Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 23
Filtrar
Más filtros

Banco de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
2.
Clin Exp Rheumatol ; 42(7): 1421-1426, 2024 07.
Artículo en Inglés | MEDLINE | ID: mdl-38372716

RESUMEN

OBJECTIVES: The association of systemic lupus erythematosus (SLE) and human immunodeficiency virus (HIV) remains scarcely described in the literature. Our objectives were to describe the characteristics of SLE in patients living with HIV (SLE-PLHIV) and compare it with SLE characteristics in patients without HIV infection. METHODS: We performed a retrospective study of 13 patients with SLE-PLHIV diagnosed between 1975 and 2020 in four different French hospitals. These patients were compared in a case-control study with a 1:5 ratio to age-, sex- and year of diagnosis- matched patients with SLE without HIV infection. RESULTS: Median (IQR) age at SLE diagnosis for patients with SLE and HIV infection was 43 years (36-53). There were 77% women. Main clinical manifestations were polyarthrtitis (84%), cutaneous lupus (69%), kidney disease (54%), serositis (15%) and autoimmune cytopenias (auto-immune haemolytic anaemia and/or immune thrombocytopenia) (31%). There were no neuropsychiatric manifestations. All patients had positive antinuclear antibody test with a titre ≥1:160. Anti-dsDNA antibodies were present in 75% of patients, and anti-Sm antibodies in 33%. SLE-PLHIV had more frequently renal manifestations (54 vs. 16%, p=0.006) and autoimmune cytopenia (31 vs 8%, p=0.04) than patients without HIV infection. CONCLUSIONS: SLE and HIV infection appear to be a rare association. Patients with SLE-PLHIV seem to have more renal manifestations and autoimmune cytopenias than patients with SLE without HIV infection.


Asunto(s)
Infecciones por VIH , Lupus Eritematoso Sistémico , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/epidemiología , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/inmunología , Femenino , Estudios Retrospectivos , Adulto , Infecciones por VIH/inmunología , Infecciones por VIH/epidemiología , Infecciones por VIH/complicaciones , Infecciones por VIH/diagnóstico , Masculino , Persona de Mediana Edad , Estudios de Casos y Controles , Francia/epidemiología , Anticuerpos Antinucleares/sangre , Factores de Riesgo
3.
Curr Rheumatol Rep ; 26(7): 269-277, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38652403

RESUMEN

PURPOSE OF THE REVIEW: Antiphospholipid syndrome (APS) is a rare systemic autoimmune disorder that can escalate into a 'thrombotic storm' called the catastrophic antiphospholipid syndrome (CAPS), frequently requiring ICU admission for multiple organ failure. This review aims to offer insight and recent evidence on critically-ill APS patients. RECENT FINDINGS: The CAPS classification criteria define this condition as the involvement of at least three organs/systems/tissues within less than a week, caused by small vessel thrombosis, in patients with elevated antiphospholipid antibodies levels. These criteria do not encompass the full spectrum of critically-ill thrombotic APS patients and they need to be cautiously used for the bedside diagnosis of CAPS. Thrombocytopenia is the laboratory hallmark of CAPS, sometimes dropping below 20G/L, but a complete thrombotic microangiopathy pattern is infrequent. Anticoagulation is the pivotal treatment for APS and CAPS, associated with improved outcome. Triple therapy - the combination of anticoagulation, high-dose corticosteroids, and either plasma exchange or intravenous immunoglobulins - remains the standard treatment for CAPS patients. Eculizumab, an anti-C5 monoclonal antibody, may be useful in refractory patients. Despite significant progress, CAPS mortality rate remains high. Its diagnosis and management are complex, requiring a close multidisciplinary cross talk between APS specialists and intensivists.


Asunto(s)
Síndrome Antifosfolípido , Unidades de Cuidados Intensivos , Humanos , Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/terapia , Anticoagulantes/uso terapéutico , Anticuerpos Antifosfolípidos/sangre , Anticuerpos Antifosfolípidos/inmunología , Intercambio Plasmático , Enfermedad Crítica
4.
Rheumatology (Oxford) ; 61(2): 775-780, 2022 02 02.
Artículo en Inglés | MEDLINE | ID: mdl-33836046

