A Comparison Study of Lymph Node Tuberculosis and Sarcoidosis Involvement to Facilitate Differential Diagnosis and to Establish a Predictive Score for Tuberculosis.

Background: Tuberculosis (TB) and sarcoidosis are two common granulomatous diseases involving lymph nodes. Differential diagnosis is not always easy because pathogen demonstration in tuberculosis is not always possible and both diseases share clinical, radiological and histological patterns. The aim of our study was to identify factors associated with each diagnosis and set up a predictive score for TB. Methods: All cases of lymph node tuberculosis and sarcoidosis were retrospectively reviewed. Demographics, clinical characteristics, laboratory and imaging data, and microbiological and histological results were collected and compared. Results: Among 441 patients screened, 192 patients were included in the final analysis. The multivariate analysis showed that weight loss, necrotic granuloma, normal serum lysozyme level and hypergammaglobulinemia were significantly associated with TB. A risk score of TB was built based on these variables and was able to discriminate TB versus sarcoidosis with an AUC of 0.85 (95% CI: 0.79-0.91). Using the Youden's J statistic, its most discriminant value (-0.36) was associated with a sensitivity of 80% and a specificity of 75%. Conclusions: We developed a score based on weight loss, necrotic granuloma, normal serum lysozyme level and hypergammaglobulinemia with an excellent capacity to discriminate TB versus sarcoidosis. This score needs still to be validated in a multicentric prospective study.

Epidemiology, clinical presentation, treatment, and outcome of neurosarcoidosis: A mono-centric retrospective study and literature review.

Introduction: Neurosarcoidosis is a rare granulomatous disorder, and treatment guidelines are mainly based on retrospective studies. Materials and methods: This retrospective study was performed to provide a detailed description of the clinical characteristics and treatment outcomes of patients with neurosarcoidosis followed at Cliniques Universitaires Saint Luc in Belgium. The second objective of our study was to perform a comparative literature review of neurosarcoidosis, with a focus on treatment outcomes with the use of TNF-α antagonist. Results: Among 180 patients with sarcoidosis followed in our hospital, 22 patients with neurosarcoidosis were included in the final analysis. Our literature research identified 776 articles of which 35 articles met our inclusion criteria, including 1,793 patients diagnosed with neurosarcoidosis. In our cohort, the majority of patients (86%) were diagnosed with systemic sarcoidosis which was similar to that reported in the literature (83%). Serum CRP and calcemia were elevated only in 33 and 18% of patients, respectively. Serum lysozyme and angiotensin-converting enzyme were elevated in 79 and 16% of patients, respectively. Lumbar puncture and CSF fluid analysis were performed in 15/22 patients and were abnormal in all patients. Brain MRI was performed in 21/22 patients and showed abnormalities in 16 patients consisting of parenchymal lesions in 63%, hypothalamic-pituitary axis lesions in 38%, and meningeal enhancement in 31%. In both cohort patients, methotrexate was the most frequently used treatment (>45% of cases) with a favorable outcome in an average of 50% of patients. A TNF-α antagonist was administered in 9% of patients in our cohort and in 27% of patients in the literature review. The proportion of favorable outcomes in literature research was significantly higher in patients treated with TNF-α antagonists compared to methotrexate (p < 0.0001), mycophenolate mofetil (p < 0.0001), or azathioprine (p < 0.0001). Conclusion: The results of our cohort and literature review confirm that neurosarcoidosis occurred most frequently in the context of systemic sarcoidosis. Methotrexate is the most frequent second-line therapy. The effectiveness of therapy with TNF-α antagonists is well-demonstrated and associated with a better outcome. Their earlier use during the disease course among aggressive and/or refractory neurosarcoidosis should be considered.

Intravitreal Aflibercept Treatment Strategies in Routine Clinical Practice of Neovascular Age-Related Macular Degeneration in Belgium: A Retrospective Observational Study.

