What is your diagnosis? Young boy complains of recurrent red eye

Optometry Times JournalJune digital edition 2024
Volume 16
Issue 06

Pediatric TINU syndrome is rare, but responds well to treatment.

Closeup of young boy with inflamed eye Image Credit: AdobeStock/Janeberry

Image Credit: AdobeStock/Janeberry

An 11-year-old boy presented to the Medical University of South Carolina Storm Eye Institute on June 7, 2023, complaining of recurrent pink eye since March 2023. The patient’s mother said she had not put her son back on medication since the previous occurrence. The patient presented with an ice pack on the right eye, with no relief. Prior to this exam, the patient was diagnosed with episcleritis vs scleritis based on the appearance of episcleritis and the pain described as consistent with scleritis. Viral conjunctivitis was ruled out due to lack of other infected family members and patient history, despite his having follicular conjunctivitis. The patient was treated with 250 mg ibuprofen 3 times a day and topical fluorometholone ophthalmic ointment 0.1% (FML; Allergan) 4 times a day. He was advised to return to the clinic if his symptoms worsened or did not improve.

The patient had an unremarkable medical history with no known allergies. His entering uncorrected visual acuities were 20/30 OD, 20/25 –1 OS, and no improvement with pinhole. IOPs were 10 OD and 11 OS using applanation tonometry. All other testing was within normal limits for his age. A slit lamp and fundus exam revealed mild nasal bulbar injection in the right eye along with fine keratic precipitates in each eye and trace pigment dusting on the lens. All other findings were normal for age.

Clinical presentation

Tubulointerstitial nephritis is characterized by inflammation in the renal tubules and interstitium. Uveitis is an inflammatory condition affecting the eye’s uveal tract. In tubulointerstitial nephritis and uveitis (TINU) syndrome, the 2 manifestations occur concurrently or sequentially, with varying intervals between them.

Uveitis in TINU syndrome commonly presents as bilateral, granulomatous anterior uveitis with mild to moderate pain, photophobia, redness, floaters, and decreased visual acuity. TINU primarily involves the anterior chamber with conjunctival injection, anterior chamber cells, and flare. Posterior segment involvement, such as vitritis, retinitis, or vasculitis, may occur but is less common. The uveitis in TINU syndrome is typically nongranulomatous, although some cases may exhibit granulomatous inflammation.1

Renal involvement in TINU syndrome manifests as acute interstitial nephritis characterized by nonspecific symptoms such as decreased urine output, fatigue, edema, hypertension, weight loss, fatigue, malaise, and low-grade fever.2,3


Findings from a study revealed an estimated 2.2 cases per million individuals per year, and among pediatric patients with uveitis, the rate of TINU cases was 2% to 5%.2,3 The median age of onset was 15 years, and most patients were female. TINU has been found in all ethnic groups.

Due to the condition’s rarity, more studies are needed to understand the etiologies of TINU. The pathophysiology may be an autoimmune reaction triggered by an antigen that causes type 3 hypersensitivity. These immune complexes in the kidney deposit into the uveal tract, thus activating the inflammatory response of uveitis.

Diagnostic testing

Diagnostic workup plays a vital role in confirming TINU. Combining laboratory blood work, imaging, and clinical evaluation provides a comprehensive approach to differentiating between etiologies of uveitis.

Serological markers such as antinuclear antibodies (ANAs), rheumatoid factor, and HLA-B27 can help clinicians investigate and rule out other autoimmune causes. Infectious causes, such as bacterial, viral, and fungal, must be considered in lab testing.

Clinicians can use urinalysis for blood urea nitrogen and serum creatinine levels to assess renal function. Higher eosinophil levels can provide evidence for TINU but are not consistently present.3 Renal biopsy is the gold standard for confirming the diagnosis of TINU syndrome, revealing lymphocytic infiltration and interstitial edema.4

Differential diagnosis

There are various etiologies to rule out when evaluating a patient with anterior uveitis. Juvenile idiopathic arthritis–associated uveitis is the most common cause in children. However, in this case, the patient had no joint symptoms. Systemic autoimmune diseases such as juvenile systemic lupus and granulomatosis with polyangiitis can be associated with uveitis.

Infectious causes can be viral, such as herpes simplex virus, varicella-zoster virus, and cytomegalovirus. Bacterial etiologies include tuberculosis, Lyme disease, and syphilis. Parasitic infections like toxoplasmosis can also present with uveitis.

