Nine year follow-up of a rare case of angioedema due to acquired C1-inhibitor deficiency with late onset and good response to attenuated androgen

Background: Acquired angioedema due to C1 inhibitor deficiency (AAE-C1-INH) is a very rare disease. In clinical practice, it may be difficult to differentiate AAE-C1-INH from hereditary angioedema due to C1-INH deficiency (HAE-C1-INH). In both conditions, patients are at an increased risk of death from asphyxiation due to upper airway obstruction. The association of AAE-C1-INH with lymphoproliferative and autoimmune diseases, and with presence of anti-C1-INH antibodies has been well documented, and treatment of the underlying condition may result in complete remission of angioedema. Objectives: To discuss the clinical evaluation, diagnosis, and treatment outcomes of AAE-C1-INH in the context of the care of 2 patients with recurrent isolated angioedema. Methods: Two patients were followed up prospectively at our clinic. Measurements of C3, C4, C1-INH, and C1q levels were carried out by nephelometry, and the functional activity of C1-INH was determined by a chromogenic assay. Hematological investigation included morphological and immunophenotyping analysis of peripheral blood, bone marrow, and spleen histopathology. Sequencing of the 8 exons and adjacent intronic regions of the SERPING1 gene was performed using the Sanger method. Results: Two patients were diagnosed with AAE-C1-INH associated with splenic marginal zone lymphoma during follow-up. Conclusions: Close follow-up, including detailed clinical history, physical examination, and laboratory tests, of our patients with AAE-C1-INH was essential for the early diagnosis and successful treatment of the lymphoproliferative disease, leading to the resolution of the angioedema attacks.

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A follow‐up survey of patients with acquired angioedema due to C1‐inhibitor deficiency

Journal of Internal Medicine ◽

10.1111/joim.13182 ◽

2020 ◽

Author(s):

Zs. Pólai ◽

Zs. Balla ◽

N. Andrási ◽

K. V. Kőhalmi ◽

Gy. Temesszentandrási ◽

...

Keyword(s):

C1 Inhibitor ◽

C1 Inhibitor Deficiency ◽

Acquired Angioedema

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The Janus faces of acquired angioedema: C1-inhibitor deficiency, lymphoproliferation and autoimmunity

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2015-0195 ◽

2016 ◽

Vol 54 (2) ◽

Cited By ~ 13

Author(s):

Maddalena Alessandra Wu ◽

Roberto Castelli

Keyword(s):

B Cell ◽

Late Onset ◽

Lymphoproliferative Disease ◽

Response To Treatment ◽

C1 Inhibitor ◽

Variable Response ◽

C1 Inhibitor Deficiency ◽

Acquired Angioedema ◽

Laryngeal Mucosa ◽

Increased Risk

AbstractSeveral clinical and biological features of lymphoproliferative diseases have been associated with an increased risk of developing autoimmune manifestations. Acquired deficiency of C1-inhibitor (C1-INH) (AAE) is a rare syndrome clinically similar to hereditary angioedema (HAE) characterized by local increase in vascular permeability (angioedema) of the skin and the gastrointestinal and oro-pharyngo-laryngeal mucosa. Bradykinin, a potent vasoactive peptide, released from high molecular weight kininogen when it is cleaved by plasma kallikrein (a serine protease controlled by C1-INH), is the mediator of symptoms. In total 46% of AAE patients carry an underlying hematological disorder including monoclonal gammopathy of uncertain significance (MGUS) or B cell malignancies. However, 74% of AAE patients have anti-C1-INH autoantibodies without hematological, clinical or instrumental evidence of lymphoproliferative disease. Unlike HAE patients, AAE patients usually have late-onset symptoms, do not have a family history of angioedema and present variable response to treatment due to the hypercatabolism of C1-INH. Experiments show that C1-INH and/or the classical complement pathway were consumed by the neoplastic lymphatic tissues and/or anti-C1-INH neutralizing autoantibodies. Therapy of AAE follows two directions: 1) prevention/reversal of the symptoms of angioedema; and 2) treatment of the associated disease. Different forms of B cell disorders coexist and/or evolve into each other in AAE and seem to be dominated by an altered control of B cell proliferation, thus AAE represents an example of the strict link between autoimmunity and lymphoproliferation.

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How Angioedema Quality of Life Questionnaire Can Help Physicians in Treating C1-Inhibitor Deficiency Patients?

