duration. The late phase develops 4 to 6 hours after the initial response and may last up to 2 days. Neutrophils, eosinophils, macrophages, lymphocytes, basophils, and mast cells are involved in the late-phase inflammatory reaction, resulting in tissue damage. 

Inhibits release of histamine from mast cell Selective Hi antagonist Inhibits type I hypersensitivity Antihistamine Decreases chemotaxis and eosinopil activation Antihistamine Decreases chemotaxis and eosinophil activation Inhibits release of histamine from mast cell Selective Hi antagonist Affinity for H2, ai 2, and 5HT2-receptor... 

It has also been hypothesized that a type I hypersensitivity reaction may be involved in some patients. A definitive pathogenic mechanism for episcleritis has still not been established. 

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. 

---