RESUMEN
We investigated using a custom NGS panel of 149 genes the mutational landscape of 64 consecutive adult patients with tyrosine kinase fusion-negative hypereosinophilia (HE)/hypereosinophilic syndrome (HES) harboring features suggestive of myeloid neoplasm. At least one mutation was reported in 50/64 (78%) patients (compared to 8/44 (18%) patients with idiopathic HE/HES/HEUS used as controls; p < .001). Thirty-five patients (54%) had at least one mutation involving the JAK-STAT pathway, including STAT5B (n = 18, among which the hotspot N642H, n = 13), JAK1 (indels in exon 13, n = 5; V658F/L, n = 2), and JAK2 (V617F, n = 6; indels in exon 13, n = 2). Other previously undescribed somatic mutations were also found in JAK2, JAK1, STAT5B, and STAT5A, including three patients who shared the same STAT5A V707fs mutation and features consistent with primary polycythemia. Nearly all JAK-STAT mutations were preceded by (or associated with) myelodysplasia-related gene mutations, especially in RNA-splicing genes or chromatin modifiers. In multivariate analysis, neurologic involvement (hazard ratio [HR] 4.95 [1.87-13.13]; p = .001), anemia (HR 5.50 [2.24-13.49]; p < .001), and the presence of a high-risk mutation (as per the molecular international prognosis scoring system: HR 6.87 [2.39-19.72]; p < .001) were independently associated with impaired overall survival. While corticosteroids were ineffective in all treated JAK-STAT-mutated patients, ruxolitinib showed positive hematological responses including in STAT5A-mutated patients. These findings emphasize the usefulness of NGS for the workup of tyrosine kinase fusion-negative HE/HES patients and support the use of JAK inhibitors in this setting. Updated classifications could consider patients with JAK-STAT mutations and eosinophilia as a new "gene mutated-entity" that could be differentiated from CEL, NOS, and idiopathic HES.
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Síndrome Hipereosinofílico , Mutación , Factor de Transcripción STAT5 , Humanos , Síndrome Hipereosinofílico/genética , Síndrome Hipereosinofílico/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Adulto , Anciano , Factor de Transcripción STAT5/genética , Janus Quinasa 2/genética , Transducción de Señal , Janus Quinasa 1/genética , Anciano de 80 o más Años , Pirimidinas/uso terapéutico , Adulto JovenRESUMEN
PURPOSE: The study aims to determine the impact of initial management in Vogt-Koyanagi-Harada syndrome (VKHS). METHODS: Patients diagnosed with a VKHS between January 2001 and December 2020 in two French tertiary centers were included in a retrospective study. RESULTS: Fifty patients were included with a median duration of follow-up of 29.8 months. All patients received oral prednisone after methylprednisolone in all but four of them. Five patients received at least one associated immunosuppressive therapy (IST) within the first 6 months and 26 patients received IST during the entire follow-up period. Twenty-eight patients presented at least one relapse at a median of 5.4 months from diagnosis. Multivariate analyses demonstrated a significant association between relapse and delayed treatment (>26 days) (HR = 3.69, CI95% 1.30-10.47, p = .01), whereas no association was observed between relapse and the number of corticosteroid pulses at initial management. CONCLUSION: An early corticosteroid treatment within the first 26 days of symptoms decreased the relapse rate.
