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.