Clinical Utility of 18F-FDG PET/CT in the Work-up of Children with Uveitis.

PURPOSE: To evaluate 18F-fluorodeoxyglucose Positron Emission Tomography/ultra low dose Computed Tomography (18F-FDG PET/ ULD CT) in the work-up of pediatric uveitis. METHODS: Retrospective study of 12 children followed for uveitis who underwent whole body 18F-FDG PET/ULD CT between 2011 and 2019. RESULTS: The average age of the patients was 11 years. A total of 100% of patients presented with bilateral uveitis, 50% had panuveitis and 92% had various choroidal involvement. Relevant information for diagnosis was provided in four patients. 5/12 had an abnormal 18F-FDG uptake. Of these, three patients had pathognomonic images of active granulomatous diseases. Three patients underwent PET CT-guided biopsies of which two were positive for sarcoidosis. CONCLUSION: 18F-FDG PET/CT provided important information for final diagnosis in approximately 30% (4/12) of pediatric patients with bilateral uveitis. Whole body FDG PET/ULD CT can contribute to the final diagnosis thanks to pathognomonic image of active granulomatous disease and/or by indicating metabolically active site of biopsy that would not be visualized in thorax CT.

Neurosyphilis cerebrospinal fluid findings in patients with ocular syphilis.

Purpose: To evaluate neurosyphilis cerebrospinal fluid (CSF) findings and initial ophthalmic manifestations in patients with syphilitic uveitis.Methods: We retrospectively reviewed the records of CSF analysis of 14 patients with syphilitic uveitis with treponemal analysis - chemiluminescent immunoassay and TPHA- and non-treponemal analysis - Rapid Plasma Reagin test - RPR.Results: 86% were males and 43% HIV+. Ocular signs of syphilis lead to the diagnosis of syphilis in 78% of patients. Typical syphilitic uveitis presentations included: acute syphilitic posterior placoid chorioretinitis (50% of patients), retinitis (21% of patients) and punctate inner retinitis (7% of patients). 57% of patients had definite neurosyphilis by the CDC criteria, while 71% had CSF abnormalities suggestive of central nervous system involvement.Conclusion: Based on international guidelines, the frequent CSF abnormalities found in syphilitic uveitis patient supports the diagnosis of neurosyphilis in a majority of patients.

Broncho-alveolar lavage (BAL) for the diagnosis of sarcoidosic uveitis.

PURPOSE: To evaluate the use of BAL for the diagnosis of sarcoidosic uveitis. METHODS: Retrospective study of 109 consecutive patients with uveitis and minimum 2 signs of ocular sarcoidosis who had a BAL and chest imaging. BAL(+) was defined as an alveolar (a) lymphocytosis (L) aL > 15% with aCD4/CD8 > 3.5. Serum angiotensin converting enzyme (sACE), tuberculin skin test and gallium scan were tested in 83, 95 and 24 patients. RESULTS: BAL was + in 26.6% of patients (86.2% females, mean age 50.8y) with mean aL = 46.8% and mean aCD4/CD8 = 8.5 which significantly differed form BAL(-) patients: 62.5% females, p < 0.02, mean age 43.6y, p < 0.05, mean aL = 17.2%, p < 0.001 and mean aCD4/CD8 = 1.8, p < 0.001. BAL(+) patients had 31% of bilateral hilar adenopathy (BHL(+)), and 59.1% of elevated sACE which significantly differed form BAL(-) patients: 8.8%, p = < 0.01 and 14.8% p < 0.001. CONCLUSION: Our findings suggest that BAL have a high diagnostic value and might be a useful additional test for the diagnosis of sarcoidosic uveitis, even with normal chest imaging.

Mycophenolate mofetil monotherapy in the management of paediatric uveitis.

PURPOSE: To evaluate effectiveness and safety of mycophenolate mofetil (MMF) monotherapy in paediatric autoimmune uveitis. METHODS: We reviewed medical records of patients, 18 years of age or younger, with autoimmune uveitis treated with MMF at our practice from 2005 to 2009. The dose and duration of MMF therapy, inflammation status, visual acuity, previous immunomodulatory therapies, and adverse effects were recorded. In addition, the following subgroups were defined: (1) Durable Disease Control: patients whose uveitis remained quiescent for at least 2 years on MMF monotherapy, with no more than two flare-ups successfully treated with an increase in MMF dosage and/or a short course (<1 month) of corticosteroids; (2) Short-term Inflammation Control: patients whose uveitis remained quiescent for less than 2 years, with no more than one flare-up successfully treated with an increase in MMF dosage and/or a short course of corticosteroids, or who initially achieved inflammation control but discontinued MMF because of significant adverse effects. RESULTS: A total of 38 out of 52 patients (73.1%) obtained inflammation control following 2 months of MMF monotherapy, achieving ≤ 0.5+ grading in anterior chamber cell/flare and vitreous haze. In the cross-sectional analysis, 25 patients (48.1%) met the criteria for Durable Disease Control, and 13 others (25.0%) qualified for Short-term Inflammation Control. Visual acuity remained stable or improved in 94.2% of the study population. Six patients (11.5%) discontinued MMF because of significant adverse effects, the most common of which was gastrointestinal disturbances. CONCLUSION: MMF monotherapy appears to be an effective and safe treatment in paediatric autoimmune uveitis.