RESUMEN

OBJECTIVES: GCA is a large vessel vasculitis for which triggering factors remain unknown. Clonal haematopoiesis (CH) was associated with atherosclerosis through the induction of inflammation in myeloid cells, and data suggest that CH expansion and inflammation may support each other to induce a pro-inflammatory loop. Our objective was to describe the impact of JAK2p.V617F-mutated myeloproliferative neoplasms (MPNs) on GCA and to screen MPN-free patients for CH mutations. METHODS: We performed a retrospective case-control study comparing the characteristics of 21 GCA patients with MPN and 42 age- and gender-matched GCA patients without MPN. Also, 18 GCA patients were screened for CH through next-generation sequencing (NGS). RESULTS: The most frequent associated MPN was essential thrombocythaemia (ET; n = 11). Compared with controls, GCA patients with MPN had less-frequent cephalic symptoms (71.4 vs 97.6%; P = 0.004) and higher platelet counts at baseline [485 × 109/l (interquartile range 346-586) vs 346 (296-418); P = 0.02]. There was no difference between groups for other clinical features. Overall survival was significantly shorter in patients with MPN compared with controls [hazard ratio 8.2 (95% CI 1.2, 56.6); P = 0.03]. Finally, screening for CH using NGS in 15 GCA patients without MPN revealed CH in 33%. CONCLUSION: GCA patients with MPN display higher platelet counts and shorter overall survival than controls. This association is not fortuitous, given the possible pathophysiological relationship between the two diseases. CH was found in one-third of GCA patients, which may be higher than the expected prevalence for a similar age, and should be confirmed in a larger cohort.


Asunto(s)
Hematopoyesis Clonal , Arteritis de Células Gigantes/etiología , Enfermedades Mielodisplásicas-Mieloproliferativas/complicaciones , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Hematopoyesis Clonal/genética , Femenino , Arteritis de Células Gigantes/genética , Arteritis de Células Gigantes/mortalidad , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Janus Quinasa 2/genética , Masculino , Enfermedades Mielodisplásicas-Mieloproliferativas/genética , Enfermedades Mielodisplásicas-Mieloproliferativas/mortalidad , Recuento de Plaquetas , Estudios Retrospectivos , Análisis de Supervivencia
5.
Rheumatology (Oxford) ; 60(9): 4355-4360, 2021 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-33347592

RESUMEN

OBJECTIVES: Only a third of patients with eosinophilic granulomatosis with polyangiitis (EGPA) are ANCA-positive, mainly directed against MPO. ANCA directed against PR3 are rarely found in EGPA. We aimed to examine the significance of PR3-ANCA in EGPA. METHODS: We set up a retrospective European multicentre cohort including 845 patients. Baseline characteristics and outcomes were analysed and compared according to ANCA status. RESULTS: ANCA status was available for 734 patients: 508 (69.2%) ANCA-negative, 210 (28.6%) MPO-ANCA and 16 (2.2%) PR3-ANCA. At baseline, PR3-ANCA patients, compared with those with MPO-ANCA and ANCA-negative, less frequently had active asthma (69% vs 91% and 93%, P = 0.003, respectively) and peripheral neuropathy (31% vs 71% and 47%, P < 0.0001), more frequently had cutaneous manifestations (63% vs 38% and 34%, P = 0.03) and pulmonary nodules (25% vs 10% and 8%, P = 0.046), and lower median eosinophil count (1450 vs 5400 and 3224/mm3, P < 0.0001). Vasculitis relapse-free survival was shorter for PR3-ANCA (hazard ratio 6.05, P = 0.005) and MPO-ANCA patients (hazard ratio 1.88, P = 0.0002) compared with ANCA-negative patients. CONCLUSION: PR3-ANCA EGPA patients differ from those with MPO-ANCA and negative ANCA, and share clinical features with granulomatosis with polyangiitis. This suggests that PR3-ANCA EGPA could be a particular form of PR3-ANCA-associated vasculitis.


Asunto(s)
Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Síndrome de Churg-Strauss/inmunología , Granulomatosis con Poliangitis/inmunología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
7.
Blood ; 130(8): 1007-1013, 2017 08 24.
Artículo en Inglés | MEDLINE | ID: mdl-28679734

