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.

CRP, D-dimer, fibrinogen and ESR as predictive markers of response to standard doses of levocetirizine in patients with chronic spontaneous urticaria

“…Thus, the role of total IgE in CSU should be better characterized in further research. IgG-anti-IgE/FceRI autoantibodies play a role in a subpopulation of CSU patients (8). We observed that positive ASST is associated with more severe disease, higher serum levels of CRP and D-dimer.…”

The role and relevance of mast cells in urticaria

“…Studies showing the presence of IgG‐anti‐IgE and IgG‐anti‐FcεRI antibodies are summarized in Table . The evidence in support of this mechanism of CSU has been reviewed recently . Removal of IgE and subsequent loss of mast cell FcεRI would explain the slow onset of action of omalizumab seen in up to 30% of patients responding to omalizumab .…”

“…IgE antibodies to local autoallergens, or Type 2b, viz. IgG autoantibodies to IgE or its receptor, is considered to be the most frequent causes of CSU . In both cases, the mast cell is likely to be the axial cell in producing the wheals.…”

Hereditary Angio-Oedema for Dermatologists

“…Abdominal attacks are very painful and might mimic acute abdomen with a risk of surgery being performed [96]. In patients with associated urticaria, the angio-oedematous lesions can be the result of an autoimmune process [97, 98]. Angio-oedema can be mistaken for anaphylaxis and vice versa, since laryngeal angio-oedema is one of the most severe manifestations of anaphylaxis [99].…”