Hereditary angioedema

AbstractA 14-year-old African American female presented to the emergency department with spontaneous, sudden-onset lip swelling for 1 h. On examination, there was significant water-bag edema of the upper lip extending to the philtrum and premaxilla. Nasopharyngeal laryngoscopy revealed a patent airway without edema. She was initiated on intravenous dexamethasone, famotidine, and diphenhydramine, after which her edema improved but did not resolve. She was subsequently transferred to a local pediatric hospital and upon further testing she was found to have a C1 esterase inhibitor de novo gene mutation. Angioedema causes localized, non-pitting edema of the dermis, subcutaneous and submucosal tissue, and often manifests in the lips, face, mouth, and throat. Signs of laryngeal involvement include change in voice, stridor, dysphagia, and dyspnea. When laryngeal edema is present, it may necessitate definitive airway management and patients should be monitored in the intensive care unit.

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Waldenstrom's Microglobulinemia Presenting with Recurrent Angioedema Secondary to C1q Esterase Inhibitor (C1 INH) Deficiency

Blood ◽

10.1182/blood.v116.21.5009.5009 ◽

2010 ◽

Vol 116 (21) ◽

pp. 5009-5009 ◽

Cited By ~ 1

Author(s):

Nneamaka N Enwemnwa ◽

Abhinav B. Chandra ◽

Porselvi Chockalingam ◽

Jack Burton

Keyword(s):

B Cell ◽

Total Protein ◽

Laryngeal Edema ◽

Low Grade ◽

Normal Range ◽

C1 Esterase Inhibitor ◽

Life Threatening ◽

History Of ◽

C1inh Deficiency ◽

Esterase Inhibitor

Abstract Abstract 5009 Description: A 57 year-old Bangladeshi man presented to the emergency room with a 4-day history of shortness of breath, productive cough and sensation of choking. He had a history of recurrent dyspnea, chest pain and chronic bilateral pedal edema. He had recent admissions for similar complaints at different hospitals where he was diagnosed with low grade non-Hodgkin lymphoma not requiring treatment and was discharged with bronchodilators and anti-tussives. He was symptom-free between episodes. There was no fever, night sweats or weight loss and there was no history of asthma. Physical exam revealed moderate dyspnea with some stridor, cervical lymphadenopathy with many firm and mobile small lymph nodes. There was no hepato-splenomegaly, urticaria or rashes. Results of routine blood tests including CBC and C-reactive protein were normal. Chest X-ray showed mild pulmonary congestion and CT images of the chest and abdomen showed multiple lymph nodes of about 1–1.5 cm in size. X-rays of the hands showed multiple small lytic lesions. Laryngoscopy showed laryngeal edema. Bone marrow biopsy showed a few paratrabecular areas with increased numbers of small lymphocytes and a lymph node biopsy revealed low grade B-cell lymphoma with plasmacytic differentiation, which was positive for CD19, 20, 22, 38, and CD44. Serum viscosity was 1.6. Immunological studies showed a low C4 at 4 mg/dl (normal range 10–40 mg/dl), low C1q at <3.6 (normal range 5–8.6), C1 esterase inhibitor low-normal at 16 (normal range 11–26). Serum immunoglobulins showed IgM gammopathy with low IgA and normal IgG levels. Beta-2 microglubulin was also elevated at 4.93 mg/dl (normal range < 2.51). Serum protein electrophoresis showed a monoclonal IgM spike measuring 1.5 g/dl with immunofixation positive for a IgM kappa band. Total protein, alpha2- and beta-globulins were elevated and urine electrophoresis was positive for kappa light chains. A diagnosis of Waldenström's macroglobulinemia with angioneurotic edema was made. He was treated with 4 cycles of bortezomib (Velcade®), dexamethasone and rituximab. The patient's angioedema and respiratory symptoms improved dramatically. Follow-up serum electrophoresis showed a very good response to treatment, with a major decrease in total protein and the M-spike. Complement levels returned to normal. Discussion: C1 is the first protein of the classical and kinin pathways which is an arm of the innate immune system. Triggering factors activate the complement cascade and lead to activation of C1 which in turn cleaves C2, the product of which is an inflammatory mediator responsible for angioedema by causing increased capillary permeability and extravasations. In C1INH deficiency, this process occurs uninhibited, triggered by minimal stimulation. C1q esterase inhibitor deficiency is a rare manifestation of Waldenström's macroglobulinemia with very few reported cases in literature. Symptoms are non-allergic, non-pruritic and clinical presentation depends on parts of the anatomy affected and may be as mild as inconvenient skin blotching up to life-threatening laryngeal edema or shock. They vary widely, often self limiting and recurrent. Angioedema, acquired or inherited, is complement mediated, characterized by low levels of complement proteins during attacks. C1INH deficiency can be acquired due to increased consumption or/and inactivation by circulating autoantibodies or secondary to lymphoproliferative diseases that lead to increased catabolism. These are often associated with B-cell disorders but may be associated with other disease patterns. Symptomatology is variable and periods of remission and recurrence lead to easy misdiagnosis and incomplete treatment. Proper diagnosis is dependent on awareness and knowledge of the various clinical presentations, adequate and focused use of laboratory analyses and immunopathology studies. The key to treatment is first therapy of the acute stage (in our patient with the use of intravenous steroids) and then more specific treatment of the underlying disease entity (in our patient with bortezomib, dexamethasone and rituximab). Conclusion: Waldenstrom's macroglobulinemia presenting with angioedema is rare, often misdiagnosed and acquired C1 esterase inhibitor deficiency should be at least ruled out, as presentation is varied and could be potentially life-threatening. Disclosures: No relevant conflicts of interest to declare.

