Review and feature articleChronic urticaria: Pathogenesis and treatment☆,☆☆,★
Section snippets
Autoimmunity and chronic urticaria: historical observations
The first suggestion that patients with chronic urticaria and angioedema might have an autoimmune diathesis was the observation that there is an increased incidence of antithyroid antibodies in such patients relative to the incidence in the population at large.10 These include anti-microsomal (perioxidase) and anti-thyroidglobulin antibodies, as are associated with Hashimoto thyroiditis.11 Patients might have clinical hypothyroidism, and a small number might have hyperthyroidism if thyroid
Functional assays of anti-IgE receptors
Assays for anti-IgE receptor antibody have included in vivo methods and in vitro assays. The autologous skin test,2., 15. as noted above, provided one of the first clues that a subset of patients with chronic urticaria have an autoimmune disorder. Basophils are frequently used as an in vitro surrogate for mast cells, and secretion of histamine as a result of incubation with patient sera or purified IgG was readily demonstrated19., 20., 21. but was not observed if the source of basophils was
Binding assays for anti-receptor antibody
Attempts to quantitate IgG antibody to the α subunit have, in general, been unsuccessful. Initial attempts to demonstrate the presence of the antibody by means of immunoblotting22., 29. have not proved useful because positive reactions might be seen in other autoimmune disorders29 or occasionally with sera22 from subjects with no history of urticaria. In addition, studies of the relationship of a positive immunoblot result with histamine release did not yield a significant correlation23; sera
The role of complement
The notion that complement might contribute to the histamine release observed with sera from patients with chronic urticaria was suggested by studies in which complement depletion or inactivation appeared to diminish histamine release.20., 29. A series of reports by Ferrer et al28 and Kikuchi and Kaplan23., 33. then documented not only a role for complement but also more specifically activation of the classical pathway and generation of C5a. First, we demonstrated that the addition of purified
The cellular infiltrate
Mast cell degranulation certainly initiates the inflammatory process in autoimmune chronic urticaria and is assumed to also do so in idiopathic chronic urticaria. However, no alternative mechanism for mast cell degranulation in the idiopathic groups has been suggested to date. Yet the histology of the 2 groups is virtually indistinguishable and differs only in minor ways. There is, however, considerable heterogeneity evident when individual patients are compared. Common to all biopsy specimens
Treatment considerations
A review of the treatment of chronic urticaria has been recently published,48 including a critical assessment of approaches that are evidence based. The mainstay of initial treatment is the use of antihistaminic agents active at the H1 receptor. Alternate-day steroids may be used for patients with severe disease,1., 48. and immunosuppressive agents, such as cyclosporine, can also be used for patients with severe disease.49., 50., 51. Cyclosporine also inhibits basophil and mast cell
References (58)
Chronic urticaria
J Allergy Clin Immunol
(2000)- et al.
Syndrome of idiopathic chronic urticaria and angioedema with thyroid autoimmunity: a study of 90 patients
J Allergy Clin Immunol
(1989) - et al.
Antithyroid antibodies in chronic urticaria and angioedema
J Allergy Clin Immunol
(2003) - et al.
Prevalence and functional role of anti-IgE autoantibodies in urticaria syndromes
J Invest Dermatol
(1988) - et al.
Characteristics of histamine-releasing activity in the sera of patients with chronic idiopathic urticaria
J Allergy Clin Immunol
(1996) - et al.
Assessment of autoimmunity in patients with chronic urticaria
J Allergy Clin Immunol
(1997) - et al.
Comparative studies of functional and binding assays for IgG anti-Fc (epsilon) RI alpha (alpha subunit) in chronic urticaria
J Allergy Clin Immunol
(1998) - et al.
Mechanisms of autoimmune activation of basophils in chronic urticaria
J Allergy Clin Immunol
(2001) - et al.
Chronic urticaria serum induces histamine release, leukotrienes production, and basophil CD63 surface expression—inhibitory effects of anti-inflammatory drugs
J Allergy Clin Immunol
(2000) - et al.
Dermal mast cell activation by autoantibody against the high affinity IgE receptor in chronic urticaria
J Invest Dermatol
(1996)
Complement dependence of histamine release in chronic urticaria
J Allergy Clin Immunol
Natural anti FcεRIα antibodies may interfere with diagnostic tests for chronic urticaria
J Autoimmun
A role for C5a in augmenting IgG-dependent histamine release from basophils in chronic urticaria
J Allergy Clin Immunol
Studies of the cellular infiltrate of chronic idiopathic urticaria: prominence of T lymphocytes, monocytes, and mast cells
J Allergy Clin Immunol
Cutaneous inflammatory cell infiltrate in chronic idiopathic urticaria: comparison of patients with and without anti-Fc-epsilon RI or anti-IgE autoantibodies
J Allergy Clin Immunol
Localization of eosinophil granule major basic protein in chronic urticaria
J Invest Dermatol
Increased expression of endothelial cell adhesion molecules due to mediator release from human foreskin mast cells stimulated by autoantibodies in chronic urticaria sera
J Invest Dermatol
Classification of anti FcεRI and anti-IgE autoantibodies in chronic urticaria and correlation with disease activity
J Allergy Clin Immunol
Anti-FceRI autoantibodies and basophil histamine releasability in chronic idiopathic urticaria
J Allergy Clin Immunol
Evidence for aberrant regulation of the P21 Ras pathway in PBMCCs of patients with chronic urticaria
J Allergy Clin Immunol
Oral cyclosporine for severe chronic idiopathic urticaria and angioedema
J Am Acad Dermatol
Anti-inflmmatory effect of cyclosporin A on human skin mast cells
J Invest Dermatol
The hypocomplementeric urticarial-vasculitis syndrome: therapeutic response to hydroxychoroqine
J Allergy Clin Immunol
Sedational performance impairment of dephenhydramine and second-generation antihistaminics: a meta-analysis
J Allergy Clin Immunol
Urticaria and angioedema
Beneficial effects of Helicobacter pylori eradication on chronic idiopathic urticaria
Dig Dis Sci
Prevalence of Helicobacter pylori associated gastritis in chronic urticaria
Int Arch Allergy Immunol
Etiological aspects of chronic urticaria
Int J Dermatol
Remission ration of chronic urticaria: “spontaneous” healing as result of eradication of Helicobacter pylori?
Hautarzt
Cited by (0)
- ☆
(Supported by a grant from GlaxoSmithKline, Inc, Research Triangle Park, NC)
- ☆☆
Series editor: Harold S. Nelson, MD
- ★
Disclosure of potential conflict of interest: A. P. Kaplan—none disclosed.