University of Iowa Health Care

Ophthalmology and Visual Sciences

EyeRounds.org

Tubulointerstitial Nephritis and Uveitis Syndrome (TINU)

Prashant K. Parekh, MD, MBA and James C. Folk, MD

December 2, 2015

Chief compliant

Foggy vision and floaters

History of Present Illness

The patient is an 18-year-old female who presented with a four month history of foggy vision, floaters, and eye redness/irritation in both eyes (OU). She initially sought ophthalmic care and was prescribed artificial tears and tobramycin-dexamethasone drops for “pink eye.” Her visual acuity continued to worsen in both eyes. She developed mild light sensitivity in both eyes as well as mild, circumferential headaches during the four months leading up to ophthalmologic evaluation. She denied auras, pulsatile ringing of the ears, or transient visual obscurations. Ibuprofen and acetaminophen had not helped her headaches. She denied recent travel or close contact with people who had traveled to other countries.

Review of Systems

She had a recurrent cold sore on her left upper lip. She denied joint pains, nausea/vomiting, diarrhea, or other new skin lesions. She was up to date with all of her vaccinations.

Past Ocular History

  • Corrective lenses for near vision

Past Medical History

  • None

Ocular medications

  • None

Family history

  • Non-contributory

Social History

  • College student
  • She lives with 15 cats and 1 dog
  • Works part-time as a babysitter

Ocular Examination

  • Visual acuity without correction
    • Right eye (OD): 20/30, no improvement with pinhole testing
    • Left eye (OS): 20/25, no improvement with pinhole testing
  • Intraocular pressure
    • OD: 12 mmHg
    • OS: 14 mmHg
  • Ocular motility/alignment: Orthophoric in primary gaze and full motility OU
  • Pupils
    • OU: Equal and briskly reactive to light; the left pupil had an irregular shape; no relative afferent pupillary defect OU
  • Visual fields: Full to confrontation OU
  • External: Normal OU
  • Anterior segment
    • OD
      • Conjunctiva/sclera: Clear and quiet
      • Cornea: Many fine, non-mutton fat keratic precipitates centrally and inferiorly
      • Anterior chamber (AC): 2+ cell, 2+ flare [Figure 1]
      • Iris: Patchy central posterior synechia
      • Lens: Trace nuclear sclerosis with pigment flecks on the anterior capsule

2+ anterior chamber cell in the right eye

Figure 1: 2+ anterior chamber cell in the right eye

    • OS
      • Conjunctiva/sclera: Clear and quiet
      • Cornea: Many fine, non-mutton fat keratic precipitates centrally and inferiorly
      • AC: 2+ cell, 2+ flare
      • Iris: Patches of central posterior synechiae for 360 degrees around the pupillary margin
      • Lens: Trace nuclear sclerosis

Patches of central posterior synechiae for 360 degrees around the pupillary margin of the left eye

Figure 2. Patches of central posterior synechiae for 360 degrees around the pupillary margin of the left eye

  • Dilated fundus exam
    • OU
      • Vitreous: 2+ anterior vitreous cell with mild white vitreous opacities just posterior to the ora serrata
      • Optic Nerve: Normal and without edema
      • Macula: Normal contour, no cystoid macular edema
      • Vessels: Normal course and caliber without sheathing or neovascularization
      • Periphery: Normal and without lesions

2+ anterior vitreous cell (present bilaterally)

Figure 3. 2+ anterior vitreous cell (present bilaterally)

Clinical Course

This young, previously healthy female had acute bilateral uveitis that was centered anteriorly, although there was prominent vitreous inflammation. We considered the following differential diagnosis.

  • HLA-B27 related diseases such as ankylosing spondylitis and reactive arthritis syndrome
  • Inflammatory bowel disease associated uveitis
  • Psoriatic arthritis
  • Tubulointerstitial nephritis and uveitis syndrome (TINU)
  • Sarcoidosis
  • Viral disease: Herpes simplex I&II, varicella zoster virus (VZV), cytomegalovirus (CMV)
  • Syphilis
  • Tuberculosis
  • Lyme disease

Her laboratory studies showed a normal complete blood count. Her urinalysis demonstrated trace protein, 3+ leukocyte esterase, 8 white blood cells and 11 red blood cells. The urine protein-to-creatinine ratio was normal. Beta-2 microglobulin was elevated at 3169 and 1474, in urine and serum, respectively (normal: 0-300). Toxoplasma, bartonella, lyme, and syphilis serologies were negative. ANA and ANCA were normal. Purified protein derivative testing was non-reactive. The patient was referred to Nephrology, who performed a renal biopsy which demonstrated a focal tubulointerstitial inflammatory infiltrate containing lymphocytes and nonspecific histiocytes – confirming the diagnosis of TINU.

Diagnosis

Tubulointerstitial nephritis and uveitis syndrome (TINU)

DISCUSSION

Tubulointerstitial nephritis and uveitis syndrome (TINU) is a rare syndrome (less than 1-2% of all patients seen by ophthalmologists), that was first described in 1975 [1].