Clinical Reviews in Allergy & Immunology ◽

10.1007/s12016-021-08850-9 ◽

2021 ◽

Author(s):

Zsuzsanna Balla ◽

Bettina Ignácz ◽

Lilian Varga ◽

Kinga Viktória Kőhalmi ◽

Henriette Farkas

Keyword(s):

Quality Of Life ◽

Prospective Trial ◽

Life Questionnaire ◽

C1 Inhibitor ◽

C1 Inhibitor Deficiency ◽

Acquired Angioedema ◽

Quality Of Life Questionnaire ◽

Validated Questionnaire

AbstractThe Angioedema Quality of Life Questionnaire (AE-QoL) is an angioedema (AE)-specific validated questionnaire, which surveys the quality of life of diagnosed patients. The questionnaire has been used in multiple clinical trials. Our aim was to investigate how the questionnaire can assist physicians in the everyday practice of following up and managing C1-inhibitor deficiency patients. In a prospective trial conducted in our center between 2016 and 2018, 125 hereditary angioedema and 10 diagnosed with acquired angioedema completed an AE-QoL during their annual follow-up visit. Laboratory indices (i.e., complement levels) were obtained for each patient. Statistical analysis comparing clinical data with QoL parameters was performed. Results of the analysis show that AE-QoL total score and number of AE attacks per year correlated well (r = 0.47; p < 0.0001). Women reached higher AE-QoL total score values than men, over a 3-year period (p = 0.0014). The highest AE-QoL total scores were reached by the 41–60-year age group; we obtained a similar result, when analyzing the four domains. No correlation was found between the AE-QoL total score and complement parameters. Patients with a negative correlation between AE-QoL total score and number of AE attacks had a positive correlation with psychologic attributes like fatigue/mood and fears/shame domains. Patients that acquired HAE showed a significant correlation between the annual number of AE attacks and the AE-QoL total scores (r = 0.46; p < 0.0001). The study establishes the use of AE-QoL as a clinical tool for follow-up which can help in the complex assessment of both hereditary and acquired HAE patients, and help to develop better therapeutic strategies.

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Traumatic avulsion management by allotransplantation. A rare case report with two years of successful follow-up

International Journal of Medical and Dental Case Reports ◽

10.15713/ins.ijmdcr.22 ◽

2015 ◽

Vol 2 ◽

pp. 1-4

Author(s):

Nandini R. Katta ◽

P. Poornima ◽

A. Shruthi ◽

N. B. Nagaveni

Keyword(s):

Case Report ◽

Rare Case ◽

Rare Case Report

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Acquired angioedema with C1-inhibitor deficiency: similarities and differences with hereditary angioedema

Alergologia ◽

10.26416/aler.3.1.2019.2268 ◽

2019 ◽

Vol 1 (3) ◽

pp. 27

Author(s):

Noémi-Anna Bara ◽

Valentin Nădăşan

Keyword(s):

Hereditary Angioedema ◽

C1 Inhibitor ◽

C1 Inhibitor Deficiency ◽

Acquired Angioedema ◽

Similarities And Differences

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The Global Registry for Hereditary Angioedema due to C1-Inhibitor Deficiency

Clinical Reviews in Allergy & Immunology ◽

10.1007/s12016-021-08855-4 ◽

2021 ◽

Author(s):

Andrea Zanichelli ◽

Henriette Farkas ◽

Laurance Bouillet ◽

Noemi Bara ◽

Anastasios E. Germenis ◽

...

Keyword(s):

Hereditary Angioedema ◽

Rare Condition ◽

C1 Inhibitor ◽

C1 Inhibitor Deficiency ◽

Therapeutic Decisions ◽

Life Threatening ◽

Enhance Patient Care ◽

Electronic Support ◽

The Impact ◽

Global Registry

AbstractHereditary angioedema (HAE) is a rare condition, mostly due to genetic deficiency of complement C1 inhibitor (C1-INH). The rarity of HAE impedes extensive data collection and assessment of the impact of certain factors known to affect the course of this disabling and life-threatening disease. Establishing a global registry could assist to overcome such issues and provides valuable patient data from different countries. The HAE Global Registry is a disease-specific registry, with web-based electronic support, where data are provided by physicians and patients through a dedicated application. We collected data between January 1, 2018, and August 31, 2020. Data on 1297 patients from 29 centers in 5 European countries were collected. At least one attack was recorded for 497 patients during the study period. Overall, 1182 patients were diagnosed with HAE type 1 and 115 with type 2. At the time of database lock, 389 patients were taking long-term prophylactic medication, 217 of which were on danazol. Most recorded attacks affected the abdomen, were generally moderate in severity, and occurred in patients who were not on prophylactic treatment (70.6%, 6244/8848). The median duration of attacks was 780 min (IQR 290–1740) in patients on prophylactic medication and 780 min (IQR 300–1920) in patients not on continuous prophylactic medication. In conclusion, the establishment of a registry for C1-INH-HAE allowed collection of a large amount of data that may help to better understand the clinical characteristics of this disease. This information may enhance patient care and guide future therapeutic decisions.

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