|Year : 2015 | Volume
| Issue : 2 | Page : 92-95
Hereditary angioedema: A case report and literature review
Srikant Behera, Lubna Zafar, Asif Hasan
Department of Medicine, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh, India
|Date of Web Publication||9-Mar-2016|
Room No-701, Rifa Guest House, Gulzar Appartment, Medical Road, Aligarh Muslim University, Aligarh - 202 002, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Hereditary angioedema (HAE), also known as Quincke's disease, is an autosomal dominant condition characterized by painless and nonpitting swelling of soft tissues. It is not an allergic phenomenon, as it appears to be on initial examination, thus fails to respond to injectable steroids and adrenaline. The disease may become potentially life threatening due to involvement of airway, thus early suspicion, recognition, and treatment of disease are important. We present here a case of 22-year-old female who developed sudden facial swelling and breathlessness. In the presence of poor response to anti-allergic treatment, past and family history of similar complaints, and low C1 esterase levels, a diagnosis of HAE was made.
Keywords: Bradykinin, C1 esterase inhibitor, hereditary angioedema
|How to cite this article:|
Behera S, Zafar L, Hasan A. Hereditary angioedema: A case report and literature review. Indian J Allergy Asthma Immunol 2015;29:92-5
|How to cite this URL:|
Behera S, Zafar L, Hasan A. Hereditary angioedema: A case report and literature review. Indian J Allergy Asthma Immunol [serial online] 2015 [cited 2019 Jul 17];29:92-5. Available from: http://www.ijaai.in/text.asp?2015/29/2/92/178276
| Introduction|| |
HAE is a debilitating disease characterized by sudden attacks of brawny, non-pitting, and often painful edema. It is caused either by absolute deficiency or improper function of C1 esterase inhibitor in plasma. The severity of presenting symptoms varies widely, even among family members. Any part of the body can be involved; however extremities, face and intestinal tract are the most common. Involvement of the upper respiratory system, may lead to asphyxiation, which is the primary cause of death among HAE patients. HAE is not an allergic phenomenon and does not respond to epinephrine, antihistamines and corticosteroids. Diagnosis can be established by low levels of C1 esterase Inhibitor. Management of HAE is multifactorial; it includes patient education, avoidance of inciting factors specific to the patient, management of acute angioedema episodes and maintenance/ prophylaxis therapy.
| Case report|| |
A 22-year-old married female presented to Emergency Department of Jawaharlal Nehru Medical College, Aligarh, with complaints of facial swelling predominantly periorbital area [Figure 1], throat tightness, and breathlessness. The symptoms started 6 h before presentation when she had sustained minor trauma below her left eye by a mobile phone. The swelling first appeared on the area of trauma and gradually progressed to involve the whole face. There is no history of oral contraceptive pill (OCP) or any other drug intake. Furthermore, there is no history of any food allergy or insect bite. There was no associated pruritus, stridor, nausea, vomiting, pain abdomen, syncope, chest pain, or palpitations. She has experienced similar but less severe episodes in the past and has received treatment at private clinics, with poor or delayed recovery. She had never been investigated and the symptoms were attributed to allergy.
On examination, her pulse rate was 114/min, respiratory rate 30/min with O 2 saturation 96% on room air, temperature 99°F, and blood pressure (supine) 100/60 mmHg.
There was swelling over her face including lips but no rash or cyanosis. The systemic examination revealed no abnormal signs. All biochemical investigations were normal except for mild iron deficiency anemia. Chest X-ray and ultrasonography abdomen were also normal.
She was admitted to the Intensive Care Unit and a provisional diagnosis of systemic anaphylaxis was made and was administered 0.5 ml of 1:1000 (1 mg/ml) epinephrine subcutaneous, diphenhydramine 50 mg intravenous (IV), and hydrocortisone 100 mg IV, but the patient did not improve. The family history was reviewed and it revealed that her father and uncle had expired at young age during similar but severe episodes. Her elder brother has also been admitted multiple times with similar complaints.
