{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:41:41Z","timestamp":1785426101963,"version":"3.56.0"},"reference-count":86,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T00:00:00Z","timestamp":1778976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education","award":["RS-2025-25440216"],"award-info":[{"award-number":["RS-2025-25440216"]}]},{"award":["RS-2025-25440216"],"award-info":[{"award-number":["RS-2025-25440216"]}],"id":[{"id":"https:\/\/ror.org\/00b3tsf98","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Histamine, present in almost all tissues, exerts diverse biologic actions through four receptors expressed across multiple organs and cell types. Histamine concentrations are elevated in various conditions. A wide spectrum of clinical manifestations where histamine levels increase has been described. When plasma histamine concentrations are increased, multiple symptoms may occur via histamine receptor-mediated signaling. These clinical situations are defined as histamine-mediated syndrome (HMS). Recent reports describe the use of an immunoglobulin\/histamine complex (IHC) to treat conditions beyond classical allergic diseases, such as allergic rhinitis (AR) and chronic urticaria (CU). Baseline plasma histamine levels in AR and CU can be higher than expected. This suggests histamine-driven comorbid manifestations in tissues and organs expressing histamine receptors. Accordingly, HMS may be more common in routine practice than is generally appreciated. IHC may represent a rational therapeutic option for HMS. In this review, we define HMS and integrate the available evidence to propose a systematic clinical framework.<\/jats:p>","DOI":"10.3390\/ijms27104494","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T14:40:31Z","timestamp":1779115231000},"page":"4494","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Histamine-Mediated Syndrome (HMS): Beyond Allergy and Therapeutic Potential of Immunoglobulin\/Histamine Complex (IHC)"],"prefix":"10.3390","volume":"27","author":[{"given":"Hyuk Soon","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, College of Natural Science, Dong-A University, Busan 49315, Republic of Korea"},{"name":"Department of Health Sciences, The Graduate School of Dong-A University, Busan 49315, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geunwoong","family":"Noh","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, Cheju Halla General Hospital, Jeju 63127, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/B978-0-12-820107-7.00023-9","article-title":"Histamine receptors, agonists, and antagonists in health and disease","volume":"180","author":"Panula","year":"2021","journal-title":"Handb. Clin. Neurol."},{"key":"ref_2","first-page":"1","article-title":"Treatment of hay fever with the antihistaminic pyrteen","volume":"10","author":"Morin","year":"1953","journal-title":"Ther. Umsch."},{"key":"ref_3","first-page":"1","article-title":"Immune basis of allergic reactions","volume":"29","author":"Berin","year":"2019","journal-title":"J. Investig. Allergol. Clin. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"123172","DOI":"10.1016\/j.lfs.2024.123172","article-title":"Targeting histamine in metabolic syndrome: Insights and therapeutic potential","volume":"358","author":"Wang","year":"2024","journal-title":"Rev. Life Sci."},{"key":"ref_5","first-page":"403","article-title":"Inhibition of rat mast cell degranulation and histamine release by histamine-rat gammaglobulin conjugate","volume":"59","author":"Ishikawa","year":"1979","journal-title":"Int. Arch. Allergy Appl. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/BF02991725","article-title":"Efficacy of histaglobulin on allergic rhinitis","volume":"49","author":"Narayana","year":"1997","journal-title":"Indian J. Otolaryngol. Head Neck Surg."},{"key":"ref_7","first-page":"285","article-title":"Studies on the production of anti-histamine antibody in the rabbits immunized with \u201cHistobulin\u201d: A new histamine-human-\u03b3-globulin complex developed by authors","volume":"20","author":"Ito","year":"1971","journal-title":"Jpn. J. Allergol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1016\/j.jaci.2024.12.1081","article-title":"Novel insights on the biology and immunologic effects of histamine: A road map for allergists and mast cell biologists","volume":"155","author":"Maurer","year":"2025","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1113\/jphysiol.1910.sp001406","article-title":"The physiologic action of beta-iminazolylethylamine","volume":"41","author":"Dale","year":"1910","journal-title":"J. Physiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"S127","DOI":"10.1038\/sj.bjp.0706440","article-title":"Histamine and its receptors","volume":"147","author":"Parsons","year":"2006","journal-title":"Br. J. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1113\/jphysiol.1927.sp002369","article-title":"The nature of the vasodilator constituents of certain tissue extracts","volume":"62","author":"Best","year":"1927","journal-title":"J. Physiol."},{"key":"ref_12","first-page":"209","article-title":"Vascular reactions of the skin to injury, part 11: The liberation of histamine-like substance in the injured skin, the underlying cause of factitious urticaria and of wheals produced by burning: And observations upon the nervous control of certain skin reactions","volume":"11","author":"Lewis","year":"1924","journal-title":"Heart"},{"key":"ref_13","first-page":"287","article-title":"Histamime and antihistamines in amaphylaxis","volume":"17","author":"Winbery","year":"2002","journal-title":"Clin. Allergy Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Shahid, M., Khardori, N., Khan, R., and Tripathi, T. (2011). Biomedical Aspects of Histamine: Current Perspectives, Springer.","DOI":"10.1007\/978-90-481-9349-3"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Thangam, E.B., Jemima, E.A., Singh, H., Baig, M.S., Khan, M., Mathias, C.B., Church, M.K., and Saluja, R. (2018). The Role of Histamine and Histamine Receptors in Mast Cell-Mediated Allergy and Inflammation: The Hunt for New Therapeutic Targets. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01873"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.alit.2019.05.009","article-title":"Decreased intracellular histamine concentration and basophil activation in anaphylaxis","volume":"69","author":"Yamaga","year":"2020","journal-title":"Allergol. Int."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1021\/bi00846a001","article-title":"Histidine decarboxylase of Lactobacillus 30a. II. Purification, substrate specificity, and stereospecificity","volume":"7","author":"Chang","year":"1968","journal-title":"Biochemistry"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/S0021-9258(18)33275-7","article-title":"Pyruvoyl-dependent histidine decarboxylases from Clostridium perfringens and Lactobacillus buchneri. Comparative structures and properties","volume":"258","author":"Recsei","year":"1983","journal-title":"J. Biol. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1084\/jem.102.3.307","article-title":"Mast cells as sources of tissue histamine","volume":"102","author":"Graham","year":"1955","journal-title":"J. Exp. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4177","DOI":"10.1007\/s10238-023-01141-x","article-title":"An update on mechanisms of pruritus and their potential treatment in primary cutaneous T-cell lymphoma","volume":"23","author":"Hu","year":"2023","journal-title":"Clin. Exp. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"C99","DOI":"10.1007\/BF02007785","article-title":"Macrophages and lymphocytes: Alternative sources of histamine","volume":"41","author":"Braam","year":"1994","journal-title":"Agents Actions"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1084\/jem.153.2.293","article-title":"Histamine production during the antiallograft response. Demonstration of a new lymphokine enhancing histamine synthesis","volume":"153","author":"Dy","year":"1981","journal-title":"J. Exp. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1159\/000085108","article-title":"Histamine in allergic inflammation and immune modulation","volume":"137","author":"Jutel","year":"2005","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Shulpekova, Y.O., Nechaev, V.M., Popova, I.R., Deeva, T.A., Kopylov, A.T., Malsagova, K.A., Kaysheva, A.L., and Ivashkin, V.T. (2021). Food intolerance: The role of histamine. Nutrients, 13.","DOI":"10.3390\/nu13093207"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Hrubisko, M., Danis, R., Huorka, M., and Wawruch, M. (2021). Histamine intolerance\u2014The more we know the less we know. A review. Nutrients, 13.","DOI":"10.3390\/nu13072228"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/978-3-642-75840-9_14","article-title":"Catabolism of histamine","volume":"Volume 97","year":"1991","journal-title":"Handbook of Experimental Pharmacology: Histamine and Histamine Antagonists"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1093\/ajcn\/85.5.1185","article-title":"Histamine and histamine intolerance","volume":"85","author":"Maintz","year":"2007","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1016\/j.anai.2010.08.005","article-title":"The basics of histamine biology","volume":"106","author":"Lieberman","year":"2011","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6105","DOI":"10.1038\/s41467-022-33880-y","article-title":"Structural basis for recognition of antihistamine drug by human histamine receptor","volume":"13","author":"Peng","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_30","first-page":"81","article-title":"Gastric acid secretion: Activation and inhibition","volume":"67","author":"Sachs","year":"1994","journal-title":"Yale J. Biol. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"109045","DOI":"10.1016\/j.intimp.2022.109045","article-title":"Histamine H3R antagonist counteracts the impaired hippocampal neurogenesis in lipopolysaccharideinduced neuroinflammation","volume":"110","author":"Wang","year":"2022","journal-title":"Int. Immunopharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.molimm.2014.05.007","article-title":"Functional characterization of histamine H4 receptor on human mast cells","volume":"62","author":"Jemima","year":"2014","journal-title":"Mol. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1111\/all.12875","article-title":"Human basophil chemotaxis and activation are regulated via the histamine H4 receptor","volume":"71","author":"Mommert","year":"2016","journal-title":"Allergy"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1046\/j.0954-7894.2002.01314.x","article-title":"H1-antihistamines: Inverse agonism, anti-inflammatory actions and cardiac effects","volume":"32","author":"Leurs","year":"2002","journal-title":"Clin. Exp. Allergy"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/0091-6749(81)90134-2","article-title":"Effects of infused histamine: Analysis of the effects of H-1 and H-2 histamine receptor antagonists on cardiovascular and pulmonary responses","volume":"68","author":"Kaliner","year":"1981","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/0091-6749(85)90801-2","article-title":"Mediator release in local heat urticaria: Protection with combined H1 and H2 antagonists","volume":"76","author":"Irwin","year":"1985","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_37","first-page":"6","article-title":"Current concepts of histamine actions through H1 and H2 receptors","volume":"8","author":"Summers","year":"1982","journal-title":"Compr. Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1111\/j.1398-9995.1989.tb01070.x","article-title":"Effects of topical treatment with H1 and H2 antagonists on clinical symptoms and nasal vascular reactions in patients with allergic rhinitis","volume":"44","author":"Holmberg","year":"1989","journal-title":"Allergy"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1111\/j.1365-2222.2008.03041.x","article-title":"Localization and function of histamine H3 receptor in the nasal mucosa","volume":"38","author":"Suzuki","year":"2008","journal-title":"Clin. Exp. Allergy"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"391","DOI":"10.2500\/105065899781367483","article-title":"Combined histamine H1 and H3 receptor blockade produces nasal decongestion in an experimental model of nasal congestion","volume":"13","author":"McLeod","year":"1999","journal-title":"Am. J. Rhinol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1177\/000348940411300707","article-title":"Immunohistochemical localization of histamine receptor subtypes in human inferior turbinates","volume":"113","author":"Nakaya","year":"2004","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Stark, H. (2013). Histamine metabolism. Histamine H4 Receptor: A Novel Drug Target in Immunoregulation and Inflammation, Versita.","DOI":"10.2478\/9788376560564"},{"key":"ref_43","first-page":"103","article-title":"Histamine receptors in the lung","volume":"33","author":"Barnes","year":"1991","journal-title":"Agents Actions Suppl."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1042\/bst0200122","article-title":"Multiple histamine receptors: Properties and functional characteristics","volume":"20","author":"Hill","year":"1992","journal-title":"Biochem. Soc. Trans."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1111\/j.1476-5381.2009.00151.x","article-title":"The role of histamine H4 receptor in immune and inflammatory disorders","volume":"157","author":"Zampeli","year":"2009","journal-title":"Br. J. Pharmacol."},{"key":"ref_46","first-page":"457","article-title":"The basal plasma histamine level and eosinophil count in allergic and non-allergic patients","volume":"90","author":"Kimura","year":"1999","journal-title":"Fukuoka Igaku Zasshi"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/0009-8981(77)90441-7","article-title":"Blood and urine histamine levels in normal and pathological states as measured by a radiochemical assay","volume":"79","author":"Horakova","year":"1977","journal-title":"Clin. Chim. Acta"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1007\/BF01965513","article-title":"Histamine content and mast cell numbers in tissues of normal and athymic rats","volume":"17","author":"Aldenborg","year":"1986","journal-title":"Agents Actions"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/S0091-6749(82)80005-5","article-title":"Effects of infused histamine: Correlation of plasma histamine levels and symptoms","volume":"69","author":"Kaliner","year":"1982","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Hirasawa, N. (2019). Expression of histidine decarboxylase and its roles in inflammation. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20020376"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2820","DOI":"10.1021\/acssynbio.2c00205","article-title":"Discovery of 8-hydroxyquinoline as a histamine receptor 2 blocker scaffold","volume":"11","author":"Kruyer","year":"2022","journal-title":"ACS Synth. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"zsy183","DOI":"10.1093\/sleep\/zsy183","article-title":"Histamine: Neural circuits and new medications","volume":"42","author":"Scammell","year":"2019","journal-title":"Sleep"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e2100100","DOI":"10.1002\/mnfr.202100100","article-title":"A novel potent sleep-promoting effect of turmeric: Turmeric increases non\u2013rapid eye movement sleep in mice via histamine H1 receptor blockade","volume":"65","author":"Um","year":"2021","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1080\/1744666X.2019.1596800","article-title":"Recent advances in our understanding of mast cell activation\u2014Or should it be mast cell mediator disorders?","volume":"15","author":"Theoharides","year":"2019","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"S161","DOI":"10.1016\/j.jaci.2009.12.981","article-title":"Anaphylaxis","volume":"125","author":"Simons","year":"2010","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_56","first-page":"219","article-title":"Plasma level of histamine in aspirin-sensitive urticaria","volume":"59","author":"Asad","year":"1987","journal-title":"Ann. Allergy"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s11882-010-0162-7","article-title":"The role of the histamine H4 receptor in atopic dermatitis","volume":"11","author":"Mommert","year":"2011","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1034\/j.1600-0625.2002.110102.x","article-title":"Pathophysiology of pruritus in atopic dermatitis: An overview","volume":"11","author":"Stander","year":"2002","journal-title":"Exp. Dermatol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"164","DOI":"10.5021\/ad.2018.30.2.164","article-title":"A Histamine-Free Diet Is Helpful for Treatment of Adult Patients with Chronic Spontaneous Urticaria","volume":"30","author":"Son","year":"2018","journal-title":"Ann. Dermatol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.bjorl.2018.09.007","article-title":"Individualize treatment for allergic rhinitis based on key nasal clinical manifestations combined with histamine and leukotriene D4 levels","volume":"86","author":"Shen","year":"2020","journal-title":"Braz. J. Otorhinolaryngol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.iac.2013.09.001","article-title":"Mastocytosis","volume":"34","author":"Carter","year":"2014","journal-title":"Immunol. Allergy Clin. N. Am."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1007\/s12016-015-8487-6","article-title":"Mast cell activation syndrome","volume":"54","author":"Frieri","year":"2018","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_63","first-page":"26","article-title":"Histamine intolerance","volume":"62","year":"2013","journal-title":"Ceskoslovenska Fysiol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Jochum, C. (2024). Histamine intolerance: Symptoms, diagnosis, and beyond. Nutrients, 16.","DOI":"10.3390\/nu16081219"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.aller.2015.05.001","article-title":"Histamine, histamine intoxication and intolerance","volume":"43","author":"Buday","year":"2015","journal-title":"Allergol. Immunopathol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1111\/j.1365-2222.1993.tb00293.x","article-title":"Abnormalities in histamine pharmacodynamics in chronic urticaria","volume":"23","author":"Kanny","year":"1993","journal-title":"Clin. Exp. Allergy"},{"key":"ref_67","first-page":"966","article-title":"Histobulin as a complementary but essential therapeutic for intravenous immune globulin therapy of Pfeiffer Weber-Christian disease with multiple allergic diseases and its effects on allergic disease: A case report","volume":"29","author":"Noh","year":"2020","journal-title":"Clin. Case Rep."