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Antiprotozoarios , Leishmaniasis Visceral , Linfadenopatía , Antiprotozoarios/uso terapéutico , Humanos , Leishmaniasis Visceral/complicaciones , Leishmaniasis Visceral/diagnóstico , Leishmaniasis Visceral/tratamiento farmacológico , Linfadenopatía/diagnóstico por imagen , Linfadenopatía/tratamiento farmacológico , Linfadenopatía/etiologíaRESUMEN
PURPOSE: Uveitis can be associated with meningitis (uveomeningitis) and the inflammation shared with the central nervous system. We aimed to describe the characteristics and outcome of uveomeningitis. METHODS: We retrospectively analyzed 110 consecutive adult patients with uveomeningitis. RESULTS: The main causes of uveomeningitis were Vogt-Koyanagi-Harada (31%), syphilis (16%), sarcoidosis (12%), Behçet's disease (7%), and multiple sclerosis (5%). Sixteen percent of uveomeningitis remained of undetermined origin. Compared to etiology-matched uveitis without meningitis, patients with uveomeningitis were younger, had more frequent neurological manifestations, and had more frequent abnormal cerebral magnetic resonance imaging findings. In contrast, no ocular feature upon examination was significantly associated with the presence of meningitis. Patients with uveomeningitis were more frequently treated with immunosuppressants but uveitis relapse and systemic complications did not differ between groups. CONCLUSION: Uveomeningitis is associated with a limited spectrum of diseases. Meningitis does not seem to impact ocular and extraocular outcomes. Therefore, lumbar puncture should be performed on an individual basis during the diagnostic workup of uveitis.
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Síndrome de Behçet , Meningitis , Uveítis , Síndrome Uveomeningoencefálico , Adulto , Humanos , Síndrome Uveomeningoencefálico/diagnóstico , Estudios Retrospectivos , Uveítis/tratamiento farmacológico , Síndrome de Behçet/complicacionesRESUMEN
Background: This study aimed to assess the diagnostic relevance of CD4/CD8 ratio in cerebrospinal fluid (CSF) for the etiological diagnosis work-up of uveitis.Methods: We consecutively included patients who were referred to our department for the diagnostic workup of intermediate and/or posterior uveitis. Etiological diagnoses were established in a blind manner regarding CD4/CD8 ratio.Results: Fifty-two patients were included. A diagnosis of ocular sarcoidosis was made in 15 (29%) patients, 21% had another determined diagnosis while 50% remained of undetermined origin. Median CD4/CD8 ratio in CSF was 4.57 (IQR 3.39-5.47) in ocular sarcoidosis, 1.74 (1.60-3.18) in uveitis due to other determined cause (P = .008), and 2.83 (2.34-3.54) in those with uveitis of undetermined origin (P = .007). CD4/CD8 ratio >3.23 was associated with a diagnosis of ocular sarcoidosis.Conclusion: Determination of CD4/CD8 ratio in CSF can be useful for diagnosis work-up since a CD4/CD8 ratio >3.23 in CSF is associated with ocular sarcoidosis.
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Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Inmunofenotipificación/métodos , Sarcoidosis/inmunología , Uveítis/diagnóstico , Adulto , Biomarcadores/líquido cefalorraquídeo , Relación CD4-CD8 , Femenino , Citometría de Flujo , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sarcoidosis/líquido cefalorraquídeo , Sarcoidosis/complicaciones , Uveítis/líquido cefalorraquídeo , Uveítis/etiologíaRESUMEN
To identify clinical presentations, main causes, and prognosis of ophthalmic involvement in chronic lymphocytic leukemia (CLL), we performed a systematic review of articles describing CLL ophthalmic involvement in January 2019, using the PubMed database. We found 86 articles describing 123 cases of patients with ophthalmic involvement associated with CLL. Ophthalmic symptoms were CLL's first manifestation in 25.6% of patients and revealed Richter transformation in 11.0%. There were three main causes of ophthalmic features: CLL-infiltration (52.0%), lymphoma (26.0%), and infection (15.4%), with specific clinical and radiological characteristics. CLL-infiltration was mostly bilateral, whereas lymphoma was usually unilateral (P = 0.02). Optic neuropathy was always secondary to CLL-infiltration, and in those cases, cerebrospinal fluid immunophenotyping was a potential alternative to invasive biopsy as it confirmed the diagnosis in 4 patients (36.4%). On the contrary, lymphoma usually presented as adnexal involvement (P = 0.04), particularly as an orbital mass (P = 0.004). Infections concerned mostly patients previously treated for CLL (P < 0.0001), and main presentations included posterior uveitis (P = 0.0002) and retinal infiltrates (P < 0.0001). Overall, the prognosis was poor, as 29.3% of the patients died within 36 months of follow-up, and 26.1% had a partial or total visual loss. Eye infections were associated with the poorest prognosis as 47% of patients died, with a 6-month-median survival.
