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      A Rare Case of Tubulointerstitial Nephritis and Uveitis Syndrome Treated with a Multi-Specialty Approach

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          Abstract

          Patient: Female, 23

          Final Diagnosis: Tubulointerstitial nephritis and uveitis syndrome

          Symptoms: Abdominal pain • eye redness

          Medication: —

          Clinical Procedure: —

          Specialty: Opthalmology

          Objective:

          Rare disease

          Background:

          It is important for an ophthalmologist and nephrologist to look for hidden causes of uveitis and nephritis, respectively. Delay in diagnosis leads to increased morbidity and failure to systemically manage the patient results in future recurrence of disease. It is likely that TINU remains underdiagnosed and could potentially account for some of the cases of idiopathic uveitis, especially when greater than 50% of uveitis cases have no identifiable cause.

          Fewer than 300 cases of tubulointerstitial nephritis and uveitis (TINU) syndrome have been reported. In TINU syndrome, inflammation affects the renal tubules, interstitial tissue, and uveal tract. Its pathogenesis remains poorly understood.

          Case Report:

          We report a rare case of TINU syndrome in a 23-year-old female who was treated using a multispecialty approach. Her primary care physician diagnosed her with proteinuria and acute kidney injury and referred her to the nephrologist, who later referred her to the ophthalmologist. A left kidney biopsy confirmed acute inter-stitial nephritis. Following the discovery of a “pink eye”, the patient was referred to ophthalmology and diagnosed with anterior uveitis, confirming TINU syndrome. Without the additional findings of uveitis, the diagnosis would have been missed. Resolution was obtained through steroid therapy.

          Conclusions:

          Correctly diagnosing TINU syndrome requires a multispecialty approach and may not be obvious upon initial presentation. Therefore, the ophthalmologist needs to consider TINU in the differential diagnosis for a patient with bilateral uveitis and evaluate a urinalysis for proteinuria as part of the work up.

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          Most cited references26

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          Causes of uveitis in the general practice of ophthalmology. UCLA Community-Based Uveitis Study Group.

          Most uveitis case series have come from tertiary care centers, and the relative frequencies of disorders they report may reflect referral bias. We sought information about the types of uveitis encountered in the general practice of ophthalmology. We prospectively examined 213 consecutive cases of general uveitis, defined as intraocular inflammation other than cytomegalovirus retinopathy, seen by a group of community-based comprehensive ophthalmologists. This group of cases was compared with 213 consecutive cases of general uveitis examined by a uveitis specialist at a university referral center in the same community. All cases were categorized by anatomic site of inflammation and disease course, and, if possible, they were assigned a specific diagnosis. Cases of cytomegalovirus retinopathy and masquerade syndrome seen during the same intervals were recorded separately. The distribution of general uveitis cases by anatomic site of disease was significantly different between the community-based practices (anterior, 90.6%; intermediate, 1.4%; posterior 4.7%; panuveitis, 1.4%) and the university referral practice (anterior, 60.6%; intermediate, 12.2%; posterior, 14.6%; panuveitis, 9.4%; P < .00005). A cause or clinical syndrome could be assigned to 47.4% of cases in the community-based practices, and to 57.8% of cases in the university referral practice (P = .03). HLA-B27-associated anterior uveitis, cytomegalovirus retinopathy, and toxoplasmic retinochoroiditis were among the five most common forms of uveitis in both practice settings. The relative frequencies with which various forms of uveitis are seen in a tertiary referral center do not necessarily reflect the experience of ophthalmologists from the community in which the center is located. Anterior uveitis and disorders of sudden onset constitute a greater proportion of cases seen by community-based comprehensive ophthalmologists.
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            Modified C-reactive protein might be a target autoantigen of TINU syndrome.

