Acute and chronic desensitization of penicillin-allergic patients using oral penicillin.

The efficacy, safety and mechanisms of penicillin desensitization were studied in 24 adults and two children with serious infections that required therapy with a beta-lactam drug. Indications for desensitization included debilitating as well as life-endangering infections. Increasing oral doses of phenoxymethyl penicillin were administered at 15-minute intervals to a cumulative dose of 1.3 million units. Parenteral therapy with the beta-lactam drug of choice was instituted at that point. Immunologic complications of desensitization or therapy, ranging from pruritus to serum sickness, occurred in 12 patients. The appearance of gradually worsening wheezing led to abandonment of the procedure in one subject with cystic fibrosis and severe pulmonary disease. The remaining 25 patients were successfully desensitized and received full-dose parenteral therapy. Chronic desensitization was maintained in seven individuals with twice daily oral penicillins for 3 weeks to more than 2 years. No allergic complications of chronic desensitization or recurrent full-dose parenteral therapy were detected. Skin test reactions to one or all penicillin determinants became negative in 11 of 15 patients retested after acute desensitization. Two desensitized patients became skin test negative, remained skin test negative after cessation of desensitization, and tolerated subsequent beta-lactam therapy without allergic reactions or resensitization. The results of this study provide new evidence that acute and chronic penicillin desensitization is useful and an acceptably safe approach and suggest that antigen-specific mast cell desensitization contributes to the protection against anaphylaxis.

Biphasic and protracted anaphylaxis.

We performed a prospective study of anaphylaxis in 25 consecutive patients. Three distinct clinical patterns were observed: uniphasic, biphasic, and protracted anaphylaxis. Thirteen patients (52%) experienced a single episode. Biphasic anaphylaxis occurred in five patients (20%), two episodes of hypotension or laryngeal edema separated by asymptomatic intervals of 1 to 8 hours. Initial therapy included large doses of glucocorticoids in three of the five patients. Seven patients (28%) suffered hypotension, lower respiratory obstruction, or laryngeal obstruction that persisted 5 to 32 hours despite vigorous therapy that included systemic glucocorticoids. Recurrent or prolonged reactions were 2.8-fold more likely if the onset was 30 or more minutes after exposure to the stimulus or if the offending agent had been administered by mouth (p less than 0.03). Fatal reactions occurred in one patient who was taking propranolol and in one who was adrenal insufficient. The results of this study demonstrate that biphasic and protracted anaphylaxis are common, despite glucocorticoid therapy. Potentially life-endangering recurrences occurred in five (28%) of the 18 patients who responded to initial therapy. These observations indicate that patients should be followed carefully after apparent remission of anaphylaxis.

Penicillin allergy and desensitization in serious infections during pregnancy.

Penicillin allergy presents a major obstacle to the successful management of some antepartum infections. We studied 15 pregnant women with histories of penicillin allergy confirmed by positive immediate wheal-and-flare skin tests. Thirteen had syphilis, one listeria sepsis, and one Streptococcus viridans endocarditis. Each patient was desensitized over four to six hours by oral administration of increasing doses of penicillin V. At the completion of the procedure, full-dose parenteral therapy with penicillin G or ampicillin was instituted. No extracutaneous reactions were detected. Five of the subjects (33 per cent) experienced pruritus (three) or urticaria (two), but no interruption of desensitization or therapy was necessary. All clinically apparent maternal infections were cured. The pregnancy complicated by listeriosis aborted in the first trimester. The 11 neonates delivered to date are normal. These results indicate that oral desensitization is an acceptably safe approach to therapy in pregnant women who are allergic to penicillin and have infections that require beta-lactam drugs.