Chest computerized tomography in the evaluation of uveitis in elderly women

doi:10.1016/S0002-9394(02)01333-8

American Journal of Ophthalmology

Volume 133, Issue 4, April 2002, Pages 499-505

https://doi.org/10.1016/S0002-9394(02)01333-8 Get rights and content

Abstract

PURPOSE: To describe the usefulness of chest computerized tomography (CT) in the evaluation of uveitis in elderly women and the clinical characteristics of patients with an abnormal chest CT scan.

DESIGN: Prospective noncomparative case series.

METHODS: We evaluated 30 elderly women, aged 61–83 years, with chronic iritis, vitritis, or choroiditis and with no definitive cause for their uveitis. All patients underwent a battery of diagnostic laboratory studies and chest CT.

RESULTS: The diagnostic examination in most patients included serum angiotensin converting enzyme level, serum lysozyme, rapid plasma reagin level, fluorescent treponemal antibody-absorption test, purified protein derivative skin test, and chest x-rays. Chest CT performed on all patients showed parenchymal, mediastinal, and/or hilar adenopathy in 17 patients (57%). Histopathologic confirmation of sarcoidosis with noncaseating granulomas in the biopsy specimens was obtained in 14 patients: eight by mediastinoscopy, two by bronchoscopy, two by conjunctival biopsy, one by nasal biopsy, and one by vitreous biopsy.

CONCLUSIONS: Chest CT can be useful in elderly female patients with chronic uveitis for identifying mediastinal lymphadenopathy and other lesions suggestive of sarcoidosis, as well as to help guide tissue confirmation and to rule out other diagnoses including lymphoma.

Section snippets

Methods

Fifty-two patients (44 women, 8 men) underwent chest CT as part of their laboratory evaluation between June 1997–June 2001 in the Uveitis Department of the Cole Eye Institute. Thirty-two patients (29 women, 3 men) were over age 60. This series includes all patients who met the following inclusion criteria: chronic uveitis defined as chronic iridocyclitis, vitritis, or choroiditis, age greater than 60 years, female gender, and no definitive cause for the uveitis. Also included are our two

Results

Twenty-eight patients with chronic uveitis over the age of 60 years were prospectively evaluated and combined with our two previously reported patients (median 72 ± 5.2 years; range 61–83 years; Table 1). 4 Characteristics of all 30 patients are listed in Table 1. All patients were elderly women and each had received a careful clinical history and complete ophthalmologic examination. Twenty-five (83%) patients were Caucasian, three (10%) were African American, and two (7%) were Indian. Six

Discussion

Although uveitis presenting for the first time in elderly patients is well recognized, the final diagnosis is usually idiopathic, making treatment problematic.2 Despite undergoing a standard battery of diagnostic tests, the underlying cause is often not discovered. To complicate matters further, several of the possible diagnoses can have overlapping test results.

All patients in our study underwent a battery of tests; however, in 27 patients, a diagnosis was not evident before the chest CT scans

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Cited by (88)

