The internal drivers of CSU

Unlike allergic reactions, chronic spontaneous urticaria (CSU) is driven by internal mechanisms rather than external factors.¹

Explore the mechanisms that drive CSU

Mast cells are the key internal driver of CSU^2,3

While the pathogenesis of CSU is still not fully elucidated, it is primarily a mast cell-driven disease with IgE (autoallergic) and IgG (autoimmune) mechanisms contributing to histamine release and symptom manifestation.^2,3

Illustration showing mast cells with BTK, IgE, igG and histamine and proinflammatory mediators.

Mast cell degranulation results in histamine and other proinflammatory mediator release leading to CSU symptoms such as wheals, pruritus, and angioedema.^2,3

CSU is an internally driven disease caused by immune dysregulation and mast cell degranulation—histamine release is just the downstream result.^1,4

BTK and intracellular signaling

BTK is one key mediator of mast cell degranulation, and its signaling is activated by both IgE and IgG inflammatory pathways.^2,3

Illustration showing signaling of BTK and how IgE- and IgG mediated mechanisms converge at the FcεR1.

IgE- and IgG-mediated mechanisms converge at the FcεRI receptor, activating BTK.¹

Intracellular BTK signaling mediates the degranulation of mast cells and other immune cells that drive histamine and other proinflammatory mediator release.^1–3

What is the role of BTK and what causes the release of histamine and other proinflammatory mediators in CSU?

Dr Finklea, a dermatology specialist in CSU management, highlights the pathogenesis of CSU.

Other internal mediators of CSU: basophils and B cells

Basophils

In basophils, IgE and IgG similarly trigger the BTK signaling cascade, causing degranulation and the release of proinflammatory mediators.³

B cells

Overexpression of BTK in autoimmune B cells may promote IgE- and IgG-autoantibody production.⁵

Help your patients understand their CSU.

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BTK=Bruton's tyrosine kinase; FcεRI=high-affinity IgE receptor; IgE=immunoglobulin E; IgG=immunoglobulin G.

References:
1. Kaplan A, Lebwohl M, Giménez-Arnau AM, Hide M, Armstrong AW, Maurer M. Allergy. 2023;78(2):389–401. doi:10.1111/all.15603
2. Min TK, Saini SS. Allergy Asthma Immunol Res. 2019;11(4):470–481. doi:10.4168/aair.2019.11.4.470
3. Maurer M, Eyerich K, Eyerich S, et al. Int Arch Allergy Immunol. 2020;181(5):321–333. doi:10.1159/000507218
4. Altman K, Chang C. Clin Rev Allergy Immunol. 2013;45(1)47–62. doi:10.1007/s12016-012-8326-y
5. Mendes-Bastos P, Brasileiro A, Kolkhir P, et al. Allergy. 2022;77(8):2355–2366. doi:10.1111/all.15261