From the Department of Dermatology and Venereo-logy, Government Medical College Hospital, Sector 32, Chandigarh 160 047, India.
Reprint requests: Dr. A.J. Kanwar, Professor and Head, Department of Dermatology and Venereology, Government Medical College Hospital, Sector 32, Chandigarh 160 047, India.

Manuscript Received: August 10, 1999;
Initial review completed: September 28, 1999;
Revision Accepted: October 25, 1999

Angioedema, characterized by non-pitting, erythematous swelling of soft tissues, can be hereditary or acquired. Hereditary angioedema (HAE) is an autosomal dominant disease due to mutations at C1 inhibitor gene. The defective gene does not produce sufficient levels of C1 inhibitor in plasma which leads to auto-activation of C1 and consumption of C2 and C4. It is further classified into Type I (lower production of C1 inhibitor proteins) and Type II (functional defect of C1 inhibitor with normal plasma levels)(1,2). Acquired angioedema may be a manifestation of urticaria; it has recently been described with drugs like angiotensin converting enzyme (ACE) inhibitors.

An 11-year-old male child presented with 5 years’ history of recurrent episodes (6-7/year) of swelling of hands, feet and face along with hoarsness of voice and difficulty in breathing. Each episode would last 2-3 days and subside by taking some home remedies. There was occasional pain abdomen, diffuse in nature at the beginning of episode but there was no itching, redness or eczematization. There was apparently no relation of these episodes to any food, drugs or other incidental illnesses. Family history revealed history of similar episodes in mother since childhood and in elder brother of the patient who died of respiratory distress at the age of 8 years during a similar attack.

On examination, patient had mild non-pitting edema of eye lids, lips and dorsa of hands with slight heaviness of voice. Indirect laryngo-scopy revealed mild laryngeal edema involving aryepiglottic folds, true and false vocal cords. A clinical diagnosis of hereditary angio-neurotic edema (HAE) was made.

The blood counts, urinalysis, hepatic and renal functions were normal. Serum C4 estimation was done as a screening test of common pathway. It was decreased to 0.14 g/L (normal 0.20-0.50 g/L). Estimation of C1 esterase inhibitor proteins also showed decreased levels of 29% (normal 70-130). Patient was treated with stanazolol 1 mg twice daily orally for 6 weeks which led to remission of the present attack. Dose was reduced to 1 mg once daily for 6 months during which remission was maintained. Hepatic functions were monitored regularly during the treatment and no abnormality was detected. The parents were counselled about the nature of disorder. Although mother had infrequent and very mild attacks which did not require any active intervention at the time of presentation, her serum C4 was decreased to 0.06 g/L and C1 esterase inhibitor was decreased to 29%. Levels of both these parameters were normal in the father of the child.

Angioedema whether acquired or hereditary can be life threatening at times as head and neck region is almost always affected(2). Before modern treatment was available, fatality rates upto 20% have been described in hereditary angioedema. Mode of death in such cases have been due to sudden onset laryngeal edema resulting in asphyxia(1,2). Early detection, patient and parent education can avert such untoward incidents as the condition is easily preventable and treatable. Different types of treatment may be required according to the state of disease in a particular patient, however there is not a clear correlation between the clinical severity and laboratory abnormalities.

Treatment of acute attack of HAE is not easy as it responds poorly to antihistamines, steroids or adrenaline. Treatment of choice for an established attack is purified C1 esterase inhibitor concentrate, if available.(3) Fresh frozen plasma may tide over the crisis in an emergency if the synthetic inhibitor is not available. Surgical intervention in the form of tracheostomy may be life-saving in absence of other measures.

Short term prophylaxis is best provided by androgens like stanazolol or danazol which increase the production of C1 inhibitor. Androgenic side effects in women and children are the limiting factors in long term use of these drugs. However, very small doses used intermittently can also keep a patient relatively asymptomatic. Epsilon-aminocaproic acid (12-18g daily) or transexamic acid is less effective than androgens.

Prophylactic agents have a definite role prior to elective surgery (specially in the head and neck region) which can precipitate an acute attack.

With the advent of serological diagnosis and modern therapy, HAE if recognized early, should be a completely preventable disease. Baranwal et al.(4) recently reported three cases seen by them in Chandigarh. Although C1 esterase inhibitor concentrate has recently become available in India, it is very expensive. Similarly fresh frozen plasma is not easy to procure in emergency conditions. It therefore becomes all the more important to prevent development of acute attacks to avoid fatalities. Exact mode of action of androgens in HAE has been not clear, however it is postulated that these drugs exert their therapeutic effect through increase in the hepatic synthesis of C1 inhibitor protein. Long-term adverse effects of these androgenic drugs include virilization, increase in low density cholesterol and their probable association with hepatic neoplasia. Stanazolol should be preferred to danazol in the treatment of HAE as it has less androgenic side effects and is cheaper.

We are thankful to Prof. Malcolm W. Greaves, St John’s Institute of Dermatology, London for this help in carrying out estimation of C1 esterase protein levels.

1. Agostoni A, Caacardi M. Herditary and acquired C1 inhibitor deficiency: Biological and clinical characteristics in 235 patients. Medicine 1992; 71: 206-215.

2. Megerian CA, Arnold JE, Berger M. Angioedema. 5 years experience with a review of the disorder’s presentation and treatment. Laryngoscope 1992; 102: 256-260.

3. Waytes AT, Rosen FS, Frank MM. Treatment of hereditary angioedema with a vapour treated C1 inhibitor concentrate. N Engl J Med 1996; 334: 1630-1634.

4. Baranwal AK, Singh S, Kumar L. Hereditary angioneurotic edema. Indian Pediatr 1999; 36: 187-189