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Leucemia Linfocítica Crónica de Células B , Linfoma de Células B Grandes Difuso , Biopsia , Humanos , Leucemia Linfocítica Crónica de Células B/complicaciones , Leucemia Linfocítica Crónica de Células B/diagnóstico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , PronósticoRESUMEN
Catastrophic antiphospholipid syndrome is the most severe complication of antiphospholipid syndrome. Vitamin K antagonists are the reference treatment for preventing relapsing thrombotic complications in patients with antiphospholipid syndrome. Direct oral anticoagulants are nonetheless sometimes used in this setting. We report two cases of women who were triple-positive for antiphospholipid antibodies and developed catastrophic antiphospholipid syndrome in the week after the introduction of rivaroxaban. The first patient, who had had a previous thrombotic event, had multiorgan failure 3 days after vitamin K antagonists was replaced by rivaroxaban, and the second developed a similar clinical presentation 7 days after introduction of the same treatment. Both catastrophic antiphospholipid syndrome episodes were successfully treated with heparin followed by vitamin K antagonists, corticosteroids, and plasmapheresis. These two cases highlight for the inefficacy of rivaroxaban preventing severe thrombotic events such as catastrophic antiphospholipid syndrome and thus provide further support for recommendations that vitamin K antagonists must remain the reference anticoagulant in patients with triple-positive antiphospholipid antibodies.
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Anticuerpos Antifosfolípidos/sangre , Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/fisiopatología , Rivaroxabán/efectos adversos , Corticoesteroides/uso terapéutico , Adulto , Anciano , Anticoagulantes/uso terapéutico , Síndrome Antifosfolípido/tratamiento farmacológico , Enfermedad Catastrófica , Femenino , Heparina/uso terapéutico , Humanos , Rivaroxabán/uso terapéutico , Trombosis/tratamiento farmacológicoRESUMEN
Purpose: The diagnostic workup of uveitis is challenging, with 30 to 50% of cases remaining of undetermined etiology despite multiple investigations. Sarcoid granuloma-related increase of 1,25(OH)2D levels could be helpful for the diagnosis of ocular sarcoidosis.Methods: Monocentric retrospective cohort study of patients for whom serum 25(OH)D and 1,25(OH)2D levels were measured during the etiologic workup of unexplained uveitis in a tertiary referral center. The diagnoses of uveitis' underlying diseases were established according to international diagnostic criteria.Results: Fifty-nine patients were included. The diagnosis of defined, presumed or probable sarcoidosis was made in 37% of patients while 41% of cases remained of undetermined origin. The median serum levels of 25(OH)D in patients with ocular sarcoidosis and in those with uveitis due to another cause were 34.50 [21.2-40.8] and 43.20 [32.2-58.3] nmol/L (P=0.02), respectively. In the same subgroups of patients, the median serum levels of 1,25(OH)2D were 132.4 [107.4-163.9] and 108.0 [84.30-130.5] pmol/l (P=0.02), and the median 1,25(OH)2D/25(OH)D ratio was 4.17 [3.11-5.09] and 2.56 [1.54-3.37] (P=0.0007) respectively. A 1,25(OH)2D/25(OH)D ratio >3.5 was associated with the diagnosis of sarcoidosis with a 68 % sensitivity and a 78% specificity and, in univariate analysis, was associated with an abnormal chest CT-scan (OR=5.7, P=0.003), granulomas on bronchial biopsy (OR=14.7, P=0.007) and bronchoalveolar lavage fluid lymphocytosis (OR=12.4, P=0.0006).Conclusion: The measurement of serum 25(OH)D and 1,25(OH)2D levels is a useful tool in the etiological workup of patients with unexplained uveitis, since a high 1,25(OH)2D/25(OH)D ratio is suggestive of ocular sarcoidosis.
