Pathophysiology of Hereditary Angioedema (HAE) Beyond the SERPING1 Gene

Sharma, Jyoti; Jindal, Ankur Kumar; Banday, Aaqib Zaffar; Kaur, Anit; Rawat, Amit; Singh, Surjit; Longhurst, Hilary

doi:10.1007/s12016-021-08835-8

Cited by 23 publications

(20 citation statements)

References 70 publications

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“…13 Bradykinin release, which is known to mediate angioedema in HAE with C1-INH deficiency, has been implicated in HAE-nl-C1INH associated with mutations in F12, PLG, KNG1, and HS3ST6. 3,7,8,14 Patients with HAE-nl-C1INH tend to experience attacks that are similar to those experienced by patients with type I or type II HAE. 2,6 However, facial and oropharyngeal involvement are relatively more common in HAE-nl-C1INH, and mortality related to asphyxiation has been reported.…”

Section: Introductionmentioning

confidence: 95%

“…2,4,6 Although some patients have a mutation in a gene that encodes coagulation FXII (F12), plasminogen (PLG), angiopoietin 1 (ANGPT1), kininogen 1 (KNG1), myoferlin (MYOF), or heparan sulfate glucosamine 3-O-sulfotransferase 6 (HS3ST6), most HAE-nl-C1INH patients are classified as HAEunknown (ie, no mutation identified). 2,[6][7][8][9][10][11][12] Dysregulation of the contact system (kallikreinbradykinin formation) appears to play a role in the pathophysiology of HAE-nl-C1INH, 3 with evidence of higher plasma kallikrein activity in patients with HAE-nl-C1INH versus controls without swelling or patients with idiopathic histaminergic angioedema. 13 Bradykinin release, which is known to mediate angioedema in HAE with C1-INH deficiency, has been implicated in HAE-nl-C1INH associated with mutations in F12, PLG, KNG1, and HS3ST6.…”

Section: Introductionmentioning

confidence: 99%

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Clinical profile and treatment outcomes in patients with hereditary angioedema with normal C1 esterase inhibitor

Jones

Bansal²,

Bernstein

et al. 2022

World Allergy Organization Journal

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Background: Hereditary angioedema (HAE) is often caused by low serum levels or functional deficiency in C1 inhibitor (C1-INH); however, in some cases, C1-INH serum level and function are measured as normal (HAE-nl-C1INH). Management of HAE-nl-C1INH is similar to management of HAE with C1-INH deficiency, including on-demand therapy for angioedema attacks and, potentially, prophylaxis. Recombinant human C1 esterase inhibitor (rhC1-INH) is indicated for treatment of acute HAE attacks. This study assessed the clinical profile and treatment outcomes in an HAE-nl-C1INH population with a history of rhC1-INH treatment.Methods: Medical records containing patient-reported outcomes from ten US treatment centers were analyzed retrospectively for medical history, angioedema attack characteristics, attack treatments, and clinical outcomes.Results: Twenty-three patients were included, with wide US geographic representation. Most patients (87.0%) were female; median age was 36.0 years (range, 19-67 years). Of 20 patients with available data, 4 had their first angioedema attack during childhood (aged <12 years), 3 during adolescence (aged 12-17 years), and 13 during adulthood (aged 18-29 years, n ¼ 7; aged 30 years, n ¼ 6). Median age at HAE-nl-C1INH diagnosis was 31.5 years (range, 9-59 years). Previous failed treatments included high-dose antihistamines (n ¼ 20) and corticosteroids (n ¼ 20). Use of US Food and Drug Administration (FDA)-approved HAE therapy positively impacted patientreported assessments of angioedema attacks. Most patients were taking rhC1-INH or lanadelumab as prophylaxis and icatibant or rhC1-INH for acute management. Most patients reported improved disease control with these therapies, including reductions in angioedema attack frequency and severity. Although most patients were receiving prophylactic therapy, availability of treatment for breakthrough attacks was important. Conclusion:Findings from this retrospective study support use of FDA-approved HAE medications for prophylaxis and acute treatment of HAE attacks in patients with HAE-nl-C1INH. Individualized HAE treatment regimens were needed to optimize therapeutic outcomes.