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C1-Esterase Inhibitor Concentrate For Acute Attacks Of Laryngeal Edema In Hereditary Angioedema (HAE): Fixed Dosing Vs Body Weight-Adjusted Dosing

Journal of Allergy and Clinical Immunology ◽

10.1016/j.jaci.2013.12.155 ◽

2014 ◽

Vol 133 (2) ◽

pp. AB37

Author(s):

Konrad Bork ◽

Jonathan A. Bernstein ◽

Henrike Feuersenger ◽

Thomas Machnig ◽

Timothy J. Craig

Keyword(s):

Body Weight ◽

Hereditary Angioedema ◽

Laryngeal Edema ◽

C1 Esterase Inhibitor ◽

Acute Attacks ◽

Esterase Inhibitor

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Successful long-term prophylaxis of hereditary pregnancy-associated angioedema with plasma-derived C1-inhibitor concentrate: a case report

Medical Immunology (Russia) ◽

10.15789/1563-0625-slp-2062 ◽

2021 ◽

Vol 22 (6) ◽

pp. 1215-1220

Author(s):

D. V. Demina ◽

A. O. Makeeva ◽

L. M. Kudelya ◽

E. V. Novikova ◽

V. A. Kozlov

Keyword(s):

Pregnant Women ◽

Vascular Permeability ◽

Fresh Frozen Plasma ◽

Laryngeal Edema ◽

Type I ◽

Hormonal Changes ◽

Cesarean Section Delivery ◽

C1 Esterase Inhibitor ◽

Esterase Inhibitor

Hereditary angioedema (HAE) is a rare autosomal dominant disease caused by quantitative (type I) or functional (type II) deficiency in C1 esterase inhibitor (C1-INH). It may be caused by new mutations in up to 20% of patients. Prevalence of HAE is uncertain but is estimated to be approximately 1 case per 50,000 persons, without known differences among ethnic groups. C1-INH protein is a serine protease inhibitor that is important in controlling vascular permeability by acting on the initial phase of the complement activation, blood clotting, and fibrinolysis. Deficiency in functional C1-INH protein permits release of bradykinin, a key mediator of vascular permeability. Symptoms typically begin since childhood, worsening at puberty, and persist throughout the life, with unpredictable clinical course. The patients with HAE suffer from recurrent, acute attacks of edema that can affect any body sites, causing potentially life-threatening disorders (laryngeal edema). Results of clinical studies show that minor traumas, stress and medical interventions may be frequent precipitants of swelling episodes, but many attacks occur without an apparent cause. Pregnancy-associated hormonal changes may affect the course of C1-INH angioedema attacks by worsening, improving, or having no impact at all, but a higher percentage of pregnant women experienced an increase in C1-INH-HAE attack rates. Therapeutic options for patients with HAE are limited during pregnancy. C1-INH concentrate is recommended as the first-line therapy for pregnant women with HAE for on-demand treatment, shortterm and long-term prophylaxis, due to its safety and efficiency. Other therapies, e.g., treatment with fresh frozen plasma, androgens, icatibant, antifibrinolytics, may show variable efficacy, or cause undesirable side effects. The case below illustrates the successful treatment of HAE in a pregnant woman with C1 esterase inhibitor (C1-INH) concentrate. This patient had a very mild course of HAE during her lifetime and didn’t get any treatment. During pregnancy, she experienced a significant increase in the frequency of attacks, and the decision was made to start replacement therapy with a plasma-derived, double virus-inactivated C1-INH concentrate as a long-term prophylaxis throughout the full term of her pregnancy, before, during and after the cesarean section delivery.

