scholarly journals Ecallantide for the Treatment of Hereditary Angiodema in Adults

2011 ◽  
Vol 5 ◽  
pp. CMC.S4434 ◽  
Author(s):  
Michael Lunn ◽  
Erin Banta
Keyword(s):  
Upper Airway ◽  
The United States ◽  
Reversible Inhibitor ◽  
Plasma Kallikrein ◽  
Autosomal Dominant Disorder ◽  
Clinical Disorder ◽  
Life Threatening ◽  
The Complement System ◽  
Submucosal Edema ◽  
Esterase Inhibitor

Hereditary angioedema (HAE) is a clinical disorder characterized by a deficiency of C1 esterase inhibitor (C1-INH). HAE has traditionally been divided into two subtypes. Unique among the inherited deficiencies of the complement system, HAE Types I and II are inherited as an autosomal dominant disorder. The generation of an HAE attack is caused by the depletion and/or consumption of C1-inhibitor manifested as subcutaneous or submucosal edema of the upper airway, face, extremities, or gastrointestinal tract mediated by bradykinin. Attacks can be severe and potentially life-threatening, particularly with laryngeal involvement and treatment of acute attacks in the United States has been severely limited. In December 2009 the FDA approved ecallantide for the treatment of acute HAE attacks. Ecallantide is a small recombinant protein acting as a potent, specific and reversible inhibitor of plasma kallikrein which binds to plasma kallikrein blocking its binding site, directly inhibiting the conversion of high molecular weight kininogen to bradykinin. Administered subcutaneously, ecallantide was demonstrated in two clinical trials, EDEMA3 and EDEMA4, to decrease the length and severity of acute HAE attacks. Although there is a small risk for anaphylaxis, which limits home administration, ecallantide is a novel, safe, effective and alternative treatment for acute HAE attacks.

Caregivers’ role in managing hereditary angioedema and perceptions of treatment-related burden

2021 ◽  
Vol 42 (3) ◽  
pp. S11-S16 ◽  
Author(s):  
Timothy J. Craig ◽  
Aleena Banerji ◽  
Marc A. Riedl ◽  
Jessica M. Best ◽  
Jinky Rosselli ◽  
...  
Keyword(s):  
Hereditary Angioedema ◽  
Genetic Disease ◽  
Online Survey ◽  
Scientific Literature ◽  
Upper Airway ◽  
The United States ◽  
Care Recipient ◽  
Psychosocial Impacts ◽  
Life Threatening ◽  
Familial Caregivers

Hereditary angioedema (HAE) is a rare genetic disease that results in recurrent, debilitating, and potentially life-threatening swelling episodes in the extremities, genitals, gastrointestinal tract, and upper airway. Patients can experience significant burdens related to their disease. Informal or familial caregivers often support patients with HAE and likely share in the disease-related burdens, although there are limited HAE caregiver‐focused reports in the scientific literature. In the United States, we conducted an online survey of adults caring for an individual with HAE to better understand their experiences with the disease and identify psychosocial impacts of providing care for a patient with HAE. Thirty caregivers provided responses to the survey. Most caregivers were family members of the care recipient and many had HAE themselves. Caregivers reported participating in a number of medical-related tasks and experiencing some burdens as a result of caring for a person with HAE.

scholarly journals Blastomycosis of the Vocal folds with Life-Threatening upper Airway Obstruction: A Case Report

2002 ◽  
Vol 81 (12) ◽  
pp. 852-855 ◽  
Author(s):  
Celso T. Ebeo ◽  
Kenneth Olive ◽  
Ryland P. Byrd ◽  
Girish Mirle ◽  
Thomas M. Roy ◽  
...  
Keyword(s):  
Lower Respiratory Tract ◽  
Pulmonary Infection ◽  
Upper Airway ◽  
Vocal Folds ◽  
The United States ◽  
Inappropriate Therapy ◽  
Airway Compromise ◽  
Inflammatory Phase ◽  
Life Threatening ◽  
Laryngeal Involvement

Blastomycosis is a chronic fungal disease that primarily affects the lower respiratory tract. The acute inflammatory phase of the primary pulmonary infection is characterized by a lymphohematogenous spread to extrapulmonary sites, especially the skin. The presence of disseminated infection with Blastomyces dermatitidis in the larynx is unusual. In areas of the United States where this fungus is endemic, failure to consider laryngeal involvement might lead to inappropriate therapy and thus worsening inflammation and airway compromise.

