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Rapid intravenous desensitization to antithymocyte globulin in a patient with aplastic anemia

2004; Wolters Kluwer; Volume: 77; Issue: 2 Linguagem: Inglês

10.1097/01.tp.0000093465.31906.ca

1534-6080

Ronald M. Ferdman, Mary Wakim, Joseph A. Church, Thomas Hofstra, Danny Thomas, Yuri Genyk,

Urticaria and Related Conditions

Adverse reactions to heterologous sera such as antithymocyte globulin (ATG) are common, with rates of serum sickness reported as high as 75% or more (1). Type I, immunoglobulin (Ig)E-mediated immediate hypersensitivity, reactions are less common, but anaphylaxis to ATG has resulted in fatalities even when appropriate precautions were taken (2,3). Before initiating therapy, skin testing is advised, and if reactive, treatment with ATG is not recommended (4). A prior history of anaphylaxis to ATG also precludes its use. Typical management of IgE-mediated drug allergies is substitution with a therapeutically equivalent but immunologically dissimilar agent. If substitution is not possible, patients can be desensitized, and standard desensitization protocols exist to a variety of drugs. There have been two reports of attempts to desensitize to ATG (2,3). Of these, only one of four patients was able to complete a full treatment course. We report a case of successful desensitization to ATG. A 17-year-old male patient, receiving tacrolimus and prednisone, developed aplastic anemia after living-donor liver transplantation for fulminant nontypable viral hepatitis. An intradermal skin test (0.1 cc of 1:1,000 diluted ATG) was administered according to protocol (4). Within 15 min, a 20-mm wheal developed, accompanied by postural dizziness and hypotension (81/44 mm Hg). Nevertheless, ATG was believed to be the best therapeutic option. While monitored in the intensive care unit, the patient was desensitized according to the schedule outlined in Table 1. Pretreatment included diphenhydramine and ranitidine; prednisone 60 mg daily and tacrolimus were continued. He showed no acute reactions during the procedure, but 1 hr after reaching full maintenance dose, generalized urticaria developed that lasted the duration of the 4-day infusion. The urticaria was ameliorated with diphenhydramine. Symptoms did not progress beyond the urticaria and resolved after the infusion ended. The patient did not develop serum sickness. Table 1: Antithymocyte globulin continuous desensitization infusion protocolOf four reported cases of attempted ATG desensitization, only one was successful (2). This was in an otherwise healthy 6-year-old girl with aplastic anemia who had a positive intradermal skin test (wheal=8 mm to 1:10 ATG). The second patient in this series was a 64-year-old man with underlying heart disease treated with a beta-2-adrenergic blocker (wheal=6.5 mm to 1:10 ATG). Within minutes of starting the desensitization, he died of refractory anaphylactic shock. In a more recent series (3), a 69-year-old man and a 46-year-old woman developed anaphylaxis during the desensitization and 18 hr into the continuous infusion, respectively (wheals=11 mm and 10 mm to 1:1,000 ATG, respectively). An abnormal skin test may not prove IgE-mediated sensitivity to ATG, because false positive intradermal skin tests (when performed according to the package insert) have been reported (2). However, the large wheal in our patient and the resolution of his urticaria on cessation of the ATG infusion support an IgE-mediated mechanism. Modified from existing protocols (5), the desensitization method described here delivers “smoother” incremental dosing that may be more efficacious than conventional intermittent bolus-dosing protocols. Premedication with antihistamines and glucocorticoids may also have helped. In the other successful desensitization, the patient was also premedicated, whereas the other three patients were not. Premedication may block non-IgE–mediated components of the reaction. Last, both successful procedures were in younger patients, presumably with less preexisting underlying cardiopulmonary disease. Serum sickness, an IgG-mediated process, is unrelated to IgE-mediated anaphylaxis. Skin testing will not predict the risk for serum sickness, and desensitization will not influence the development of serum sickness. The fact that our patient did not develop serum sickness is unrelated to the desensitization. Desensitization also does not affect the efficacy of the drug. Indeed, our patient’s aplastic anemia improved after ATG treatment. ATG desensitization remains a high-risk procedure that should only be performed when the benefits outweigh the potential for life-threatening reactions. Candidates for desensitization would include patients with an abnormal skin test or who have had a prior anaphylactic reaction to ATG. In selected cases, desensitization may allow the use of this potentially lifesaving medication. Ronald M. Ferdman Mary Wakim Joseph A. Church Thomas C. Hofstra Danny Thomas Yuri S. Genyk