Systemic Associations of Sarcoid Uveitis: Correlation With Uveitis Phenotype and Ethnicity
2021, American Journal of Ophthalmology
Citation Excerpt :
The frequency and seriousness of associated systemic associations of sarcoidosis draws attention to the importance of making the diagnosis in disease previously deemed “idiopathic.” High-resolution CT chest offers higher sensitivity for sarcoid lung involvement,9 and a study of 30 older female subjects previously described as “idiopathic” uveitis observed CT abnormalities in 17, with sarcoidosis identified on biopsy in 14 (46.7%).27 Cardiac disease may occur with normal serum angiotensin-converting enzyme levels and in the absence of associated lung disease.28
To examine systemic associations of sarcoid uveitis and association with uveitis clinical phenotype and ethnicity.
Retrospective cross-sectional study.
A total of 362 subjects with definite or presumed sarcoid uveitis from Moorfields Eye Hospital, Royal Victorian Eye and Ear, and Auckland District Health Board.
Data were collected from the review of clinical notes, imaging, and investigations. Sarcoidosis was diagnosed in accordance with the International Workshop on Ocular Sarcoidosis guidelines.
Diagnosis of associated systemic disease secondary to sarcoidosis.
A total of 362 subjects with sarcoid uveitis were identified. Median age was 46 years, and 226 (62.4%) were female. Granulomatous anterior uveitis (47.8%), intermediate uveitis with snowballs (46.4%), and multifocal choroiditis (43.1%) were the most frequent clinical presentations, and disease was bilateral in 313 (86.5%). Periphlebitis was observed in 21.0%, and solitary optic nerve or choroidal granuloma in 11.3%. Lung parenchymal disease was diagnosed in 200 subjects (55.2%), cutaneous sarcoid in 98 (27.1%), sarcoid arthritis in 57 (15.7%), liver involvement in 21 (5.8%), neurosarcoid in 49 (13.5%), and cardiac sarcoid in 16 subjects (4.4%). Subjects with cardiac sarcoid were less likely to have granulomatous anterior uveitis (P = .017). Caucasian subjects were older at presentation (48 vs 41 years; P = .009), had less granulomatous anterior uveitis (26.4% vs 51.7%; P < .001), and were less likely to present with cutaneous involvement (23.1% vs 35.4%; P = .040).
Ophthalmologists need to be aware of the systemic associations of sarcoid uveitis, in particular potentially life-threatening complications such as cardiac sarcoidosis. Differences observed in uveitis phenotype and between ethnicities require further investigation.
Revising the Diagnosis of Idiopathic Uveitis by Peripheral Blood Transcriptomics
2021, American Journal of Ophthalmology
Citation Excerpt :
Table 4 describes these 11 subjects in more detail. Table 4 relies in part on the consistent phenotype of uveitis that is characteristic of ankylosing spondylitis,36 the relatively frequent finding of disc edema accompanying the bilateral anterior uveitis of TINU,37 and the >50% likelihood that a female ≥61 years of age with idiopathic uveitis will have sarcoidosis.38 In addition, 1 subject had microscopic colitis and retinal vasculitis.
To test the hypothesis that idiopathic uveitis can be categorized into subtypes based on gene expression from blood.
Case control study.
We applied RNA-Seq to peripheral blood from patients with uveitis associated with 1 of 4 systemic diseases, including axial spondyloarthritis (n = 17), sarcoidosis (n = 13), inflammatory bowel disease (n = 12), tubulo-interstitial nephritis with uveitis (n = 10), or idiopathic uveitis (n = 38) as well as 18 healthy control subjects evaluated predominantly at Oregon Health and Science University. A high-dimensional negative binomial regression model implemented in the edgeR R package compared each disease group with the control subjects. The 20 most distinctive genes for each diagnosis were extracted. Of 80 genes, there were 75 unique genes. A classification algorithm was developed by fitting a gradient boosting tree with 5-fold cross-validation. Messenger RNA from subjects with idiopathic uveitis were analyzed to see if any fit clinically and by gene expression pattern with one of the diagnosable entities.
For uveitis associated with a diagnosable systemic disease, gene expression profiling achieved an overall accuracy of 85% (balanced average of sensitivity plus specificity, P < .001). Although most patients with idiopathic uveitis presumably have none of these 4 associated systemic diseases, gene expression profiles helped to reclassify 11 of 38 subjects.
Peripheral blood gene expression profiling is a potential adjunct in accurate differential diagnosis of the cause of uveitis. Validation of these results and characterization of the gene expression profile from additional discrete diagnoses could enhance the value of these observations.
Utility of Screening Investigations for Systemic Sarcoidosis in Undifferentiated Uveitis
2019, American Journal of Ophthalmology
To establish the utility of screening investigations for systemic sarcoidosis in a large cohort of subjects presenting with undifferentiated uveitis.
