Diagnosis, Course, and Management of Angioedema in Patients With Acquired C1-Inhibitor Deficiency

Zanichelli, Andrea; Azin, Giulia Maria; Wu, Maddalena Alessandra; Suffritti, Chiara; Maggioni, L.; Caccia, Sonia; Perego, Francesca; Vacchini, Romualdo; Cicardi, Marco

doi:10.1016/j.jaip.2016.12.032

Cited by 72 publications

(95 citation statements)

References 40 publications

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“…An MGUS (monoclonal gammopathy of undetermined significance) is frequently associated with AAE [8]. Its pathogenesis is related to the consumption of C1-INH by neoplastic lymphatic tissues and/or the formation of anti-C1 inhibitor neutralizing autoantibodies [9]. Interestingly, the first AE attack often predates by several years the onset of hematological disease [10].…”

Section: Acquired Aementioning

confidence: 99%

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Hereditary and Acquired Angioedema: Heterogeneity of Pathogenesis and Clinical Phenotypes

Bova

Feo

Parente

et al. 2018

Int Arch Allergy Immunol

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Recurrent angioedema (AE) without wheals is increasingly recognized as a clinical entity and a frequent cause of admission to the emergency room. The Hereditary Angioedema Working Group (HAWK) classification allowed the scientific community to go beyond the semantic confusion that dominated this topic for decades. This classification distinguishes hereditary and acquired forms of AE, either related or unrelated to C1 inhibitor deficiency. Recently, additional mechanisms have been involved in the AE pathogenesis, including the uncontrolled activation of factor XII, generation of vasoactive mediators that induce dysregulation of endothelial functions, and bidirectional interactions between mast cell-derived mediators and the plasma contact system. Thus, recurrent AE can be determined by multiple and concurrent mechanisms that may generate distinct clinical phenotypes of the disease. Frequency, severity, and the location of attacks are quite different from patient to patient and, even in the same patient, they may change throughout the course of life. The severity of the clinical phenotype strongly influences the burden of the disease and patients’ quality of life. Despite major advances in our understanding of recurrent AE, many unsolved questions remain, leaving several unmet needs for patients and caregivers. This review is focused on a description of different AE phenotypes and the concurrent mechanisms leading to their pathogenesis. A better definition of cellular and molecular pathways responsible for the distinct AE phenotypes may help to improve diagnosis and may lead to a personalized approach to prophylaxis and treatment of the disease.

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Section: Acquired Aementioning

confidence: 99%

“…The attacks mainly affect the face, the upper respiratory tract and abdomen, and the frequency of attacks is unpredictable. The rate of attacks is usually reduced by the treatment of the underlying disease [9].…”

Section: Doi: 101159/000486312mentioning

confidence: 99%

Hereditary and Acquired Angioedema: Heterogeneity of Pathogenesis and Clinical Phenotypes

Bova

Feo

Parente

et al. 2018

Int Arch Allergy Immunol

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“…AAE is uncommon. However, recently series have reported the presentation, associations and responses to treatment in large cohorts of patients with AAE [2, 7, 12]. This patient, in addition to having AAE, met the Sapporo Criteria for the diagnosis of Antiphospholipid Syndrome [13].…”

Section: Discussionmentioning

confidence: 99%

“…Clinically the two are differentiated by the later onset of symptoms in AAE and the lack of family history of angioedema [1]. The prevalence of AAE has been estimated to be around 1: 600,000 [2]. The association of AAE with APS has been reported rarely [3–6], though its association preceding or following MGUS (monoclonal gammopathy of undetermined significance) and lymphomas is a common one [7].…”

Section: Introductionmentioning

confidence: 99%

Case report presenting the diagnostic challenges in a patient with recurrent acquired angioedema, antiphospholipid antibodies and undetectable C2 levels

Bonnin

DeBrosse

Moncrief

et al. 2018

Allergy Asthma Clin Immunol

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BackgroundAngioedema secondary to acquired C1 inhibitor deficiency (AAE) is a rare disease. It usually is associated with lymphoproliferative disorders. We present a case of AAE in a patient with antiphospholipid syndrome (APS), a non-Hodgkin lymphoproliferative disorder (NHL) with undetectable levels of C2, C4, and an undetectable CH50. The co-existence of AAE, APS, and NHL, with an undetectable C2 level, to the best of our knowledge, has never before reported together in the same patient.Case presentationA patient with a recent history of thrombosis presented with recurrent episodes of angioedema. The workup revealed undetectable levels of C2, C4 and undetectable CH50. Quantitative levels of C1 inhibitor and C1q were low. C1 inhibitor function was less than 40%. Anti-cardiolipin antibodies were found. The patient was initially treated on demand with intravenous plasma-derived human C1-INH concentrates, (Cinryze® Shire). Later the patient received prophylactic therapy with danazol. She was diagnosed with lymphoma 3 years after her first episode of angioedema. Single agent therapy with rituximab was not only effective in treating her lymphoma but also preventing further episodes of angioedema. Anti-cardiolipin antibody titers also declined. Additionally, marked early primary pathway complement component abnormalities and CH50 also corrected, although incomplete normalization of C4 proved to be due to a heterozygous C4 deficiency.ConclusionThis case shows the unique association of AAE, APS and NHL in a patient with undetectable levels of early complement components. Additionally, this case also shows for the first time the effectiveness of rituximab therapy in all three disease states while co-existing simultaneously in the same patient.

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“…Almost 10 years later, an acquired form of C1INH deficiency (AAE) was identified [21]. AAE is highly associated with lymphoproliferative disorders and, less frequently, other malignancies or autoimmune or infectious diseases [22-24]. …”

Section: Introductionmentioning

confidence: 99%

Hereditary Angio-Oedema for Dermatologists

Bygum¹

2019

Dermatology

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Among angio-oedema patients, hereditary angio-oedema (HAE) should not be overlooked. Besides skin swellings, these patients might have very painful abdominal attacks and potentially life-threatening angio-oedema of the upper airway. They will not respond to traditional anti-allergic therapy with antihistamines, corticosteroids, and adrenaline, and instead need specific drugs targeting the kallikrein-kinin pathway. Classically, patients with HAE have a quantitative or qualitative deficiency of the C1 inhibitor (C1INH) due to different mutations in SERPING1, although a new subtype with normal C1INH has been recognised more recently. This latter variant is diagnosed based on clinical features, family history, or molecular genetic testing for mutations in F12, ANGPT1,or PLG.The diagnosis of HAE is often delayed due to a general unfamiliarity with this orphan disease. However, undiagnosed patients are at an increased risk of unnecessary surgical interventions or life-threatening laryngeal swellings. Within the last decade, new and effective therapies have been developed and launched for acute and prophylactic therapy. Even more drugs are under evaluation in clinical trials. It is therefore of utmost importance that patients with HAE are diagnosed as soon as possible and offered relevant therapy with orphan drugs to reduce morbidity, prevent mortality, and improve quality of life.

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Diagnosis, Course, and Management of Angioedema in Patients With Acquired C1-Inhibitor Deficiency

Cited by 72 publications

References 40 publications

Hereditary and Acquired Angioedema: Heterogeneity of Pathogenesis and Clinical Phenotypes

Hereditary and Acquired Angioedema: Heterogeneity of Pathogenesis and Clinical Phenotypes

Case report presenting the diagnostic challenges in a patient with recurrent acquired angioedema, antiphospholipid antibodies and undetectable C2 levels

Hereditary Angio-Oedema for Dermatologists

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