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1.
Exp Dermatol ; 33(3): e15050, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38469984

RESUMO

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory and somatic mutation) syndrome is a novel autoinflammatory, late-onset, disorder first identified in 2020. It is caused by mutations in the UBA1 gene. The most prominent clinical features reported by VEXAS patients are cutaneous and haematological, having characteristic skin features reported as the initial presenting findings of the disease. VEXAS is a severe and treatment-resistant condition with high morbidity and mortality rates. Here, we examine all case reports and case series of VEXAS syndrome through March 2023 focusing on those presenting cutaneous manifestations. We discuss these manifestations and their reported treatment strategies. In many cases, it might be first suspected and diagnosed by dermatologists, highlighting their vital role in initiating timely multidisciplinary care.


Assuntos
Doenças Hereditárias Autoinflamatórias , Síndromes Mielodisplásicas , Dermatopatias Genéticas , Humanos , Mutação , Pele , Síndrome , Doenças Hereditárias Autoinflamatórias/genética , Doenças Hereditárias Autoinflamatórias/terapia
2.
BMJ Case Rep ; 17(3)2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38471700

RESUMO

Haemifacial microsomia is an asymmetrical congenital tissue malformation developed from the first and second branchial arches with or without multi-system involvement. Alternatively recognised as Goldenhar syndrome or oculoauriculovertebral spectrum (OAVS), it is an aetiologically heterogeneous group of disorders showing dominant trends in inheritable form.We present a case of a boy in early childhood with concomitant craniofacial features of craniofacial microsomia with Loeys-Dietz syndrome. He had a unilateral hypoplastic face, asymmetrical ear malformations and multiple preauricular tags with epibulbar dermoid (features suggestive of Goldenhar syndrome). On detailed clinical evaluation, he met Beighton's criteria and was diagnosed with arterial tortuosity. Further molecular testing confirmed the diagnosis of Loeys-Dietz syndrome type II.Loeys-Dietz syndrome is characterised by aortic root enlargement or type A dissection with or without other vascular malformations and facial midline defects. Molecular testing is required to establish the diagnosis because of overlapping features with other connective tissue disorders.


Assuntos
Doenças do Tecido Conjuntivo , Síndrome de Goldenhar , Síndrome de Loeys-Dietz , Dermatopatias Genéticas , Masculino , Humanos , Pré-Escolar , Síndrome de Goldenhar/diagnóstico , Síndrome de Loeys-Dietz/complicações , Orelha Externa/anormalidades , Doenças do Tecido Conjuntivo/complicações , Dermatopatias Genéticas/complicações
3.
Rev Med Liege ; 79(3): 137-142, 2024 Mar.
Artigo em Francês | MEDLINE | ID: mdl-38487906

RESUMO

VEXAS syndrome is a new entity, described as the first one of a new class of hemato-inflammatory diseases. Through this article and based on the first case highlighted at the CHU of Liege, we offer you a review of the literature as well as an overview of different laboratory techniques used for the diagnosis of this syndrome.


Le syndrome de VEXAS est une nouvelle entité, décrite comme pionnière d'une nouvelle classe de maladies hémato-inflammatoires. Au travers de cet article et sur base du premier cas mis en évidence au CHU de Liège, nous vous proposons une revue de la littérature ainsi qu'un aperçu des différentes techniques de laboratoire permettant le diagnostic de ce syndrome.


Assuntos
Biologia Molecular , Síndromes Mielodisplásicas , Dermatopatias Genéticas , Humanos , Citometria de Fluxo , Síndrome , Mutação
4.
Arq Bras Oftalmol ; 87(2): e20220288, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38422357

RESUMO

Ligneous conjunctivitis is a rare chronic form of recurrent membranous inflammation and plasminogen deficiency. Ocular manifestations may be associated with sites other than mucous membranes, such as the oral cavity, internal ear, respiratory, genitals, and kidney. Treatment is extremely difficult because of the lack of topic plasminogen drops, and a high volume is required for systemic supplementation. This report aimed to present two patients with ligneous conjunctivitis treated with membrane excision, topical fresh-frozen plasma, and heparin intra-, and postoperatively. No recurrence was found in the ligneous membrane in the 12-month follow-up. The use of topical fresh-frozen plasma and heparin after membrane excision could be effective to avoid recurrence.


Assuntos
Conjuntivite , Plasminogênio/deficiência , Dermatopatias Genéticas , Humanos , Conjuntivite/tratamento farmacológico , Conjuntivite/cirurgia , Dermatopatias Genéticas/complicações , Dermatopatias Genéticas/terapia , Heparina/uso terapêutico
5.
Int Ophthalmol ; 44(1): 4, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38315255

