Introduction Transthyretin (TTR) cardiac amyloidosis (CA) is an underrecognized cause of cardiomyopathy in adults. Tafamidis is a novel compound associated with lower all-cause mortality compared to placebo. Herein we describe a rare case of an allergic reaction to tafamidis and its successful induction of drug tolerance. Case Presentation A 78-year-old female presented with shortness of breath and pedal edema. On examination, she had elevated jugular venous pressure, decreased breath sounds at both lung bases, a holosystolic murmur at the apex, and pitting pedal edema. Laboratory results showed chronically elevated troponin to 0.18 and brain natriuretic peptide of 1925 pg/mL. A chest x-ray revealed bilateral pleural effusions and pulmonary edema. The electrocardiogram showed low voltage QRS complexes. Echocardiogram showed left ventricular ejection fraction (LVEF) of 50 %, concentric LV hypertrophy, and stage III diastolic dysfunction. The suspicion of CA was raised. Subsequently, cardiac amyloid pyrophosphate nuclear scan was done which revealed the heart to contralateral lung counts ratio of 1.8:1, strongly suggestive of TTR-CA (Figure 1). She was started on tafamidis drug, 80 mg daily. For the initial 3 days, she tolerated the drug well, but then she started developing multiple itchy rashes over both legs associated with throat and chest tightness, as well as difficulty breathing. Tafamidis was discontinued. Diphenhydramine and topical cortisone relieved her symptoms. After one week, she tried tafamidis again with diphenhydramine an hour before but still, she developed similar symptoms. Given the strong indication for tafamidis in her case, she underwent temporary induction of drug tolerance (formerly called drug desensitization). The patient initially received 0.02 mg of tafamidis orally, with incrementally increasing doses every 20 minutes, to reach a final therapeutic dose of 80 mg. She tolerated the process well with no reactions during the protocol. Discussion Tafamidis is generally a well-tolerated drug. To our knowledge, hypersensitivity to tafamidis has not been reported in the literature. This is the first case to report IgE-mediated hypersensitivity to tafamidis that was reproducible with re-challenge to tafamidis. Additionally, this case is also the first to describe a successful temporary induction of drug tolerance to tafamidis. Given the high mortality of CA and limited options for therapy, a drug tolerance protocol for tafamidis may be beneficial for those who develop an IgE mediated hypersensitivity reaction. Transthyretin (TTR) cardiac amyloidosis (CA) is an underrecognized cause of cardiomyopathy in adults. Tafamidis is a novel compound associated with lower all-cause mortality compared to placebo. Herein we describe a rare case of an allergic reaction to tafamidis and its successful induction of drug tolerance. A 78-year-old female presented with shortness of breath and pedal edema. On examination, she had elevated jugular venous pressure, decreased breath sounds at both lung bases, a holosystolic murmur at the apex, and pitting pedal edema. Laboratory results showed chronically elevated troponin to 0.18 and brain natriuretic peptide of 1925 pg/mL. A chest x-ray revealed bilateral pleural effusions and pulmonary edema. The electrocardiogram showed low voltage QRS complexes. Echocardiogram showed left ventricular ejection fraction (LVEF) of 50 %, concentric LV hypertrophy, and stage III diastolic dysfunction. The suspicion of CA was raised. Subsequently, cardiac amyloid pyrophosphate nuclear scan was done which revealed the heart to contralateral lung counts ratio of 1.8:1, strongly suggestive of TTR-CA (Figure 1). She was started on tafamidis drug, 80 mg daily. For the initial 3 days, she tolerated the drug well, but then she started developing multiple itchy rashes over both legs associated with throat and chest tightness, as well as difficulty breathing. Tafamidis was discontinued. Diphenhydramine and topical cortisone relieved her symptoms. After one week, she tried tafamidis again with diphenhydramine an hour before but still, she developed similar symptoms. Given the strong indication for tafamidis in her case, she underwent temporary induction of drug tolerance (formerly called drug desensitization). The patient initially received 0.02 mg of tafamidis orally, with incrementally increasing doses every 20 minutes, to reach a final therapeutic dose of 80 mg. She tolerated the process well with no reactions during the protocol. Tafamidis is generally a well-tolerated drug. To our knowledge, hypersensitivity to tafamidis has not been reported in the literature. This is the first case to report IgE-mediated hypersensitivity to tafamidis that was reproducible with re-challenge to tafamidis. Additionally, this case is also the first to describe a successful temporary induction of drug tolerance to tafamidis. Given the high mortality of CA and limited options for therapy, a drug tolerance protocol for tafamidis may be beneficial for those who develop an IgE mediated hypersensitivity reaction.
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Feb 1, 2021
Reba Suri + 1
Open Access
