Disseminated candidiasis 18 years after renal transplantation
A 47-year-old male was admitted in our hospital for the first time with history of fever and cough with expectoration for about 3 weeks; he had loss of appetite and weight loss of 8 kg in 2 months. He underwent live-related donor renal transplantation in December 1993 with his mother as the kidney donor; the native kidney disease was chronic glomerulonephritis. He had a stable normal graft function till September 2010. His initial immunosuppression was with cyclosporine, azathioprine, and prednisolone, which was modified to cyclosporine (3 mg/kg/day), mycophenolate mofetil (30 mg/kg/day), and prednisolone (15 mg/day) 5 years back. Since 2 years he was self-titrating the medications and was also on irregular follow-up with the transplant unit. He was on cyclosporine 75 mg twice a day (BID), mycophenolate mofetil 1 g BID, and prednisolone 15 mg once a day (OD) when he first visited us. On examination he was conscious oriented, febrile (100°F) with blood pressure of 170/90 mm Hg, skin and oral cavity were normal. He had no edema and had a urine output of 2000 ml per day. Systemic examination including optic fundi was normal. Investigations showed normal hemogram, blood urea 62 mg/dl, serum creatinine 2.58 mg/dl, SGOT 46 IU/l, SGPT 117 IU/l, normal serum electrolytes, and C-reactive protein (CRP) 126.36 mg/l; urine examination showed 1+ proteinuria with no sediments on microscopy. Ultrasonogram abdomen and Doppler study showed normal renal allograft. Blood, urine, and sputum culture showed no growth. Transesophageal echocardiography was normal (there were no vegetations); upper Gastrointestinal (GI) endoscopy was normal. X-ray chest showed bilateral miliary mottling in the upper, middle, and lower zones []. A high resolution computed tomography of the thorax showed miliary mottling involving all the lobes of lung uniformly []. Sputum did not reveal any acid fast bacilli on Ziehl Neelsen stain and Acid-fast bacilli (AFB) culture. cytomegalovirus (CMV) serology and Polymerase chain reaction (PCR) for cytomegalovirus (in blood) were negative.\nFiber-optic bronchoscopy showed normal trache-obronchial tree with no endobronchial lesions. Broncho-alveolar lavage, brush scrapings from the bronchial wall, and transbronchial lung biopsy were taken. A lung biopsy showed macrophages laden with tiny multiple ovoid cells with a perinuclear hallow on H and E stain []; Gomori's methenamine stain highlights these ovoid bodies in brown color []. Ziehl-Neelsen stain for acid fast bacilli was negative. These features were suggestive of a yeast infection.\nCulture of broncho-alveolar lavage (BAL) and lung tissue on Sabouraud's dextrose agar grew white to cream colored, round, smooth, glabrous to waxy surfaced yeast-like colonies at 37°C and 25°C []. Lactophenol cotton blue mount and Gram stain of the colonies showed budding yeast cells. The isolate was germ tube positive and slide cultures on corn meal agar showed blastoconodia, pseudohyphae, and terminal chlamydospores [] which were suggestive of Candida albicans. The isolate was also tested using a semi-automated identification system ID 32C/mini analytic profile index (API) (antibiotic fungus is a micromethod for yeast susceptibility testing from Biomerieux, France) which confirmed the identification as Candida albicans. The isolate was susceptible to amphotericin B, flucytosine, itraconazole, fluconazole, and voriaconazole using the ATB FUNGUS 2/mini API system (Biomerieux, France). Cultures of BAL and lung tissue for mycobacterium were negative.\nAfter admission the patient developed altered sensorium. There was no focal neurological deficit. MRI brain was suggestive of multiple micro-infarcts in bilateral corona radiata and the periventricular region with few infarcts showing a rim of hemorrhage around [Figure and ].\nWith microbiological evidence of Candida albicans in lung tissue, with clinical and radiologic features suggestive of pulmonary and central nervous system (CNS) involvement, a diagnosis of disseminated candidiasis was made in this renal allograft recipient who was on a good dose of immunosuppressants. The patient was started on intravenous amphotericin B and oral flucytosine; mycophenolate mofetil was reduced to 500 mg twice a day, prednisolone to 7.5 mg daily, and cyclosporine was stopped. He was given amphotericin B-deoxycholate (AmB-d) 1 mg/kg intravenous daily and flucytosine as 25 mg/kg four times daily (dose was adjusted as per the estimated glomerular filtration rate) for 6 weeks. The patient showed marked improvement, his sensorium became normal, his serum creatinine improved to 1.6 mg/dl, fever responded, serum CRP became normal, liver enzymes improved, and the radiologic features resolved on X-ray chest at the end of 6 weeks. He was advised to take fluconazole for a period of 6 weeks.