RESUMO

PURPOSE: Actinic conjunctivitis (AC), along with cheilitis (AChe), is part of the clinical spectrum of actinic prurigo (AP), a rare photo dermatosis that affects high-risk populations. We analyzed the clinical manifestations and onset of actinic conjunctivitis (AC), and its relationship with prurigo (AP) in a susceptible population. METHODS: This prospective observational cohort study was performed on Indigenous populations from the highlands of Chiapas, Mexico. Thorough dermatological and ophthalmological examinations were performed in patients attending a primary health care center. The clinical features, labor and environmental factors, onset timing, and clinical staging of AC and AP were analyzed. RESULTS: Of the 2913 patients studied, 54 patients (108 eyes) (1.8%) had AC, and 14 patients (25.9%) had AP. The mean age at diagnosis was 36.18 ± 18.52 years (6-70 years). The mean residential altitude was 1884 ± 434.2 m above sea level. Mean self-reported sun exposure was 5.14 ± 3.1 h a day (0.5-12 h). A total of 90.7% reported exposure to biomass fuels during cooking, and 50% to farm animals. AC was the sole manifestation in 70% of the cases. All patients had nasal and temporal photo-exposed conjunctiva. Among the eyes, 12.9% were classified as stage-1, 64.8% as stage-2, and 22.2% stage-3. A total of 83.3% of the patients had hyperpigmented lesions, and 35.1% had evaporative dry eye disease. CONCLUSIONS: AC may be the initial or sole manifestation of AP. Most AC cases (87%) were initially observed at the advanced stages of the disease. Although solar exposure was not associated with late AC stages, a positive association was found with farm animal exposure. Evaporative dry eye associated with meibomian gland dysfunction has not been previously reported in patients with AC.


Assuntos
Conjuntivite , Transtornos de Fotossensibilidade , Prurigo , Dermatopatias Genéticas , Animais , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , México/epidemiologia , Prurigo/complicações , Prurigo/epidemiologia , Prurigo/patologia , Estudos Prospectivos , Povos Indígenas
6.
Front Immunol ; 15: 1354130, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38333211

RESUMO

VEXAS syndrome is an acquired autoinflammatory disease characterized in most cases by cytopenias and macrocytic anemia. Dyshematopoiesis is a frequent finding in chronic inflammatory conditions and therefore, cytopenias are not easily classified in VEXAS patients. Here we report a series of 7 patients affected by VEXAS associated cytopenias, treated at our center. The use of NGS, together with morphological assays, integrated with the WHO 2022 criteria, allowed to identify three subsets of VEXAS associated cytopenias: ICUS (idiopathic cytopenia of uncertain significance), CCUS (clonal cytopenia of uncertain significance) at high risk of clonal evolution, and MDS. This approach could help to better understand the nature of VEXAS associated cytopenias and to guide the use of specific targeted treatments in order to achieve long lasting responses.


Assuntos
Síndromes Mielodisplásicas , Dermatopatias Genéticas , Humanos , Síndromes Mielodisplásicas/terapia , Evolução Clonal , Organização Mundial da Saúde
8.
Int J Mol Sci ; 25(4)2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38396936

RESUMO

Relapsing polychondritis is a chronic autoimmune inflammatory condition characterized by recurrent episodes of inflammation at the level of cartilaginous structures and tissues rich in proteoglycans. The pathogenesis of the disease is complex and still incompletely elucidated. The data support the important role of a particular genetic predisposition, with HLA-DR4 being considered an allele that confers a major risk of disease occurrence. Environmental factors, mechanical, chemical or infectious, act as triggers in the development of clinical manifestations, causing the degradation of proteins and the release of cryptic cartilage antigens. Both humoral and cellular immunity play essential roles in the occurrence and perpetuation of autoimmunity and inflammation. Autoantibodies anti-type II, IX and XI collagens, anti-matrilin-1 and anti-COMPs (cartilage oligomeric matrix proteins) have been highlighted in increased titers, being correlated with disease activity and considered prognostic factors. Innate immunity cells, neutrophils, monocytes, macrophages, natural killer lymphocytes and eosinophils have been found in the perichondrium and cartilage, together with activated antigen-presenting cells, C3 deposits and immunoglobulins. Also, T cells play a decisive role in the pathogenesis of the disease, with relapsing polychondritis being considered a TH1-mediated condition. Thus, increased secretions of interferon γ, interleukin (IL)-12 and IL-2 have been highlighted. The "inflammatory storm" formed by a complex network of pro-inflammatory cytokines and chemokines actively modulates the recruitment and infiltration of various cells, with cartilage being a source of antigens. Along with RP, VEXAS syndrome, another systemic autoimmune disease with genetic determinism, has an etiopathogenesis that is still incompletely known, and it involves the activation of the innate immune system through different pathways and the appearance of the cytokine storm. The clinical manifestations of VEXAS syndrome include an inflammatory phenotype often similar to that of RP, which raises diagnostic problems. The management of RP and VEXAS syndrome includes common immunosuppressive therapies whose main goal is to control systemic inflammatory manifestations. The objective of this paper is to detail the main etiopathogenetic mechanisms of a rare disease, summarizing the latest data and presenting the distinct features of these mechanisms.