RESUMEN

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis that most commonly affects adults and is driven by a high frequency of mutations in BRAF, MAP2K1, and kinases promoting MAPK signaling. Because of the relative rarity of ECD, key clinical features of the disease may not be well defined. Across a multi-institutional cohort of 189 patients with ECD and ECD overlapping with Langerhans cell histiocytosis (so-called mixed histiocytosis [MH]), we identified an unexpected and heretofore undescribed frequent occurrence of myeloid neoplasms among patients with ECD and MH. Some 10.1% (19/189) of patients with ECD have an overlapping myeloid neoplasm, most commonly occurring as a myeloproliferative neoplasm (MPN), myelodysplastic syndrome (MDS), or mixed MDS/MPN overlap syndrome (including chronic myelomonocytic leukemia). Consistent with this, molecular analysis frequently detected hallmark driver mutations of myeloid neoplasms (such as JAK2V617F and CALR mutations) coexisting with those characteristic of histiocytosis (such as BRAFV600E and MAP2K1 mutations). Histiocytosis patients diagnosed with a concomitant myeloid malignancy were significantly older at diagnosis and more commonly presented with MH than those without a myeloid malignancy. In some cases, the presence of distinct kinase mutations in the histiocytosis and myeloid neoplasm resulted in discordant and adverse responses to kinase-directed targeted therapies. These data highlight the clinical importance of evaluating adults with histiocytosis for a concomitant myeloid neoplasm.


Asunto(s)
Neoplasias de la Médula Ósea/complicaciones , Neoplasias de la Médula Ósea/epidemiología , Histiocitosis de Células no Langerhans/complicaciones , Adulto , Anciano , Enfermedad de Erdheim-Chester/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia Molecular Dirigida , Prevalencia
8.
Blood ; 130(2): 176-180, 2017 07 13.
Artículo en Inglés | MEDLINE | ID: mdl-28566492

RESUMEN

Langerhans cell histiocytosis (LCH) and the non-LCH neoplasm Erdheim-Chester disease (ECD) are heterogeneous neoplastic disorders marked by infiltration of pathologic macrophage-, dendritic cell-, or monocyte-derived cells in tissues driven by recurrent mutations activating MAPK signaling. Although recent data indicate that at least a proportion of LCH and ECD patients have detectable activating kinase mutations in circulating hematopoietic cells and bone marrow-based hematopoietic progenitors, functional evidence of the cell of origin of histiocytosis from actual patient materials has long been elusive. Here, we provide evidence for mutations in MAPK signaling intermediates in CD34+ cells from patients with ECD and LCH/ECD, including detection of shared origin of LCH and acute myelomonocytic leukemia driven by TET2-mutant CD34+ cell progenitors in one patient. We also demonstrate functional self-renewal capacity for CD34+ cells to drive the development of histiocytosis in xenotransplantation assays in vivo. These data indicate that the cell of origin of at least a proportion of patients with systemic histiocytoses resides in hematopoietic progenitor cells prior to committed monocyte/macrophage or dendritic cell differentiation and provide the first example of a patient-derived xenotransplantation model for a human histiocytic neoplasm.


Asunto(s)
Células de la Médula Ósea/patología , Proteínas de Unión al ADN/genética , Enfermedad de Erdheim-Chester/patología , Células Madre Hematopoyéticas/patología , Histiocitosis de Células de Langerhans/patología , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas/genética , Adulto , Alelos , Animales , Antígenos CD34/genética , Antígenos CD34/inmunología , Células de la Médula Ósea/inmunología , Trasplante de Médula Ósea , Diferenciación Celular , Proteínas de Unión al ADN/inmunología , Células Dendríticas/inmunología , Células Dendríticas/patología , Dioxigenasas , Enfermedad de Erdheim-Chester/genética , Enfermedad de Erdheim-Chester/inmunología , Expresión Génica , Células Madre Hematopoyéticas/inmunología , Histiocitosis de Células de Langerhans/genética , Histiocitosis de Células de Langerhans/inmunología , Humanos , Inmunofenotipificación , Macrófagos/inmunología , Macrófagos/patología , Ratones , Monocitos/inmunología , Monocitos/patología , Mutación , Proteínas Proto-Oncogénicas/inmunología , Proteínas Proto-Oncogénicas B-raf/inmunología , Trasplante Heterólogo
10.
Curr Rheumatol Rep ; 21(12): 66, 2019 12 05.
Artículo en Inglés | MEDLINE | ID: mdl-31807955

RESUMEN

PURPOSE OF REVIEW: This report provides an overview of the current knowledge of molecular characterization, clinical description, and treatment of Erdheim-Chester disease (ECD), a multi-systemic adult histiocytosis of the L group. RECENT FINDINGS: The recent identification of several MAPK mutations in histiocytes of ECD lesions. Leading to targeted therapies. The discovery of the BRAFV600E mutation in ECD lesions followed by several other kinase mutations in the MAPK pathway has revolutionized our understanding of the disease pathogenesis and led to trials with targeted therapies that demonstrated robust efficacy.


