A single reaction-diffusion equation for the multifarious eruptions of urticaria

Urticaria is a common skin disorder characterized by the rapid appearance and disappearance of local skin edema and flares with itching. It is characterized by various macroscopic skin eruptions unique to patients and/or subtypes of urticaria with respect to shape, size, color, and/or duration of eruptions. Nevertheless, the mechanism underlying multifarious eruptions in urticaria is largely unknown. The eruptions are believed to be evoked by histamine release from mast cells in the skin. However, the majority of visible characteristics of urticaria cannot be explained by a simple injection of histamine to the skin. To explain the multifarious eruptions of urticaria, we developed a single reaction-diffusion model suggesting the self-activation and self-inhibition regulation of histamine release from mast cells. Using the model, we found that various geometrical shapes of eruptions typically observed in patients can be explained by the model parameters and randomness or strength of the initial stimuli to mast cells. Furthermore, we verified that the wheal-expanding speed of urticaria, which is shown to be much smaller than that of the intradermal injection experimental system may be explained by our model and a simple diffusion equation. Our study suggests that the simple reaction-diffusion dynamics, including the independent self-activating and -inhibitory regulation of histamine release, may account for the essential mechanism underlying the formation of multifarious eruptions in urticaria.

[1]  M. Hide,et al.  Impact of chronic urticaria on quality of life and work in Japan: Results of a real‐world study , 2018, The Journal of dermatology.

[2]  Y. Matsuo,et al.  The role of adenosine for IgE receptor-dependent degranulation of human peripheral basophils and skin mast cells. , 2018, Allergology international : official journal of the Japanese Society of Allergology.

[3]  Y. Yanase,et al.  Chronic spontaneous urticaria and the extrinsic coagulation system. , 2017, Allergology international : official journal of the Japanese Society of Allergology.

[4]  H. Kiyono,et al.  New era for mucosal mast cells: their roles in inflammation, allergic immune responses and adjuvant development , 2014, Experimental & Molecular Medicine.

[5]  M. Steinhoff,et al.  Mast cells are critical for the limitation of thrombin‐induced skin inflammation , 2018, Experimental dermatology.

[6]  Y. Matsuo,et al.  Neuromedin U directly induces degranulation of skin mast cells, presumably via MRGPRX2 , 2018, Allergy.

[7]  L. Petersen,et al.  Histamine is released in the wheal but not the flare following challenge of human skin in vivo: a microdialysis study , 1997, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[8]  Hua Xie,et al.  Activation of human tonsil and skin mast cells by agonists of proteinase activated receptor‐2 , 2005, Acta Pharmacologica Sinica.

[9]  Y. Okayama,et al.  Significantly High Levels of Anti-dsDNA Immunoglobulin E in Sera and the Ability of dsDNA to Induce the Degranulation of Basophils from Chronic Urticaria Patients , 2013, International Archives of Allergy and Immunology.

[10]  Ayaka Tanaka,et al.  Efficacy of increased dose of rupatadine up to 20 mg on itching in Japanese patients due to chronic spontaneous urticaria, dermatitis, or pruritus: A post hoc analysis of phase III clinical trial , 2019, Journal of Cutaneous Immunology and Allergy.

[11]  R. Dellavalle,et al.  Global burden of urticaria: Insights from the 2016 Global Burden of Disease Study , 2018, Journal of the American Academy of Dermatology.

[12]  A. Bossios,et al.  New biological treatments for asthma and skin allergies , 2019, Allergy.

[13]  Yasuaki Kobayashi,et al.  Mathematical model for calcium-assisted epidermal homeostasis. , 2016, Journal of theoretical biology.

[14]  R. Singer,et al.  Management of chronic inducible urticaria according to the guidelines: A prospective controlled study. , 2017, Journal of dermatological science.

[15]  A. Marzano,et al.  Detection of Low-Molecular-Weight Mast Cell-Activating Factors in Serum From Patients With Chronic Spontaneous Urticaria. , 2016, Journal of investigational allergology & clinical immunology.

[16]  O. Schmetzer,et al.  IL‐24 is a common and specific autoantigen of IgE in patients with chronic spontaneous urticaria , 2017, The Journal of allergy and clinical immunology.

[17]  R. Fantozzi,et al.  The role of histamine in neurogenic inflammation , 2013, British journal of pharmacology.

[18]  Y. Yanase,et al.  Histamine and Toll-like receptor ligands synergistically induce endothelial cell gap formation by the extrinsic coagulating pathway. , 2017, The Journal of allergy and clinical immunology.

[19]  A. Kaplan,et al.  Assessment of tissue fluid histamine levels in patients with urticaria. , 1978, The Journal of allergy and clinical immunology.

[20]  J. Kochan,et al.  Autoantibodies against the high-affinity IgE receptor as a cause of histamine release in chronic urticaria. , 1993, The New England journal of medicine.

[21]  Young-Ho Jung,et al.  Prevalence and Risk Factors of Urticaria With a Focus on Chronic Urticaria in Children , 2017, Allergy, asthma & immunology research.

[22]  Sanjiv K. Jain Pathogenesis of Chronic Urticaria: An Overview , 2014, Dermatology research and practice.

[23]  T. Casale,et al.  Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria. , 2013, The New England journal of medicine.

[24]  M. Maurer,et al.  The role and relevance of mast cells in urticaria , 2018, Immunological reviews.

[25]  J. Bousquet,et al.  Unmet clinical needs in chronic spontaneous urticaria. A GA2LEN task force report 1 , 2011, Allergy.

[26]  I. Barshack,et al.  The Histopathology of Urticaria Revisited—Clinical Pathological Study , 2017, The American Journal of dermatopathology.

[27]  B. Guida,et al.  Histamine plasma levels and elimination diet in chronic idiopathic urticaria , 2000, European Journal of Clinical Nutrition.

[28]  S. Saini,et al.  Emerging Therapies in Chronic Spontaneous Urticaria , 2019, Allergy, asthma & immunology research.

[29]  R. Seifert,et al.  Histamine and Histamine Receptors in Health and Disease , 2017 .

[30]  C. Grattan,et al.  Management and diagnostic guidelines for urticaria and angio‐oedema , 2001, The British journal of dermatology.

[31]  K. Kumon,et al.  Diagnosis and long‐term management of hydrolyzed wheat protein wheat‐dependent exercise‐induced anaphylaxis , 2015, Acute medicine & surgery.

[32]  J. Garssen,et al.  Non-IgE mediated mast cell activation. , 2016, European journal of pharmacology.

[33]  T. Zuberbier,et al.  Definition, classification, and routine diagnosis of urticaria: a consensus report. , 2001, The journal of investigative dermatology. Symposium proceedings.

[34]  M. Greaves Pathology and classification of urticaria. , 2014, Immunology and allergy clinics of North America.

[35]  M. Hide,et al.  Food-dependent exercise-induced anaphylaxis due to ingestion of orange. , 2004, Acta dermato-venereologica.

[36]  Z. Jaffar,et al.  Histamine secretion from mast cells stimulated with ATP , 1990, Agents and Actions.