Tubulointerstitial nephritis and uveitis (TINU) syndrome: a systematic review of its epidemiology, demographics and risk factors

Abstract

Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare oculorenal inflammatory condition that was first described in 1975. In 2001 a major review identified 133 cases in the world literature and proposed key diagnostic criteria for the condition. Although acknowledged as rare, the limited data available prevented reliable estimates of the prevalence of the condition, and hampered elucidation of the relationship between genetic and environmental factors that contribute to its pathogenesis.In this review we have performed a systematic search on the epidemiology, demographics and proposed risk factors for TINU. Estimates of prevalence based on studies that explicitly report TINU cases suggest that it is diagnosed in 0.2–2% of patients attending specialist uveitis services, with variation reflecting a number of factors including level of diagnostic certainty required. The prevalence of uveitis in patients with tubulointerstitial nephritis (TIN) may be higher than currently recognised, particularly in the paediatric population.The prevalence of TINU is higher in younger age groups and there is a female preponderance although this gender effect appears weaker than suggested by early studies. Although important genetic contributions have been proposed, the small size of studies and variation between reports currently preclude identification of a ‘pro-TINU’ haplotype. Drugs and infections have been proposed as the leading acquired risk factors for the development of TINU; whilst the small size of TINU cohorts and issues of study design limit interpretation of many studies. Larger datasets from the renal literature suggest that the majority of these cases are precipitated by a drug-induced hypersensitivity reaction; however in many ophthalmic cases no clear precipitant is identified.

Tubulointerstitial nephritis and uveitis (TINU) syndrome and recentStreptococcusinfection in a 9-year-old girl

“…Only around 200 reported cases exist in medical literature, perhaps due to low incidence and the disorder remaining underdiagnosed 1. TINU syndrome is thought to be an immune-mediated process that may be precipitated by drugs or infection, although in many cases no cause is identified 2. While the pathogenesis of TINU syndrome remains unknown, evidence of recent Streptococcus infection in our patient may support a causative association postulated in similar previous case reports 3–5…”

“…While the pathogenesis of TINU syndrome remains unknown, it is thought to result from a confluence of host susceptibility factors and environmental triggers 10. Drugs and infections have been proposed as the leading acquired risk factors for the development of TINU syndrome,2 with delayed-type hypersensitivity reactions to such triggering agents thought to play a predominant role 13. The Streptococcus -positive throat swab on admission and subsequently raised ASO titre in our patient may support a causative association with Streptococcus infection leading to an autoimmune response that has been previously postulated 3–5.…”

Inflammatory eye and rheumatic disease

“…As so many of the uveitides have systemic associations, a multidisciplinary approach to care improves the coordination of pretreatment evaluation, treatment and decreases the required number of appointments, allowing management decisions in relation to both the ophthalmic and systemic disease to be made early in the course of the disease …”

Tubulointerstitiell nefritt og uveitt-syndrom

“…Verdi (referanseområde) Årsaken til syndromet er ukjent, men det er antatt å vaere en autoimmun tilstand som oppstår hos genetisk predisponerte individer etter eksponering for en eller flere utløsende miljøfaktorer (1). Ikke-steroide antiinflammatoriske midler (NSAID), antibiotika og infeksjon med blant annet Chlamydia trachomatis har blitt anført som utløsende årsak (5).…”

“…Den vanligste presentasjonen er uveitt og akutt nyresvikt, ofte ledsaget av feber, slapphet, ledd-og flankesmerter (1). Akutt bilateral fremre uveitt er hyppigste okulaere fenotype, men bakre uveitt og panuveitt er også beskrevet (5).…”