Chronic spontaneous urticaria: Focus on pathophysiology to unlock treatment advances

被引:62
作者
Kaplan, Allen [1 ]
Lebwohl, Mark [2 ]
Gimenez-Arnau, Ana M. [3 ,4 ]
Hide, Michihiro [5 ,6 ]
Armstrong, April W. [7 ]
Maurer, Marcus [8 ,9 ,10 ,11 ]
机构
[1] Med Univ South Carolina, Dept Med, Div Pulm & Crit Care Med Allergy & Clin Immunol, Charleston, SC USA
[2] Icahn Sch Med Mt Sinai, Dept Dermatol, New York, NY USA
[3] Univ Autonoma Barcelona, Hosp del Mar, Inst Mar Invest Med, Dept Dermatol, Barcelona, Spain
[4] Univ Pompeu Fabra, Barcelona, Spain
[5] Hiroshima Univ, Hiroshima Citizens Hosp, Dept Dermatol, Hiroshima, Japan
[6] Hiroshima Univ, Dept Dermatol, Hiroshima, Japan
[7] Univ Southern Calif, Dept Dermatol, Los Angeles, CA USA
[8] Charite Univ Med Berlin, Inst Allergol, Berlin, Germany
[9] Free Univ Berlin, Berlin, Germany
[10] Humboldt Univ, Berlin, Germany
[11] Fraunhofer Inst Translat Med & Pharmacol ITMP, Allergol & Immunol, Berlin, Germany
关键词
angioedema; dermatology; IgE; mast cells; urticaria; CHRONIC IDIOPATHIC URTICARIA; FC-EPSILON-RI; AFFINITY IGE RECEPTOR; MAST-CELL; AUTOIMMUNE URTICARIA; HISTAMINE-RELEASE; ACTIVATING-FACTOR; DISEASE-ACTIVITY; OMALIZUMAB; SKIN;
D O I
10.1111/all.15603
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
Chronic spontaneous urticaria (CSU) is a debilitating skin disease characterized by intensely itchy wheals, angioedema, or both. Symptoms recur spontaneously, on a near-daily basis, over >6 weeks; many patients experience flare-ups over several years and, consequently, reduced quality of life. Differences between the inflammatory profiles of the skin of CSU patients (wheals and nonlesional sites) and healthy controls indicate that key drivers such as mast cells, eosinophils, and basophils interact, release vasoactive mediators, and prime the skin, leaving patients predisposed to symptoms. Many cytokines and chemokines involved in these inflammatory networks and their corresponding intracellular signaling cascades have been identified. These insights informed the development of therapies such as omalizumab, dupilumab, and Bruton's tyrosine kinase (BTK) inhibitors, marking a renewed focus on pathogenesis in CSU clinical research. Despite progress, current therapies provide symptomatic control but do not appear to redress the inflammatory balance in the skin permanently. A deeper understanding of CSU pathogenesis will permit a more targeted approach to developing novel treatments with curative intent. Here, we review what is known about the pathogenesis of CSU and consider how this can be used to identify rational targets to improve patient care further.
引用
收藏
页码:389 / 401
页数:13
相关论文
共 125 条
  • [1] High-dose omalizumab use in patients with chronic spontaneous urticaria
    Aghdam, Mehran Alizadeh
    van den Broek, Fenne
    Rijken, Feiko
    Knulst, Andre Cornelis
    Rockmann, Heike
    [J]. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE, 2020, 8 (04) : 1426 - +
  • [2] An open-label, proof-of-concept study of lirentelimab for antihistamine-resistant chronic spontaneous and inducible urticaria
    Altrichter, Sabine
    Staubach, Petra
    Pasha, Malika
    Singh, Bhupinder
    Chang, Alan T.
    Bernstein, Jonathan A.
    Rasmussen, Henrik S.
    Siebenhaar, Frank
    Maurer, Marcus
    [J]. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2022, 149 (05) : 1683 - +
  • [3] The role of eosinophils in chronic spontaneous urticaria
    Altrichter, Sabine
    Frischbutter, Stefan
    Fok, Jie Shen
    Kolkhir, Pavel
    Jiao, Qingqing
    Skov, Per Stahl
    Metz, Martin
    Church, Martin K.
    Maurer, Marcus
    [J]. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2020, 145 (06) : 1510 - 1516
  • [4] IgM and IgA in addition to IgG autoantibodies against FceRIα are frequent and associated with disease markers of chronic spontaneous urticaria
    Altrichter, Sabine
    Zampeli, Vasiliki
    Ellrich, Andre
    Zhang, Ke
    Church, Martin K.
    Maurer, Marcus
    [J]. ALLERGY, 2020, 75 (12) : 3208 - 3215
  • [5] IgE Mediated Autoallergy against Thyroid Peroxidase - A Novel Pathomechanism of Chronic Spontaneous Urticaria?
    Altrichter, Sabine
    Peter, Hans-Juergen
    Pisarevskaja, Dina
    Metz, Martin
    Martus, Peter
    Maurer, Marcus
    [J]. PLOS ONE, 2011, 6 (04):
  • [6] Anti-KIT monoclonal antibody CDX-0159 induces profound and durable mast cell suppression in a healthy volunteer study
    Alvarado, Diego
    Maurer, Marcus
    Gedrich, Richard
    Seibel, Scott B.
    Murphy, Michael B.
    Crew, Linda
    Goldstein, Joel
    Crocker, Andrea
    Vitale, Laura A.
    Morani, Pamela A.
    Thomas, Lawrence J.
    Hawthorne, Thomas R.
    Keler, Tibor
    Young, Diane
    Crowley, Elizabeth
    Kankam, Martin
    Heath-Chiozzi, Margo
    [J]. ALLERGY, 2022, 77 (08) : 2393 - 2403
  • [7] Discovery of LOU064 (Remibrutinib), a Potent and Highly Selective Covalent Inhibitor of Bruton's Tyrosine Kinase
    Angst, Daniela
    Gessier, Francois
    Janser, Philipp
    Vulpetti, Anna
    Walchli, Rudolf
    Beerli, Christian
    Littlewood-Evans, Amanda
    Dawson, Janet
    Nuesslein-Hildesheim, Barbara
    Wieczorek, Grazyna
    Gutmann, Sascha
    Scheufler, Clemens
    Hinniger, Alexandra
    Zimmerlin, Alfred
    Funhoff, Enrico G.
    Pulz, Robert
    Cenni, Bruno
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2020, 63 (10) : 5102 - 5118
  • [8] [Anonymous], 2021, DUPILUMAB TREATMENT
  • [9] [Anonymous], 2021, MEPOLIZUMAB TREATMEN
  • [10] [Anonymous], 2022, UPDATE ONGOING DUPIX