Case
A 15-year-old female patient was admitted to our hospital due to progressive deterioration of her renal function with an increased serum creatinine (sCr) level of 0.95 mg/dL despite having no past history of renal disease. Two weeks prior to admission, she developed a fever >38 °C and was empirically treated with azithromycin combined with the occasional use of acetaminophen (ACP) by a local physician; however, her fever persisted. Meanwhile, she started to complain of fatigue and nausea, which prompted referral to our hospital for further workup. Her medical history was unremarkable, except for her prior treatment with escitalopram for developmental disability for 6 months. Upon admission, the patient had a weight of 47 kg (1 kg weight loss), height of 149 cm, temperature of 36.6 °C, pulse rate of 90 beats/min, and a blood pressure of 108/65 mmHg. Her bowel sounds were normal. Her abdomen was soft and flat, with lower abdominal tenderness, without rebound pain or palpable masses. The lungs were clear, and heart sounds were normal. No rash, lymphadenopathy, petechiae, or joint swelling were observed. Renal sonography showed no abnormal findings.
Diffusion-weighted images on abdominal magnetic resonance imaging showed heterogeneous high signals in both renal parenchyma and renal enlargement, which were consistent with acute tubular interstitial nephritis. No abnormalities in the fundus were observed. Aside from renal dysfunction, a serological study revealed an increased C-reactive protein (CRP) level (4.24 mg/dL) and negative findings for antineutrophil cytoplasmic antibody, antiglomerular basement membrane antibodies, anti-SSA/Ro antibodies, and anti-SSB/La antibodies. Urinalysis showed active sediments with six white blood cells and three red blood cells per high-power field. Her urinary protein creatinine ratio was 0.4 g/g⋅Cr. The urinary β2-microglobulin (b2MG)/creatinine ratio and N -acetyl-beta-d-glucosaminidase (NAG)/creatinine ratio were 3.6 μg/mg⋅Cr (reference range: <0.3 μg/mg⋅Cr) and 33.1U/g⋅Cr (reference range: 1.6–5.8 U/g⋅Cr), respectively. A drug lymphocyte stimulation test (DLST) confirmed that the patient had a negative stimulation index (SI) score for ACP but had specific high SI scores for escitalopram of 432% (cutoff value for DLST positivity, 180%). Based on the lack of findings suggesting ocular disease following ophthalmological screening and laboratory results, as well as her clinical history, drug-induced AIN was suspected. The oral administration of escitalopram was stopped. A week after admission, the patient was then found to have anterior bilateral uveitis without any apparent abnormalities of the fundus oculi during a subsequent ophthalmological review. Thereafter, a renal biopsy was performed on the following day. Under a light microscope, five glomeruli were identified within the renal parenchyma. The glomerular structures were preserved, with marked diffuse infiltration of lymphocytes and some eosinophils accompanied by partial destruction of the tubular structures (Figure 1). Immunohistochemistry did not observe any immune complex deposits among the observed glomeruli. A diagnosis of TINU syndrome was thereafter established, and the patient was started on oral prednisolone (PSL) 60 mg daily (1.3 mg/kg/day), to which a favorable response was noted. The patient’s ocular symptoms decreased 1 week after steroid administration, and her urinary b2MG/creatinine ratio and NAG/creatinine ratio decreased to 2.0 μg/mg⋅Cr and 1.8 U/g⋅Cr, respectively. PSL was tapered to 45 mg/day for 2 weeks. Relapse of uveitis was observed during steroid dose reduction, for which steroid instillation was started. Given that her eye symptoms could be controlled with steroid eye drops, the dose of the steroid was gradually tapered and discontinued 3 months after the start of steroid administration. No recurrence was observed as of 1 year after the discontinuation. The patient’s clinical course is detailed in Figure 2.