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Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Clinical profile and treatment outcomes in patients with hereditary angioedema with normal C1 esterase inhibitor

Jones

Bansal²,

Bernstein

et al. 2022

World Allergy Organization Journal

View full text Add to dashboard Cite

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“…Anything that interferes with the degradation of bradykinin or augments its generation can potentially cause angioedema. [ 5 6 ] High molecular weight kininogen (HMWK) is cleaved by activated factor XII and kallikrein to form bradykinin. Kallikrein and activated factor XII are formed by activation of pre-kallikrein and factor XII, respectively, through contact activation.…”

Section: Pathogenesis Of “Angioedema Without Wheals”mentioning

confidence: 99%

“…These patients may have mutations in factor XII, angiopoietin, kininogen, plasminogen, myoferlin, or heparan sulfate 3-O-sulfotransferase 6 gene. [ 5 7 8 9 10 11 12 13 14 ] Identification of these additional genetic defects in patients with HAE has expanded our understanding of pathogenesis of HAE and has proved that this is not limited to contact-kinin-complement pathway. Identification of genetic defects in angiopoietin, heparan sulfate 3-O-sulfotransferase 6 , and myoferlin gene has highlighted that endothelium has an important role in the pathogenesis of HAE.…”

Section: Pathogenesis Of “Angioedema Without Wheals”mentioning

confidence: 99%

“…These include a higher female predominance, more frequent involvement of face, tongue, and uvula; less frequent attacks overall, less frequent abdominal attacks, and relatively later age of onset. [ 5 ] Patients with angiopoietin gene mutation may have nail fold capillary abnormalities. [ 10 ] Hemorrhages and bruising have also been reported in the skin lesions of patients who have normal-C1-INH-HAE.…”

Section: Clinical Features Of Haementioning

confidence: 99%

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Hereditary Angioedema

Jindal

Bishnoi

Dogra

2021

Indian Dermatology Online Journal

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Hereditary angioedema (HAE) is an uncommon disorder with a global prevalence of approximately 1 in 10,000 to 1 in 50,000 population. This disease is grossly underrecognized in India because of lack of awareness and/or lack of diagnostic facilities. Clinical manifestations include swelling over face, eyes, lips, hands, feet, and genitals, abdominal pain, and life-threatening laryngeal edema. HAE should be suspected in all patients who present with angioedema without wheals and who do not respond to antihistamines and/or steroids. C1 levels, C1-INH levels, and C1-INH function should be checked in all patients suspected to have HAE. C1q levels should be assessed in patients with suspected autoimmune-mediated acquired angioedema. Management of HAE constitutes the treatment of acute attack and short-term and long-term prophylaxis. Because of lack of all first-line recommended medications, the management of HAE in India is a challenging task. Patients are managed using fresh frozen plasma (acute treatment), tranexamic acid, and attenuated androgens (prophylaxis). Even though attenuated androgens have been shown to be effective in the prevention of attacks of HAE, the side effect profile especially in children and in females is a serious concern. Hence, the treatment needs to be individualized considering the risk-benefit ratio of long-term prophylaxis. In this review, we provide an overview of diagnostic strategy for patients with HAE and the current treatment concepts with emphasis on currently available treatment options in resource-constrained settings.

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Current challenges and future opportunities in patient‐focused management of hereditary angioedema: A narrative review

Grumach

Gadir

Kessel

et al. 2023

Clinical & Translational All

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Patients with hereditary angioedema (HAE) experience a high burden of disease due to unpredictable, painful, disfiguring, and potentially life-threatening HAE attacks.Multiple HAE-specific medications for the on-demand treatment, short-term and long-term prophylaxis of HAE attacks have entered the market in recent years; however, the availability and access to these medications may vary between different countries. For this review, PubMed and EMBASE databases were searched for guidelines, consensus statements, and other publications on HAE management as well as publications on quality of life in patients with HAE. The current guidelines and recent literature on HAE management in specific countries are summarized with the aim to highlight the similarities and differences between guideline recommendations and the country-specific clinical practice. Improvement in quality of life, which is a key goal in HAE management, is also discussed and the countryspecific trends are highlighted. Finally, the ways to achieve a more patient-centric approach to HAE management within the framework set by the clinical management guidelines are examined.

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Pathophysiology of Hereditary Angioedema (HAE) Beyond the SERPING1 Gene

Cited by 23 publications

References 70 publications

Clinical profile and treatment outcomes in patients with hereditary angioedema with normal C1 esterase inhibitor

Clinical profile and treatment outcomes in patients with hereditary angioedema with normal C1 esterase inhibitor

Hereditary Angioedema

Current challenges and future opportunities in patient‐focused management of hereditary angioedema: A narrative review

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