Tubulointerstitial nephritis with uveitis in a young male patient

Juan Jose Castro-Barandica; Daniela A Esmeral-Ordonez; Karol Quintero-Lizcano; Carlos Mario Rangel

doi:10.4103/pajo.pajo_34_23

CASE REPORT

Year : 2023 | Volume : 5 | Issue : 1 | Page : 27

Tubulointerstitial nephritis with uveitis in a young male patient

Juan Jose Castro-Barandica¹, Daniela A Esmeral-Ordonez¹, Karol Quintero-Lizcano¹, Carlos Mario Rangel²
¹ Autonomous University of Bucaramanga, Bucaramanga; Virgilio Galvis Ophthalmological Center; Ophthalmologic Foundation of Santander, Floridablanca, Santander, Colombia
² Autonomous University of Bucaramanga, Bucaramanga; Virgilio Galvis Ophthalmological Center; Ophthalmologic Foundation of Santander, Floridablanca, Santander; Industrial University of Santander, Bucaramanga, Colombia

Date of Submission	18-May-2023
Date of Decision	29-May-2023
Date of Acceptance	01-Jun-2023
Date of Web Publication	27-Jul-2023

Correspondence Address:
Juan Jose Castro-Barandica
Centro Oftalmológico Virgilio Galvis, FOSCAL Internacional, Calle 157#20 – 94, Torre C, Consultorio 301, Cañaveral, Floridablanca, Santander
Colombia

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/pajo.pajo_34_23

Abstract

Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare inflammatory disorder affecting renal and ocular systems. Certain associations have been made with systemic conditions such as autoimmune diseases, infections, and even medications. We present the case of a 16-year-old male patient who presented to our service with bilateral uveitis and urinary symptoms, associated with proteinuria, glycosuria, increase in serum creatinine and beta-2 microglobulin in urine considering TINU as the main differential diagnosis. Antibiotics were considered a possible trigger in this patient. He presented an adequate response to systemic and topical steroids and systemic immunomodulators. Renal biopsy results reported interstitial tubulonephritis. TINU syndrome is a rare autoimmune condition, mainly seen in younger patients. Multiple triggers have been associated. Renal compromise usually resolves spontaneously with a relatively rare risk of incomplete recovery as well as uveal compromise. However, early diagnosis and multidisciplinary management is fundamental in these patients.

Keywords: Anterior uveitis, Autoimmune, Tubulointerstitial nephritis, Uveitis

How to cite this article:
Castro-Barandica JJ, Esmeral-Ordonez DA, Quintero-Lizcano K, Rangel CM. Tubulointerstitial nephritis with uveitis in a young male patient. Pan Am J Ophthalmol 2023;5:27

How to cite this URL:
Castro-Barandica JJ, Esmeral-Ordonez DA, Quintero-Lizcano K, Rangel CM. Tubulointerstitial nephritis with uveitis in a young male patient. Pan Am J Ophthalmol [serial online] 2023 [cited 2023 Sep 27];5:27. Available from: https://www.thepajo.org/text.asp?2023/5/1/27/382404

Introduction

Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare inflammatory disorder affecting renal and ocular systems. First described by Dobrin in 1975, it consists of an acute case of tubulointerstitial nephritis (TIN) along with uveitis with no specific systemic etiology.^[1] Certain associations have been made with systemic conditions such as autoimmune diseases, infections, and even medications.^[2] It is mainly seen in a young population (children and young adults), being the female sex more affected; lately and although being rare, it has been documented more in middle-aged patients.^[3] TINU has been reported to be responsible for approximately 32% of children under 20 years old with sudden onset bilateral anterior uveitis.^[4]

Most patients present with bilateral anterior uveitis characterized by red eye, blurry vision, pain, and photophobia among others. Regarding the renal system, TIN is caused by inflammatory cells infiltrating parenchyma and generating tubular damage, accounting for 15% of all acute kidney injuries.^[3] These patients will present with flu-like symptoms such as general malaise, headache, and abdominal pain. It is important to note that the symptoms present in an asynchronous manner, with TIN symptoms usually presenting first followed by anterior uveitis symptoms; other presentations such as posterior uveitis or panuveitis can be present in up to 20% of patients.^[1],[4],[5] Regarding physiopathology, the exact mechanism is unknown. Accepted hypotheses consider an immune-mediated reaction triggered by environmental conditions in genetically susceptible children.^[4],[5]