Asunto(s)
Enfermedad de Erdheim-Chester/diagnóstico , Enfermedad de Erdheim-Chester/genética , Enfermedad de Erdheim-Chester/terapia , Humanos
11.
Curr Oncol Rep ; 21(7): 62, 2019 05 21.
Artículo en Inglés | MEDLINE | ID: mdl-31115724

RESUMEN

PURPOSE OF REVIEW: Provide an overview of recent progress in decoding the pathogenesis and treatment of systemic histiocytoses. RECENT FINDINGS: Advances in molecular techniques over the last few years, enabling the identification of several MAPK mutations in lesion histiocytes, have revolutionized our understanding of histiocytosis that led to a revised classification and new treatments. Since the 2010 discovery of the BRAFV600E mutation in 57% of Langerhans cell histiocytosis (LCH) lesions, several other kinase mutations have been found, mostly in the MAPK pathway, and also in other key signaling pathways, in LCH, Erdheim-Chester Disease (ECD) and, less frequently, Destombes-Rosai-Dorfman disease (RDD). Those revolutionary breakthroughs enhanced our understanding of the pathogenesis of histiocytosis and led to trials with targeted therapies that demonstrated notable efficacy.


Asunto(s)
Enfermedad de Erdheim-Chester/patología , Histiocitosis de Células de Langerhans/patología , Histiocitosis Sinusal/patología , Inflamación/patología , Mutación , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas B-raf/genética , Enfermedad de Erdheim-Chester/tratamiento farmacológico , Enfermedad de Erdheim-Chester/genética , Histiocitosis de Células de Langerhans/tratamiento farmacológico , Histiocitosis de Células de Langerhans/genética , Histiocitosis Sinusal/tratamiento farmacológico , Histiocitosis Sinusal/genética , Humanos , Inflamación/tratamiento farmacológico , Inflamación/genética , Proteínas Proto-Oncogénicas B-raf/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacos
14.
Clin Exp Rheumatol ; 32(4 Suppl 84): S75-9, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25268663

RESUMEN

OBJECTIVES: To report the safety and efficacy of tocilizumab in patients with severe and refractory non-infectious uveitis. METHODS: Eight consecutive unselected patients with severe and refractory non-infectious uveitis [Birdshot chorioretinopathy (n=1), Behçet's disease (n=1) and idiopathic bilateral panuveitis (n=6)] treated with tocilizumab (8mg/kg every 4 weeks intravenously) were included. The primary outcome was the response to treatment, defined by decrease of inflammatory ocular signs. RESULTS: Four (50%) patients were of female gender and the median (IQR) age was 41 (31-47) years. The median number of previous immunosupressants was of 5.5 (4-6.7). Seven patients had been previously treated with anti-TNF-α [infliximab (n=5) and adalimumab (n=2)]. The immunosupressive drugs used in association with tocilizumab were azathioprine (n=2), mycophenolate mofetil (n=2) and methotrexate (n=2). After a median follow-up of 8 months (6-25), 6/8 (75%) improved under tocilizumab and 2 (25%) were non-responders. The visual acuity improved in five patients. The median dose of prednisolone decreased from 16mg/day (10.6-20.5) to 10 mg/day (10-13.7), at baseline and at the end of follow-up, respectively. Tolerance of tocilizumab was satisfactory and side effects included bronchitis (n=1) and grade 1 leukopenia (n=1) and thrombocytopenia (n=1). CONCLUSIONS: Tocilizumab seems to be a safe and promising therapy in severe and refractory non-infectious uveitis.


