INTRODUCTION
Angioedema is a constellation of syndromes that present a challenge to the clinician. The most commonly identified causes of angioedema are medications, allergens, and physical agents, but most cases of angioedema are idiopathic.
The most effective treatment depends on the identification of the causative agent and specially when the mechanism is not identified on the clini-cian’s knowledge and experience with innovative therapeutic regimens.
CASE REPORTA 48 year old man, presented to our Allergy Unit in May 02, because recurrent severe episodes of angioedema affecting the lips, tongue, and throat. He often presented at the Emergency room (once or twice a week for the last 3 months) with tongue and lips swelling, dysphonia and dyspnea. A fiber optic examination revealed mild laryngeal edema during some episodes, that resolved within a few hours after treatment with epinephrine, antihistamines or corticosteroids. The patient did not related episodes of abdominal pain, nauseas or vomiting.
No precipitating factor was identified. He had not been taken angiotensin-converting enzyme inhibitors. The last 4 years he was receiving levothyroxine, be-cause an autoimmune thyroiditis. There was no history of facial paralysis or hereditary angioedema.
Physical examination revealed edema limited to the lower lip, the remainder of his examination was unremarkable.
Skin prick tests to a battery of inhalants, foods, latex, Anisakis simplex and patch test to a standart serie (True test, Abelló, Spain) were negative.
Laboratory investigation revealed normal complete blood count (CBC), erythrocyte sedimentation rate, urinalysis, blood biochemistry (liver and renal function tests), C reactive protein, serum protein electrophoresis, serum immunoglobulins. Total IgE was 30 UI/ml. Antibodies anti-peroxidase were positives: 535 UI/ml (normal values up to 34). Serum immune complexes, antinuclear antibodies and rheumatoid factor were negative.
Complement study during acute and asymptomatic periods revealed normal values of C1 esterase inhibitor, C1q, C3, C4 and CH50. Funtional activity of C1 inhibitor was higher than 90 %.
Three different stool samples were negative for parasites. X-ray studies of thorax and paranasal sinuses showed normal findings.
A biopse of the lip was performed to exclude a cheilitis granulomatosa. No pathologic findings were observed in such specimen.
The patient was treated with sedating and nonsedating H1 antihistamines and corticosteroids (prednisone: 30 mg every day during 3 months) with no clinical improvement. So we decided to start treatment with dapsone 50 mgs daily (previously a deficiency of glucose 6 phosphate dehydrogenase was excluded). Clinically the patient improved and during the subsequent year, no episodes of angioedema appeared. Corticosteroids and antihistamines were stopped one month after starting treatment with dapsone. CBCs were performed weekly during the first month of therapy, monthly for the next 6 months and every 6 months thereafter. No reduction in leukocytes, platelets, or hematopoiesis was detected. No others adverse effects were observed during treatment with dapsone.
DISCUSSIONThe term angioedema describes the localizated, transient episodic edema of the deeper layers of the skin or of the mucosa of the gastrointestinal tract. Angioedema affecting the throat, may lead to obstruction of the airways and death from asphyxiation.
The most commonly identified causes of angioedema are medications, allergens and physical agents, but most cases of angioedema are idiopatic1 . Rare forms of angioedema associated with either hereditary or acquired faulty activation of the complement and kallicrein-kinin systems have been extensively described2,3 .
After excluding the most probable causes of angioedema, we conclude that our patient presented an idiopatic angioedema. In spite of treatment with antihistamines and a daily scheme of oral corticosteroids for 3 months, the patient continued with recurrent episodes so therapy with dapsone was administered.
Dapsone, a sulfone is an antibacterial drug for susceptible cases of leprosy. It is also a primary treatment for dermatitis herpetiformis and has been used with slightly greater success in urticarial vasculitis4 , bullous eruptions5 , and it has been proposed in cases of severe chronic urticaria to taper off prednisone or in cases of unacceptable side effects of steroids6 .
The mechanism of action of dapsone is poorly understood, its anti-inflamatory effects include reduction in lymphocyte responses to mitogens, suppression of neutrophil chemotaxis, and inhibition of the alternate pathway of complement activation The drug also appears to inhibit spontaneous and induced synthesis of prostaglandin E2 by polymorphonuclear leukocytes7 .
Since dapsone induces severe hemolysis in patients with glucose –6-phosphate dehydrogenase deficiency, this serum enzyme should be measured prior to initiation of such therapy. Others less frequent side effects include headaches, a mild non-he-molytic anemia and most importantly, agranulocytosis. Thereafter a complete blood counts should be monitored periodically in patients treated with dapsone8 .
As in chronic urticaria perhaps some patient with recurrent episodes of idiopathic angioedema may have a good response to dapsone, but the response may be unpredictable in each patient, and side effects must be monitored.
We conclude, that dapsone may be an alternative drug in extrem cases of chronic urticaria or idiopathic angioedema that precise corticosteroids for extended periods as a steroid-sparing drug or in cases with poor response to conventional therapy.
Correspondence:
P. González DelgadoServicio de Alergología. Hospital General de Alicante Maestro Alonso, 109 03010 Alicante. Spain E-mail: gonzalez_@gva.es