The diagnosis of TINU must be made by first ruling out other pathologies that can cause both nephritis and uveitis. Systemic conditions such as sarcoidosis, lupus, Sjögren's syndrome, Behcet's disease, tuberculosis, or syphilis can cause renal and ocular inflammation.^[4] Definitive diagnosis needs a renal biopsy for histopathological studies.^[1],[4] The most used classification for the diagnosis was established by Mandeville et al. in 2001.^[6] Recently, the Standardization of Uveitis Nomenclature (SUN) group has published a new classification reporting low misclassification rates.^[7] Due to TINU being a rare pathology, a specific schematic treatment has not been established; the main approach consists of topical steroids and cycloplegics for anterior uveitis and systemic steroids for renal compromise.^[4],[5] This pathology has few reported cases in the literature, and it is even less common in Colombia making it interesting to report.

Case Report

A 16-year-old male, previously healthy, presented with a 2-month history of redness, pain, and photophobia in the right eye. Initially, he consulted an external ophthalmologist who diagnosed anterior uveitis in the right eye and started management with topical prednisone four times a day and tropicamide twice a day. A month later, the symptoms increased and became bilateral. He reconsulted and he was referred to a fourth-level medical center. When he arrived at our center, internal medicine admitted him due to renal compromise (foamy urine symptoms). They requested kidney function tests and ordered an assessment by our ophthalmology service, given the history of bilateral anterior uveitis. When evaluated by us, the patient no longer presented ocular pain but persisted with blurry vision in the right eye and poor pupillary dilation. On physical examination, we found a best-corrected visual acuity 20/25 for the right eye and 20/20 for the left eye. Slit-lamp examination of his right eye showed fine keratic precipitates, Tyndall 2+ flare 2+, hyporeactive dyscoria with posterior synechiae in 360°, an inflammatory membrane, and a slightly opaque lens [Figure 1]a and [Figure 1]c. Regarding the fundoscopy, we found vitreous cellularity [Figure 1]g and [Figure 1]h, a well-defined hyperemic disc, a cup-disc relation of 0.4, healthy macula, applied retina in 360°, and two inferior snowball lesions. The findings in his left eye consist of anterior chamber inflammation with Tyndall 3+, pigment on the anterior capsule of the lens [Figure 1]b and [Figure 1]d, and a normal fundoscopy [Figure 1]i and [Figure 1]j. The results of the macular optical coherence tomography (OCT) correspond with the clinical findings reported previously with a vitreous cellularity and hyperreflective spots on the internal limiting membrane along with thickened choroid [Figure 1]g. Fluorescein angiography showed late disc hyperfluorescence in both eyes [Figure 1]e and [Figure 1]f. With the report of proteinuria and glycosuria in the urinalysis and an increase in serum creatinine by 1.5 mg/dL, our diagnostic impression was TINU or vasculitis, for which we requested 24-hour urine creatinine clearance, beta-2 microglobulin in urine; renal ultrasound, liver function, and a complete blood count amongst others. The abnormal laboratory results were proteinuria of 504 mg/24 h, a complete blood count that showed hypochromic normocytic anemia, alanine aminotransferase (ALT-GPT) of 100 u/L, beta-2 microglobulin in urine: 13.74 μg/mL (normal values: 0–0.3 μg/mL) and the ultrasound which showed slight changes in the echogenicity of the renal cortex, a right interpolar renal cortical scar. Results for antinuclear antibodies, antineutrophil cytoplasmic antibodies (C and P) were negative, ruling out systemic lupus erythematosus and vasculitis. During reinterrogation, the patient mentioned that he had received management for Helicobacter pylori 4 months ago with clarithromycin, amoxicillin, and esomeprazole. Considering the results of laboratory analysis and clinical findings, the patient is considered to have definite TINU syndrome based on the criteria of Mandeville et al.^[6] Ophthalmology indicated management with topical prednisolone 1% 1 drop every hour in both eyes, ophthalmic ointment of tobramycin and dexamethasone at night in both eyes to guarantee the availability of corticosteroid, and mydriatic management with tropicamide 1% 1 drop every 8 h in both eyes. Internal medicine prescribed oral prednisolone 50 mg/day (registered weight of 56 kg). With posterior improvement of renal function and improvement of anterior chamber inflammation, the patient is discharged with an order for ambulatory follow-up by pediatric nephrology and uveitis. Pediatric nephrology requested renal biopsy and changed management to oral azathioprine 50 mg every 12 h, oral prednisolone 10 mg daily, and calcitriol plus Vitamin D daily. Ophthalmology decreased progressively topical management. The renal biopsy reported diffuse interstitial inflammatory lymphocyte infiltrates with no fibrosis along with a nonnephrotic proteinuria that is compatible with a moderate TIN. At the moment, the patient no longer requires topical management.

