Journal Information
Vol. 12. Issue 3.
Pages 174-175 (May - June 2016)
Vol. 12. Issue 3.
Pages 174-175 (May - June 2016)
Letter to the Editor
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Differential Diagnosis of Acute Bilateral Uveitis in the Rheumatologist's Office
Diagnóstico diferencial de uveítis bilateral aguda en la consulta del reumatólogo
Águeda Prior-Española,
Corresponding author

Corresponding author.
, Melania Martínez-Morilloa, Susana Holgado-Péreza, Francisco Javier Juegab
a Servicio de Reumatología, Hospital Universitario Germans Trias i Pujol, Badalona, Barcelona, Spain
b Servicio de Nefrología, Hospital Universitario Germans Trias i Pujol, Badalona, Barcelona, Spain
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Tables (1)
Table 1. Differential Diagnosis of Uveitides According to Their Most Common Pattern of Presentation.
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To the Editor,

Given the multiorgan involvement in systemic diseases, there is a growing trend toward the establishment of multidisciplinary services for outpatient care. In recent years, we are witnessing the creation of units shared with dermatologists, pulmonologists or nephrologists and, recently, ophthalmologists. Uveitis is an isolated condition in 50% of the cases; however, a detailed interview, thorough physical examination and general laboratory tests with an immunological study reveal an underlying rheumatic disease in the remaining 50%.1 There are conditions, like the spondyloarthropathies and sarcoidosis, with which uveitis is frequently associated; however, there are less common diseases that we should not overlook.

We report the case of a 46-year-old woman with a history of hepatitis C virus, endometriosis and migraine who presented with red eye and a sharp pain in her left eye. She was diagnosed with anterior uveitis and, once infection had been ruled out as the cause, was treated with topical glucocorticoids. Over the following weeks, she developed anterior uveitis in her right eye and it appeared anew in the contralateral eye, neither of which resolved completely with the treatment. She had no accompanying clinical manifestations or signs or symptoms suggestive of autoimmune or infectious disease. Laboratory tests revealed acute renal failure, with a creatinine level of 2.15mg/dL and proteinuria of 1g in 24h, with no microhematuria, glycosuria or sterile pyuria. Given the suspicion of an underlying systemic disease, the patient was referred for further evaluation. She underwent an immunological study that included rheumatoid factor, antineutrophil cytoplasmic antibodies (ANCA) and antinuclear antibodies (ANA), all of which were negative; her complement and immunoglobulin levels were normal, tests for HLA-B27 and HLA-B51 were both negative, and her angiotensin-converting enzyme level was normal. In view of the progressive deterioration of her glomerular filtration rate, renal biopsy was performed. The results of the histological study were consistent with acute tubulointerstitial nephritis. On the basis of the clinical, analytical and histological findings, she was diagnosed with tubulointerstitial nephritis with uveitis (TINU), and a regimen of oral glucocorticoids was begun at doses of 0.5mg/kg/day, and tapered until they were discontinued after 8 months of treatment. The patient's renal function returned to normal, the proteinuria disappeared and, after 12 months of follow-up, she has had no new episodes of uveitis.

Acute tubulointerstitial nephritis with uveitis (TINU syndrome) is an uncommon disorder that is somewhat unknown to rheumatologists. It should be considered in the differential diagnosis of those patients with recurrent uveitis who are frequently to be found in our offices.1 Depending on the pattern of presentation, the differential diagnosis of uveitides includes the diseases summarized in Table 1. The differential diagnosis of acute anterior uveitis should include spondyloarthropathies, cytomegalovirus infections, herpes simplex or herpes zoster, relapsing polychondritis, systemic lupus erythematosus, Behçet's disease and TINU syndrome. Bilateral involvement further limits the alternatives to spondyloarthropathies, Behçet's disease and TINU syndrome. Thus, it is very important that the study of these patients include the determination of renal function and urinalysis. This syndrome was first described in 1975 by Dobrin et al.2 and, to date, some 250 cases have been reported,3–5 the majority in the pediatric, ophthalmology and nephrology literature. The mean age at presentation is 15 years (range: 9–74 years), and there is female predominance. The risk factors reported for the development of acute tubulointerstitial nephritis include infections, drugs (anti-inflammatory agents, antibiotics) and autoimmune diseases.1,4–6 The presenting clinical signs and symptoms of interstitial nephritis are generally nonspecific: fever, weight loss, fatigue and malaise. The usual laboratory findings are leukocytosis, anemia, elevated acute phase reactant levels (erythrocyte sedimentation rate or C-reactive protein), microhematuria, proteinuria, glycosuria and/or pyuria. The ocular symptoms of uveitis include eye pain, red eye, loss of visual acuity and photophobia. The nephritis and uveitis do not normally present at the same time, a circumstance that further complicates the diagnosis. In 65% of the cases, nephritis is diagnosed first, in 21% it is uveitis that develops earlier, and in the remaining 15%, they appear simultaneously.1 Mandeville et al.6 published a number of diagnostic criteria that require histological confirmation or extensive clinical evidence of acute tubulointerstitial nephritis and of uveitis. The kidney disease can have a good prognosis if treatment is begun early with systemic glucocorticoids. However, tubulointerstitial fibrosis and deterioration of the chronic renal function may develop if the disease goes untreated. For this reason, early diagnosis is essential. Recurrence of the uveitis is common (41%), but does not predict or imply recurrences of the kidney disease.7

Table 1.

Differential Diagnosis of Uveitides According to Their Most Common Pattern of Presentation.

Type of uveitis  Associated diseases 
Acute anterior
Unilateral  Spondyloarthropathies, cytomegalovirus, herpes simplex, herpes zoster, relapsing polychondritis, systemic lupus erythematosus, Kawasaki disease 
Bilateral  TINU syndrome, spondyloarthropathies, Behçet's disease 
Chronic anterior  Juvenile chronic arthritis, Sjögren's syndrome, sarcoidosis, tuberculosis 
Intermediate  Multiple sclerosis, Lyme disease, Whipple's disease, sarcoidosis, TINU syndrome 
Posterior  Toxoplasmosis, cytomegalovirus, tuberculosis, syphilis, Sjögren's syndrome, Vogt-Koyanagi-Harada syndrome, sarcoidosis, Behçet's disease 
Panuveitis  Vogt-Koyanagi-Harada syndrome, sarcoidosis, Behçet's disease, juvenile chronic arthritis, tuberculosis 
Retinal vasculitis  Behçet's disease, systemic lupus erythematosus, granulomatosis with polyangitis, syphilis 

The TINU syndrome is a condition in which the renal involvement can have a good prognosis with systemic glucocorticoid therapy. It is important that we know about it and include it in the differential diagnosis of uveitides and in that of acute tubulointerstitial nephritides. We consider multidisciplinary units to be increasingly necessary for cases like the one described here, as they would enable more precise diagnostic and therapeutic approaches.

R. Kadanoff, B. Lipps, A. Khanna, S. Hou.
Tubulointerstitial nephritis with uveitis (TINU): a syndrome rheumatologists should recognize: a case report and review of the literature.
J Clin Rheumatol, 10 (2004), pp. 25-27
R.S. Dobrin, R.L. Vernier, A.L. Fish.
Acute eosinophilic interstitial nephritis and renal failure with bone marrow-lymph node granulomas and anterior uveitis: a new syndrome.
Am J Med, 59 (1975), pp. 325-333
F. Mackensen, H. Billing.
Tubulointerstitial nephritis and uveitis syndrome.
Curr Opin Ophtalmol, 20 (2009), pp. 525-531
C. Li, T. Su, R. Chu, X. Li, L. Yang.
Tubulointerstitial nephritis with uveitis in Chinese adults.
Clin J Am Soc Nephrol, 9 (2014), pp. 21-28
S. Parameswaran, N. Mittal, K. Joshi, M. Rathi, H.S. Kohli, V. Jha, et al.
Tubulointerstitial nephritis with uveitis syndrome: a case report and review of literature.
Indian J Nephrol, 20 (2010), pp. 103-105
J.T. Mandeville, R.D. Levinson, G.N. Holland.
The tubulointerstitial nephritis and uveitis syndrome.
Surv Ophtalmol, 46 (2001), pp. 195-208
L. Zhou, Y. Li, F. Liu, Y. Peng, Y. Liu, J. Li.
Excellent outcome of tubulointerstitial nephritis and uveitis: case report and five-year follow-up.
Ren Fail, 34 (2012), pp. 934-936

Please cite this article as: Prior-Español Á, Martínez-Morillo M, Holgado-Pérez S, Juega FJ. Diagnóstico diferencial de uveítis bilateral aguda en la consulta del reumatólogo. Reumatol Clin. 2016;12:174–175.

Copyright © 2015. Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología
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