Hereditary angioedema

Abstract

Hereditary angioedema is caused by an absolute deficiency or the functional inactivity of CI esterase inhibitor in plasma. A precise diagnosis is important because, unlike allergic forms of mucocutaneous edema, this condition does not respond to epinephrine, antihistamines, or corticosteroids. We report the case of a 24-year-old man who experienced an acute attack after he had stopped taking his prophylactic medication.

Introduction

Hereditary angioedema is caused by an absolute deficiency or the functional inactivity of C1 esterase inhibitor in plasma. It is characterized by a recurrent, circumscribed, nonpitting, subepithelial edema involving any part of the body. [1] Cutaneous lesions are usually well circumscribed, although circumoral edema sometimes spreads to the contiguous mucosa. Pain and pruritus beyond that caused by distention of the skin and subcutaneous tissue are unusual. Visceral involvement is manifested by severe colic followed by watery diarrhea, which usually occurs late in the course of the disease. [2] Hereditary angioedema presenting as a recurrent airway obstruction caused by laryngeal edema is rare and potentially fatal. [1-3]

The diagnosis is based primarily on a history of episodic angioedema and a positive family history of the disease (transmission is autosomal-dominant). Acute attacks can be precipitated by trauma, surgery, mental stress, and high estrogen states. [3] A low level of complement factor C4 is present in 80 to 85% of cases, and the diagnosis is confirmed by low levels of C1 esterase inhibitor. [2]

Case report

We examined a 24-year-old man who had experienced six episodes of angioedema during the previous 20 years. All of these episodes involved varying degrees of laryngeal edema. The patient's grandfather, father, paternal aunt, and brother had all had this condition. The diagnosis was confirmed by a low level ([less than]50% of normal) of C1 esterase inhibitor. The patient's latest episode occurred after he had failed to take his usual prophylactic dose of danazol (200 mg/day) during the previous 2 weeks.

At the emergency room, the patient reported that he had experienced a sudden onset of throat discomfort, dysphagia, and dysphonia. During the examination, but prior to any instrumentation of the airway, the onset of respiratory distress led to an urgent nasal fiberoptic laryngoscopy and fiberoptically guided intubation while the patient was awake. He was treated simultaneously with 500 U of purified C1 esterase inhibitor concentrate. The patient's epiglottis, vocal folds, and surrounding laryngeal structures were noted to be edematous at the time of intubation.

The patient remained intubated for 24 hours. Following extubation of the trachea, a repeat fiberoptic upper airway examination was undertaken under controlled conditions. This examination revealed that the patient had a posteriorly displaced tongue base secondary to swelling of the floor of the mouth along with edema of the epiglottis and supraglottis (figure). Although the edema had diminished somewhat by the time this examination had been performed, the pyriform fossae were still obliterated.

Discussion

The precise diagnosis of hereditary angioedema is important because, unlike allergic forms of mucocutaneous edema, hereditary angioedema does not respond to epinephrine, antihistamines, or corticosteroids. The treatment of acute attacks is largely supportive, and priority is given to securing an adequate airway.

C1 esterase inhibitor concentrate has recently become available outside Europe, where it has become the therapy of choice for life-threatening attacks. An intravenous infusion of 500 to 1,000 U has an onset of action of 30 minutes to 2 hours and lasts for 3 to 5 days. [2] If C1 esterase inhibitor concentrate is not available, an infusion of 2 to 4 U of fresh-frozen plasma might be useful in replacing inhibitor levels.

Prophylaxis is recommended for patients who experience recurrent attacks of laryngeal edema. [2] Danazol (50 to 600 mg/day) and stanozolol (1 to 4 mg/day) have been shown to be effective. Patients who require surgery--especially surgery involving the head, neck, or respiratory tract--have a particularly high risk of developing laryngeal angioedema. Studies have documented the effectiveness of pretreatment with danazol (600 mg/day) or stanozolol (4 mg q6h) for 5 to 7 days preoperatively, along with C1 esterase inhibitor (1,000 to 2,000 U) or fresh-frozen plasma (2 to 4 U) during the 24 hours prior to surgery. [2,4] Even with prophylactic measures, close perioperative observation is still recommended. [4]

From the Department of Anaesthesia and Intensive Care (Dr. Joynt) and the Division of Otorhinolaryngology, Department of Surgery (Dr. Abdullah and Dr. Wormald), Prince of Wales Hospital, The Chinese University of Hong Kong.

Reprint requests: Dr. G.M. Joynt, Department of Anaesthesia and Intensive Care, Prince of Wales Hospital, The Chinese University of Hong Kong, 30-32 Ngan Shing St., Shatin, N.T., Hong Kong, SAR, China. Phone: +852-2632-2735; fax: +852-2637-2422; e-mail: gavinmjoynt@cuhk.edu.hk

References

(1.) Frank MM, Gelfand JA, Atkinson JP. Hereditary angioedema: The clinical syndrome and its management. Ann Intern Med 1976;84:580-93.

(2.) Sim TC, Grant JA. Hereditary angioedema: Its diagnostic and management perspectives. Am J Med 1990;88:656-64.

(3.) Nielsen EW, Gran JT, Straume B, et al. Hereditary angio-oedema: New clinical observations and autoimmune screening, complement and kallikrein-kinin analyses. J Intern Med 1996;239: 119-30.

(4.) Maves KK, Weiler JM. Tonsillectomy in a patient with hereditary angioedema after prophylaxis with C1 inhibitor concentrate. Ann Allergy 1994;73:435-8.

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