RESUMEN
BACKGROUND: A new autoinflammatory syndrome related to somatic mutations of UBA1 was recently described and called VEXAS syndrome ('Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic syndrome'). OBJECTIVES: To describe clinical characteristics, laboratory findings and outcomes of VEXAS syndrome. METHODS: One hundred and sixteen patients with VEXAS syndrome were referred to a French multicentre registry between November 2020 and May 2021. The frequency and median of parameters and vital status, from diagnosis to the end of the follow-up, were recorded. RESULTS: The main clinical features of VEXAS syndrome were found to be skin lesions (83%), noninfectious fever (64%), weight loss (62%), lung involvement (50%), ocular symptoms (39%), relapsing chondritis (36%), venous thrombosis (35%), lymph nodes (34%) and arthralgia (27%). Haematological disease was present in 58 cases (50%): myelodysplastic syndrome (MDS; n = 58) and monoclonal gammopathy of unknown significance (n = 12; all patients with MGUS also have a MDS). UBA1 mutations included p.M41T (45%), p.M41V (30%), p.M41L (18%) and splice mutations (7%). After a median follow-up of 3 years, 18 patients died (15·5%; nine of infection and three due to MDS progression). Unsupervised analysis identified three clusters: cluster 1 (47%; mild-to-moderate disease); cluster 2 (16%; underlying MDS and higher mortality rates); and cluster 3 (37%; constitutional manifestations, higher C-reactive protein levels and less frequent chondritis). The 5-year probability of survival was 84·2% in cluster 1, 50·5% in cluster 2 and 89·6% in cluster 3. The UBA1 p.Met41Leu mutation was associated with a better prognosis. CONCLUSIONS: VEXAS syndrome has a large spectrum of organ manifestations and shows different clinical and prognostic profiles. It also raises a potential impact of the identified UBA1 mutation.
Asunto(s)
Gammopatía Monoclonal de Relevancia Indeterminada , Síndromes Mielodisplásicos , Humanos , Inflamación/genética , Mutación/genética , Síndromes Mielodisplásicos/diagnóstico , Enzimas Activadoras de UbiquitinaRESUMEN
INTRODUCTION: Patients with sickle cell trait (SCT) are commonly considered as asymptomatic carriers. However, some clinical manifestations may occur. METHODS: Here we present a retrospective descriptive study about SCT subjects with at least one complication diagnosed in a sickle cell disease referral center, in Paris, between 2008 and 2019. We also performed a literature review on the complications of SCT subjects. RESULTS: Six patients (between 19 and 65 years old) were included. SCT was already known only for 4 of them at the time of the complication. Four patients presented with a splenic infarct after a stay in high altitude or a plane trip, one of them was associated with papillary necrosis; one patient had isolated papillary necrosis, and the last one had splenic sequestration. These complications happened for most of them after exposure to an unusual situation of hypoxia or deshydratation. Five out of 6 patients had a marked elevated C reactive protein. CONCLUSION: SCT may cause acute ischemic complications in a context of prolonged hypoxia or dehydration. The most commonly reported are the splenic infarct and the renal papillary necrosis. A study of hemoglobin should be considered in these clinical situations in patients with compatible ethnic origin.
Asunto(s)
Necrosis Papilar Renal/diagnóstico , Rasgo Drepanocítico/complicaciones , Infarto del Bazo/diagnóstico , Adulto , Anciano , Anemia de Células Falciformes/complicaciones , Femenino , Humanos , Isquemia/diagnóstico , Isquemia/etiología , Necrosis Papilar Renal/etiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Rasgo Drepanocítico/diagnóstico , Rasgo Drepanocítico/patología , Infarto del Bazo/etiología , Adulto JovenRESUMEN
INTRODUCTION: Opioid therapy for pain relief is associated with several adverse effects. Herein, we report the potential consequences of opioid use on the adrenal function. OBSERVATION: A 49-year-old woman with sickle cell anemia (Hemoglobin SS) was admitted for the treatment of a vaso-occlusive crisis. Morphine was used for pain management, provided by intravenous intermittent dosing (patient-controlled analgesia). She developed during the hospitalization low blood pressure, due to secondary adrenal insufficiency (cortisol 74 nmol/L; ACTH 2.9pmol/L). Pituitary gland was normal on brain magnetic resonance imaging and adrenal function recovered after morphine discontinuation. CONCLUSION: Opioids suppress cortisol secretion, primarily mediated by direct negative effect on hypothalamus and pituitary gland. Further studies are needed to define the incidence and the clinical significance of opioid-induced adrenal insufficiency, as well as the need for hormone replacement.