Evaluation of a diagnostic test.
Retrospective review of consecutive subjects presenting to Auckland District Health Board with undifferentiated uveitis who underwent screening for sarcoidosis.
Seven hundred nine subjects were included in the study. Systemic sarcoidosis was identified in 10.7%, and was biopsy proven in 43.4%. Sensitivity and specificity were highest for computed tomography (CT) of the chest (98.0% and 100%) and for chest radiograph (CXR; 57.6% and 100%). Serum ACE was elevated in 43 subjects, of whom 29 (67.4%) had systemic sarcoidosis. Sensitivity of serum ACE was 38.2% and specificity 97.8%, with an area under the curve (AUC) of 0.801. Lymphopenia was observed in 40 subjects, of whom 18 (45.0%) had systemic sarcoidosis. Sensitivity of lymphopenia was 23.7%, with specificity 96.5% and AUC 0.761. All subjects with elevated ACE and lymphopenia had evidence of systemic sarcoidosis. Biopsy was performed in 50 subjects, positive in 33 subjects (66.0%). Mediastinal biopsy was the most frequent (26 subjects). Skin biopsy was performed in 11 subjects (positive in 8). Only 1 subject with a positive skin biopsy had elevated ACE, lymphopenia, and bihilar lymphadenopathy on CXR.
Sensitivity and specificity were highest for chest CT. Although CXR had excellent specificity, CXR screening alone would still miss many cases of sarcoidosis. Combined elevated ACE and lymphopenia were strongly suggestive of systemic sarcoidosis, and biopsy of skin lesions may detect patients otherwise missed by routine screening tests.
Reclassifying Idiopathic Uveitis: Lessons From a Tertiary Uveitis Center
2019, American Journal of Ophthalmology
Idiopathic uveitis is frequently the most common diagnosis in series from uveitis clinics. This study sought to determine the percentage of patients initially diagnosed as idiopathic, noninfectious uveitis referred to a tertiary uveitis center who were subsequently found to have an identifiable cause of uveitis.
Retrospective case series.
We performed a computerized database analysis of 179 consecutive patients who were referred to our practice with the diagnosis of idiopathic, noninfectious uveitis between 2008 and 2016. Patients were evaluated by a thorough history and ophthalmic examination with selected laboratory testing targeted by clues from the history and examination. Standardization of Uveitis Nomenclature (SUN) criteria were used to better assess different types of uveitis.
Fifty-two out of 179 (29.0%) patients initially diagnosed with idiopathic uveitis were subsequently diagnosed with an underlying condition. Among patients referred with a diagnosis of idiopathic disease, female patients were most commonly affected (121/179; 67.6%). Among subsequent diagnoses, sarcoidosis was the most common (19/52 or 36.5%), followed by HLA-B27-associated uveitis (11/52, 21.1%), infectious uveitis (6/52, 11.5%), tubulointerstitial nephritis with uveitis (6/52, 11.5%), and juvenile idiopathic uveitis (4/52, 7.7%). Other diagnosable conditions included Behçet disease, multifocal choroiditis, panuveitis, Crohn disease, multiple sclerosis, and relapsing polychondritis. An underlying condition was not found in 127 of 179 (70.9%) patients.
We report that 29% of patients referred to our tertiary uveitis center diagnosed as “idiopathic” had an associated identifiable cause. Identifying an underlying condition associated with uveitis could be potentially lifesaving for some illnesses (eg, sarcoidosis with cardiac involvement) and is critical to management (eg, infection). Although we were able to use limited testing to classify many patients who had been previously incorrectly labeled with idiopathic uveitis, idiopathic uveitis remains the most common diagnosis in our uveitis clinic.
Serum Angiotensin-Converting Enzyme Has a High Negative Predictive Value in the Investigation for Systemic Sarcoidosis
2018, American Journal of Ophthalmology
Citation Excerpt :
Kaiser and associates examined the role of chest CT in 30 older female subjects (aged 61–83 years) previously deemed “idiopathic.” CXR was abnormal in 8 subjects and chest CT abnormal in 17, with sarcoid diagnosed on biopsy in 14 subjects.25 The value of making a diagnosis in an otherwise asymptomatic subject must be weighed against the risk of radiation exposure and the cost of further investigation.
To examine whether measurement of serum angiotensin-converting enzyme (ACE) is useful in diagnosing sarcoidosis in undifferentiated uveitis.
Evaluation of a diagnostic test.
Data collection was performed from 1035 consecutive subjects presenting with uveitis to Moorfields Eye Hospital undergoing measurement of serum ACE as part of baseline investigations for underlying systemic disease. The main outcome measures were sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of elevated serum ACE.
