Pruritus in allergy and immunology
Open accessAbstract
Although evolutionarily conserved to expel ectoparasites and aid in the clearance of toxins and noxious environmental stimuli from the host, the type 2 immune response can become pathologic in the setting of a variety of allergic disorders. Itch can be a behavioral extension of type 2 immunity by evoking scratching and, in the setting of disease, can become chronic and thus highly pathologic as well. Classically, our understanding of itch mechanisms has centered around the canonical IgE-mast cell-histamine axis. However, therapies aimed at blocking the histaminergic itch pathway have been largely ineffective, suggesting the existence of nonhistaminergic itch pathways. Indeed, recent advances in itch biology have provided critical new insight into a variety of novel therapeutic avenues for chronic itch in the setting of a number of allergic disorders. Here we highlight how these new developments will likely inform the problem of pruritus in a variety of well-established and emerging conditions in the field of allergy.
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The itch-scratch reflex contributes to further disruption of epidermal barrier function, keratinocyte damage, and activation of local dendritic cells, which further activate the adaptive immune response and subsequent inflammatory reaction.
“The itch-scratching reflex contributes to further disruption of the epidermal barrier function, keratinocyte damage and activation of local dendritic cells, which in turn will further activate the adaptive immune response and subsequent inflammatory reaction29,181,182.”
From Atopic dermatitis: an expanding therapeutic pipeline for a complex disease (2022) · cites this paper as [182]
The Prurigo Nodularis section (page not available) says itch is believed to drive rash development and describes chronic scratching, supporting a general link between itch and skin lesions. The Atopic Dermatitis section discusses barrier-derived cytokines and immune inflammation, but the copy does not establish that scratching damages keratinocytes or activates dendritic cells, which then amplify the adaptive immune response. (LLM, conf=0.74)
Experimental — accuracy not yet measuredItch mechanisms are complex, involving multiple mediators that activate peripheral sensory neurons, and they offer several pharmacological targets.
“The mechanisms that underlie itching sensation are complex, involving multiple mediators that initiate the activation of peripheral sensory neurons. They offer a number of potential targets for pharmacological intervention29,180–182.”
From Atopic dermatitis: an expanding therapeutic pipeline for a complex disease (2022) · cites this paper as [182]
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Cites
Identification of a mast cell specific receptor crucial for pseudo-allergic drug reactions
McNeil, B. D., Pundir, P., Meeker, S., Han, L., Undem, B., Kulka, M., & Dong, X.-Z. (2014) · Nature · doi:10.1038/nature14022 · Cited by 1,164 · see citing works
Omalizumab for the Treatment of Chronic Idiopathic or Spontaneous Urticaria
Maurer, M., Rosén, K. E., Hsieh, H.-J., Saini, S. S., Grattan, C., Giménez‐Arnau, A. M., Agarwal, S. K., Doyle, R. L., Canvin, J., Kaplan, A. P., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1215372 · Cited by 1,104 · see citing works
Sensory Neurons Co-opt Classical Immune Signaling Pathways to Mediate Chronic Itch
Oetjen, L. K., Mack, M. R., Feng, J., Whelan, T. M., Niu, H., Guo, C. J., Chen, S., Trier, A. M., Xu, A. Z., Tripathi, S. V., et al. (2017) · Cell · doi:10.1016/j.cell.2017.08.006 · Cited by 1,092 · see citing works