},{"key":"ref_68","first-page":"57","article-title":"Therapeutic effectiveness of histaglobin preparations in patients with allergic rhinitis and chronic urticaria","volume":"71","author":"Gushchin","year":"1999","journal-title":"Ter. Arkhiv"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/S1567-5769(03)00031-6","article-title":"Modulation of the Th1\/Th2 bias by an immunoglobulin histamine complex in the ovalbumin allergy mouse model","volume":"3","author":"Ayoub","year":"2003","journal-title":"Int. Immunopharmacol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/S0192-0561(00)00037-0","article-title":"The anti-allergic drug histaglobin inhibits NF-kappa B nuclear translocation and down-regulates proinflammatory cytokines","volume":"22","author":"Ayoub","year":"2000","journal-title":"Int. J. Immunopharmacol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1111\/j.1365-2222.2007.02666.x","article-title":"Histamine as an immune modulator in chronic inflammatory responses","volume":"37","author":"Jutel","year":"2007","journal-title":"Clin. Exp. Allergy"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2846","DOI":"10.1111\/all.15381","article-title":"Effects of the immunoglobulin\/histamine complex in chronic spontaneous urticaria focusing on remission induction","volume":"77","author":"Kim","year":"2022","journal-title":"Allergy"},{"key":"ref_73","first-page":"807","article-title":"Histaglobin treatment of bronchial asthma in children","volume":"45","author":"Szczypiorski","year":"1970","journal-title":"Pediatr. Pol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1002\/ccr3.3472","article-title":"Immunotherapy using Histobulin in atopic dermatitis","volume":"9","author":"Noh","year":"2020","journal-title":"Clin. Case Rep."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1186\/s13223-021-00612-8","article-title":"Induction of remission in chronic urticaria by immunotherapy using immunoglobulin\/histamine complex (Histobulin): A case report","volume":"17","author":"Kim","year":"2021","journal-title":"Allergy Asthma Clin. Immunol."},{"key":"ref_76","first-page":"390","article-title":"Effects of Histobulin (Immunoglobulin\/Histamine Complex) on Depression and Anxiety in Chronic Urticaria: Psychiatric Manifestations or Psychiatric Comorbidities of Chronic Urticaria: A Case Report","volume":"6","author":"Kim","year":"2021","journal-title":"J. Clin. Exp. Immunol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1186\/s13256-023-03937-7","article-title":"Effects of the immunoglobulin\/histamine complex on panic disorder concurrent with chronic spontaneous urticaria: A case report","volume":"17","author":"Kim","year":"2023","journal-title":"J. Med. Case Rep."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e6885","DOI":"10.1002\/ccr3.6885","article-title":"Treatment of primary eosinophilic colitis using immunoglobulin\/histamine complex","volume":"11","author":"Kim","year":"2023","journal-title":"Clin. Case Rep."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.neubiorev.2008.12.004","article-title":"Itch and pain","volume":"34","author":"Schmelz","year":"2010","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e14","DOI":"10.12771\/emj.2026.01207","article-title":"Nociceptive pain as a clinical presentation of chronic urticaria and disappearance with immunoglobulin\/histamine complex therapy: A case report","volume":"49","author":"Kim","year":"2026","journal-title":"Ewha Med. J."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s11882-025-01245-2","article-title":"Targeting mast cells in chronic spontaneous urticaria","volume":"26","author":"Zarabian","year":"2026","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"112947","DOI":"10.1016\/j.biopha.2022.112947","article-title":"Histamine H3 receptor antagonists\u2014Roles in neurological and endocrine diseases and diabetes mellitus","volume":"150","author":"Abdulrazzaq","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_83","first-page":"1047","article-title":"Histamine fixation by heparin","volume":"145","author":"Parrot","year":"1951","journal-title":"Comptes Rendus Seances Soc. Biol. Fil."},{"key":"ref_84","first-page":"492","article-title":"The histamine-fixing power of blood serum; its modification after an injection of normal human serum or of an azoprotein of histamine","volume":"46","author":"Parrot","year":"1954","journal-title":"J. Physiol."},{"key":"ref_85","first-page":"1","article-title":"[Histaminopexy]","volume":"17","author":"Rostafinska","year":"1964","journal-title":"Wiad. Lek."},{"key":"ref_86","first-page":"263","article-title":"Research on the mode of action of a new series of derivatives which can be used in the treatment of allergy","volume":"47","author":"Parrot","year":"1955","journal-title":"J. Physiol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/10\/4494\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T04:27:10Z","timestamp":1779164830000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/10\/4494"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,17]]},"references-count":86,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["ijms27104494"],"URL":"https:\/\/doi.org\/10.3390\/ijms27104494","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,17]]}}}