Asunto(s)
Antiinflamatorios/administración & dosificación , Anticuerpos Monoclonales Humanizados/administración & dosificación , Síndrome de Behçet/tratamiento farmacológico , Uveítis/tratamiento farmacológico , Adulto , Anciano , Antiinflamatorios/efectos adversos , Anticuerpos Monoclonales Humanizados/efectos adversos , Síndrome de Behçet/complicaciones , Resistencia a Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Uveítis/etiología
15.
Joint Bone Spine ; 91(6): 105756, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38964624

RESUMEN

OBJECTIVE: Previous studies have provided evidence that the discontinuation of hydroxychloroquine (HCQ), and chloroquine (CQ), in patients with systemic lupus erythematosus (SLE) is associated with an increased risk of disease flares, with limited information on the level of disease activity at the time of HCQ/CQ discontinuation. Here we aimed to describe the risk of SLE flare after withdrawal of HCQ or CQ in patients with SLE in remission. METHODS: Case-control study (1:2) comparing the evolution of patients with SLE after HCQ/CQ withdrawal for antimalarial retinopathy (cases) with patients with SLE matched for sex, antimalarial treatment duration and age at SLE diagnosis, whose antimalarial treatment was continued throughout the entire follow-up period (controls). To be included in the study, patients had to be in remission for at least one year according to the DORIS classification. The primary endpoint was the proportion of patient experiencing a flare according to the SELENA-SLEDAI Flare Index after a 36-month follow-up. RESULTS: We studied 48 cases and 96 controls. The proportion of patients experiencing a flare was significantly higher in the HCQ/CQ withdrawal group as compared to the maintenance group (15 [31.3%] patients versus 12 [12.5%]; OR 3.1 [95%CI 1.2-8.2], P=0.01). Withdrawal of HCQ/CQ was inferior with respect to occurrence of severe SLE flare (12 [25.0%] vs 11 [11.5%]; OR 2.5 [95%CI 0.9-6.9], P=0.053) and time to first flare (HR 6.3 [2.0-19.9], P<0.005). Elevated serum levels of anti-dsDNA antibodies were identified as a risk factor for SLE flare following HCQ/CQ discontinuation (HR 5.4 [1.5-18.7], P<0.01). CONCLUSION: Withdrawal of HCQ or CQ in patients with SLE in remission is associated with a 3-fold increased risk of relapse.

16.
Semin Arthritis Rheum ; 66: 152417, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38394986

RESUMEN

BACKGROUND: Long-term hydroxychloroquine (HCQ) or chloroquine (CQ) intake causes retinal toxicity in 0.3-8 % of patients with rheumatic diseases. Numerous risk factors have been described, eg, daily dose by weight, treatment duration, chronic kidney disease, concurrent tamoxifen therapy and pre-existing retinal or macular disease. However, those factors cannot explain the entire risk of developing antimalarial retinopathy. OBJECTIVE: This study was undertaken to identify new risk factors associated with HCQ or CQ retinopathy (QRNP) in systemic lupus erythematosus (SLE) patients. METHODS: This case-control (1:2) study compared SLE patients with QRNP (cases) to those without (controls). Controls were matched for sex and known QRNP risk factors: HCQ and/or CQ treatment duration (±1 year) and age (±5 year) at SLE diagnosis. RESULTS: Forty-eight cases were compared to 96 SLE controls. Multivariable logistic-regression analysis retained the following as independent determinants significantly associated with QRNP: concomitant selective serotonin-reuptake inhibitor (SSRI) or serotonin- and norepinephrine-reuptake inhibitor (SNRI) intake (OR [95 % confidence interval] 6.6 [1.2 to 40.9]; p < 0.01); antiphospholipid syndrome (OR=8.9 [2.2 to 41.4] p < 0.01); blood hydroxychloroquine/desethylchloroquine concentration ([HCQ]/[DCQ]) ratio <7.2 (OR 8.4 [2.7 to 30.8]; p < 0.01) or skin phototype ≥4 (OR 5.5 [1.4 to 26.5]; p = 0.02), but not daily HCQ dose, blood [HCQ] or body mass index. CONCLUSION: The results of this case-control study identified blood [HCQ]/[DCQ] ratio, concurrent SSRI/SNRI therapy, skin phototype ≥4 and antiphospholipid syndrome as new risk factors for QRNP.


Asunto(s)
Antirreumáticos , Cloroquina , Hidroxicloroquina , Lupus Eritematoso Sistémico , Enfermedades de la Retina , Humanos , Hidroxicloroquina/efectos adversos , Hidroxicloroquina/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/inducido químicamente , Femenino , Cloroquina/efectos adversos , Cloroquina/uso terapéutico , Enfermedades de la Retina/inducido químicamente , Factores de Riesgo , Masculino , Adulto , Estudios de Casos y Controles , Persona de Mediana Edad , Antirreumáticos/efectos adversos , Antimaláricos/efectos adversos , Antimaláricos/uso terapéutico
17.
Arthritis Rheumatol ; 76(1): 141-145, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37561109