            The cross-reactive antigen(s) of tubulointerstitial nephritis and uveitis (TINU) syndrome from renal tubulointerstitia and ocular tissue remain unidentified. The authors' recent study demonstrated that the presence of serum IgG autoantibodies against modified C-reactive protein (mCRP) was closely associated with the intensity of tubulointerstitial lesions in lupus nephritis. The study presented here investigates the possible role of IgG autoantibodies against mCRP in patients with TINU syndrome. mCRP autoantibodies were screened by ELISA with purified human C-reactive protein in 9 patients with TINU syndrome, 11 with drug-associated acute interstitial nephritis, 20 with IgA nephropathy, 19 with minimal change disease, 20 with ANCA-associated vasculitis, 6 with Sjogren's syndrome, and 12 with amyloidosis. mCRP expression was analyzed by immunohistochemistry in renal biopsy specimens from the 9 patients with TINU syndrome and 40 from disease controls. Frozen normal human kidney and iris were used to demonstrate co-localization of human IgG and mCRP from patients with TINU syndrome with laser scanning confocal microscopy. The mCRP autoantibodies were detected in all nine patients with TINU syndrome, significantly higher than that of those with disease controls (P < 0.05). The renal histologic score of mCRP in TINU syndrome was significantly higher than that in disease controls (P < 0.05). The staining of mCRP and human IgG were co-localized in renal and ocular tissues. It is concluded that mCRP might be a target autoantigen in TINU syndrome.
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              The tubulointerstitial nephritis and uveitis syndrome.

              The world's medical literature on tubulointerstitial nephritis and uveitis (TINU) syndrome was reviewed, and data on 133 patients with TINU syndrome were identified. The median age of onset was 15 years (range 9-74 years) with a 3:1 female-to-male predominance. Common laboratory abnormalities included elevated Westergren erythrocyte sedimentation rates and elevated urinary beta-2-microglobulin levels. Ocular symptoms preceded systemic symptoms in 21% of cases, and followed systemic symptoms by up to 14 months in 65% of cases. Uveitis involved only the anterior segment in 80% of cases. Uveitis was bilateral at presentation in 77% of cases. Patients were treated with systemic corticosteroids in 80% of cases and with immunosuppressive drugs in 9% of cases. Uveitis recurred or followed a chronic course in 56% of patients and persisted for several years in some cases. Ocular complications (including posterior synechiae, cataracts, and elevated intraocular pressure) were reported in 21% of cases. The visual prognosis appears to be good. Persistent renal dysfunction was reported in 11% of cases, including five patients who required renal dialysis. TINU syndrome is a distinct clinical entity that may be under-recognized and may account for some cases of unexplained chronic or recurrent uveitis. It is important for ophthalmologists, nephrologists, and primary care providers to be familiar with this disorder to ensure early diagnosis and appropriate treatment.
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                Author and article information

                Journal
                Am J Case Rep
                Am J Case Rep
                amjcaserep
                The American Journal of Case Reports
                International Scientific Literature, Inc.
                1941-5923
                2016
                21 November 2016
                : 17
                : 869-873
                Affiliations
                [1 ]Madigan Army Medical Center, Tacoma, WA, U.S.A.
                [2 ]Department of Internal Medicine and The Transitional Residency, St. Elizabeth Youngstown Hospital, Youngstown, OH, U.S.A.
                [3 ]Eye Care Associates, Poland, OH, U.S.A.
                [4 ]Department of Surgery, Northeast Ohio Medical University, Rootstown, OH, U.S.A.
                [5 ]Department of Medicine, Northeast Ohio Medical University, Nephrology Associates, Inc., Youngstown, OH, U.S.A.
                Author notes

                Authors’ Contribution:

                [A]

                Study Design

                [B]

                Data Collection

                [C]

                Statistical Analysis

                [D]

                Data Interpretation

                [E]

                Manuscript Preparation

                [F]

                Literature Search

                [G]

                Funds Collection

                Conflict of interest: None declared

                Corresponding Author: Erdal Sarac, e-mail: esarac2000@ 123456yahoo.com
                Article
                900701
                10.12659/AJCR.900701
                5119685
                27867184
                157fedfb-a4a5-4aa3-b98d-cfb777dabcc0
                © Am J Case Rep, 2016

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License

                History
                : 21 July 2016
                : 14 September 2016
                Categories
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                glucocorticoids,nephritis, interstitial,uveitis, anterior

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