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Sudden unexpected death due to hereditary angioedema — A case report

IP International Journal of Forensic Medicine and Toxicological Sciences ◽

10.18231/j.ijfmts.2021.015 ◽

2021 ◽

Vol 6 (2) ◽

pp. 60-65

Author(s):

S Narayanan ◽

S Ramalingam ◽

R Narendar

Keyword(s):

Case Report ◽

Mortality Rate ◽

Hereditary Angioedema ◽

Laryngeal Edema ◽

Inhibitor Protein ◽

Unexpected Death ◽

C1 Esterase Inhibitor ◽

First Case ◽

C1 Esterase Inhibitor Protein ◽

Esterase Inhibitor

Angioedema related to deficiency of the C1- esterase inhibitor protein (C1-inh) is characterized by lack of response to therapies, which include antihistamines, steroids and epinephrine. In case of laryngeal edema, mortality rate is an estimated mammoth 30 percent. The first case of such acquired form of angioedema related to the deficiency in C1- esterase inhibitor was published in 1972. In the present case, we entail details of one such case.,

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Miescher’s cheilitis: A case report with literature review

Journal of Pathology of Nepal ◽

10.3126/jpn.v8i1.19465 ◽

2018 ◽

Vol 8 (1) ◽

pp. 1313-1316

Author(s):

Ram Chandra Adhikari ◽

Mahesh Shah

Keyword(s):

Laboratory Tests ◽

Granulomatous Inflammation ◽

Complement C3 ◽

Inflammatory Disorder ◽

Upper Lip ◽

Gradual Improvement ◽

Topical Tacrolimus ◽

C1 Esterase Inhibitor ◽

Normal Limits ◽

Esterase Inhibitor

Miescher’s cheilitis is an inflammatory disorder characterized by chronic lip swelling due to granulomatous inflammation. It is rare disorder first described by Miescher in 1945. It is monosymptomatic form of Melkersson-Rosenthal syndrome. We report a case of Miescher’s cheilitis in a 59-year old lady presented with recurrent swelling and erythema of upper lip and submental area with no features of facial palsy and fissuring of tongue. Laboratory tests including serum complement C3, C4 and C1 esterase inhibitor functional were within normal limits. The biopsy from the upper lip revealed dermal edema, dilated lymphatic channels and multiple granulomas. After exclusion of other causes of orofacial granulomatosis, the diagnosis of Miescher’s cheilitis was made. Patient was treated with oral hydroxychloroquine and topical tacrolimus and mometasone cream with gradual improvement.

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Hereditary Angioedema: a Challenging Diagnosis for the Gastroenterologist

Journal of Interdisciplinary Medicine ◽

10.1515/jim-2016-0072 ◽

2016 ◽

Vol 1 (3) ◽

pp. 287-292

Author(s):

Gabriella Gábos ◽

Dumitru Moldovan ◽

Daniela Dobru

Keyword(s):

Quality Of Life ◽

Differential Diagnosis ◽

Hereditary Angioedema ◽

Genetic Disorder ◽

Laryngeal Edema ◽

Cutaneous Manifestations ◽

C1 Esterase Inhibitor ◽

High Degree ◽

Esterase Inhibitor

Abstract Hereditary angioedema (HAE) caused by a deficiency of C1 esterase inhibitor enzyme (C1-INH) is a very rare, autosomal dominantly inherited genetic disorder, characterized by recurrent peripheral angioedema, painful abdominal attacks and episodes of laryngeal edema. Abdominal attacks are frequent symptoms in adult HAE patients, occurring in more than 90% of the cases. Angioedema in the bowel or abdomen can occur in the absence of cutaneous manifestations and may be easily misdiagnosed unless the clinician has a high degree of awareness to include HAE in the differential diagnosis. Misdiagnosis is associated with inadequate treatments, including unnecessary surgical procedures. Any patient who presents recurrent episodes of swelling should be evaluated for HAE caused by C1-INH deficiency. New therapies could save lives and dramatically improve their quality of life.

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