Although the patient was experiencing recurrences of uveitis, genetic testing for HLA-B27 was performed to rule out acute anterior uveitis associated with ankylosing spondylitis. Behçet disease is rare in children but can present with oral and genital ulcers, skin lesions, and uveitis. In this case, the patient met the demographics in which Behçet disease is more prevalent, and therefore it was considered in the diagnostic testing. However, no other signs or symptoms matched the diagnosis, and it was ruled out.

Trauma must be considered in all cases of uveitis, regardless of age. A thorough case history and clinical evaluation presented no evidence of trauma. Other syndromes associated with uveitis include Vogt-Koyanagi-Harada disease and sarcoidosis. Furthermore, idiopathic anterior uveitis can be diagnosed as a diagnosis of exclusion. Due to the lab results, the patient was identified as having TINU.5

Diagnosis and treatment

This patient was diagnosed with bilateral nongranulomatous uveitis and began taking prednisolone acetate ophthalmic suspension 1% (Pred Forte; Allergan) 4 times per day. He was sent to the laboratory for blood work, which revealed an elevated lysozyme level but an angiotensin-converting enzyme level within normal limits. The patient also had an elevated C-reactive protein level and erythrocyte sedimentation rate, a urinalysis result of high white blood cells, and trace blood on the dipstick but no red blood cells on microscopy. Glucose and protein were present. ANA test results were negative. The patient also had a 12-lb weight loss since March and increased urination, but his hemoglobin A1C level was within normal limits. He was referred to the pediatric nephrology department with a tentative diagnosis of TINU, which was confirmed after he received a kidney biopsy.

Systemic corticosteroids are considered the mainstay of therapy, and their early initiation is crucial to prevent long-term complications. Prednisone at a dose of 1 to 2 mg/kg/day is commonly prescribed, followed by a gradual tapering regimen over several months.6 In cases of severe uveitis, additional immunosuppressive agents such as methotrexate or azathioprine may be employed as steroid-sparing agents.7

In this case, the patient and parents received education on the potential adverse effects of beginning oral prednisone, including hyperglycemia, increased energy, mood changes, weight gain, and elevated blood pressure. After extensive counseling, the parents were amenable to starting the steroid. The follow-up was 4 weeks following the start of prednisone to check on the patient’s tolerance of and response to the medication. Rheumatology colleagues were amenable to the plan and were seeking immunomodulators as options for long-term treatment.


Uveitis in TINU syndrome generally responds well to treatment, resulting in the resolution of inflammation and preservation of visual function. The use of systemic corticosteroids, often in combination with immunosuppressive agents, helps control ocular inflammation and prevent recurrence. Visual outcomes are typically favorable, with study data reporting good visual acuity outcomes in most patients.6,7

Further research is needed to better understand the pathogenesis of TINU syndrome and improve patient outcomes. By increasing awareness and knowledge about this rare syndrome, clinicians can enhance their ability to diagnose and manage TINU syndrome effectively.

  1. Rosenberg, A. Z., et al. (2017). Tubulointerstitial nephritis with uveitis in children and adults. Clinical Journal of the American Society of Nephrology, 12(4), 591-600.
  2. Mandeville JT, Levinson RD, Holland GN. The tubulointerstitial nephritis and uveitis syndrome. Surv Ophthalmol. 2001;46(3):195-208. doi:10.1016/s0039-6257(01)00261-2
  3. Mackensen F, Smith JR, Rosenbaum JT. Enhanced recognition, treatment, and prognosis of tubulointerstitial nephritis and uveitis syndrome. Ophthalmology. 2007;114(5):995-999. doi:10.1016/j.ophtha.2007.01.002
  4. Cunningham, E. T., et al. (2017). Tubulointerstitial nephritis and uveitis syndrome. In Uveitis (pp. 307-312). Springer.
  5. Kotake, S., et al. (2004). Clinical features and complications of anterior uveitis in Japan. Archives of Ophthalmology, 122(5), 639-643.
  6. Dolz-Marco, R., et al. (2015). Tubulointerstitial nephritis and uveitis syndrome: Long-term outcomes and visual prognosis. Journal of Ophthalmic Inflammation and Infection, 5(1), 46.
  7. Tomkins-Netzer O, et al. (2014). Treatment of bilateral uveitis associated with tubulointerstitial nephritis and uveitis syndrome. Ophthalmology. 121(1), 232-238.
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