Spanish cohort of VEXAS syndrome: clinical manifestations, outcome of treatments and novel evidences about UBA1 mosaicism.

BACKGROUND: The vacuoles, E1-enzyme, X linked, autoinflammatory and somatic (VEXAS) syndrome is an adult-onset autoinflammatory disease (AID) due to postzygotic UBA1 variants. OBJECTIVES: To investigate the presence of VEXAS syndrome among patients with adult-onset undiagnosed AID. Additional studies evaluated the mosaicism distribution and the circulating cytokines. METHODS: Gene analyses were performed by both Sanger and amplicon-based deep sequencing. Patients' data were collected from their medical charts. Cytokines were quantified by Luminex. RESULTS: Genetic analyses of enrolled patients (n=42) identified 30 patients carrying UBA1 pathogenic variants, with frequencies compatible for postzygotic variants. All patients were male individuals who presented with a late-onset disease (mean 67.5 years; median 67.0 years) characterised by cutaneous lesions (90%), fever (66.7%), pulmonary manifestations (66.7%) and arthritis (53.3%). Macrocytic anaemia and increased erythrocyte sedimentation rate and ferritin were the most relevant analytical abnormalities. Glucocorticoids ameliorated the inflammatory manifestations, but most patients became glucocorticoid-dependent. Positive responses were obtained when targeting the haematopoietic component of the disease with either decitabine or allogeneic haematopoietic stem cell transplantation. Additional analyses detected the UBA1 variants in both haematopoietic and non-haematopoietic tissues. Finally, analysis of circulating cytokines did not identify inflammatory mediators of the disease. CONCLUSION: Thirty patients with adult-onset AID were definitively diagnosed with VEXAS syndrome through genetic analyses. Despite minor interindividual differences, their main characteristics were in concordance with previous reports. We detected for the first time the UBA1 mosaicism in non-haematopoietic tissue, which questions the previous concept of myeloid-restricted mosaicism and may have conceptual consequences for the disease mechanisms.

Neuro-Behçet Disease in the Central University Hospital of Asturias. / Enfermedad de neuro-Behçet en el Hospital Universitario Central de Asturias.

OBJECTIVE: To describe the frequency and profile of patients with neuro-Behçet's disease (NBD) at the Central University Hospital of Asturias between 1981 and June 2018. PATIENTS AND METHODS: Retrospective study including epidemiological, clinical, neuroimaging, cerebrospinal fluid (CSF) study, histopathology, treatment and evolution characteristics. Clinical characteristics are differentiated between patients with Behçet without neurological affectation and NBD. RESULTS: We found 10 cases of NBD (25.6%). The mean age was 29.7years, and it was more frequent in males. Sixty percent had parenchymal involvement. The non-parenchymal involvement included a case with cerebral venous thrombosis and two cases with isolated aseptic meningitis. Findings of vasculitis were found on cerebral magnetic resonance imaging, and alteration in the biochemistry of the CSF. One patient presented a striking motor disability. Ocular involvement was greater in the group of patients without neurological involvement (P=0.009). CONCLUSIONS: NBD is a relatively frequent presentation, especially in males and in the parenchymal form. We did not find a systemic clinical marker of neurological involvement.

Enfermedad de neuro-Behçet en el Hospital Universitario Central de Asturias / Neuro-Behçet Disease in the Central University Hospital of Asturias

Objetivo: Describir frecuencia y perfil de pacientes con neuro-Behçet (NB) del Hospital Universitario Central de Asturias desde 1981 hasta junio del 2018. Pacientes y métodos: Estudio retrospectivo que incluye características: epidemiológicas, clínicas, neuroimagen, estudio de líquido cefalorraquídeo (LCR), histopatología, tratamiento y evolución. Se diferencian características clínicas entre pacientes con Behçet sin afectación neurológica y NB. Resultados: Se describen 10 casos de NB (25,6%). La edad media al diagnóstico, 29,7años, siendo más frecuente en varones. El 60% tienen afectación parenquimatosa. En la afectación no parenquimatosa se incluyen un caso con trombosis venosa cerebral y dos con meningitis aséptica aislada. Se encontraron hallazgos de vasculitis en la resonancia magnética cerebral y alteración en la bioquímica del LCR. Un paciente presentó discapacidad motora llamativa. La afectación ocular ha sido mayor en el grupo de los pacientes sin afectación neurológica (p=0,009). Conclusiones: El NB es relativamente frecuente, sobre todo en varones y en la forma parenquimatosa. No se encuentra un marcador clínico propio de la afectación neurológica.(AU)

Objective: To describe the frequency and profile of patients with neuro-Behçet's disease (NBD) at the Central University Hospital of Asturias between 1981 and June 2018. Patients and methods: Retrospective study including epidemiological, clinical, neuroimaging, cerebrospinal fluid (CSF) study, histopathology, treatment and evolution characteristics. Clinical characteristics are differentiated between patients with Behçet without neurological affectation and NBD. Results: We found 10 cases of NBD (25.6%). The mean age was 29.7years, and it was more frequent in males. Sixty percent had parenchymal involvement. The non-parenchymal involvement included a case with cerebral venous thrombosis and two cases with isolated aseptic meningitis. Findings of vasculitis were found on cerebral magnetic resonance imaging, and alteration in the biochemistry of the CSF. One patient presented a striking motor disability. Ocular involvement was greater in the group of patients without neurological involvement (P=0.009). Conclusions: NBD is a relatively frequent presentation, especially in males and in the parenchymal form. We did not find a systemic clinical marker of neurological involvement.(AU)

Vasculitis del sábado noche / Saturday night vasculitis

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Anemia megaloblástica / Megaloblastic anemia

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