scholarly journals Hereditary angio-oedema as a rare cause of small-bowel obstruction

2019 ◽  
Vol 12 (10) ◽  
pp. e231186
Author(s):  
Bilal Jamil ◽  
Muhammad Saulat Naeem ◽  
Tochukwu Anachebe ◽  
Muhammad Hamid Majeed
Keyword(s):  
Small Bowel ◽  
Small Bowel Obstruction ◽  
Bowel Obstruction ◽  
Autosomal Dominant ◽  
Autosomal Dominant Disorder ◽  
Mucosal Tissues ◽  
The Face ◽  
Life Threatening ◽  
History Of ◽  
Esterase Inhibitor

A 52-year-old man with known hereditary angio-oedema (HAE) presented with a 2-day history of progressive severe abdominal pain, distension, nausea, vomiting and constipation. CT of his abdomen and pelvis showed small-bowel obstruction and ascites. HAE is a rare autosomal dominant disorder caused by a C1 esterase deficiency and involves episodic oedema of subcutaneous and mucosal tissues. It commonly affects the face and limbs, causing deformity; the respiratory tract, causing life-threatening laryngeal swelling; and the gastrointestinal tract, causing small-bowel obstruction. An infusion of a C1 esterase inhibitor was given to the patient. His symptoms resolved within 6 hours, and a repeat CT showed complete resolution 24 hours later. Small-bowel obstruction in HAE is often misdiagnosed, leading to ineffective treatment and unnecessary surgery. Therefore, this should be suspected in patients with HAE presenting with an acute abdomen, and clinicians should understand the unique treatment required.

scholarly journals Acquired complement C1 esterase inhibitor deficiency in a patient with a rare SERPING1 variant with unknown significance

2019 ◽  
Vol 12 (9) ◽  
pp. e231122
Author(s):  
Eva Rye Rasmussen ◽  
Kasper Aanæs ◽  
Marianne Antonius Jakobsen ◽  
Anette Bygum
Keyword(s):  
Abdominal Pain ◽  
Upper Airway ◽  
Allergic Reactions ◽  
C1 Inhibitor ◽  
C1 Esterase Inhibitor ◽  
Wide Range ◽  
Unknown Significance ◽  
Life Threatening ◽  
Vasoactive Mediator ◽  
Esterase Inhibitor

Angioedema (AE) is caused by a wide range of diseases and pharmaceuticals; it can become life-threatening when located to the airways. Patients with deficiency or malfunction of complement C1 esterase inhibitor (hereditary or acquired) experience recurrent AE due to an accumulation of the vasoactive mediator bradykinin (BK). Complement C1 inhibitor normally decreases BK production, so a reduced function hereof causes increased levels. The diagnosis of hereditary or acquired AE can be difficult due to similarities to allergic reactions (swelling, abdominal pain, rash). We describe a 35-year-old man presenting with upper-airway AE progressing rapidly and promptly required cricothyroidotomy. Complement and autoantibody screening together with sequencing of SERPING1 were performed and gave the diagnosis of acquired complement C1 esterase inhibitor deficiency. The patient is unusual to have this disease before the age of 40 years. No associated comorbidities were found. It is important to know that antiallergic medication is not effective in BK-mediated AE.

Cutaneous manifestations of complement deficiencies

Lupus ◽  
2010 ◽  
Vol 19 (9) ◽  
pp. 1096-1106 ◽  
Author(s):  
D. Lipsker ◽  
G. Hauptmann
Keyword(s):  
Complement System ◽  
Lupus Erythematosus ◽  
Gastrointestinal Symptoms ◽  
Cutaneous Manifestations ◽  
Inhibitor Level ◽  
Life Threatening ◽  
Severe Infections ◽  
The Complement System ◽  
Esterase Inhibitor

In this review we address the main cutaneous manifestations and diseases associated with deficiencies in components of the complement system. The first part is devoted to hereditary angioedema, in which acute, sometimes life-threatening recurrent attacks of acute swelling, usually associated with gastrointestinal symptoms, occur. It is related to a structural or functional deficiency of C1 esterase inhibitor. Patients usually have lowered C4 levels, and diagnosis relies on determination of antigenic and/or functional C1 inhibitor level. The second part focuses on lupus erythematosus, as deficiencies in early components of the complement system, such as C1q, C1r, C1s, C2 or C4, are the strongest known disease susceptibility genes for the development of human systemic lupus erythematosus. Severe infections early in life and marked photosensitivity in a patient with lupus erythematosus are clues to an underlying complement deficiency. The genetic background and the clinical associations of the different components of the complement system will be detailed. Lupus (2010) 19, 1096—1106.

Assessment on hereditary angioedema burden of illness in Brazil: A patient perspective

2019 ◽  
Vol 40 (3) ◽  
pp. 193-197 ◽  
Author(s):  
Anderson Abdon Barbosa ◽  
Raquel de Oliveira Martins ◽  
Renata Martins ◽  
Anete Sevciovic Grumach
Keyword(s):  
Hereditary Angioedema ◽  
Burden Of Illness ◽  
Family Members ◽  
The United States ◽  
Consent Form ◽  
South American ◽  
Similar Data ◽  
Autosomal Dominant Disorder ◽  
Life Threatening ◽  
Subcutaneous Tissues

Background: Hereditary angioedema (HAE) is an autosomal dominant disorder that affects ∼1 in 50,000 individuals. The disorder is characterized by spontaneous and gradual episodes of edema in subcutaneous tissues or mucosal membrane that may endanger the patient's life. Previous studies that concern HAE treatment and burden of illness in the United States and Europe suggest an improvement in the control of HAE. However, no similar data are available in South American patients. The purpose of the present study was to evaluate the burden of disease and compliance to therapy of patients with HAE in Brazil. Methods: We developed a structured questionnaire to assess the variables that influence the diagnosis and treatment of Brazilian patients with HAE. The questionnaire was evaluated by allergists with expertise in HAE and was reformatted before applying it. The consent form was included before survey access; approval from the ethic committee of Faculdade de Medicina do ABC (Santo André, São Paulo, Brazil) was ensured. The Brazilian association of patients with HAE distributed the survey by e-mail to associated patients all over the country, and responses were accepted within a period of 3 months after signing a consent form. Results: Ninety patients (67 women, 23 men; average age, 36.5 years) responded; the main findings were the following: 53 of 90 (64%) had no need of visiting emergency departments in the past 6 months; 71 of 90 (79%) reported life-threatening fear due to their diagnosis; 73 of 90 (83%) had other family members affected, but 54 of 73 of these affected relatives did not look for specific HAE treatment; and 26 of 90 (29%) reported death due to asphyxia or throat swelling in family members. Conclusion: Patients with HAE report understanding how severe their diagnosis represent, but they did not ponder how important their commitment to treatment may decrease the constant fear brought by the disease in its possible swelling crisis. Family data supported this conclusion.

Hereditary and acquired angioedema

2019 ◽  
Vol 40 (6) ◽  
pp. 441-445 ◽  
Author(s):  
Gayatri Patel ◽  
Jacqueline A. Pongracic
Keyword(s):  
Factor Xii ◽  
Autosomal Dominant Disorder ◽  
Acquired Angioedema ◽  
Enzyme Replacement ◽  
Life Threatening ◽  
Type 3 ◽  
Esterase Inhibitor

Hereditary angioedema (HAE) is an autosomal dominant disorder defined by a deficiency of functional C1 esterase inhibitor (C1-INH). Acquired angioedema is due to either consumption (type 1) or inactivation (type 2) of CI-INH. Both HAE and acquired angioedema can be life-threatening. Of the three types of HAE, type 1 is most common, occurring in approximately 85% of patients and characterized by decreased production of C1-INH, which results in reduced functional activity to 5‐40% of normal. Type 2 occurs in 15% of cases; C1-INH is detectable in normal or elevated quantities but is dysfunctional. Also, HAE with normal CI-INH (previously called type 3 HAE) is rare and characterized by normal complement studies. Specific genetic mutations have been linked to factor XII, angiopoietin-1, and plasminogen gene. Patients with unknown mutations are classified as unknown. The screening test for types 1 and 2 is complement component C4, which is low to absent at times of angioedema and during quiescent periods. A useful test to differentiate HAE from acquired angioedema is C1q protein, which is normal in HAE and low in acquired angioedema. The management of HAE has been transformed with the advent of disease-specific therapies. On-demand therapy options include plasma and recombinant C1-INH for intravenous infusion; ecallantide, an inhibitor of kallikrein; and icatibant, a bradykinin β2 receptor antagonist, both administered subcutaneously. For long-term prophylaxis, intravenous or subcutaneous C1-INH enzyme replacement and lanadelumab, a monoclonal antibody against kallikrein that is administered subcutaneously, are effective agents.

