Page 609 - Clinical Immunology_ Principles and Practice ( PDFDrive )

586 ParT fivE Allergic Diseases

Allergen

IgE
Substance P
Anti-FceRI
Stem cell factor

C5a

Codine
Anti-IgE
IgE

fiG 42.1 Spontaneous wheals in severe spontaneous urticaria
showing superficial pink swellings with pale edematous centers.
fiG 42.3 Schematic representation of a mast cell or basophil
illustrating activation of the immunoglobulin E (IgE) receptor by
cross-linking with immunological stimuli (allergen/specific IgE
binding, anti-IgE, or anti-FcεRI autoantibodies) or independent
activation by nonimmunological stimuli (substance P, stem cell
factor, codeine, or C5a) leading to degranulation.

8
D 2 [PGD 2 ]) and cytokines. In contrast, nonimmunological
stimulation of mast cells by neuropeptides, opiates, or C5a leads
to rapid release of histamine within 15–20 seconds, without
generation of eicosanoids and cytokines. Moreover, prolonged
and subthreshold immunological stimulation may result in a
state of receptor desensitization. For example, desensitization
of FcεRI may lead to basophil hyporesponsiveness to anti-IgE
9
fiG 42.2 Angioedema of the mouth in acquired C1 esterase in autoimmune CSU. However, desensitization of receptors by
inhibitor deficiency. immunological stimulation does not affect nonimmunological
release.

TABLE 42.1 Etiopathogenesis of Urticaria Allergic Urticaria
The classic example of immunological mast-cell activation via
acute high-affinity IgE receptors is IgE-mediated urticaria (often termed
Idiopathic allergic urticaria). Cross-linking of receptor-bound IgE leads to
Infection-related the release of diverse preformed mediators and newly synthesized
Allergic (mediated by specific IgE)
lipid mediators and cytokines, resulting in the early- and late-
Chronic phase IgE-mediated allergic inflammatory responses.
Idiopathic IgE-mediated mast-cell activation can present as acute urticaria
Autoimmune (IgG against IgE or FcεRI) in those individuals previously sensitized to exogenous aller-
Infection-related gens. IgE to autoantibodies are implicated in chronic wheeling.
Drug-induced Examples include some food- and drug-induced urticarias and
Diet-related latex-induced contact urticaria. Allergic urticaria to inhaled
allergens (e.g., latex, animal epithelia) is often accompanied by
respiratory symptoms. Generalized allergic urticaria may progress
receptors and activation sites for neuropeptides and basic to anaphylaxis. Allergic urticaria resolves rapidly on withdrawal
secretagogues. of allergen exposure and recurs with each reexposure to the
Skin mast cell activation is central to the pathophysiology of allergen or cross-reactive agents.
CU. Mast cells can be activated by a variety of immunological
and nonimmunological triggers (Fig. 42.3). Immunological and Autoimmune Urticaria
nonimmunological pathways of mast-cell activation are character- Functional autoantibodies directed against the extracellular α-
ized by distinct patterns of mediator release. Immunological chain of FcεRI on dermal mast cells or basophils or, less frequently,
activation of mast cells is triggered by cross-linking of high-affinity against receptor-bound IgE have been demonstrated in 25–50%
9,10
IgE receptors (FcεRI) by antigen bound to antigen-specific IgE, of adult and pediatric patients with CSU. The pathophysiology
by anti-FcεRIα, or by anti-IgE antibodies. Histamine release of autoimmune CU involves cross-linking of high-affinity IgE
peaks at 5–10 minutes, followed by de novo synthesis of lipid- receptors by autoantibodies leading to degranulation of mast
derived mediators (leukotriene C4 [LTC4] and prostaglandin cells and basophils. There is good evidence that activation of