Early onset of chemotherapy can reduce the incidence of ATRA syndrome in newly diagnosed acute promyelocytic leukemia (APL) with low white blood cell counts: results from APL 93 trial.

Treatment combining ATRA and chemotherapy (CT) has improved the outcome of APL patients, by comparison with CT alone. ATRA syndrome is a life-threatening complication of ATRA treatment whose prophylaxis remains somewhat controversial. In APL93 trial, newly diagnosed APL patients CT) and ATRA with early addition of CT, on day 3 of ATRA treatment (ATRA + CT). The incidence of ATRA syndrome in the ATRA --> CT arm was 18% (22/122) as compared to 9.2% (17/184) in the ATRA + CT arm (P = 0.035). In the ATRA --> CT arm, three (2.5%) patients died from ATRA syndrome, as compared to one (0.5%) in the ATRA + CT group. Early addition of chemotherapy to ATRA in newly diagnosed APL with low WBC counts significantly reduced the incidence of ATRA syndrome.

Incidence, clinical features, and outcome of all trans-retinoic acid syndrome in 413 cases of newly diagnosed acute promyelocytic leukemia. The European APL Group.

All trans-retinoic acid (ATRA) syndrome is a life-threatening complication of uncertain pathogenesis that can occur during the treatment of acute promyelocytic leukemia (APL) by ATRA. Since its initial description, however, no large series of ATRA syndrome has been reported in detail. We analyzed cases of ATRA syndrome observed in an ongoing European trial of treatment of newly diagnosed APL. In this trial, patients 65 years of age or less with an initial white blood cell count (WBC) less than 5,000/microL were initially randomized between ATRA followed by chemotherapy (CT) (ATRA-->CT group) or ATRA with CT started on day 3; patients with WBC greater than 5,000/microL received ATRA and CT from day 1; patients aged 66 to 75 received ATRA-->CT. In patients with initial WBC less than 5, 000/microL and allocated to ATRA-->CT, CT was rapidly added if WBC was greater than 6,000, 10,000, 15,000/microL by days 5, 10, and 15 of ATRA treatment. A total of 64 (15%) of the 413 patients included in this trial experienced ATRA syndrome during induction treatment. Clinical signs developed after a median of 7 days (range, 0 to 35 days). In two of them, they were in fact present before the onset of ATRA. In 11 patients, they occurred upon recovery from the phase of aplasia due to the addition of CT. Respiratory distress (89% of the patients), fever (81%), pulmonary infiltrates (81%), weight gain (50%), pleural effusion (47%), renal failure (39%), pericardial effusion (19%), cardiac failure (17%), and hypotension (12%) were the main clinical signs, and 63 of the 64 patients had at least three of them. Thirteen patients required mechanical ventilation and two dialysis. A total of 60 patients received CT in addition to ATRA as per protocol or based on increasing WBC; 58 also received high dose dexamethasone (DXM); ATRA was stopped when clinical signs developed in 30 patients. A total of 55 patients (86%) who experienced ATRA syndrome achieved complete remission (CR), as compared with 94% of patients who had no ATRA syndrome (P = .07) and nine (14%) died of ATRA syndrome (5 cases), sepsis (2 cases), leukemic resistance (1 patient), and central nervous system (CNS) bleeding (1 patient). None of the patients who achieved CR and received ATRA for maintenance had ATRA syndrome recurrence. No significant predictive factors of ATRA syndrome, including pretreatment WBC, could be found. Kaplan Meier estimates of relapse, event-free survival (EFS), and survival at 2 years were 32% +/- 10%, 63% +/- 8%, and 68% +/- 7% in patients who had ATRA syndrome as compared with 15% +/- 3%, 77% +/- 2%, and 80% +/- 2% in patients who had no ATRA syndrome (P = .05, P = .003, and P = .03), respectively. In a stepwise Cox model that also included pretreatment prognostic variables, ATRA syndrome remained predictive for EFS and survival. In conclusion, in this multicenter trial where CT was rapidly added to ATRA in case of high or increasing WBC counts and DXM generally also used at the earliest clinical sign, the incidence of ATRA syndrome was 15%, but ATRA syndrome was responsible for death in only 1.2% of the total number of patients treated. However, occurrence of ATRA syndrome was associated with lower EFS and survival.