Self-citationIL-31: A new link between T cells and pruritus in atopic skin inflammation
Sonkoly, E., Müller, A., Lauerma, A., Pivarcsi, A., Soto, H., Kemény, L. V., Alenius, H. T., Dieu‐Nosjean, M., Meller, S., Rieker, J., et al. (2006) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2005.10.033 · Cited by 1,000 · see citing works
The Epithelial Cell-Derived Atopic Dermatitis Cytokine TSLP Activates Neurons to Induce Itch
Wilson, S. R., Thé, L., Batia, L. M., Beattie, K., Katibah, G. E., McClain, S. P., Pellegrino, M., Estandian, D., & Bautista, D. M. (2013) · Cell · doi:10.1016/j.cell.2013.08.057 · Cited by 989 · see citing works
Sensory Neuron-Specific GPCR Mrgprs Are Itch Receptors Mediating Chloroquine-Induced Pruritus
Liu, Q., Tang, Z., Surdenikova, L., Kim, S., Patel, K., Kim, A., Ru, F., Guan, Y., Weng, H.-J., Geng, Y., et al. (2009) · Cell · doi:10.1016/j.cell.2009.11.034 · Cited by 820 · see citing works
Cevikbas, F., Wang, X., Akiyama, T., Kempkes, C., Savinko, T., Antal, A. S., Kukova, G., Buhl, T., Ikoma, A., Buddenkotte, J., et al. (2013) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2013.10.048 · Cited by 806 · see citing works
A gastrin-releasing peptide receptor mediates the itch sensation in the spinal cord
Sun, Y.-G., & Chen, Z. (2007) · Nature · doi:10.1038/nature06029 · Cited by 792 · see citing works
Guttman‐Yassky, E., Bissonnette, R., Ungar, B., Suárez‐Fariñas, M., Ardeleanu, M., Esaki, H., Suprun, M., Estrada, Y. D., Xu, H., Peng, X., et al. (2018) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2018.08.022 · Cited by 706 · see citing works
Cellular and molecular immunologic mechanisms in patients with atopic dermatitis
Werfel, T., Allam, J., Biedermann, T., Eyerich, K., Gilles, S., Guttman‐Yassky, E., Hoetzenecker, W., Knol, E. F., Simon, H., Wollenberg, A., et al. (2016) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2016.06.010 · Cited by 593 · see citing works
Anti–Interleukin-31 Receptor A Antibody for Atopic Dermatitis
Ruzicka, T., Hanifin, J. M., Furue, M., Pulka, G., Mlynarczyk, I., Wollenberg, A., Galus, R., Etoh, T., Mihara, R., Yoshida, H., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1606490 · Cited by 592 · see citing works
The Cells and Circuitry for Itch Responses in Mice
Mishra, S. K., & Hoon, M. A. (2013) · Science · doi:10.1126/science.1233765 · Cited by 507 · see citing works
Grimbaldeston, M. A., Nakae, S., Kalesnikoff, J., Tsai, M. M., & Galli, S. J. (2007) · Nature Immunology · doi:10.1038/ni1503 · Cited by 486 · see citing works
IgE, Mast Cells, and Eosinophils in Atopic Dermatitis
Liu, F., Goodarzi, H., & Chen, H. (2011) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-011-8252-4 · Cited by 472 · see citing works
Saini, S. S., Bindslev‐Jensen, C., Maurer, M., Grob, J., Başkan, E. B., Bradley, M. S., Canvin, J., Rahmaoui, A., Georgiou, P., Alpan, O., et al. (2014) · Journal of Investigative Dermatology · doi:10.1038/jid.2014.306 · Cited by 469 · see citing works
Omalizumab-induced reductions in mast cell FcεRI expression and function
Beck, L. A., Marcotte, G. V., MacGlashan, D., Togias, A. G., & Saini, S. S. (2004) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2004.06.032 · Cited by 456 · see citing works
Mast Cells Are Key Promoters of Contact Allergy that Mediate the Adjuvant Effects of Haptens
Dudeck, A., Dudeck, J., Scholten, J., Petzold, A., Surianarayanan, S., Köhler, A., Peschke, K., Voehringer, D., Waskow, C., Krieg, T. M., et al. (2011) · Immunity · doi:10.1016/j.immuni.2011.03.028 · Cited by 455 · see citing works
Topical tofacitinib for atopic dermatitis: a phase II a randomized trial