RESUMEN

OBJECTIVE: Erdheim-Chester disease (ECD) is rare histiocytosis with a wide range of clinical manifestations. Somatic mutations are key to the pathogenesis of the disease; however, the relationship between germline genetic variants and ECD has not been examined so far. The present study aims to explore the inherited genetic component of ECD by performing the first genome-wide association study. METHODS: After quality controls, a cohort of 255 patients with ECD and 7,471 healthy donors was included in this study. Afterward, a logistic regression followed by in silico functional annotation was performed. RESULTS: A signal at the 18q12.3 genomic region was identified as a new susceptibility locus for ECD (P = 2.75 × 10-11 ; Odds Ratio = 2.09). This association was annotated to the SETBP1 gene, which is involved in clonal haematopoiesis. Functional annotation of this region and of the identified suggestive signals revealed additional genes that could be potentially involved in the pathogenesis of the disease. CONCLUSION: Overall, this work demonstrates that germline genetic variants can impact on the development of ECD and suggests new pathways with a potential pathogenic role.


Asunto(s)
Enfermedad de Erdheim-Chester , Humanos , Enfermedad de Erdheim-Chester/genética , Enfermedad de Erdheim-Chester/patología , Estudio de Asociación del Genoma Completo , Genómica , Células Germinativas/patología
18.
EClinicalMedicine ; 73: 102658, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38841707

RESUMEN

Background: Erdheim-Chester disease (ECD) is a rare histiocytosis that may overlap with Langerhans Cell Histiocytosis (LCH). This "mixed" entity is poorly characterized. We here investigated the clinical phenotype, outcome, and prognostic factors of a large cohort of patients with mixed ECD-LCH. Methods: This retrospective study was performed at two referral centers in France and Italy (Pitié-Salpêtrière Hospital, Paris; Meyer Children's Hospital, Florence). We included children and adults with ECD diagnosed in 2000-2022 who had biopsy-proven LCH, available data on clinical presentation, treatment and outcome, and a minimum follow-up of one year. Outcomes included differences in clinical presentation and survival between mixed ECD-LCH and isolated ECD; we also investigated response to treatments and predictors of survival in the mixed cohort. Survival was analyzed using the Kaplan-Maier method and differences in survival with the long-rank test. Cox regression models were used to evaluate the potential impact of age and gender on survival and to identify predictors of non-response and survival. Findings: Out of a cohort of 502 ECD patients, 69 (14%) had mixed ECD-LCH. Compared to isolated ECD, mixed ECD-LCH occurred more frequently in females (51 vs. 26%, p < 0.001) and in patients with multisystem disease (≥4 sites). Mixed ECD-LCH more frequently involved long bones (91 vs. 79%, p = 0.014), central nervous system (51 vs. 34%, p = 0.007), facial/orbit (52 vs. 38%, p = 0.031), lungs (43 vs. 28%, p = 0.009), hypothalamic/pituitary axis (51 vs. 26%, p < 0.001), skin (61 vs. 29%, p < 0.001), and lymph nodes (15 vs. 7%, p = 0.028); the BRAFV600E mutation was also more frequent in mixed ECD-LCH (81 vs. 59%, p < 0.001). Targeted treatments (BRAF and/or MEK inhibitors) induced response more frequently than conventional therapies (interferon-α, chemotherapy), either as first-line (77 vs. 29%, p < 0.001) or as any line (75 vs. 24%, p < 0.001). After a median follow-up of 71 months, 24 patients (35%) died. Survival probability was comparable between ECD alone and mixed ECD-LCH (log-rank p = 0.948). At multivariable analysis, age at diagnosis (HR 1.052, 95% CI 1.008-1.096), associated hematologic conditions (HR 3.030, 95% CI 1.040-8.827), and treatment failure (HR 9.736, 95% CI 2.919-32.481) were associated with an increased risk of death, while lytic bone lesions with a lower risk (HR 0.116, 95% CI 0.031-0.432). Interpretation: Mixed ECD-LCH is a multisystem disease driven by the BRAFV600E mutation and targeted treatments are effective. Age at diagnosis, bone lesion patterns, associated hematologic conditions, and treatment failure are the main predictors of death in mixed ECD-LCH. Funding: None.

