Amiodarone/amphotericin-B-liposomal/immunosuppressants

Abstract

Thyroiditis, isolated Cryptococcus neoformans pericarditis and renal dysfunction: case report A 52-year-old man developed thyroiditis during treatment with amiodarone, isolated Cryptococcus neoformans pericarditis during immunosuppressive treatment with antithymocyte-globulin, mycophenolate, prednisone and tacrolimus, and renal dysfunction during treatment with amphotericin-B-liposomal [routes and durations of treatments to reactions onsets not stated; not all indications, dosages and outcomes stated]. The man had a past medical history of orthotopic heart transplantation 1 year previously due to a genetic cardiomyopathy. Thereafter, he had been receiving chronic immunosuppressive treatment with prednisone, tacrolimus, and mycophenolate. Also, it was reported that he had been receiving treatment with amiodarone. He presented to the hospital with worsening fatigue and syncope. Additionally, he had a history of post-transplant rejection within a month of transplant, which was treated with antithymocyte globulin. Two weeks prior to the hospitalisation, an endomyocardial biopsy showed no evidence of cellular or antibody-mediated rejection. However, he was diagnosed with amiodarone-induced thyroiditis and was started on thiamazole [methimazole] with increase in prednisone dose (high dose). He reported a 3 month history of fatigue, but denied chills, fevers, palpitations, chest pain, headaches, cough, photophobia, visual problems, skin lesions or neck stiffness. Physical examination on admission was notable for increased jugular venous pressure and wheezing in the right lung base. Electrocardiogram showed diffuse low QRS voltages, sinus tachycardia with premature atrial complexes, and left posterior fascicular block. Echocardiogram showed normal left and right ventricular systolic function and a rapidly increasing pericardial effusion, which was not present on his most recent study 4 days prior. The man underwent pericardiocentesis, and following 48 hours of incubation, cultures tested positive for Cryptococcus neoformans. Subsequent echocardiograms revealed a persistent and loculated pericardial effusion. The fluid was drained through a pericardial window. Histopathology of the pericardial tissue showed numerous yeasts morphologically compatible with Cryptococcus sp. While Cryptococcus sp. was predominantly detected within the proteinaceous lining of the pericardial tissue, some organisms were detected within the pericardial tissue as well. Fungal culture from the pericardium grew Cryptococcus neoformans. Blood cultures, cerebrospinal fluid fungal culture, HIV serology and cryptococcal antigen in spinal fluid and serum were negative. Lumbar puncture revealed an opening pressure of 22cm H2O with zero WBCs and normal protein. CT scan of the chest, abdomen and pelvis, and brain MRI were unremarkable. His treatment was started with amphotericin-b-liposomal [liposomal amphotericin B] 3 mg/kg/day and flucytosine as induction antifungal therapy. Doses of mycophenolate and tacrolimus were decreased and steroid doses were slowly tapered. After 10 doses of amphotericin-B-liposomal over 3 weeks, his treatment was changed to high-dose fluconazole monotherapy due to development of volume overload and progressive renal dysfunction. Renal dysfunction was attributed to amphotericin-B-liposomal. Right and left heart catheterisation showed increased right and left sided filling pressures with diastolic equalisation, respirophasic concordance and low cardiac output compatible with cardiogenic shock due to restrictive cardiomyopathy. Repeat echocardiograms revealed no pericardial effusion. He eventually became anuric requiring haemodialysis. A cardiac MRI revealed a thick pericardium with pericardial adhesions to the right ventricular free wall. However, there was no other evidence such as interventricular dependence or haemodynamic changes to suggest constrictive pericarditis. He was considered to have isolated Cryptococcus neoformans pericarditis and immunosuppressive treatment was considered as risk factor for Cryptococcus neoformans infection. He was discharged on fluconazole (renally adjusted) for maintenance therapy. At the time of this report fluconazole therapy was ongoing with close monitoring. Serial echocardiograms showed resolution of the pericardial effusion.