Bissonnette, R., Papp, K. A., Poulin, Y. P., Gooderham, M., Raman, M., Mallbris, L., Wang, C., Purohit, V. S., Mamolo, C. M., Papacharalambous, J., et al. (2016) · British Journal of Dermatology · doi:10.1111/bjd.14871 · Cited by 420 · see citing works
Treatment of atopic dermatitis with tralokinumab, an anti–IL-13 mAb
Wollenberg, A., Howell, M. D., Guttman‐Yassky, E., Silverberg, J. I., Kell, C., Ranade, K., Moate, R., & van der Merwe, R. (2018) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2018.05.029 · Cited by 408 · see citing works
Wollenberg, A., Oranje, A. P., Deleuran, M. S., Simon, D., Szalai, Z. Z., Kunz, B., Svensson, Å., Barbarot, S., von Kobyletzki, L., Taı̈eb, A., et al. (2016) · Journal of the European Academy of Dermatology and Venereology · doi:10.1111/jdv.13599 · Cited by 396 · see citing works
Different activation signals induce distinct mast cell degranulation strategies
Gaudenzio, N., Sibilano, R., Marichal, T., Starkl, P. M., Reber, L. L., Cénac, N., McNeil, B. D., Dong, X., Hernandez, J. D., Sagi‐Eisenberg, R., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci85538 · Cited by 380 · see citing works
Meixiong, J., Anderson, M. C., Limjunyawong, N., Sabbagh, M. F., Hu, E., Mack, M. R., Oetjen, L. K., Wang, F., Kim, B., & Dong, X. (2019) · Immunity · doi:10.1016/j.immuni.2019.03.013 · Cited by 371 · see citing works
Self-citationSimpson, E. L., Flohr, C., Eichenfield, L. F., Bieber, T. R. M., Sofen, H. L., Taı̈eb, A., Owen, R., Putnam, W. S., Castro, M., DeBusk, K. P. A., et al. (2018) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2018.01.017 · Cited by 330 · see citing works
Liu, B., Tai, Y., Achanta, S., Kaelberer, M. M., Caceres, A. I., Shao, X., Fang, J., & Jordt, S. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1606608113 · Cited by 324 · see citing works
Bao, L., Zhang, H., & Chan, L. S. (2013) · JAK-STAT · doi:10.4161/jkst.24137 · Cited by 321 · see citing works
Guttman‐Yassky, E., Silverberg, J. I., Nemoto, O., Forman, S. B., Wilke, A. V., Prescilla, R. P., de la Peña, A., Nunes, F. P., Janes, J., Gamalo, M., et al. (2018) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2018.01.018 · Cited by 319 · see citing works
Matterne, U., Apfelbacher, C., Loerbroks, A., Schwarzer, T., Büttner, M., Ofenloch, R. F., Diepgen, T. L., & Weißhaar, E. (2011) · Acta Dermato Venereologica · doi:10.2340/00015555-1159 · Cited by 265 · see citing works
The Itch–Scratch Cycle: A Neuroimmune Perspective
Mack, M. R., & Kim, B. S. (2018) · Trends in Immunology · doi:10.1016/j.it.2018.10.001 · Cited by 255 · see citing works
Self-citationKimber, I., Basketter, D. A., Gerberick, G. F., & Dearman, R. J. (2002) · International Immunopharmacology · doi:10.1016/s1567-5769(01)00173-4 · Cited by 247 · see citing works
Gericke, J., Metz, M., Ohanyan, T., et al. (2016) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2016.07.047 · Cited by 223 · see citing works
Treatment of recalcitrant atopic dermatitis with the oral Janus kinase inhibitor tofacitinib citrate
Levy, L., Urban, J. R., & King, B. (2015) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2015.06.045 · Cited by 215 · see citing works
Ständer, S., Schäfer, I., Phan, N. Q., Blome, C., Herberger, K., Heigel, H., & Augustin, M. (2010) · Dermatology · doi:10.1159/000319862 · Cited by 206 · see citing works
Iking, A., Grundmann, S. A., Chatzigeorgakidis, E., Phan, N. Q., Klein, D., & Ständer, S. (2012) · Journal of the European Academy of Dermatology and Venereology · doi:10.1111/j.1468-3083.2012.04481.x · Cited by 195 · see citing works
Eckman, J. A., Hamilton, R. G., Gober, L. M., et al. (2008) · Journal of Investigative Dermatology · doi:10.1038/jid.2008.55 · Cited by 156 · see citing works
Diagnosis and management of contact dermatitis.