A dangerous cause of airway obstruction: deep neck infection

2020 ◽  
Keyword(s):  
Airway Obstruction ◽  
Upper Airway ◽  
Deep Neck Infection ◽  
Jugular Vein Thrombosis ◽  
Neck Infection ◽  
Vein Thrombosis ◽  
Lethal Complications ◽  
Life Threatening ◽  
Fascial Spaces ◽  
Emergency Doctors

Deep neck infection (DNI) is an infection in the fascial spaces of the neck. Complications of DNI, including mediastinitis, internal jugular vein thrombosis, and upper airway obstruction, are severe and potentially life threatening. Therefore, early identification and accurate management of DNI are essential. We review the anatomy of the deep spaces of the neck to determine the route of DNI spread so that emergency doctors, physicians, and otorhinolaryngologists can quickly recognize the development of lethal complications of DNI, such as asphyxia from airway obstruction.

A Fatal Case of Powassan Virus Encephalitis

2020 ◽  
Vol 79 (11) ◽  
pp. 1239-1243
Author(s):  
Qiqi Yu ◽  
Eduard Matkovic ◽  
Sarah Reagan-Steiner ◽  
Amy M Denison ◽  
Rebecca Osborn ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Neuronal Degeneration ◽  
Fatal Case ◽  
Central Nervous System Involvement ◽  
Immunohistochemical Analysis ◽  
The United States ◽  
Nodule Formation ◽  
Powassan Virus ◽  
Life Threatening ◽  
Autopsy Tissues

Abstract Powassan virus (POWV) is a flavivirus of the tick-borne encephalitis serogroup that causes a rare and potentially life-threatening neuroinvasive disease. Viral transmission occurs during zoonotic spillover from mammals by the bite of an infected tick in endemic regions of North America. The number of reported POWV cases has recently increased in the United States. We report a fatal case of POWV meningoencephalomyelitis in Northern Wisconsin following a documented tick bite. Histologic examination of the brain demonstrated widespread intraparenchymal and perivascular lymphohistocytic infiltration, microglial nodule formation, and marked neuronal degeneration, most severely involving the substantia nigra, anterior horn of spinal cord and cerebellum. Although no viral inclusions were seen in routine light microscopy, electron microscopy identified multiple neurons containing cytoplasmic clusters of virus particles ∼50 nm in diameter. POWV infection was confirmed using immunohistochemical analysis and reverse transcription-polymerase chain reaction. This report demonstrates in detail regional central nervous system involvement and ultrastructural characteristics of Powassan viral particles by transmission electron microscopy, while highlighting the utility of evaluating fixed autopsy tissues in cases of unexplained meningoencephalomyelitis.

Chromogenic Peptide Substrate Assays for Plasma Inhibitors of Plasma Kallikrein: Identification of the Major Inhibitors

1979 ◽  
Author(s):  
M.J. Gallimore ◽  
E. Amundsen ◽  
M. Larsbraaten ◽  
K. Lyngaas ◽  
E. Fareid
Keyword(s):  
Plasma Concentrations ◽  
Gel Filtration ◽  
Plasma Kallikrein ◽  
Peptide Substrate ◽  
Total Inhibition ◽  
Α2 Macroglobulin ◽  
Dependent Inhibition ◽  
Plus Fraction ◽  
Time Dependent Inhibition ◽  
Esterase Inhibitor

Plasma inhibitors of plasma kallikrein(KK) were studied using chromogenic peptide substrate assays. Both “immediate” and “time-dependent” inhibition was detected. Sephadex G-150 gel filtration revealed that fractions containing α2-macroglobulin (α2 M), C1 - esterase inhibitor (CIINH) and a low molecular weight component(KKI3) gave “immediate” inhibition. When fractions were tested for “total” inhibition (incubation of enzyme plus fraction for 300 seconds at 37°C) CIINH was found to be the major inhibitor. Both the α2M and KKI3-containing fractions exhibited more inhibition than in the “immediate” inhibition assay. Studies with purified preparations of CIINH and α2 M indicated that these are the two most important plasma inhibitors of KK. Preparations of α1-antitrypsin (α1AT), antithrombin III (ATIII) and α2-antiplasmin (α2AP) produced insignificant inhibition. When “total” KK inhibition in plasma samples from 20 healthy subjects was compared with plasma concentrations of CIINH, α2M and α1AT (immunochemical assays) a very good correlation (r=0.81) was found between percentage inhibition and CIINH concentration. Correlation values for the other antiproteases were α2M r=0.36 and α1AT r=0.19.

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