Impact of systemic treatments on the course of HLA-B27-associated uveitis: A retrospective study of 101 patients.

PURPOSE: To investigate the efficacy and tolerance of systemic treatments for the prevention of HLA-B27-associated acute uveitis (AU) recurrence. METHODS: Retrospective review of patients with HLA-B27-associated uveitis followed in our tertiary center over a 15-year period. Systemic treatments were prescribed to patients with frequent (more than 2 flares per year) or severe uveitis, according to a step-up strategy. RESULTS: 101 patients (51.5% of men, 88.1% of white Europeans) with a median age of 37 years. AU was mostly recurrent (68.3%) and associated with spondyloarthritis (60.4%). After a median follow-up duration of 22 months (3-73), 37.6% of the patients have received systemic treatment. 88.5% of the patients have been treated with sulfasalazine (SSZ) for ophthalmologic purposes (23/26). Methotrexate (MTX) and anti-TNFα agents have been initiated for a rheumatologic indication in 81.8% (9/11) and 100% of the patients (13/13), respectively. The annual uveitis relapse rate significantly decreased on SSZ (0.37 recurrences/year versus baseline 2.46 recurrences/year; p<0.001) and MTX (1.54 recurrences/year versus 4.17/year; p = 0.008). Patients under ADA for ophthalmologic purposes (n = 2) did not experience any recurrence. CONCLUSION: We report an open-label strategy to prevent the recurrences of HLA-B27-associated AU. First-line sulfasalazine reduced uveitis relapses. The use of anti-TNFα agents for ophthalmologic purposes was unnecessary with rare exceptions.

Evaluating the cost-consequence of a standardized strategy for the etiological diagnosis of uveitis (ULISSE study).

MAIN OBJECTIVE: To prospectively assess the cost-consequence of a standardized diagnostic strategy as to compared to an open one for the etiological diagnosis of uveitis. DESIGN: This was a prospective, non-inferiority, multicentre, randomized controlled trial. METHODS: We included all consecutive patients with uveitis who had visited at least one of the Departments of Ophthalmology. In the standardized group, patients had a minimal work-up regardless of the type of uveitis (including evaluation of the CBC, ESR, C-reactive protein, tuberculin skin test, syphilis serology and chest X-ray). Depending on ophthalmological findings, further investigations could be performed. In the open strategy, ophthalmologists were free to order any kind of investigation. The main outcome was the mean cost per patient of each strategy. RESULTS: 903 uveitis patients were included from January, 2010 to May, 2013. The mean cost per patient of the standardized strategy was 182.97 euros [CI 95% (173.14; 192.80)], and the mean cost per patient of the open strategy was 251.75 euros [CI 95% (229.24; 274.25)]. Therefore, the mean cost per patient of the standardized strategy was significantly lower than the mean cost per patient of the open strategy (p<0.001). There were significantly fewer visits (p<0.001), fewer radiological procedures (p<0.004) and fewer laboratory investigations (p<0.001) in the standardized group. CONCLUSION: A standardized strategy is a cost-saving approach for the etiological diagnosis of uveitis.

18F-fluorodeoxyglucose positron emission tomography is useful for the diagnosis of intraocular sarcoidosis in patients with a normal CT scan.

