Case Presentation: A 24-year-old woman with no medical history presented with eight weeks of nausea, vomiting, and fevers. Six weeks prior to admission she had a positive monospot test, positive EBV IgG, and negative EBV IgM. Two weeks prior, she developed cyclical fevers, night sweats, and weight loss. She presented to the ED due to inability to tolerate oral intake. She denied joint pain, hair loss, rash, and oral ulcers. On exam, she was mildly tachycardic (109 beats/min) and anxious. She had no tonsillar enlargement, lymphadenopathy, splenomegaly, or rashes. Labs were significant for creatinine of 4.14 (baseline 0.82), BUN of 34, hemoglobin of 9.1, and white blood cell (WBC) count of 7.0×10^9/L. CT chest/abdomen/pelvis showed no lymphadenopathy, hydronephrosis, or abscess. She received 2L of normal saline with little change in creatinine.While inpatient, creatinine levels rose to a maximum of 4.33. Maximum temperature was 38.6°C with negative blood cultures. HIV, Lyme disease, tick-borne illnesses, syphilis, and legionella were negative. Her ESR was elevated to >130 and CRP was 29.5. Rheumatologic consult considered lupus, Goodpasture’s disease, vasculitis, and adult-onset Still’s disease. RF, ANA, ANCA, complement C3 and C4, GBM IgG, SSA/SSB, Smith antibody, and ferritin were within normal range. Urine dip had 1+ glucose, 1+ protein, and 8+ WBC without hematuria. Microscopy revealed 5-10 WBC per HPF, granular casts, and 2 WBC casts, decreasing suspicion for glomerulonephritis. Acute tubular necrosis (ATN) and acute interstitial nephritis (AIN) were still considerations. Renal biopsy demonstrated AIN with eosinophils. The patient began 60 mg prednisone daily for 15 days followed by a 4-week taper. Her creatinine was down to 1.14 after one week.

Discussion: Internists commonly encounter acute mononucleosis. Less commonly considered, however, are the late phase sequelae. Subclinical renal involvement is relatively common with proteinuria and hematuria in 14% and 11% of patients, respectively.[1] EBV-induced AIN is rare and defined primarily in case reports. The mechanism is not well understood with evidence for both direct viral infection and immune-mediated damage.[1] Without prompt recognition and treatment, AIN may cause acute renal failure.Symptoms of EBV classically resolve in two to four weeks but may extend up to six months. Worsening or persistent EBV symptoms in the setting of AKI should raise concern for EBV AIN. The diagnosis of AIN is associated with elevated serum creatinine and urinalysis with WBC, WBC casts, and eosinophilia. Yet WBC casts are not sensitive or specific for AIN, nor does a normal UA exclude AIN. Renal biopsy is required for definitive diagnosis.High dose steroids are the treatment of choice for AIN. The rate of recovery to baseline kidney function is 60-65%. The rate of irreversible kidney injury ranges from 5-10%. Partial recovery with persistent reduction in kidney function occurs in about 10-20% of cases.[2] In a review of 27 cases of EBV AIN, one patient required a renal transplant, two patients died of non-renal complications, and 24 patients fully recovered.[3] Resolution of AIN can lead to improvement in symptoms originally misattributed to EBV infection alone.

Conclusions: EBV is a rare cause of acute interstitial nephritis that should be considered in patients with known infection and absence of other risk factors for acute kidney injury. Worsening or persistent EBV symptoms should prompt primary care providers to check renal function.

IMAGE 1: Interstitial inflammation and tubulitis diagnostic of AIN (H&E stain, 40x)

IMAGE 2: Glomerular casts with necrotic debris characteristic of ATN, a minor component on biopsy (PAS stain, 40x)