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Immunopathogenesis of urticaria: a clinical perspective on histamine and cytokine involvement

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Abstract

Background

Urticaria is a clinical condition characterized by the appearance of wheals (hives), angioedema, or both. Over the last several decades, a better understanding of the mechanisms at play in the immunopathogenesis of urticaria has underscored the existence of numerous urticaria subtypes. Separating the different kinds of urticaria explicitly helps find the best detection method for the management of this skin disorder. Subtypes of urticaria also include both spontaneous and physical types. The conventional ones include spontaneous urticaria, constituting both acute and chronic urticaria. Therefore, a broad and effective therapy is essential for the diagnosis and treatment of urticaria.

Methods

To understand the immunopathogenesis of urticaria, various databases, including PubMed, Scopus, and Web of Science, were used to retrieve original articles and reviews related to urticaria. While information on several clinical trials were obtained from clinicaltrials.gov database.

Results

This article highlights the immunopathogenesis involved in the intricate interaction between cellular infiltration, immune reactions, coagulation cascades, and autoantibodies that underlie urticaria's pathophysiology.

Conclusion

The recent progress in understanding urticaria can help to understand the intricate characteristics in the immunopathogenesis of urticaria and could play a beneficial role in the management of urticaria.

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Availability of data and materials

Data sharing is not applicable to this article because no new data were created or analysed in this study.

Abbreviations

AAS:

Angioedema Activity Score

ADGRE2:

Adhesion g-protein-coupled receptor e2

AECT:

Angioedema control test

AE-QoL:

Angioedema- quality of life questionnaire

ASST:

Autologous serum skin test

AU:

Acute urticaria

BCR:

B cell receptor

BTK:

Bruton’s tyrosine kinase

C5aR:

Complement component 5 receptor

CholU-QoL:

Cholinergic urticaria-quality of life questionnaire

CholU:

Cholinergic urticaria

CholUAS:

Cholinergic urticaria activity score

CHRM3:

Cholinergic receptor m3

CIndU:

Chronic inducible urticaria

ColdU:

Cold urticaria

ColdUAS:

Cold urticaria activity score

COX1:

Cyclooxygenase 1

CRP:

C-reactive protein

CRTh2:

Chemoattractant receptor- homologous molecule expressed on t helper 2 cell

CSU:

Chronic spontaneous urticaria

CU:

Chronic urticaria

CU-Q2oL:

Chronic urticaria-quality of life questionnaire

dsDNA:

Double-stranded deoxyribonucleic acid

ECP:

Eosinophil cationic protein

EPO:

Erythropoietin

ESR:

Erythrocyte sedimentation rate

FP:

Fusion protein

HIV:

Human immunodeficiency viruses

ICAM:

Intercellular adhesion molecule

IL-6:

Interleukin-6

ILC-2:

Skin-resident group 2 innate lymphoid cells

IV:

Intravenous

LPS:

Lipopolysaccharides

LYN:

Lck/yes novel tyrosine kinase

mAb:

Monoclonal antibody

MBP:

Myelin basic protein

MCP3:

Monocyte chemotactic protein-3

MRGPRX2:

Mas-related g protein coupled receptor × 2

NSAID:

Non-steroidal anti-inflammatory drugs

OSMRβ:

Oncostatin M receptor- β

PAF:

Platelet activating factor

PAR1:

Protease-activated receptor-1

PAR2:

Protease-activated receptor-2

PAR3:

Protease-activated receptor-3

PECAM:

Platelet endothelial cell adhesion molecule

RANTES:

Regulated upon activation normal T cell expressed and secreted

SC:

Subcutaneous injection

SCF:

Stem cell factor

Siglec 8:

Sialic acid- binding immunoglobulin- like lectin 8

SM:

Small-molecule drug

SYK:

Spleen tyrosine kinase

TGF:

Transforming growth factor

TNF:

Tumour necrosis factor

TPO:

Thrombopoietin

TSLP:

Thymic stromal lymphopoietin

UAS:

Urticaria activity score

UAS:

Urticaria activity score

UCT:

Urticaria control test

UTI:

Urinary tract infections

VCAM:

Vascular cell adhesion protein

VEGF:

Vascular endothelial growth factor

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Acknowledgements

We are thankful to Central Ayurveda Research Institute (Kolkata), under the Central Council for Research in Ayurvedic Sciences, Ministry of AYUSH, Government of India, New Delhi, Central Council for Research in Unani Medicine, CCRUM (Ministry of AYUSH), UGC-DSA, DST, UGC-UPE, RUSA 2.0, India. We are also thankful to the Bioequivalence Study Centre, Department of Pharmaceutical Technology; Jadavpur University, UGC (Rajiv Gandhi National Fellowship), India. We also acknowledge the State Government Research Fellowship Scheme (Ref. no.: P-1/RS/08/23 dated 19.01.2023).

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Authors and Affiliations

  1. Bioequivalence Study Centre, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700032, India

    Rudranil Bhowmik, Md. Adil Shaharyar, Arnab Sarkar, Avishek Mandal, Kumar Anand & Sanmoy Karmakar

  2. Chaudhary Charan Singh University, Formerly, Meerut University, Meerut, Uttar Pradesh, India

    Humira Shabana

  3. Regional Ayurveda Research Institute (RARI) CCRAS Under Ministry of AYUSH, Thapla, Ganiyadeoli, Ranikhet Almora, Uttarakhand, India

    Achintya Mitra

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  1. Rudranil Bhowmik
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Contributions

Rudranil Bhowmik; Md. Adil Shaharyar and Sanmoy Karmakar conceived the idea and Arnab Sarkar prepared the images. Avishek Mandal; Arnab Sarkar, Kumar Anand; Humira Shabana and Achintya Mitra performed the literature search. Rudranil Bhowmik drafted and revised the manuscript. Sanmoy Karmakar supervised the work.

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Correspondence to Sanmoy Karmakar.

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Bhowmik, R., Shaharyar, M.A., Sarkar, A. et al. Immunopathogenesis of urticaria: a clinical perspective on histamine and cytokine involvement. Inflamm. Res. 73, 877–896 (2024). https://doi.org/10.1007/s00011-024-01869-6

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