AIM: To assess the usefulness of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET/CT) and the predictive factors for the diagnosis of sarcoidosis in patients with uveitis who have normal thoracic tomography. METHODS: We retrospectively reviewed 67 consecutive patients with uveitis of unknown aetiology or a suspected sarcoidosis. All patients with normal thoracic tomography underwent an 18F-FDG PET/CT, which was blindly reinterpreted. We then assessed the proportion of positive 18F-FDG PET/CT and the impact on the final aetiology, using Abad's criteria for the diagnosis of intraocular sarcoidosis. RESULTS: 19 of the 67 patients (28.4%) had mediastinal hypermetabolic foci on their 18F-FDG PET/CT consistent with sarcoidosis. It identified a biopsy site in two cases, which were consistent with sarcoidosis. At the end of the study, six patients (10%) had a proven sarcoidosis, six patients (9%) were considered as having a presumed sarcoidosis and 18 patients (26.9%) as having indeterminate sarcoidosis. 18F-FDG PET/CT enabled the diagnosis of presumed sarcoidosis in these six patients. An older age at diagnosis (p=0.004) and the presence of synechiae (p=0.02) were significantly related to an abnormal 18F-FDG PET/CT, with a trend for an elevated ACE (p=0.0993). We established a nomogram to estimate the probability of having positive findings on the 18F-FDG PET/CT according to different predictive factors. CONCLUSION: 18F-FDG PET/CT enabled the diagnosis of intraocular sarcoidosis even in patients with a normal CT scan. Older age at diagnosis, presence of synechiae and elevated ACE are associated with positive findings on 18F-FDG PET/CT consistent with sarcoidosis.

A Comparative Study of Characteristics and Outcomes of Patients with Proved and Suggested Sarcoid Uveitis Occurring after Ophthalmic Procedure.

PURPOSE: To describe patients with new onset sarcoid uveitis occurring after an ophthalmic procedure and compare them with patients with sarcoid uveitis without ocular procedure. METHODS: Retrospective analysis of case records from patients with postophthalmic procedure sarcoid uveitis seen at our institution between April 2004 and October 2016. Patients with a previous history of uveitis were not included. Each patient was randomly matched with four controls from our incident cohort of new onset sarcoid uveitis without ophthalmic procedure. RESULTS: We identified 11 patients (8.5%) from our incident cohort of sarcoid uveitis (n=130), who were all women, with a postophthalmic procedure uveitis (mostly after cataract surgery (36%)). These patients were older (69.7 vs 52.7 years) and presented more synechiae than controls. After a mean follow-up of 30 (3-60) months, there was no significant difference between the postprocedure and the control group with regard to demography, clinical presentation, disease course, treatment, and outcome. CONCLUSIONS: Sarcoid uveitis has similar characteristics in patients with new onset sarcoid uveitis after or without ophthalmic procedure. As a consequence, ophthalmic intervention should be seen as a potential trigger of latent sarcoidosis.

Impact of Brain Atrophy on Early Neurological Deterioration and Outcome in Severe Ischemic Stroke Treated by Intravenous Thrombolysis.

BACKGROUND: Brain atrophy has shown a protective effect on the risk of early neurological deterioration (END) related to malignant edema in patients with hemispheric infarction but could be deleterious on the outcome. AIMS: We aimed to assess whether brain atrophy has an impact on the risk of END and on the outcome in severe ischemic strokes after intravenous (IV) thrombolysis. METHODS: From a prospective thrombolysis registry, 137 patients who had a National Institutes of Health Stroke Scale (NIHSS) ≥15, MRI at admission, and IV thrombolysis were included. Relative cerebral volume was calculated. END was defined as a ≥2-points deterioration 72-h NIHSS and a good outcome as a modified Rankin Scale (mRS) ≤2 at 3 months. A multiple logistic regression analysis with a stepwise backward procedure was performed. RESULTS: END and a good outcome were observed, respectively, in 20 (14.6%) and 48 (37.5%) patients. In univariate analysis, predictors of END included age (p = 0.049), diabetes (p = 0.041), and parenchymal hemorrhage (p = 0.039). In multivariate analysis, age (p = 0.018) was significantly associated with END. Brain atrophy was not associated with END even in subgroup analysis according to the baseline infarct size. In univariate analysis, age (p = 0.003), prestroke mRS (p = 0.002), hypertension (p = 0.006), baseline NIHSS (p = 0.002), END (p = 0.002), proximal occlusion (p = 0.006), and recanalization at 24 h (p < 0.001) were associated with a good outcome. Only baseline NIHSS (p = 0.006) was associated with a good outcome after adjustment. CONCLUSIONS: We did not find any impact of brain atrophy on the risk of END and the outcome at 3 months in severe ischemic strokes after IV thrombolysis.