Usatine, R. P., & Riojas, M. (2010) · PubMed · Cited by 155 · see citing works
Kostner, L., Anzengruber, F., Guillod, C., et al. (2016) · Immunology and Allergy Clinics of North America · doi:10.1016/j.iac.2016.08.014 · Cited by 146 · see citing works
Nakagawa, H., Nemoto, O., Igarashi, A., & Nagata, T. (2017) · British Journal of Dermatology · doi:10.1111/bjd.16014 · Cited by 145 · see citing works
Nppb Neurons Are Sensors of Mast Cell-Induced Itch
Solinski, H. J., Kriegbaum, M. C., Tseng, P., Earnest, T., Gu, X., Barik, A., Chesler, A. T., & Hoon, M. A. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.02.089 · Cited by 138 · see citing works
Askenase, P. W., & Loverent, H. V. (1983) · Immunology Today · doi:10.1016/0167-5699(83)90046-4 · Cited by 137 · see citing works
Prurigo nodularis: systematic analysis of 58 histological criteria in 136 patients
Weigelt, N., Metze, D., & Ständer, S. (2009) · Journal of Cutaneous Pathology · doi:10.1111/j.1600-0560.2009.01484.x · Cited by 134 · see citing works
Anti-IgE as a mast cell–stabilizing therapeutic agent
Chang, T. W., & Shiung, Y.-Y. (2006) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2006.04.005 · Cited by 123 · see citing works
Yosipovitch, G., Ständer, S., Kerby, M. B., Larrick, J. W., Perlman, A. J., Schnipper, E. F., Zhang, X., Tang, J. Y., Luger, T. A., & Steinhoff, M. S. (2018) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2018.02.030 · Cited by 121 · see citing works
Prurigo nodularis and lichen simplex chronicus
Lotti, T., Buggiani, G., & Prignano, F. (2008) · Dermatologic Therapy · doi:10.1111/j.1529-8019.2008.00168.x · Cited by 121 · see citing works
Pruritus in Elderly Patients—Eruptions of Senescence
Berger, T. G., & Steinhoff, M. S. (2011) · Seminars in Cutaneous Medicine and Surgery · doi:10.1016/j.sder.2011.04.002 · Cited by 118 · see citing works
Ständer, S., Kwon, P., Hirman, J., Perlman, A. J., Weisshaar, E., Metz, M., & Luger, T. A. (2019) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2019.01.052 · Cited by 118 · see citing works
Prurigo Nodularis and Its Management
Zeidler, C., Yosipovitch, G., & Ständer, S. (2018) · Dermatologic Clinics · doi:10.1016/j.det.2018.02.003 · Cited by 112 · see citing works
Haas, S., Capellino, S., Phan, N. Q., Böhm, M., Luger, T. A., Straub, R. H., & Ständer, S. (2010) · Journal of Dermatological Science · doi:10.1016/j.jdermsci.2010.03.020 · Cited by 107 · see citing works
Kollmeier, A. P., Francke, K., Chen, B., et al. (2014) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.114.215749 · Cited by 86 · see citing works
Innate Lymphoid Cells in the Skin
Kim, B. (2014) · Journal of Investigative Dermatology · doi:10.1038/jid.2014.401 · Cited by 81 · see citing works
Self-citationThe Unique Molecular Signatures of Contact Dermatitis and Implications for Treatment
Leonard, A., & Guttman‐Yassky, E. (2018) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-018-8685-0 · Cited by 81 · see citing works
Dupilumab Treatment for Generalized Prurigo Nodularis
Beck, K. M., Yang, E., Sekhon, S., et al. (2018) · JAMA Dermatology · doi:10.1001/jamadermatol.2018.3912 · Cited by 80 · see citing works
CGRP‐immunoreactive nerves in prurigo nodularis – an exploration of neurogenic inflammation
Liang, Y., Jacobi, H. H., Reimert, C. M., Haak‐Frendscho, M., Marcusson, J. A., & Johansson, O. (2000) · Journal of Cutaneous Pathology · doi:10.1034/j.1600-0560.2000.027007359.x · Cited by 79 · see citing works
Schneider, E. H., & Seifert, R. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.05.004 · Cited by 78 · see citing works
Leukotriene receptor antagonists for chronic urticaria: a systematic review
de Silva, N. L., Damayanthi, H., Rajapakse, A. C., et al. (2014) · Allergy Asthma and Clinical Immunology · doi:10.1186/1710-1492-10-24 · Cited by 73 · see citing works
Liu, X., Wan, L., Huo, F., et al. (2014) · Molecular Pain · doi:10.1186/1744-8069-10-4 · Cited by 71 · see citing works
Chronic Spontaneous Urticaria: Pathogenesis and Treatment Considerations
Kaplan, A. P. (2017) · Allergy Asthma and Immunology Research · doi:10.4168/aair.2017.9.6.477 · Cited by 66 · see citing works
Parnes, J. R., Sullivan, J. T., Chen, L., & Dias, C. S. (2019) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.1401 · Cited by 56 · see citing works
Cytokine modulation of atopic itch
Trier, A. M., & Kim, B. (2018) · Current Opinion in Immunology · doi:10.1016/j.coi.2018.05.005 · Cited by 55 · see citing works
Self-citationPeripheral blood eosinophilia in atopic dermatitis.
