Tubulointerstitial nephritis and uveitis

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Tubulointerstitial nephritis and uveitis
Classification and external resources
OMIM 607665


Disease Entity

Disease

Tubulointerstitial Nephritis and Uveitis Syndrome (TINU) describes a rare form of bilateral non-granulomatous anterior uveitis found in a sub-population of patients with tubulointerstitial nephritis (TIN). It was first described in 1975 by Dobrin et.al. The uveitis is usually mild and the nephritis self-limited. However, cases of chronic uveitis and renal failure have been reported.

Etiology

Although the cause of TINU is unknown research has revealed various associations. Certain HLA genotypes (including HLA-DQA1*01:04 and DRB1*14) increase the relative risk of developing TINU in certain populations [1]. Medications have also been implicated (ex. antibiotics or NSAIDS), the drug causing hypersensitivity reaction or hapten-induced cytokine production and immune reaction. Another possibility links dysfunction or targeted disruption of similar enzymes in the renal tubule and ciliary epithelium.

Risk Factors

Prevalence: TINU is a relatively rare disease, accounting for less than 1-2% of all patients presenting to ophthalmology [2]. It is also a small percent of patients with a first episode of acute non-granulomatous anterior uveitis [3]. The true prevalence is unknown and probably higher due to undiagnosed cases labeled idiopathic. In average, TINU occurs in approximately 65% of patients with TIN [4].

Epidemiology: TINU occurs predominately in young females. The median age of onset is 15 years old with patient’s ages ranging from 9 to 74 [4][2]. It affects both sexes, with an overall predominance of females but a trend towards a male predominance in younger age groups [2]. There is no association with particular racial or ethnic groups, or any geographical regions [4][2].

Pathophysiology

The underlying pathogenesis of TIN and TINU is unknown, but thought to be immune mediated [4]. Renal biopsy of patients with TIN typically shows inflammatory cells (lymphocytes, plasma cells and histiocytes) and edema in the renal interstitium [4][2]. The glomerulus and blood vessels are relatively spared. Immune precipitates are not found.

Diagnosis

History

Patients will usually present with typical anterior uveitis symptoms (eye pain, redness, decreased vision and photophobia). Symptoms of TIN are vague and include fever, malaise, fatigue and flank pain. The ocular symptoms can precede (21%) by up to two months, occur concurrently (15%) or follow TIN (65%) [4].

Physical examination

Signs

In greater than 80% of cases, uveitis is bilateral, acute in onset, non-granulomatous and affects only the anterior segment [4]. However, there have been case reports of posterior uveitis and panuveitis [4][2].

Symptoms

Patients will usually present with typical anterior uveitis symptoms (eye pain, redness, decreased vision and photophobia). Symptoms of TIN are vague and include fever, malaise, fatigue and flank pain. The ocular symptoms can precede (21%) by up to two months, occur concurrently (15%) or follow TIN (65%) [4].

Clinical diagnosis

A reliable diagnosis can usually be made from a full ophthalmic exam and usual laboratory evaluation (which includes beta-2 microglobulin detection in the urine or other kidney function tests). However, a definitive diagnosis of TIN can only be made with renal biopsy.

Differential diagnosis

A number of conditions can present with both renal manifestations and uveitis. These include: TINU, systemic lupus erythematosis, Sjogren syndrome, syphilis, sarcoidosis, granulomatosis with polyangiitis (formerly Wegener's), Behcet disease, Epstein-Barr virus associated infectious mononucleosis, tuberculosis, toxoplasmosis, brucellosis, histoplasmosis, and Hyper IgG4 disease [4][2].

Management

Standard treatment for anterior uveitis with topical local steroids can be effective. However, with the high frequency of recurrent disease, long term follow-up is recommended for these patients [2]. If kidney functions do not quickly normalize, a short course of high dose IV or oral steroids is often used. Coordination by nephrology and ophthalmology can be useful.

Surgery

N/A

Surgical follow up

N/A

Prognosis

Long term ocular complications are rare. Uveitis will often persist longer than the nephritis and requires longer term local therapy, rarely lasting more than a year [2]. Recurrence of uveitis can occur in patients with TINU, reported as high as 40% [4][2]. Most recurrences occur within the first few months of stopping therapy, but have occurred as late as two years later [4]. Renal outcomes are also generally good with nephritis often spontaneously resolving, but there have been cases of chronic renal failure following TINU [2]. In contrast to uveitis, nephritis rarely recurs.

Additional Resources

References

  1. Mackensen et al Br J Ophth. 2011,95:971-976.
  2. 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 Mackensen et al Curr Opin Ophth. 2009,20:252-531.
  3. Birnbaum, et. al. Arch Ophthalmol. 2012;130(11):1389-1394.
  4. 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 Mandeville et al. Surv Ophth. 2001,46(3):195-208.