In view of patient's repeated episodes of edema, precipitated by minimal trauma, and a strong family history, the possibility of hereditary angioedema (HAE) was suspected. The patient was administered 4 units of fresh frozen plasma (FFP); however, prior to transfusion, a blood sample was withdrawn for estimating serum level of C4 and C1 esterase. The serum C4 level was 8 mg/dl (normal 10-40 mg/dl) and C1 esterase level was 38 mg/dl (normal 195-345 mg/dl). Thus, the diagnosis of HAE was confirmed. The patient improved [Figure 2] and was discharged on the 5 th day after educating her and her family members regarding the disease and triggering factors. She was prescribed tablet danazol 100 mg twice daily and was advised to report to emergency if angioedema develops.
| Discussion|| |
HAE is a rare genetic disorder and the reported incidence varies from 1:10000 to 1:50000.  The incidence in India has not been established yet. It is caused by either absolute deficiency or improper function of C1 esterase inhibitor (C1-INH) in plasma. C1-INH protein regulates the level of C2 and C4 complement. However, it also affects the kinin-generating system by inhibiting kallikrein, and this is the primary basis for occurrence of angioedema in patients with HAE. Three types of HAE have been described on basis of levels of C1-INH. , Type 1 HAE: it is the most common type and is caused by decreased production or absence of C1-INH. Type 2 HAE: it is less common than Type 1 and is characterized by normal or elevated C1-INH level indicating functional impairment. Type 3 HAE: It is a rare variety, has been described in females only, and presents as normal function C1-INH levels. However, this entity is controversial.
HAE is a debilitating disease characterized by sudden attacks of brawny, nonpitting, and often painful edema. This condition usually first manifests in childhood and worsens during puberty affecting both sexes equally.  As estrogen increases disease severity, women tend to have more severe disease than men. The severity of presenting symptoms varies widely, even among family members. There is also increased likelihood of developing autoimmune diseases. 
The inciting factors for HAE includes physical injury, medical or dental procedures, psychological stress, menstruation, infections or certain medications such as exogenous estrogen (OCP) and angiotensin-converting enzyme inhibitors.  Any part of the body can be involved; however, extremities, face, upper respiratory system (oropharynx, larynx), intestinal tract, and genitor-urinary tract are the most common.  Involvement of the upper respiratory system may lead to asphyxiation, which is the primary cause of death among HAE patients.  Among untreated patients, death from asphyxiation during laryngeal attacks has been reported in as many as 30% of cases  and the possibility of asphyxiation from a first laryngeal attack is cause for concern.
Since HAE is not an allergic phenomenon, pruritus does not occur concomitant with the swelling  and does not respond to epinephrine, antihistamines, and corticosteroids. Diagnosis can be established based on proper history, careful clinical examination and appropriate laboratory testing, for example, low levels of C1-INH or low C1-INH functional level. A low level of complement factor C4 is often present. 
Management of HAE is multifactorial. It includes patient education, avoidance of inciting factors specific to the patient, management of acute angioedema episodes (acute phase), long-term maintenance/prophylaxis, and prophylaxis prior to dental or medical procedures (short-term prophylaxis). The treatment of acute attack is largely supportive and securing an adequate airway should be a priority. The therapy of choice for life-threatening attacks is any of the approved HAE-specific agents [Table 1] such as C1-INH concentrate (plasma-derived or recombinant) or novel agents such as ecallantide and icatibant.  An IV infusion of 500-1000 U of plasma-derived C1-INH concentrate (Berinert-P) has an onset of action of 30 min to 2 h and last for 3-5 days. Recent understanding of pathophysiology of HAE and evidence showing that bradykinin is the main mediator of HAE, causing vasodilatation and increased permeability of vessels, has led to the development of novel agents which either inhibits bradykinin or blocks its receptors. First agent ecallantide which is a kallikrein inhibitor and another drug icatibant which is a bradykinin receptor antagonist has been approved for acute management. , When an HAE-specific agent is not available, FFP should be used to treat attacks of HAE. Initially, 2 units of FFP to be given and this dose can be repeated every 2-4 h until the attack begins to subside and there is clinical improvement. If the comorbid conditions of the patient are at the risk for volume overload, then dosing of 10-15 ml/kg body weight is recommended, with monitoring of volume status and cardiopulmonary function.  An infusion of 2-4 U of FFP is useful in replacing inhibitor levels.  Our patient improved after 4 unit of FFP transfusion and the condition resolved in 4-5 days [Figure 3]. FFP is generally effective in treating acute attacks of angioedema. However, FFP administration has risk of possible transmission of contagious disease, including hepatitis B and C and HIV infection. Since it is a biological product, anaphylactic shock may occur or resurgence of angioedema due to the fact that FFP consists of supplement factors, including C4. 