INTRODUCTION: STELLAR was a Belgian, multicentre, retrospective, observational chart review that described the utilization (number of injections and treatment regimen) and effectiveness of intravitreal aflibercept (IVT-AFL) in patients with anti-vascular endothelial growth factor (VEGF) treatment-naïve neovascular age-related macular degeneration (nAMD) during the first 12 months of IVT-AFL treatment. METHODS: Patients initiating IVT-AFL between July 2013 and July 2017 were included in STELLAR. Primary endpoints were number of visits and IVT-AFL injections, and number of patients who received ≥ 7 versus < 7 IVT-AFL injections during the first 12 months of treatment. RESULTS: A total of 337 patients completed ≥ 12 months of IVT-AFL treatment. The mean number of visits and mean number of injections during the first 12 months was 9.8 and 7.1 injections, respectively (64% received ≥ 7 injections). Overall, 96% of patients received ≥ 3 initial monthly injections. Of the 337 patients, 180 received VT-AFL as needed (pro re nata), 141 received it as treat-and-extend dosing and 16 received it as fixed dosing. The proportion of patients who received treat-and-extend dosing increased year-on-year. Mean best-corrected visual acuity (BCVA) (± standard deviation) was 61.6 (± 14.9) Early Treatment Diabetic Retinopathy Study (ETDRS) letters at baseline and improved by + 3.9 and + 5.7 ETDRS letters at 3 and 12 months, respectively. Mean BCVA improvement was numerically greater in patients who received ≥ 7 versus < 7 injections during the first 12 months 7 (+ 6.5 vs. + 4.4 ETDRS letters) and in patients who received ≥ 3 versus < 3 initial monthly injections (+ 5.2 vs. - 0.25 ETDRS letters [3 at months]; + 5.9 vs + 1.2 ETDRS letters [at 12 months]). No specific adverse events were reported. CONCLUSION: Most patients in this Belgian study received ≥ 7 IVT-AFL injections during a mean of 9.8 visits over the 12 months assessed. IVT-AFL was an effective treatment for nAMD in clinical practice, with numerically higher BCVA gains in patients receiving ≥ 7 versus < 7 injections over the first 12 months and ≥ 3 versus < 3 injections in the first 3 months.

Acute Susac Syndrome in a Recent User of Adulterated Cocaine: Levamisole as a Triggering Factor?

Susac syndrome (SS) is a central nervous system vasculitis characterized by the clinical triad of encephalopathy, sensorineural hearing loss, and visual disturbance caused by branch retinal artery occlusion. It is considered as an inflammatory disorder, and an autoimmune etiology is suggested. A 29-year-old man with a history of recent cocaine abuse developed the clinical features of SS. Toxicological analysis including hair testing revealed that cocaine had been adulterated with levamisole. After an initial clinical improvement following corticosteroid therapy, the introduction of mycophenolate mofetil was justified a few weeks later by the progression (or relapse) of the retinal injury, followed by complete recovery. The presence of levamisole has been documented in patients with multifocal inflammatory leukoencephalopathy (MIL). Further investigations are needed to determine if levamisole as an adulterant of cocaine could also play a role in the development of rapidly progressive leukoencephalopathy in young men, with Susac or Susac-like syndromes as possible variants of MIL.

A sarcoidosis-lymphoma syndrome revealed by hypopituitarism.

SUMMARY: A 26-year-old woman presented with persistent headache and tiredness. Biological investigations disclosed a moderate inflammatory syndrome, low PTH-hypercalcemia and complete anterior hypopituitarism. A magnetic resonance imaging (MRI) of the pituitary gland was performed and revealed a symmetric enlargement with a heterogeneous signal. Ophthalmological examination showed an asymptomatic bilateral anterior and posterior uveitis, and a diagnosis of pituitary sarcoidosis was suspected. As the localization of lymphadenopathies on the fused whole-body FDG-PET/computerized tomography (CT) was not evoking a sarcoidosis in first instance, an excisional biopsy of a left supraclavicular adenopathy was performed showing classic nodular sclerosis Hodgkin's lymphoma (HL). A diagnostic transsphenoidal biopsy of the pituitary gland was proposed for accurate staging of the HL and surprisingly revealed typical granulomatous inflammation secondary to sarcoidosis, leading to the diagnosis of a sarcoidosis-lymphoma syndrome. The co-existence of these diseases constitutes a diagnostic challenge and we emphasize the necessity of exact staging of disease in order to prescribe adequate treatment. LEARNING POINTS: The possibility of a sarcoidosis-lymphoma syndrome, although rare, should be kept in mind during evaluation for lymphadenopathies. In the case of such association, lymphoma usually occurs after sarcoidosis. However, sarcoidosis and lymphoma can be detected simultaneously and development of sarcoidosis in a patient with previous lymphoma has also been reported. An accurate diagnosis of the disease and the respective organ involvements, including biopsy, is necessary in order to prescribe adequate treatment.

Intraocular T-cell Lymphoma: Clinical Presentation, Diagnosis, Treatment, and Outcome.