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25-Hidroxivitamina D 2/sangre , Calcitriol/sangre , Sarcoidosis/complicaciones , Uveítis/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sarcoidosis/sangre , Sarcoidosis/diagnóstico , Tomografía Computarizada por Rayos X , Uveítis/sangre , Uveítis/etiologíaAsunto(s)
Artritis Reumatoide , Gripe Humana , Corticoesteroides , Estudios Transversales , Humanos , Motivación , VacunaciónRESUMEN
BACKGROUND: The early diagnosis of cancer is of crucial importance and a key prognostic factor. Cancer-associated retinopathy (CAR) can be symptomatic prior to other manifestations directly related to malignant tumors. The aim of this study was to show that, in selected cases, ophthalmic findings are consistent enough with the diagnosis of CAR to trigger investigations aimed at detecting a previously unknown malignancy. METHODS: This was a monocentric retrospective case series performed in a tertiary referral center. Patients with a diagnosis of CAR were included. Diagnosis was based on the clinical presentation, the visual field and electroretinogram alterations. The clinical presentation, visual field testing and electroretinographic results were analyzed as well as the malignancies identified following the diagnosis of CAR. Follow-up data was collected. RESULTS: Four patients (two men, two women, median age 65.5 years) were included. All patients presented with posterior segment inflammation at initial presentation as well as advanced visual field loss and an extinguished electroretinogram. The best corrected decimal visual acuity was 0.8 or better in both eyes of three patients and decreased to 0.3 OD and O.2 OS in one patient due to a bilateral macular edema. No patient had a previously known history of cancer. Once the diagnosis of CAR was made, investigations aimed at identifying a malignant tumors subsequently led to the diagnosis of two cases of small cell lung tumors, of one prostate carcinoma and of a uterine sarcoma. The treatment of CAR included plasmapheresis, systemic corticosteroids, azathioprine, cyclosporine and periocular or intraocular corticosteroid injections. In all cases the intraocular inflammation resolved, but pigment mottling, diffuse retinal atrophy, optic disc pallor and arterial narrowing were among manifestations observed during the follow-up of the patients. CONCLUSION: In selected patients, findings suggestive of CAR can be useful for the early detection of a cancer.
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Diagnóstico Precoz , Síndromes Paraneoplásicos Oculares/diagnóstico , Retina/patología , Enfermedades de la Retina/diagnóstico , Anciano , Anciano de 80 o más Años , Electrorretinografía , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , Persona de Mediana Edad , Nervio Óptico/patología , Estudios Retrospectivos , Tomografía de Coherencia ÓpticaRESUMEN
The aim of the study was to assess the efficacy and safety of rituximab (RTX) for treating systemic lupus erythematosus (SLE)-associated immune cytopenias. This multicenter retrospective cohort study of adults from French referral centers and networks for adult immune cytopenias and SLE involved patients ≥18 years old with a definite diagnosis of SLE treated with RTX specifically for SLE-associated immune cytopenia from 2005 to 2015. Response assessment was based on standard definitions. In total, 71 patients, 61 women (85.9%), with median age 36 years [interquartile range 31-48], were included. The median duration of SLE at the time of the first RTX administration was 6.1 years [2.6-11.6] and the reason for using RTX was immune thrombocytopenia (ITP) for 44 patients (62.0%), autoimmune hemolytic anemia (AIHA) for 16 (22.5%), Evans syndrome for 10 (14.1%), and pure red cell aplasia for one patient. Before receiving RTX, patients had received a mean of 3.1 ± 1.3 treatments that included corticosteroids (100%), and hydroxychloroquine (88.5%). The overall initial response rate to RTX was 86% (91% with ITP, 87.5% with AIHA, and 60% with Evans syndrome), including 60.5% with complete response. Median follow-up after the first injection of RTX was 26.4 months [14.3-71.2]. Among 61 initial responders, relapse occurred in 24 (39.3%); for 18, RTX retreatment was successful in 16 (88.8%). Severe infections occurred after RTX in three patients, with no fatal outcome. No cases of RTX-induced neutropenia were observed. In conclusion, RTX seems effective and relatively safe for treating SLE-associated immune cytopenias.