Mean age of the sample was 41.7 years and 56.1% of subjects were female. Sarcoidosis was the underlying cause for the uveitis in 110 subjects (10.6%) and was more common in adults, female subjects, black subjects, and subjects with intermediate uveitis or panuveitis. ACE was elevated in 196 subjects (18.9%) and elevated levels were observed in 85 subjects eventually diagnosed with underlying sarcoidosis (true positive 77.3%) and in 111 subjects with an alternate diagnosis (false positive 12.0%). In adult subjects, sensitivity of serum ACE was 78.1%, specificity 90.0%, and PPV 43.6%, but the NPV was 97.0%. The test performed well, with area under curve (AUC) 0.897 (95% confidence interval [CI] 0.854–0.941). Serum ACE performed less well in distinguishing sarcoid uveitis in pediatric subjects, with sensitivity 60.0%, specificity 78.5%, and PPV 10.0%, but again NPV was high at 96.9% and AUC was 0.828 (95% CI 0.571–1.000).
Serum ACE had a very high negative predictive value for sarcoid uveitis, eliminating the need for further screening tests in subjects with normal serum ACE, unless clinical suspicion was high.
Uveitis: Diagnostic work-up. Recommendations from an expert committee
2018, Revue de Medecine Interne
La démarche diagnostique au cours des uvéites n’est pas standardisée. Elle doit prendre en compte l’épidémiologie des uvéites, cibler les affections les plus sévères et/ou les plus fréquentes, et/ou susceptibles de bénéficier d’un traitement spécifique. Ce travail a été réalisé afin de proposer des recommandations pour le diagnostic des uvéites.
Les recommandations ont été établies par un groupe de 15 experts, internistes, ophtalmologistes et rhumatologues, à partir d’une revue de la littérature et de l’étude ULISSE qui est la première étude prospective à avoir évalué une stratégie diagnostique pour les uvéites. Sont exclues de ces recommandations les uvéites de l’enfant, de l’immunodéprimé, les vascularites rétiniennes sévères et les entités purement ophtalmologiques.
Le bilan paraclinique doit en premier lieu être orienté par les éléments de l’interrogatoire et les signes cliniques. La sérologie syphilitique est la seule sérologie systématique. Les sérologies toxoplasmose et herpès virus seront réalisées en cas de suspicion diagnostique et avant tout prélèvement oculaire. En l’absence de cause identifiée, nous proposons un bilan paraclinique orienté par les caractéristiques de l’uvéite. Il comporte un typage HLA B27 (uvéite antérieure aiguë unilatérale non granulomateuse), un dosage de l’enzyme de conversion de l’angiotensine, un test IFN-γ release assay (IGRA) et un scanner thoracique (uvéite chronique), une IRM cérébrale associée à une ponction de chambre antérieure avec dosage de l’interleukine 10 (uvéite intermédiaire ou postérieure après 40 ans). La rentabilité d’examens complémentaires non orientés est très faible.
Nous proposons une stratégie diagnostique pour les uvéites. Les recommandations doivent être actualisées régulièrement. La place des examens les plus invasifs reste à définir.
Diagnostic work-up of uveitis involves many uncertainties. Search for an etiology should take into account the epidemiology of uveitis and focus on the most severe diseases or those, which can be treated. This work was undertaken to establish recommendations for the diagnosis work-up of uveitis.
Recommendations were developed by a multidisciplinary panel of 15 experts, including internists, ophthalmologists and a rheumatologist and are based on a review of the literature with regard to effectiveness of investigations and the results of the ULISSE study, which is the first prospective study assessing the efficiency of a standardized strategy for the etiological diagnosis of uveitis. Children, immunocompromised patients, severe retinal vasculitis and specific ophthalmological entities are excluded from these recommendations.
Investigations should be first guided by the history and physical examination. Serological screening for syphilis is the only test appropriate in all forms of uveitis. If no diagnosis is made after this stage, we propose investigations guided by the anatomic characteristics of uveitis. It includes HLA B27 testing (in unilateral acute anterior non-granulomatous uveitis), serum angiotensin converting enzyme, interferon-gamma release assay and chest CT (chronic uveitis), cerebral MRI and anterior chamber tap with IL10 analysis (intermediate or posterior uveitis in patients over 40 years). Investigations ordered in the absence of orientation are almost always unhelpful.
We propose a strategy for the etiologic diagnosis of uveitis. The recommendations should be updated regularly. The efficiency of more invasive investigations has yet to be evaluated.

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Original articleChest computerized tomography in the evaluation of uveitis in elderly women

Abstract

Section snippets

Methods

Results

Discussion

Ophthalmology

Am J Ophthalmol

Surv Ophthalmol

Mayo Clinic Proc

Ophthalmology

Ann Thorac Surg

Ophthalmology

Chest

Am J Ophthalmol

Ophthalmology

Original article
Chest computerized tomography in the evaluation of uveitis in elderly women