scholarly journals Malignancy and immune disorders in patients with hereditary angioedema

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Peter Stepaniuk ◽  
Amin Kanani
Keyword(s):  
Hereditary Angioedema ◽  
Cervical Dysplasia ◽  
Case Series ◽  
Immune Disorders ◽  
C1 Inhibitor ◽  
C1 Inhibitor Deficiency ◽  
Immune Disorder ◽  
Acquired Angioedema ◽  
Increased Risk ◽  
High Index Of Suspicion

Abstract Background Hereditary angioedema (HAE) is an inherited condition manifesting as recurrent angioedema episodes which is caused by deficiency or dysfunction of C1 inhibitor. Although complement dysregulation has historically been shown to be associated with various malignancy and immune disorders, it is currently not known if HAE patients are at an increased risk of developing malignancy or autoimmune conditions. Case presentation We reviewed the charts of 49 HAE patients and identified 6 patients who had a co-existing malignancy diagnosis (two with breast cancer, one with melanoma, one with pancreatic cancer, one with renal cancer and one with cervical dysplasia) and 6 patients who had a diagnosis of a co-existing immune disorder (two with rheumatoid arthritis, two with ulcerative colitis, one with chronic urticaria with hypothyroidism and one with Sjogren’s syndrome). Nearly all malignancy cases occurred in older HAE patients (> 50 years) and malignancy was diagnosed before HAE in 3 of the patients. Conclusions Our case series identified multiple hereditary angioedema (HAE) patients with co-existing malignancy and immune disorders. Based on these findings, we would advocate that physicians managing HAE patients should maintain a high index of suspicion for these conditions and that in patients with angioedema, C1 inhibitor deficiency and malignancy, a diagnosis of HAE should still be considered in addition to acquired angioedema (AAE).

scholarly journals Malignancy and Immune Disorders in Patients With Hereditary Angioedema

2021 ◽  
Author(s):  
Peter Stepaniuk ◽  
Amin Kanani
Keyword(s):  
Hereditary Angioedema ◽  
Cervical Dysplasia ◽  
Case Series ◽  
Immune Disorders ◽  
Immune Disorder ◽  
Disease States ◽  
Increased Risk ◽  
Complement Dysregulation ◽  
Autoimmune Conditions ◽  
High Index Of Suspicion

Abstract Background With the advent of new therapies, patients with hereditary angioedema (HAE) are living longer lives. Although complement dysregulation has been linked to various disease states, it is currently not known if HAE patients are at an increased risk of developing malignancy or autoimmune conditions. Case Presentation : We reviewed the charts of 49 HAE patients and identified 6 patients who had a co-existing malignancy diagnosis (two with breast cancer, one with melanoma, one with pancreatic cancer, one with renal cancer and one with cervical dysplasia) and 6 patients who had a diagnosis of a co-existing immune disorder (two with rheumatoid arthritis, two with ulcerative colitis, one with chronic urticaria with hypothyroidism and one with Sjogren’s syndrome). Nearly all malignancy cases occurred in older HAE patients (> 50 years) and malignancy was diagnosed before HAE in 3 of the patients. Conclusions Our case series has identified multiple hereditary angioedema (HAE) patients with co-existing malignancy and immune disorders. Based on these findings, we would advocate that physicians managing HAE patients should maintain a high index of suspicion for these conditions.

Acquired Angioedema due to C1 Inhibitor Deficiency Preceding Splenic Marginal Zone Lymphoma: Further Insights from Clinical Practice

2020 ◽  
Vol 181 (12) ◽  
pp. 941-946
Author(s):  
Mariana Paes Leme Ferriani ◽  
Orlando Trevisan-Neto ◽  
Julia S. Costa ◽  
Janaina M.L. Melo ◽  
Adriana S. Moreno ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Marginal Zone ◽  
Marginal Zone Lymphoma ◽  
Splenic Marginal Zone Lymphoma ◽  
C1 Inhibitor ◽  
C1 Inhibitor Deficiency ◽  
Acquired Angioedema ◽  
Risk Of Death ◽  
Increased Risk

<b><i>Background:</i></b> 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. <b><i>Objectives:</i></b> 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. <b><i>Methods:</i></b> 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 <i>SERPING1</i> gene was performed using the Sanger method. <b><i>Results:</i></b> Two patients were diagnosed with AAE-C1-INH associated with splenic marginal zone lymphoma during follow-up. <b><i>Conclusions:</i></b> 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.