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Anemia Hemolítica Autoinmune/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Lupus Eritematoso Sistémico/complicaciones , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Rituximab/uso terapéutico , Adulto , Anemia Hemolítica Autoinmune/etiología , Anemia Hemolítica Autoinmune/inmunología , Susceptibilidad a Enfermedades , Supervivencia sin Enfermedad , Evaluación de Medicamentos , Quimioterapia Combinada , Femenino , Fiebre/inducido químicamente , Estudios de Seguimiento , Humanos , Inmunosupresores/efectos adversos , Infecciones/etiología , Estimación de Kaplan-Meier , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/inmunología , Masculino , Persona de Mediana Edad , Púrpura Trombocitopénica Idiopática/etiología , Púrpura Trombocitopénica Idiopática/inmunología , Aplasia Pura de Células Rojas/tratamiento farmacológico , Aplasia Pura de Células Rojas/etiología , Aplasia Pura de Células Rojas/inmunología , Estudios Retrospectivos , Rituximab/efectos adversos , Trombocitopenia/tratamiento farmacológico , Trombocitopenia/etiología , Trombocitopenia/inmunología , Resultado del TratamientoRESUMEN
The authors report the case of a 53-year-old man with diffuse cutaneous and mediastinal pulmonary sarcoidosis and well-controlled steroid-induced diabetes. He was hospitalized for cellulitis of his left leg. His standard treatment for sarcoidosis consisted of prednisone and methotrexate. Prednisone was stopped at his admission. He received antibiotics for 4 weeks to treat the cellulitis. In parallel, the leg wound was treated with daily silver sulfadiazine applications until necrosis removal, then by skin autografting. Four successive procedures were performed, but all failed despite lack of surgical problem or local infection. Methotrexate was stopped after the fourth grafting procedure failed; the fifth, and final, autografting procedure was successfully performed.
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Celulitis (Flemón)/patología , Celulitis (Flemón)/terapia , Fármacos Dermatológicos/efectos adversos , Rechazo de Injerto/inducido químicamente , Metotrexato/efectos adversos , Sarcoidosis Pulmonar/fisiopatología , Cicatrización de Heridas/efectos de los fármacos , Antibacterianos/administración & dosificación , Celulitis (Flemón)/etiología , Fármacos Dermatológicos/administración & dosificación , Femenino , Humanos , Extremidad Inferior , Masculino , Metotrexato/administración & dosificación , Persona de Mediana Edad , Prednisona/administración & dosificación , Sarcoidosis Pulmonar/complicaciones , Trasplante de Piel , Resultado del Tratamiento , Cicatrización de Heridas/fisiologíaRESUMEN
PURPOSE: To identify predictors of treatment success in syphilitic uveitis (SU). DESIGN: Retrospective multicentric analysis of patients treated for SU. PARTICIPANTS: A total of 95 eyes (66 patients, mean [standard deviation] aged 49 [12.5] years, 31 [47%] of whom were human immunodeficiency virus [HIV]+) were analyzed. METHODS: Activity of SU was assessed at 1 week and 1 month after treatment onset, and at last follow-up. Improvement was defined by a ≥2-step decrease of both anterior chamber and vitreous haze inflammation levels, and by the size reduction in chorioretinal lesions. MAIN OUTCOME MEASURES: Recovery was defined as the resolution of inflammation in all anatomic structures at 1 month. RESULTS: Panuveitis and posterior uveitis were the most frequent findings. Inflammatory parameters were higher in HIV+ patients. Recovery was reported in 65% and 85% of eyes at 1 month and at last follow-up, respectively. In multivariate analysis, after adjusting for initial best-corrected visual acuity and the antimicrobial treatment regimen, clinical improvement at 1 week (corrected risk ratios [cRR], 3.5 [2.3-3.8]; P = 0.001) was predictive of recovery at 1 month, whereas the use of periocular dexamethasone injections (cRR, 0.05 [0.02-0.6]; P = 0.01) and methylprednisolone pulses negatively affected the outcomes of eyes. CONCLUSIONS: Early improvement is the strongest predictor of ophthalmological recovery in SU.