Epidemiology

The true prevalence of this syndrome is unknown, likely secondary to poor recognition of the disease [2]. The largest case series review of 133 patients (as of this writing) demonstrated the median age of presentation to be between ages 14-15, with females three times more likely to have the disease compared to males [3]. There does not appear to be any racial or ethnic predilection.

Pathology/Etiology

The precise pathophysiology is unknown, but one hypothesis describes auto-antibody formation against uveal and tubular cells from hapten-induced cytokine production to certain antibiotics and non-steroidal anti-inflammatory drugs [4]. A strong correlation between the HLA-DRB1 and HLA-DQA1 genes and biopsy-confirmed TINU syndrome has also been confirmed by independent groups [4].

Signs/Symptoms/Testing

Patients with this disease typically present with eye redness, light sensitivity, decreased vision, new floaters, and intraocular inflammation. Patients with TINU will have elevated beta-2 microglobulin levels in their urine and serum. This should prompt referral to a nephrologist for consideration of a renal biopsy, the definitive method to diagnose TINU. Characteristic histologic findings include tubulointerstitial necrosis and/or fibrosis with preserved glomeruli, interstitial edema, and cellular infiltration of predominantly CD4-positive lymphocytes [4].

Treatment

Ophthalmologists can manage the intraocular inflammation with topical corticosteroids (i.e., 1% prednisolone acetate) and long-acting cycloplegics (e.g., cyclopentolate, atropine); however, severe cases may necessitate the use of oral prednisone [2]. From a prognostic standpoint, patients tend to recover close to baseline visual acuity with treatment, which is typically less than one year in duration. The uveitic component of TINU can recur in up to 40% of patients, so periodic ophthalmologic monitoring is recommended; the nephritic component spontaneously resolves in most cases with a rare recurrence risk [6].

Epidemiology

  • Primarily affects young, female patients (median age 14-15, 3:1 female to male ratio), but has been diagnosed in adults up to age 74
  • No racial or ethnic predilection
  • Affects 1-2% of patients in specialized uveitis centers
  • Reported associations with HLA-DRB1 and HLA-DQA1

Signs/Symptoms

  • Conjunctival injection
  • Fine keratic precipitates
  • Anterior chamber cell/flare
  • Peripheral anterior synechiae
  • Central posterior synechiae
  • Anterior vitreous cell
  • Vitreous opacities
  • Cystoid macular edema
  • Epiretinal membrane
  • Decreased visual acuity
  • Photophobia
  • Floaters

Labs/Testing

  • Serum urea nitrogen and creatinine (potentially elevated if renal function is impaired)
  • Serum and urine beta-2 microglobulin (elevated)
  • Nephrology consultation for renal monitoring and biopsy to confirm tubulointerstitial involvement

 

Treatment

  • Topical steroids and cycloplegics
  • Oral steroids or other steroid-sparing immunomodulators may be required for severe inflammation

References

  1. Dobrin RS, Vernier RL, Fish AL. Acute eosinophilic interstitial nephritis and renal failure with bone marrow-lymph node granulomas and anterior uveitis. A new syndrome. Am J Med 1975;59(3):325-333. [PMID 1163543]
  2. Mackensen F, Smith JR, Rosenbaum JT. Enhanced recognition, treatment, and prognosis of tubulointerstitial nephritis and uveitis syndrome. Ophthalmology 2007;114(5):995-999. [PMID 17383731]
  3. Mandeville JT, Levinson RD, Holland GN. The tubulointerstitial nephritis and uveitis syndrome. Surv Ophthalmol 2001;46(3):195-208. [PMID 11738428]
  4. Abed L, Merouani A, Haddad E, Benoit G, Oligny LL, Sartelet H. Presence of autoantibodies against tubular and uveal cells in a patient with tubulointerstitial nephritis and uveitis (TINU) syndrome. Nephrol Dial Transplant 2008;23(4):1452-1455. [PMID 18156461]
  5. Hettinga YM, Scheerlinck LM, Lilien MR, Rothova A, de Boer JH. The value of measuring urinary β2-microglobulin and serum creatinine for detecting tubulointerstitial nephritis and uveitis syndrome in young patients with uveitis. JAMA Ophthalmol 2015;133(2):140-145. [PMID 25356569]
  6. Takemura T, Okada M, Hino S, Fukushima K, Yamamoto S, Miyazato H, Maruyama K, Yoshioka K. Course and outcome of tubulointerstitial nephritis and uveitis syndrome. Am J Kidney Dis 1999;34(6):1016-1021. [PMID 10585310]

Suggested Citation Format

Parekh PK, Folk JC. Tubulointerstitial Nephritis and Uveitis Syndrome (TINU). EyeRounds.org. posted December 2, 2015; Available from http://EyeRounds.org/cases/226-TINU.htm

last updated: 12/2/2015
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