title: Autoimmune chronic spontaneous urticaria: What we know and what we do not know.
abstract: Chronic spontaneous urticaria (CSU) is a mast cell-driven skin disease characterized by the recurrence of transient wheals, angioedema, or both for more than 6 weeks. Autoimmunity is thought to be one of the most frequent causes of CSU. Type I and II autoimmunity (ie, IgE to autoallergens and IgG autoantibodies to IgE or its receptor, respectively) have been implicated in the etiology and pathogenesis of CSU. We analyzed the relevant literature and assessed the existing evidence in support of a role for type I and II autoimmunity in CSU with the help of Hill's criteria of causality. For each of these criteria (ie, strength of association, consistency, specificity, temporality, biological gradient, plausibility, coherence, experiment, and analogy), we categorized the strength of evidence as "insufficient," "low," "moderate," or "high" and then assigned levels of causality for type I and II autoimmunity in patients with CSU from level 1 (causal relationship) to level 5 (causality not likely). Based on the evidence in support of Hill's criteria, type I autoimmunity in patients with CSU has level 3 causality (causal relationship suggested), and type II autoimmunity has level 2 causality (causal relationship likely). There are still many aspects of the pathologic mechanisms of CSU that need to be resolved, but it is becoming clear that there are at least 2 distinct pathways, type I and type II autoimmunity, that contribute to the pathogenesis of this complex disease.
authors: Department of Dermatology and Venereology, I.M. Sechenov First Moscow State Medical University, Moscow, Russia; Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors: Pavel
authors: P
authors: Kolkhir
authors: Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors: Martin K
authors: MK
authors: Church
authors: Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors: Karsten
authors: K
authors: Weller
authors: Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors: Martin
authors: M
authors: Metz
authors: Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors: Oliver
authors: O
authors: Schmetzer
authors: Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Berlin, Germany. Electronic address: marcus.maurer@charite.de.
authors: Marcus
authors: M
authors: Maurer
mesh_terms: D000818:Animals; D015551:Autoimmunity; D002908:Chronic Disease; D006801:Humans; D014581:Urticaria / Q000209:etiology* / Q000276:immunology
keywords: Chronic spontaneous urticaria; Hill's criteria of causality; IgE–anti-self; IgG–anti-FcεRI/IgE; autoimmunity; causality