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Antibacterianos/uso terapéutico , Infecciones Bacterianas del Ojo/tratamiento farmacológico , Sífilis/tratamiento farmacológico , Uveítis/tratamiento farmacológico , Adulto , Azitromicina/uso terapéutico , Doxiciclina/uso terapéutico , Infecciones Bacterianas del Ojo/diagnóstico , Infecciones Bacterianas del Ojo/microbiología , Femenino , Prueba de Absorción de Anticuerpos Fluorescentes de Treponema , Estudios de Seguimiento , Seropositividad para VIH , Humanos , Masculino , Persona de Mediana Edad , Penicilina G Benzatina/uso terapéutico , Reacción en Cadena de la Polimerasa , Pronóstico , Estudios Retrospectivos , Sulfadiazina/uso terapéutico , Sífilis/diagnóstico , Sífilis/microbiología , Serodiagnóstico de la Sífilis , Uveítis/diagnóstico , Uveítis/microbiología , Agudeza Visual/fisiologíaRESUMEN
PURPOSE: This study aimed at reporting lymphocytic meningitis in patients diagnosed with sympathetic ophthalmia (SO). METHODS: In this single-center retrospective observational case series, we reviewed cases diagnosed with SO. We analyzed the patients' inciting injuries, the characteristics of uveitis and the cerebrospinal fluid (CSF) analyses. RESULTS: Nine patients were diagnosed with SO and CSF analyses were available in all cases. Four cases had lymphocytic pleocytosis, 3 of which showed marked CSF inflammation with more than 300 lymphocytes/mm3. The inciting event in these 3 patients was a globe perforation injury, whereas 4 patients without meningitis had SO following a surgical intervention. CONCLUSIONS: In this case series of patients with SO, lymphocytic meningitis was a common finding. The prevalence of meningitis in patients with SO and its value for the diagnosis of the disease needs to be further studied.
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Leucocitosis/diagnóstico , Linfocitos/patología , Meningitis/diagnóstico , Oftalmía Simpática/diagnóstico , Adulto , Anciano , Femenino , Angiografía con Fluoresceína , Humanos , Leucocitosis/líquido cefalorraquídeo , Masculino , Meningitis/líquido cefalorraquídeo , Persona de Mediana Edad , Oftalmía Simpática/líquido cefalorraquídeo , Prevalencia , Estudios Retrospectivos , Punción Espinal , Adulto JovenRESUMEN
OBJECTIVE: The diagnostic workup of uveitis is a challenge due to the wide range of diagnoses and the lack of a well-codified diagnostic procedure. We aimed to evaluate the relevance of diagnostic investigations for the etiological diagnosis of uveitis. METHODS: Retrospective cohort study of patients referred for etiological diagnosis of uveitis. Uveitis related to ophthalmological diseases or occurring during the course of previously diagnosed diseases were not included. RESULTS: Three hundred patients were included. Chest CT-scan was suggestive of sarcoidosis in 83 (29%). Features associated with abnormal CT-scan were: snowballs and/or peripheral multifocal choroiditis (PMC) upon ocular examination (P=0.004), blood lymphopenia (P<0.0001), angiotensin converting enzyme (ACE) level>1.5 ULN (P=0.0003). Bronchoscopy showed granuloma in 18 (11%) while alveolar lymphocytosis suggestive of sarcoidosis was reported in 45 (27%). Presence of granuloma on bronchial biopsies was always associated with chest CT-scan abnormalities, whereas 31% of patients with alveolar lymphocytosis had normal CT-scans. Features associated with contributive bronchoscopy were: snowballs and/or PMC (P=0.003), ACE>1.5 ULN (P=0.007), abnormal chest-CT scan (P<0.0001). Salivary gland biopsy revealed granuloma in 12 patients (5%). Cerebral MRI was abnormal in 15 patients (9%) who mostly presented with snowballs and/or retinal vasculitis. Finally, the main causes of uveitis were latent tuberculosis (25%) and sarcoidosis (22%), but 34% remained of undetermined origin. Uveitis relapses were observed in 31% and did not differ between patients with an identified diagnosis and those with idiopathic uveitis. CONCLUSION: Identification of factors associated with abnormal investigations might improve the optimal diagnostic workup adapted to each patient.