Contribution of diagnostic tests for the etiological assessment of uveitis, data from the ULISSE study (Uveitis: Clinical and medicoeconomic evaluation of a standardized strategy of the etiological diagnosis).

PURPOSE: ULISSE is the only study that prospectively assessed the efficiency of a standardized strategy, compared to an open strategy for the etiologic diagnosis of uveitis. Our aim was to evaluate the diagnostic yield of the tests prescribed in the ULISSE study to clarify their relevance. METHODS: ULISSE is a non-inferiority, prospective, multicenter and cluster randomized study. The standardized strategy is a two-steps strategy: in the first step, common standard tests were performed, and in the second step, tests were guided by the clinical and anatomic type of uveitis. We reported the relevance of the diagnostic tests used in the standardized strategy, as well as the profitability of the tests that were prescribed to more than twenty patients in each group. Based on diagnostic criteria, either an ophthalmologist, or an internist, established the profitability of a test by considering whether the test lead to a diagnosis or not. RESULTS: Among the 676 patients included (standardized 303; open 373), a diagnosis was made for 152 (50.4%) in the standardized group and 203 (54.4%) in the open group. The most common entities were HLA-B27 associated uveitis (22%), spondyloarthritis (11%), sarcoidosis (18%), tuberculosis (10.7%) and herpes virus infections (8.5%). Among the first step's systematic tests, tuberculin skin test was the most contributive investigation (17.1%), followed by chest X-ray (8.4%), C reactive protein and ESR (6.6% and 5.1%), complete blood count (2.2%) and VDRL (2.0%). The second step's most often contributive tests were: HLA B27 (56.3%), chest-CT (30.3%) and angiotensin converting enzyme (ACE) (16.5%). HLA B27 and ACE were significantly more contributive in the standardized group than in the open group. Immunological tests were never contributive. Among the free investigations, or among the investigations guided by clinical or paraclinical findings, the most often contributive tests were: Quantiferon® (24%), electrophoresis of serum protein (7.8%) and sacroiliac imagery (46.4%). Intracellular serologies (1.7%), serum calcium (2.1%) and hepatic tests (3.3%) were exceptionally contributive. Among the third intention tests, labial salivary gland biopsies were contributive in 17.9% of cases, but the profitability of other invasive investigations (anterior chamber tap, vitrectomy, bronchoscopy and lumbar puncture) or specialized imagery (18F-FDG PET, Brain MRI) could not be determined since these test were rarely performed. CONCLUSION: Only a few diagnostic tests are useful for the etiological assessment of uveitis. They are often cheap, simple, more often guided by the clinical findings, and lead to an etiological diagnosis in most patients. On the other hand, some tests are never or exceptionally contributive, such as immunological tests or intracellular serologies. Further studies are required to evaluate the profitability of third intention imagery and invasive investigations.

Randomized Controlled Trial Evaluating a Standardized Strategy for Uveitis Etiologic Diagnosis (ULISSE).

PURPOSE: To prospectively assess the efficiency of a standardized diagnostic approach, compared to an open strategy, for the etiologic diagnosis of uveitis. DESIGN: Noninferiority, prospective, multicenter, clustered randomized controlled trial. METHODS: Consecutive patients with uveitis, who visited 1 of the participating departments of ophthalmology, were included. In the standardized group, all patients had a minimal evaluation regardless of the type of uveitis (complete blood count, erythrocyte sedimentation rate, C-reactive protein, tuberculin skin test, syphilis serology, and chest radiograph) followed by more complex investigations according to ophthalmologic findings. In the open group, the ophthalmologist could order any type of investigation. Main outcome was the percentage of etiologic diagnoses at 6 months. RESULTS: Nine hundred and three patients with uveitis were included from January 2010 to May 2013 and the per-protocol population comprised 676 patients (open 373; standardized 303). Mean age at diagnosis was 46 years. Anatomic distribution of uveitis was as follows: anterior (60.8% and 72.3%, P = .0017), intermediate (11.7% and 12.3%, P = .8028), posterior (17.8% and 8.2%, P = .0004), and panuveitis (15.3% and 15.2%, P = .9596). An etiologic diagnosis was established in 54.4% of cases in the open group and 49.5% in the standardized group (P = .2029). The difference between both strategies (standardized minus open) was -4.9% (95% CI [-12.5%; 2.6%]). There were more investigations in the open group than in the standardized group (5371 vs 3759, P < .0001). CONCLUSION: The standardized strategy appears to be an efficient diagnostic approach for the etiologic diagnosis of uveitis, although its noninferiority cannot be proved.

