Urticaria pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Anahita Deylamsalehi, M.D.[2]

Overview

There are numerous mechanisms hypothesized to be responsible in pathogenesis of urticaria. One of the prominent urticaria pathogenesis seems to be inflammatory processes due to increased immune cells activity. Basophils, mast cells, macrophages, neutrophils and T cells are some of the most common immune cells known to be responsible in pathogenesis of urticaria. Among them, basophils and mast cells have more eminent role in urticaria development and their activation has been related to some intracellular signal defect and/or autoimmune disorders. Some immunoglobins, such as IgE have been detected in patients suffering from urticaria. For instance , IgE anti-IL-24 is one of these IgE autoantigens that have been found in all patients with chronic spontaneous urticaria. Moreover, complement system is also responsible in pathogenesis of chronic spontaneous urticaria and role of some complements, such as C3, C4 and C5 have been established. Based on numerous studies, urticaria patients may have some genetical changes. Upregulation of 506 genes and downregulation of 51 genes have been reported in the affected skin with chronic spontaneous urticaria. Most of the upregulated genes were involve in adhesion (such as SELE (1q24)), cell activation (such as CD69), and chemotaxis (such as CCL2). It is crystal clear that urticaria is associated with autoimmune diseases such as hashimoto's thyroiditis. Other associations are mastocytisis such as urticaria pigmentosa, atopic diseases such as atopic dermatitis, hay fever and allergic asthma and Systemic lupus erythematosus and angioedema.

Pathophysiology

Wheal formation pathogenesis

There are some factors responsible in pathogenesis of wheals:[1]

Acute urticaria

Chronic spontaneous urticaria

There are numerous mechanisms hypothesized to be responsible in pathogenesis of chronic spontaneous urticaria:[4][5][6][7][8][9][10][11][12][13][14][15][16]


Macrophages, neutrophils, T cells, and mast cellsMMP-9 → Cleavage of pro-inflammatory chemokines/cytokines → Migration and activation of more immune cells


Mediator Effects
Histamine Vasodilatation, increased vascular permeability
LTC4 Similar to histamine
LTB4 Potentiate vasodilatation, increased vascular permeability, and smooth muscle contraction
PGD2 Chemotaxis for both neutrophils and eosinophils
Tumor necrosis factor-alpha hyperexpression of adhesion molecules on endothelial cells, chemotaxis for neutrophils and boost leukocyte rolling and adhesion
Interleukin-1 Proinflammation, mast cells and lymphocyte actication
Interleukin-4 Chemotaxis for both neutrophils and eosinophils
Interleukin-5 Chemotaxis for eosinophils
Interleukin-6 Lymphocyte actication, proinflammation
Interleukin-8/CXCL2 Neutrophils chemotaxis, degranulation, respiratory burst and adhesion to endothelial cells.
MCP-1/CCL2 Chemotaxis for eosinophils
MIP-1 alpha/CCL3 Chemotaxis for eosinophils
Interleukin-16 Chemotaxis for T cell
RANTES/CCL5 Chemotaxis for eosinophils

Non-Allergic Urticaria

Mechanisms other than allergen-antibody interactions are known to cause histamine release from mast cells. Many drugs, such as morphine, can induce direct histamine release not involving any immunoglobulin molecule. Also a diverse group of signaling substances called neuropeptides have been found to be involved in emotionally induced urticaria. Dominantly inherited cutaneous and neurocutaneous porphyrias (porphyria cutanea tarda, hereditary coproporphyria, variegate porphyria and erythropoietic protoporphyria) have been associated with solar urticaria. The occurrence of drug-induced solar urticaria may be associated with porphyrias.

Genetics

Abbreviations: AICU: aspirin-intolerant chronic urticaria; AIU: aspirin-intolerant urticaria; CU: chronic urticaria;

Genes Associated phenotype Country
FcεRIα AICU Korea
FcεRIβ AICU Korea
FcεRIγ AICU Korea
HNMT AICU Korea
TNF-α AIU Korea
TGF-β1 CU, AICU Iran
ADORA3 AIU Korea
IL-10 AIU Korea
ALOX5 AIU Korea
CYSLTR1 AICU Korea
LTC4S AIU Poland, Venezuela
PTGER4 AICU Korea
CYP2C9 AIU Korea
ACE CU with angioedema Turkey
PTPN22 CU Poland

Associated Conditions

Microscopic Pathology

The following changes have been found in microscopic evaluation of urticaria:[4][32][21][3]

References

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