Acute interstitial nephritis and drug rash with secondary to Linezolid
A 54-year-old male case of alcoholic cirrhosis (Child A) and diabetes mellitus without any evidence of nephropathy was admitted at our center with 2-day history of altered sensorium and fever. There was no prior history of headache, vomiting, seizures, or decreasing urine output. On physical examination, patient was febrile, disoriented, pulse rate was 100/min, blood pressure was 150/70 mmHg, mild icterus, and pedal edema was present. There was no evidence of focal neurological deficit or signs of meningism. Fundus examination revealed no features of papilledema or retinitis. Bilateral pupils were equal and reacting to light. Abdominal examination revealed free fluid with no organomegaly whereas other systems were unremarkable.\nLab investigations revealed Hb 9.6 gm/dL, total leukocyte count (TLC) 16 800/ mm3 with normal eosinophil counts and platelet count 1.1lac/mm3, with normal coagulation profile with INR of 1.3. Serum bilirubin was 3.0 mg/dL with AST/ALT of 87/96 IU/L. Arterial ammonia was 239 μg/dL. Viral markers were positive for IgM anti-HEV; however, HBsAg, anti-HCV, IgM anti-HAV, and HIV were negative. Ascitic fluid analysis revealed high ascites with high serum-ascites albumin gradient normal cell counts. His ultrasonography abdomen was suggestive of chronic liver disease with coarse echotexture and normal bilateral kidneys. Renal functions were normal with 1+ proteinuria with full field leucocytes and 8-10 RBC/high-power field on urine analysis. Urine culture was positive for enterococcus faecalis, with sensitivity to linezolid only.\nPatient remained in altered sensorium, and was diagnosed as a case of hepatic encephalopathy and uro-sepsis on the basis of positive urine culture. He was managed with lactulose and supportive care for liver failure. Linezolid 600 mg twice a day was started in view of positive urine culture for enterococcus. On day 3 of linezolid therapy, he developed pruritus, erythematous macular rash involving all the extremities and trunk. Peripheral blood smear showed eosinophilia with an absolute eosinophil count of 2125 cells/mm3. His serum IgE levels were also elevated (430 IU/mL). Repeat urine examination revealed 2+ proteinuria with 15-20 leukocytes with WBC casts and RBC cast, with no evidence of eosinophils. Renal functions were deranged with serum creatinine rising upto 5.2 mg/dL with decreasing urine output requiring dialytic support. Dermatological opinion was taken and a diagnosis of DRESS syndrome was made. Keeping the clinical possibility of drug-induced AIN as a cause of renal dysfunction, his drugs were reviewed and linezolid was stopped. The rash and fever subsided in a few days. However, the renal functions remained deranged. Patient recovered from hepatic encephalopathy and liver functions showed improvement. Further investigations revealed ANA and ANCA to be negative, with normal complement levels.\nRenal biopsy was performed in view of persistently deranged renal functions and microscopic hematuria. H-stained section showed normal glomeruli on light microscopy. Interstitium showed edema with moderate inflammatory infiltrate comprising predominantly of mononuclear cells with few eosinophil and proximal tubular dilatation with patchy necrosis []. Birefringent oxalate crystals were also present in tubules and interstitium with foreign body giant cell reaction []. There was no granuloma formation. The arterioles were unremarkable, with no evidence of vasculitis or thrombosis. Immunofluoroscence examination of biopsy showed no immune complex deposition. Thus, the renal biopsy established the diagnosis of acute tubulointerstitial nephritis with patchy tubular necrosis.\nPatient was managed with short course of prednisolone for 2 weeks. Renal functions gradually improved with serum creatinine level decreasing to 1.4 mg/dL, which corresponds to an estimated creatinine clearance of 56 mL/min. Patient is being regularly followed-up and has not shown any deterioration in renal functions.