Efficacy and safety of infliximab therapy in refractory upper respiratory tract sarcoidosis: experience from the STAT registry.

Background: Upper respiratory tract (URT) involvement in sarcoidosis may be refractory to corticosteroids and immunosuppressants. Whether TNF-antagonists are efficient and safe in such phenotype is unknown. Methods: STAT is a French national drug registry including patients presenting sarcoidosis treated with TNF alpha antagonists. All cases of biopsy-proven sinonasal and laryngeal sarcoidosis were extracted and retrospectively analyzed from July 2014 to July 2015. Results: Twelve patients presenting biopsy-proven sarcoidosis with URT involvement were included in the STAT registry. Infliximab appeared effective in decreasing URT symptoms, as assessed by a significant decrease of the e-POST (extra-pulmonary Physician Organ Severity Tool) (1.5 [0-2] vs 5 [1.5-5], p=0.03) and a corticosteroids-sparing effect (7.5mg per day [5-10] vs 17.5 mg per day [7.5-20], p=0.04) at the end of follow-up. Conclusions: TNF-antagonists may be an efficient treatment of refractory URT manifestations and should be discussed when prolonged or high dosages of corticosteroids despite immunosuppressive therapy are required. (Sarcoidosis Vasc Diffuse Lung Dis 2017; 34: 343-351).

Pituitary involvement in granulomatosis with polyangiitis: report of 9 patients and review of the literature.

Pituitary dysfunction is a rare manifestation of granulomatosis with polyangiitis (GPA) (Wegener). The main aim of this multicenter retrospective study was to describe the characteristics and outcomes of pituitary manifestations in patients with GPA included in the French Vasculitis Study Group database.Among the 819 GPA patients included in the database, 9 (1.1%) had pituitary involvement. The median age at diagnosis of GPA and pituitary involvement was 46 and 50.8 years, respectively. Pituitary involvement was present at onset of GPA in 1 case and occurred later in 8 patients after a median follow up of 58.5 months. When pituitary dysfunction occurred, 8 patients had active disease at other sites including ENT (n = 6), eye (n = 4), or central nervous system (n = 3) involvement. The most common hormonal dysfunctions were diabetes insipidus (n = 7) and hypogonadism (n = 7). Magnetic resonance imaging was abnormal in 7 patients. The most common lesions were an enlargement of the pituitary gland, thickening of the pituitary stalk, and loss of posterior hypersignal on T1-weighed images. All patients were treated with corticosteroid therapy and 8 patients received immunosuppressive agents for the pituitary involvement, including cyclophosphamide (n = 3), rituximab (n = 2), and methotrexate (n = 3). After a median follow-up of 9.2 years, GPA was in complete remission in 7 patients, but 8 patients were still under hormone replacement therapy. Among the 5 patients who had a subsequent MRI, 2 had complete resolution of pituitary lesions.By combining our study and the literature review, the frequency of hypogonadism and diabetes insipidus, among the patients with pituitary dysfunction, can be estimated at 78% and 71% respectively. Despite a high rate of systemic disease remission on maintenance therapy, 86% of the patients had persistent pituitary dysfunction. The patients who recovered from pituitary dysfunction had all been treated by cyclophosphamide.Pituitary disease in GPA occurs mostly several months or years after diagnosis. There is no correlation between hormonal, radiologic, and systemic outcome. Although immunosuppressive drugs improve the systemic disease, hormonal deficiencies usually persist. It is therefore important to shorten diagnostic delays and treat these patients early in the course of disease before irreversible damage occur.