Figure 1: (a) Anterior segment photography of the right eye showing dyscoria associated with posterior synechiae in 360° and an inflammatory membrane (arrow). (b) Anterior segment photography of the right eye showing conjunctival hyperemia, mydriasis, and pigment in the anterior capsule of the lens. (c) Right eye anterior segment optical coherence tomography (OCT) showing posterior synechiae at the defined level captured, with the rest of the findings under normal parameters. (d) Left eye anterior segment OCT under pharmacologic mydriasis, without alterations. (e and f) Fluorescein angiography showing late disc hyperfluorescence in both eyes without other alterations as shown by the arrows. (g) Right eye macular OCT with vitreous cellularity (circle) along with multiple parafoveal hyperreflections on the internal limiting membrane (*) and thickened choroid (rectangle). Right (h) and left (j) eye fundus photography without vascular or parenchymal lesions. (i) Left eye macular OCT without pathologic findings

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Discussion

In order to classify TINU, the Mandeville criteria categorize the patient as definite, possible, or probable TINU using a probabilistic approach considering certain defining criteria both for TIN and for uveitis.^[6] The latest classification published by the SUN group has been able to provide a simpler and more practical approach to the diagnosis along with low misclassification rates. It differs from the Mandeville classification due to simpler criteria and the elimination of possible and probable TINU concepts along with unspecific characteristics of the clinical presentation. Furthermore, they include the use of urinary beta-2 microglobulin in cases where renal biopsy is not possible for definite diagnosis.^[7]

Although initially TINU was thought to be an illness with preference for the female sex and considering our male patient, literature has identified it as a weak association.^[3],[4] Furthermore, it has been mainly described in children and young adults.^[5] Interestingly, cases of older patients such as the 62-year-old female patient reported by Aguilar et al. have been made, noticing a larger amount of presentation in an older population than initially reported.^[1],[8]

The exact physiopathology mechanism is unknown. Accepted hypotheses consider an immune-mediated reaction triggered by environmental conditions in genetically susceptible children.^[4],[5] Involvement of both cellular and humoral immunities has been studied. From a cellular immunity stance, changes in human leukocyte antigen (HLA) Class II alleles and a similar antigen between ocular and renal systems might explain the inflammatory reaction. On the other hand, humoral immunity is related due to the presence of autoantibodies against a modified C-reactive protein found in both kidneys and eyes. The causation of these findings is yet to be proven or labeled as epiphenomena.^[4]

As possible triggers, the use of certain medications such as nonsteroidal anti-inflammatory drugs and antibiotics has been identified as having a potential relation.^[9] In the case of this patient, the main risk factor we consider could have acted as a trigger for the inflammatory process and initiating TINU was the use of two antibiotics for a H. pylori infection as we mentioned initially.

TINU syndrome is a rare autoimmune condition, mainly seen in younger patients and mostly linked to female sex presenting with TIN and uveitis (primarily anterior) in an asynchronous manner. Multiple triggers have been associated, and genetic predisposition markers such as HLA Class II alleles have been studied and identified. Its management must be done in a multidisciplinary approach with internal medicine handling TIN and ophthalmology treating uveitis essentially with systemic and topical steroids. Renal compromise usually resolves spontaneously with a relatively rare risk of incomplete recovery. Uveal compromise tends to respond adequately but must be recognized quickly because prolonged inflammation leads to a higher risk of permanent visual impairment. It is important to have a high-suspicion approach to these kinds of patients due to a great risk of this condition being underdiagnosed.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the legal guardian has given consent for images and other clinical information to be reported in the journal. The guardian understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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