PURPOSE: To report on the clinical data of seven patients with T-cell intraocular lymphoma (IOL). METHODS: Retrospective case series. RESULTS: Seven immunocompetent patients, 12 eyes, 6 women, with T-cell-IOL were included from five countries. Mean age was 53.5 years (range: 25-82). Four patients had systemic-ocular lymphoma, two had CNS-ocular lymphoma, and one had systemic-CNS- ocular lymphoma. Vitritis was the most frequent clinical sign, followed by anterior uveitis and serous retinal detachment. Cytopathologic examination was performed on all ocular specimens (vitreous in six and iris mass biopsy in one patient). Adjunctive diagnostic procedures included immunohistochemistry, molecular tests, and cytokine profiling of vitreous samples. Treatment modalities included systemic chemotherapy (five patients), intravitreal methotrexate (three patients), globe radiotherapy, and intrathecal chemotherapy. Mean survival from diagnosis was 21.7 months (range: 2-69). Two patients are still alive. CONCLUSIONS: T-cell IOL has variable clinical manifestations and prognosis. Systemic involvement, SRD, and vitreoretinal involvement were frequently observed.

Acute visual loss following dapsone-induced methemoglobinemia and hemolysis.

OBJECTIVE: While methemoglobinemia is a possible complication of chronic dapsone therapy or of acute overdose, serious adverse manifestations related to methemoglobin formation remain rare. We present an unusual case with severe ischemic retinal injury. CASE REPORT: A 30-year-old African woman presented with a sudden decrease of visual acuity secondary to retinal ischemia. She was chronically treated with dapsone (50 mg/day) for a dermatologic disease and denied any drug overdose. However, the determination of serum dapsone level on admission revealed a largely supratherapeutic concentration (20,044 µg/ml compared with 1-3.5 ± 0.5 µg/ml for therapeutic levels). The methemoglobin level at admission was 32% (sulfhemoglobin 1.2%), with hemoglobin level, 7.4 g/dl, schistocytes count, 2-5%, lactate dehydrogenase level, 580 IU/l, and haptoglobin level, < 10 mg/dl. The patient had both alpha-thalassemia and sickle cell trait. She was treated with methylene blue, vitamin C, and exchange transfusion. There was no improvement in visual symptoms over time. CONCLUSIONS: In a patient with supratherapeutic serum levels of dapsone, the severity of visual injury was associated with dapsone-induced methemoglobinemia and hemolysis, and perhaps also with some hematologic predisposing factors.

Atypical spherical deposition on vitreoretinal interface associated with toxoplasmic chorioretinitis.

PURPOSE: To report the clinical and optical coherence tomography features of spherical deposits associated with recurrent toxoplasmic chorioretinitis. METHODS: Case report. RESULTS: Atypical, 100 microm to 150 microm, greyish deposits appeared along retinal arteries and veins as well as on the vitreoretinal interface in the macula of a 44-year-old Caucasian woman while she was being treated for recurrent toxoplasmic chorioretinitis with antiparasitic drugs and subconjunctival injection of betamethasone. They disappeared progressively with the systemic use of corticosteroids. Their clinical course was nicely documented by optical coherence tomography. CONCLUSIONS: Greyish spherical deposits on the vitreoretinal interface have been previously described as inflammatory reactions in asymptomatic human T-lymphotropic virus type I (HTLV-1) carriers and in patients with HTLV-1-associated uveitis. For the first time, optical coherence tomography (OCT) provided clinical correlation of this unusual presentation of toxoplasmic chorioretinitis.

Choroidal metastasis from carcinoma of the bladder.

PURPOSE: To report choroidal metastasis from the newly described nested variant of urothelial carcinoma of the bladder as the initial presentation of metastatic disease. METHODS: A 58-year-old man with a history of urothelial bladder carcinoma developed progressive decreased visual acuity in the right eye. Fundus examination showed an amelanotic choroidal tumor simulating a choroidal melanoma. Results of ancillary diagnostic tests, needle aspiration biopsy, and systemic workup failed to confirm the diagnosis of choroidal metastasis. The patient was treated with enucleation the affected right eye. RESULTS: Histopathologic analysis of the enucleated eye disclosed a choroidal metastatic carcinoma with urothelial features similar to those of the bladder carcinoma excised previously. Despite adjuvant systemic chemotherapy, the patient died 7 months after enucleation. CONCLUSION: Choroidal metastasis may be the initial manifestation of metastatic bladder carcinoma and is associated with a poor survival prognosis.