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Uveítis/diagnóstico , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosAsunto(s)
Enfermedades Autoinmunes/inmunología , Huésped Inmunocomprometido , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/prevención & control , Vacunas Neumococicas/administración & dosificación , Vacunación/estadística & datos numéricos , Corticoesteroides/uso terapéutico , Adulto , Anciano , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/tratamiento farmacológico , Estudios Transversales , Femenino , Humanos , Incidencia , Gripe Humana/inmunología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Neumonía Neumocócica/inmunología , Neumonía Neumocócica/prevención & control , Pronóstico , Medición de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: Syphilis remains a significant public health problem. We conducted a prospective study to define more precisely the clinical and biological characteristics of patients with neurosyphilis (NS), and we assessed the diagnostic value of nested polymerase chain reaction (PCR) testing for Treponema pallidum in cerebrospinal fluid (CSF) samples. METHODS: From 2001 to 2013, we included 40 patients (90% men; 45% infected with human immunodeficiency virus) with NS, defined as syphilis with neurological and/or ophthalmological symptoms and CSF abnormalities. RESULTS: Thirty patients (75%) had early, 5 (12.5%) had late, and 5 had meningovascular NS. Twenty-four patients (80%) with early NS had ophthalmological symptoms, 14 (47%) had neurological symptoms, and 8 (26%) had both. All patients with meningovascular NS had only neurological symptoms. All patients with late NS had neurological symptoms, and 2 (40%) also had ocular symptoms. Ophthalmological symptoms were present in 65% of all patients with NS, and neurological symptoms in 60%. Seventeen patients (42.5%) had CSF white blood cell counts >20/µL (mean, 57/µL), and 27 (67.5%) had high CSF protein levels (>0.5 g/L; mean value, 1 g/L). CSF PCR results were positive in 42%, and CSF VDRL results in 30%. The nested PCR assay had an overall sensitivity of 42.5%, a specificity of 97%, a positive predictive value of 77%, and a negative predictive value of 86%. CONCLUSIONS: Early NS is the most frequent presentation, with an overrepresentation of polymorphous ophthalmological symptoms. PCR is highly specific and of potential value when used with other biological parameters.
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Neurosífilis/diagnóstico , Reacción en Cadena de la Polimerasa , Treponema pallidum , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Infecciones por VIH/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Neurosífilis/líquido cefalorraquídeo , Neurosífilis/complicaciones , Neurosífilis/fisiopatología , Valor Predictivo de las Pruebas , Estudios Prospectivos , Sensibilidad y Especificidad , Adulto JovenRESUMEN
We report two cases of treatment failure in patients with osteoarticular infection associated with Staphylococcus aureus bacteremia and receiving daptomycin. Using a published population-pharmacokinetic model and daptomycin blood level in these patients, area under the curve (AUC) was calculated and compared to the pharmacological target. For the first patient, treated with 6 mg/kg every 48 hours due to acute renal failure and then every 24 hours, the AUC was 820 mg×h×L-1, with a minimal concentration of 23.5 mg/L confirming the right dose adjustment and the absence of underdosing. The methicillin-resistant Staphylococcus aureus (MRSA) strain was still susceptible to daptomycin, but it was not sufficient to observe a favorable outcome. For the second patient, treated with 10 mg/kg/d, the steady state residual concentration was 10.4 mg/L, and the calculated AUC value was 550 mg×h×L-1. AUC/MIC values evolved during treatment to be under the cut-off for bactericidal effects (> 800 hours), and the Staphylococcus aureus (SA) strain became daptomycin resistant. This study highlights the inter-individual pharmacokinetic variation leading sometimes to drug underdosing. Drug monitoring should be encouraged in order to avoid treatment failure.