19.
Joint Bone Spine ; 89(2): 105297, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34656751

RESUMEN

INTRODUCTION: The antiphospholipid syndrome (APS) (1) is defined by the development of vascular thrombosis, or pregnancy morbidity in the presence of persistent antiphospholipid antibodies (aPL). Antinuclear antibodies (ANA) can be detected in primary APS patients without any clinical systemic autoimmune disease. The presence of ANA antibodies could confer a specific phenotype in primary APS. OBJECTIVE: To evaluate the characteristics of APS patients with antinuclear antibodies without other autoimmune disease (ANA positive APS patients) in comparison with primary APS without ANA or secondary APS patients with associated systemic lupus erythematosus (SLE). METHODS: Clinical and biologic data from 195 APS were retrospectively collected and patients were classified as primary APS with positive ANA (ANA-positive APS), primary APS without any ANA (ANA-negative APS), and SLE-associated APS (SLE-APS). RESULTS: Fourty patients (21%) were classified into ANA-positive APS group, 77 (39%) in ANA-negative APS and 78 (40%) in SLE-APS. In ANA-positive APS patients, 20 patients (51%) had arterial thrombosis, 14 (41%) had veinous thrombosis and 19% had obstetrical complications. There was no difference between the three groups for the frequency of thrombotic manifestations and obstetrical complications. ANA-positive APS patients had more non-criteria manifestations than ANA-negative APS (48% versus 25%; P≤0.01). ANA-positive APS had more triple aPL positivity (59% versus 18%; P<0.001) and more thrombosis and obstetrical recurrences (63% versus 36%; P<0.01) in comparison with ANA-negative APS patients. ANA-positive APS had more triple aPL positivity than SLE-APS patients (54% versus 33%; P<0.05). ANA-positive APS and SLE-APS patients had similar clinical manifestations, and recurrences. Despite a limited follow-up (28 months (11-50)) none of the ANA-positive APS develop SLE. Antiplatelet and anticoagulant therapies were similar for the three groups. SLE-APS patients received more immunomodulatory therapies. CONCLUSION: ANA positivity in patients with APS enables to individualize a subset of patients with a more severe phenotype. Whereas the ANA positivity does not seem to be associated with the risk to develop SLE, prospective studies with a longer follow-up are necessary, in particular to evaluate the effect of additional therapies in this subset of APS.


Asunto(s)
Síndrome Antifosfolípido , Lupus Eritematoso Sistémico , Anticuerpos Antinucleares , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/diagnóstico , Femenino , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Embarazo , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos
20.
Leukemia ; 34(11): 2840-2857, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32591646

RESUMEN

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis with a putative neoplastic and inflammatory nature. The disease is driven by mutations in proto-oncogenes such as BRAF and MEK, while immune-mediated mechanisms contribute to disease development and progression. The clinical presentation of ECD is highly heterogeneous, ranging from smouldering unifocal forms to multiorgan life-threatening disease. Almost any organ can be involved, but the most common lesions include long-bone involvement, retroperitoneal fibrosis, interstitial lung disease, pericardial and myocardial infiltration, CNS, retro-orbital, and large-vessel involvement. These manifestations may mimic those of neoplastic and systemic immune-mediated diseases. Overlap with these conditions represents an emerging challenge for the clinician. A variety of treatments are efficacious for ECD, targeting both the MAPK-pathway and the immune-mediated pathomechanisms. The traditional approach is based on immunomodulatory agents (interferon-α), but recent alternatives-including anti-cytokine therapies (IL1- and TNFα-blockers) and immunosuppressants (mTOR-inhibitors)-showed promising results. However, since the detection of MAPK pathway activation in most patients and the dramatic efficacy of BRAF and MEK inhibitors, these targeted treatments represent the first-line approach in patients with severe disease forms. High rates of radiologic responses do not often mean clinical remission, especially for CNS involvement, which often results in chronic disability. This review will outline the main clinical features of ECD, with emphasis on the emerging challenges in pathogenesis and management, and on the role of recent targeted approaches.


Asunto(s)
Susceptibilidad a Enfermedades , Enfermedad de Erdheim-Chester/etiología , Biomarcadores , Biopsia , Diagnóstico por Imagen , Manejo de la Enfermedad , Enfermedad de Erdheim-Chester/diagnóstico , Enfermedad de Erdheim-Chester/epidemiología , Enfermedad de Erdheim-Chester/terapia , Predisposición Genética a la Enfermedad , Histiocitosis/complicaciones , Humanos , Inmunohistoquímica , Técnicas de Diagnóstico Molecular , Mutación , Neoplasias/complicaciones , Especificidad de Órganos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA