Tubulointerstitial nephritis and uveitis syndrome (ORPHA:91500)
A rare renal tubular disease characterized by early-onset tubulointerstitial nephritis associated with anterior uveitis.
Epidemiology
Approximately 200 cases have been reported in the literature to date, although the disease is likely under-reported. It comprises up to a third of bilateral acute onset acute uveitis in patients younger than 20 years old. Females are predominantly affected with a female:male ratio of 2.5-5:1.
Clinical description
Presentation is typically in children and adolescents (median age of onset of 15 years old) with either uveitis (U) or tubulointerstitial nephritis (TIN). Symptoms of renal involvement are non-specific and can include polyuria/polydipsia, fever, general malaise, abdominal and flank pain, fatigue, arthralgia, myalgia or a non-specific rash. Ocular signs are eye pain and redness, loss of visual acuity and photophobia, though almost 60% of patients with confirmed uveitis present no symptoms. Uveitis is typically bilateral and anterior, but intermediate or posterior uveitis may occur. Of note, uveitis and TIN may occur synchronously or metachronously.
Etiology
The pathogenesis is unclear, but likely autoimmune in origin. The role of the cellular and humoral immunity is highlighted by studies demonstrating loss of T cell-tolerance and the presence in kidney and ocular tissue of antibodies against modified C-reactive protein. Certain HLA haplotypes are associated with a higher risk of the disease.
Diagnostic methods
There are no specific non-invasive tests to establish the diagnosis. Diagnosis should be suspected in patients with polyuria/polydipsia, rise in serum creatinine, elevated markers of tubular damage (such as low-molecular weight proteins), elevated urinary eosinophils, anemia and elevated erythrocyte sedimentation rate. A definitive diagnosis can be established by renal biopsy.
Differential diagnosis
Differential diagnoses should include secondary causes of tubulointerstitial nephritis and uveitis, such as infections (ex. TBC, viral infections as EBV or HIV, bacterial infections as chlamydia or mycoplasma; toxoplasmosis, brucellosis, histoplasmosis), granulomatous diseases as sarcoidosis, Sjögren syndrome, systemic lupus erythematosus (SLE), Wegener's granulomatosis and other as Behcet's disease, ankylosing spondylitis and inflammatory bowel diseases. The renal phenotype can be similar to nephronophthisis, which can also be associated with eye manifestations, albeit not in the form of uveitis.
Management and treatment
Treatment is typically with immunosuppression. Oral corticosteroids are the first line therapy and improvement in symptoms is typically seen within days to weeks of commencement. Use of other immunosuppressive therapies, such as cyclophosphamide, cyclosporine, methotrexate or mycophenolate mofetil has been reported. Topical corticosteroids are useful for TINU-associated uveitis. A careful ophthalmological follow-up is required to monitor possible long-term complications.
Prognosis
Prognosis is favorable as the disease resolves in most of patients. However, some cases progress to end-stage renal disease. There is a low risk of visual loss; however, ocular complications (such as posterior synechiae, cystoid macular edema, disc edema, elevated intraocular pressure and cataract) have been described in 20% of patients.

                            Last update: 
                            March 2020


                            - Expert reviewer(s): 
                            Pr Detlef BÖCKENHAUER | ERKNet*


                                * European Reference Network