Jenerowicz, D., Czarnecka-Operacz, M. M., & Silny, W. (2007) · PubMed · Cited by 50 · see citing works
Interactions of the immune and sensory nervous systems in atopy
Oetjen, L. K., & Kim, B. (2018) · FEBS Journal · doi:10.1111/febs.14465 · Cited by 50 · see citing works
Self-citationImmune dysregulation underlies a subset of patients with chronic idiopathic pruritus
Xu, A. Z., Tripathi, S. V., Kau, A. L., et al. (2016) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2015.11.029 · Cited by 49 · see citing works
Gimenez-Rivera, V.-A., Siebenhaar, F., Zimmermann, C., Siiskonen, H., Metz, M., & Maurer, M. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1600236 · Cited by 45 · see citing works
Thurmond, R. L., Kazerouni, K., Chaplan, S. R., & Greenspan, A. J. (2015) · Handbook of experimental pharmacology · doi:10.1007/978-3-662-44605-8_15 · Cited by 41 · see citing works
Prurigo nodularis in HIV‐infected individuals
Matthews, S. N., & Cockerell, C. J. (1998) · International Journal of Dermatology · doi:10.1046/j.1365-4362.1998.00507.x · Cited by 41 · see citing works
Immunomodulating Agents as Antipruritics
Erickson, S. P., Nahmias, Z. P., Rosman, I. S., & Kim, B. (2018) · Dermatologic Clinics · doi:10.1016/j.det.2018.02.014 · Cited by 27 · see citing works
Self-citationKamo, A., Negi, O., Tengara, S., et al. (2013) · Journal of Investigative Dermatology · doi:10.1038/jid.2013.351 · Cited by 23 · see citing works
Beck, L. A., Hong, C., Hu, X., Chen, S., Calimlim, B., Teixeira, H. D., & Guttman‐Yassky, E. (2018) · Annals of Allergy Asthma & Immunology · doi:10.1016/j.anai.2018.09.063 · Cited by 14 · see citing works
Ruxolitinib Cream Suppresses Th2 Inflammation in Adult Patients With Atopic Dermatitis
Owens, S. L., & Howell, M. D. (2019) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2018.12.387 · Cited by 5 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [64]Mowad C, Marks J. Allergic Contact Dermatitis. In: Bolognia J, Jorizzo J, Schaffer J, editors. Dermatology 3rd ed. Philadelphia: Elsevier Saunders; 2012.
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Atopic dermatitis: an expanding therapeutic pipeline for a complex disease
Bieber, T. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00266-6 · Cited by 623 · see citing works
Clinical manifestations and genetic influences in sulfonamide-induced hypersensitivity
Asyraf, P. A., Kusnadi, I. F., Stefanus, J., Khairinisa, M. A., & Abdulah, R. (2022) · Drug Healthcare and Patient Safety · doi:10.2147/dhps.s347522 · Cited by 27 · see citing works
- Authors
- Yang, T.-L. B., & Kim, B. S.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Kim, Brian S.
- Venue
- Journal of Allergy and Clinical Immunology
- Publisher
- Elsevier BV
- Published
- 2019-08
- Volume
- 144
- Issue
- 2
- Pages
- 353-360
- ISSN
- 0091-6749 (ISSN-L)
- PMC
- PMC6690370
- OpenAlex
- W2966029164
- Cited by
- 112
- References
- 68
- Citations by year
- 2026: 9 · 2025: 11 · 2024: 15 · 2023: 23 · 2022: 24 · 2021: 21 · 2020: 8 · 2018: 1
- FWCI
- 2.57
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Allergy and Clinical Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Doris Duke Charitable Foundation
- National Institute of Arthritis and Musculoskeletal and Skin Diseases
- Topics
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Keywords
- pruritus, chronic pruritus, Th2 immune response, allergic diseases, histamine, IgE, mast cells, scratching behavior, itch mechanisms, antipruritic therapy
- MeSH terms
- Animals, Histamine, Humans, Hypersensitivity, Immunoglobulin E, Mast Cells, Pruritus
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