{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T15:57:33Z","timestamp":1788623853535,"version":"build-2803163510"},"reference-count":64,"publisher":"Oceanside Publications Inc.","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["allergy asthma proc"],"published-print":{"date-parts":[[2024,5,1]]},"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> A diagnosis of hereditary angioedema (HAE) with normal C1 esterase inhibitor (HAE-nl-C1-INH) can be challenging and pharmacologic management is not well defined.  <jats:bold>Objective:<\/jats:bold> The objective was to discuss practical considerations in the clinical\n management of HAE-nl-C1-INH by using illustrative clinical vignettes to highlight and\/or address select challenges.  <jats:bold>Methods:<\/jats:bold> This was a narrative review.  <jats:bold>Results:<\/jats:bold> Symptoms of HAE-nl-C1-INH overlap with HAE types I and II; the heterogeneity of presentation\n and symptom burden are diagnostic challenges. A patient history, with particular attention to whether urticaria or other symptoms of mast cell mediator release are present, is important because such symptoms would strongly suggest a mast cell\u2010mediated pathway. A family history of angioedema\n is informative but a lack thereof does not rule out diagnosis. Expected laboratory findings would be normal for C4, C1-INH level and function, and Complement 1q; a genetic mutational analysis may be helpful, but current assays do not include all known mutations; most cases are categorized\n as unknown. To align with guideline-directed treatment approaches, the following stepwise approach is suggested for suspected HAE-nl-C1-INH: (1) thoroughly investigate the possibility of response to histaminergic and\/or mast cell\u2010targeting treatments; (2) if patients with normal C4,\n C1-INH level and\/or function fail adequate trials with histamine\/mast cell-directed therapy or have a mutation that suggests bradykinin pathway involvement, follow HAE type I and II treatment guidelines. Response to medications approved for HAE types I\/II provides compelling support for a\n high clinical suspicion of HAE-nl-C1-INH. De-labeling an HAE-nl-C1-INH diagnosis may be appropriate if the initial diagnosis was made without adequate evaluation or if new information and\/or testing indicates that the patient does not actually have HAE.  <jats:bold>Conclusion:<\/jats:bold> Key\n unmet needs in HAE-nl-C1-INH include lack of confirmatory biomarker(s) for diagnosis and lack of prospective controlled clinical studies of pharmacologic products in this patient population.<\/jats:p>","DOI":"10.2500\/aap.2024.45.240010","type":"journal-article","created":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T04:50:02Z","timestamp":1715921402000},"page":"147-157","source":"Crossref","is-referenced-by-count":22,"title":["Hereditary angioedema with normal C1 esterase inhibitor: Current paradigms and clinical dilemmas"],"prefix":"10.2500","volume":"45","author":[{"given":"Cristine","family":"Radojicic","sequence":"first","affiliation":[{"name":"From the Division of Pulmonary, Allergy and Critical Care, Department of 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