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

2016 ◽  
Vol 54 (2) ◽  
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.

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

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.

scholarly journals Pathways of Neutrophil Granulocyte Activation in Hereditary Angioedema with C1 Inhibitor Deficiency

2021 ◽  
Author(s):  
Erika Kajdácsi ◽  
Nóra Veszeli ◽  
Blanka Mező ◽  
Zsófia Jandrasics ◽  
Kinga Viktória Kőhalmi ◽  
...  
Keyword(s):  
Hereditary Angioedema ◽  
Blood Cells ◽  
White Blood Cells ◽  
Neutrophil Granulocytes ◽  
C1 Inhibitor ◽  
C1 Inhibitor Deficiency ◽  
Prodromal Phase ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein

AbstractHereditary angioedema (HAE) with C1-inhibitor deficiency belongs to bradykinin-mediated angioedemas. It is characterized by recurrent subcutaneous and/or submucosal swelling episodes (HAE attacks) and erythema marginatum skin rash as a pre-attack (prodromal) phase. HAE attacks were shown to be accompanied by peripheral blood neutrophilia. We aimed to find molecular mechanisms that may explain the distinct role of neutrophil granulocytes in HAE. Plasma levels of blood cells and factors related to neutrophil activation (cytokines, chemokines, chemotactic factors, enzymes, and neutrophil extracellular trap) were measured in plasma samples obtained from patients during symptom-free periods (n = 77), during prodromal phase (n = 8) and attacks (n = 14), during a spontaneously resolved attack (n = 1), and in healthy controls (n = 79). Higher counts of white blood cells, lymphocytes, and neutrophil granulocytes were found in symptom-free patients compared with controls; these cell counts were elevated further during HAE attacks. The level of chemokine (C–C motif) ligand 5, monocyte chemoattractant protein-1, and myeloperoxidase were also higher in the symptom-free patients than in the controls. Levels of monocyte chemoattractant protein-1, leukotriene B4, neutrophil elastase, and myeloperoxidase were elevated during attacks. During erythema marginatum, white blood cells and monocyte count and levels of interleukin 8 were elevated compared with symptom-free period. Similar changes were detected during the attack follow-up. We conclude that the activation of NGs in symptom-free periods and a further increase observed during attacks suggests that NGs may be involved in the pathomechanism of HAE with C1-INH deficiency.

scholarly journals A case of hereditary angioedema due to C1-inhibitor deficiency with recurrent abdominal pain diagnosed 40 years after the occurrence of the initial symptom

2021 ◽  
Author(s):  
Daisuke Honda ◽  
Isao Ohsawa ◽  
Keiichi Iwanami ◽  
Hisaki Rinno ◽  
Yasuhiko Tomino ◽  
...  
Keyword(s):  
Abdominal Pain ◽  
Hereditary Angioedema ◽  
Recurrent Abdominal Pain ◽  
Acute Attack ◽  
Severe Abdominal Pain ◽  
Initial Symptom ◽  
C1 Inhibitor ◽  
Self Administration ◽  
C1 Inhibitor Deficiency ◽  
Appropriate Treatment

AbstractHereditary angioedema due to C1-inhibitor deficiency (HAE-C1-INH) is a rare disease, which induces an acute attack of angioedema mediated by bradykinin. HAE-C1-INH can cause serious abdominal pain when severe edema develops in the gastrointestinal tract. However, because it takes a long time, 13.8 years on average in Japan, from the occurrence of the initial symptom to the diagnosis due to low awareness of the disease, undiagnosed HAE-C1-INH patients sometimes undergo unnecessary surgical procedures for severe abdominal pain. We herein present a 56-year-old patient with HAE-C1-INH, who underwent numerous abdominal operations. He frequently needed hospitalization with the administration of opioid due to severe abdominal pain. However, after he was accurately diagnosed with HAE-C1-INH at 55 years of age, he could start self-administration for an acute attack with icatibant, a selective bradykinin B2 receptor antagonist. Consequently, he did not need hospitalizing for ten months after the beginning of the treatment. A series of an accurate diagnosis and appropriate treatment for HAE-C1-INH improved his quality of life. Thus, HAE-C1-INH should be considered, when we meet patients with unidentified recurrent abdominal pain. This case highlights significance of an early diagnosis and appropriate treatment for HAE-C1-INH.

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