Antihistamines, corticosteroids, and epinephrine administration are not helpful in HAE patients.
Prophylaxis is recommended for those patients who experience recurrent episodes of laryngeal edema. Drugs commonly used for prophylaxis include attenuated androgen (danazol, stanozolol, oxandrolone) and antifibrinolytic agents such as e-aminocaproic acid and tranexamic acid. Plasma-derived C1-INH has also been reported to be effective for long-term prophylaxis. The duration usually depends on the severity of disease and toxicities associated with drug therapy. 
The physicians should be aware of the disease as its presentation may mimic anaphylactic reaction and critical time may be wasted in treating it for same. The abdominal angioedema attacks can lead to unnecessary surgery. The episode may become life threatening as laryngeal edema can result in asphyxiation.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Lang DM, Aberer W, Bernstein JA, Chng HH, Grumach AS, Hide M, et al.
International consensus on hereditary and acquired angioedema. Ann Allergy Asthma Immunol 2012;109:395-402.
Kasper DL, Fausi AS, Hauser SL, Longo DL, Jameson JL, Loscalzo J, et al
. Allergies, anaphylaxis, and systemic mastocytosis. In: Harrison's Principles of Internal Medicine. 19 th
ed., Vol. 2. New delhi: McGraw Hill Education; 2015. p. 2119-20. .
Nielsen EW, Gran JT, Straume B, Mellbye OJ, Johansen HT, Mollnes TE. Hereditary angio-oedema: New clinical observations and autoimmune screening, complement and kallikrein-kinin analyses. J Intern Med 1996;239:119-30.
Nzeako UC, Frigas E, Tremaine WJ. Hereditary angioedema: A broad review for clinicians. Arch Intern Med 2001;161:2417-29.
Agostoni A, Aygören-Pürsün E, Binkley KE, Blanch A, Bork K, Bouillet L, et al.
Hereditary and acquired angioedema: Problems and progress: Proceedings of the third C1 esterase inhibitor deficiency workshop and beyond. J Allergy Clin Immunol 2004;114 3 Suppl:S51-131.
Frank MM, Gelfand JA, Atkinson JP. Hereditary angioedema: The clinical syndrome and its management. Ann Intern Med 1976;84:589-93.
Pearson KD, Buchignani JS, Shimkin PM, Frank MM. Hereditary angioneurotic edema of the gastrointestinal tract. Am J Roentgenol Radium Ther Nucl Med 1972;116:256-61.
Longhurst HJ. Management of acute attacks of hereditary angioedema: Potential role of icatibant. Vasc Health Risk Manag 2010;6:795-802.
Socker M, Boyle C, Burke M. Angio-oedema in dentistry: Management of two cases using C1 esterase inhibitor. Dent Update 2005;32:350-2, 354.
Morgan BP. Hereditary Angioedema-therapies old and new. N Engl J Med 2010;363:581-3.
Schneider L, Lumry W, Vegh A, Williams AH, Schmalbach T. Critical role of kallikrein in hereditary angioedema pathogenesis: A clinical trial of ecallantide, a novel kallikrein inhibitor. J Allergy Clin Immunol 2007;120:416-22.
Reshef A, Leibovich I, Goren A, Kidon M. Hereditary angioedema: New mechanisms and therapeutic options. Harefuah 2009;148:529-34.
[Figure 1], [Figure 2], [Figure 3]