Amiodarone
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Mixed drug reaction: case report An 81-year-old man developed mixed drug reactions manifesting as sequential anaphylaxis, type 3 serum sickness-like reaction/ type 3 hypersensitivity reaction and type 4 hypersensitivity reaction, during treatment with amiodarone for atrial fibrillation. The man started receiving amiodarone [dosage and route not stated] for atrial fibrillation associated with atrial thrombosis. His medical history was significant for ischaemic heart disease, coronary artery bypass graft 35 years ago, percutaneous angioplasty performed 10 years ago and stent occlusion. His cardiovascular disease was being treated for several years with isosorbide mononitrate, ramipril, atorvastatin and ezetimibe. No previous history of type-B allergic reactions, iodine or contrast reactions. Six days after initiation of amiodarone, he developed anaphylaxis characterised by generalised urticaria, facial angioedema, wheezing and chest pain. The man was thus admitted and was successfully treated with adrenaline and fexofenadine. Amiodarone was stopped. Subsequently, his electrocardiogram showed atrial fibrillation with no ischaemic change. Seven days after amiodarone was administered, he developed fever, polyarthralgia, a diffuse purpuric rash. An elevated C-reactive protein level and hypocomplementemia was noted. Skin biopsy showed leukocytoclasis and a perivascular eosinophilic infiltrate in the absence of other changes of vasculitis, such as fibrinoid necrosis or thrombosis. HIV, hepatitis-B and hepatitis-C serologic test results were all negative. Blood cultures, urinalysis and respiratory viral swabs did not identify any pathogen. Type 3 serum sickness-like reaction (a type 3 hypersensitivity reaction) was therefore determined. A tapering course of prednisone was thus started. Ten days after initiation of prednisone, his fever, purpuric rash and arthralgia resolved. However, he later developed a desquamating rash, mild erythroderma accompanied by eosinophilia, cervical lymphadenopathy and mild transaminitis (while receiving tapered dose of prednisone). There was no recurrence of fever or arthralgia. His C-reactive protein and complement levels were also normal. A type 4 hypersensitivity reaction was thus considered. The dose of prednisone was therefore increased again and was tapered during 6 weeks without recurrence of hypersensitivity. These mixed drug reactions (in 3 sequential phases: anaphylaxis, type 3 serum sickness-like reaction/type 3 hypersensitivity reaction and type 4 hypersensitivity reaction) were attributed to amiodarone. Subsequently, his atrial fibrillation was treated with diltiazem. He did not experience pulmonary or thyroid toxic-effects during subsequent follow-ups. Thereafter, basophil activation testing (BAT) was performed with amiodarone and the excipients povidone. Interferon gamma release assays and bromide uridine enzyme linked immunosorbent assays were also performed to determine in vitro stimulation and proliferation of his lymphocytes to amiodarone, but the results of these studie
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