Assuntos
Síndromes Mielodisplásicas , Policondrite Recidivante , Dermatopatias Genéticas , Humanos , Policondrite Recidivante/diagnóstico , Policondrite Recidivante/patologia , Autoimunidade , Colágeno , Inflamação
11.
Lancet Haematol ; 11(2): e160-e167, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38302223

RESUMO

The presence of vacuoles in myeloid and erythroid progenitor cells in bone marrow aspirates is a key feature of vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome. The mere observation of vacuolated progenitor cells is not specific to VEXAS syndrome; in this Viewpoint, we point out the causes to be considered in this situation. Vacuoles, in particular, can be observed in individuals with wild-type UBA1 and with persistent inflammatory features or myelodysplastic syndromes. However, several clues support the diagnosis of VEXAS syndrome in the presence of vacuolated bone marrow progenitors: a high number of vacuolated progenitors and of vacuoles per cell, the predominance of vacuoles in early rather than late progenitors, and the vacuolisation of both myeloid and erythroid progenitors with predominance of myeloid ones. Some criteria derived from these observations have been proposed with great diagnostic performances. However, the absence or a low proportion of vacuolated cells should not prevent UBA1 gene sequencing.


Assuntos
Medula Óssea , Síndromes Mielodisplásicas , Dermatopatias Genéticas , Humanos , Vacúolos , Mutação
14.
Nat Commun ; 15(1): 910, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38291039

RESUMO

Acquired mutations in the UBA1 gene were recently identified in patients with severe adult-onset auto-inflammatory syndrome called VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic). However, the precise physiological and clinical impact of these mutations remains poorly defined. Here we study a unique prospective cohort of VEXAS patients. We show that monocytes from VEXAS are quantitatively and qualitatively impaired and display features of exhaustion with aberrant expression of chemokine receptors. In peripheral blood from VEXAS patients, we identify an increase in circulating levels of many proinflammatory cytokines, including IL-1ß and IL-18 which reflect inflammasome activation and markers of myeloid cells dysregulation. Gene expression analysis of whole blood confirms these findings and also reveals a significant enrichment of TNF-α and NFκB signaling pathways that can mediate cell death and inflammation. This study suggests that the control of the nflammasome activation and inflammatory cell death could be therapeutic targets in VEXAS syndrome.


Assuntos
Inflamassomos , Monócitos , Síndromes Mielodisplásicas , Dermatopatias Genéticas , Adulto , Humanos , Inflamassomos/genética , Estudos Prospectivos , Células Mieloides , Mutação
15.
Ann Hematol ; 103(3): 993-997, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38214707

RESUMO

The VEXAS syndrome, a genetically defined autoimmune disease, associated with various hematological neoplasms has been attracting growing attention since its initial description in 2020. While various therapeutic strategies have been explored in case studies, the optimal treatment strategy is still under investigation and allogeneic cell transplantation is considered the only curative treatment. Here, we describe 2 patients who achieved complete molecular remission of the underlying UBA1 mutant clone outside the context of allogeneic HCT. Both patients received treatment with the hypomethylating agent azacitidine, and deep molecular remission triggered treatment de-escalation and even cessation with sustained molecular remission in one of them. Prospective studies are necessary to clarify which VEXAS patients will benefit most from hypomethylating therapy and to understand the variability in the response to different treatment strategies.


Assuntos
Antimetabólitos Antineoplásicos , Síndromes Mielodisplásicas , Dermatopatias Genéticas , Humanos , Estudos Prospectivos , Síndromes Mielodisplásicas/tratamento farmacológico , Azacitidina
17.
BMC Nephrol ; 25(1): 18, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38212709

RESUMO

BACKGROUND: Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is caused by mutations in the ubiquitin-activating enzyme1 (UBA1) gene and characterised by an overlap between autoinflammatory and haematologic disorders. CASE PRESENTATION: We reported a case of a 67-year-Japanese man receiving peritoneal dialysis (PD) who had recurrent aseptic peritonitis caused by the VEXAS syndrome. He presented with unexplained fevers, headache, abdominal pain, conjunctival hyperaemia, ocular pain, auricular pain, arthralgia, and inflammatory skin lesions. Laboratory investigations showed high serum C-reactive protein concentration and increased cell count in PD effluent. He was treated with antibiotics for PD-related peritonitis, but this was unsuccessful. Fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography images demonstrated intense FDG uptake in his left superficial temporal artery, nasal septum, and bilateral auricles. The working diagnosis was giant cell arteritis, and he was treated with oral prednisolone (PSL) 15 mg daily with good response. However, he was unable to taper the dose to less than 10 mg daily because his symptoms flared up. Since Tocilizumab was initiated, he could taper PSL dose to 2 mg daily. Sanger sequencing of his peripheral blood sample showed a mutation of the UBA1 gene (c.122 T > C; p.Met41Thr). We made a final diagnosis of VEXAS syndrome. He suffered from flare of VEXAS syndrome at PSL of 1 mg daily with his cloudy PD effluent. PSL dose of 11 mg daily relieved the symptom within a few days. CONCLUSIONS: It is crucial to recognise aseptic peritonitis as one of the symptoms of VEXAS syndrome and pay attention to the systemic findings in the patients.


Assuntos
Fluordesoxiglucose F18 , Síndromes Mielodisplásicas , Dermatopatias Genéticas , Vacúolos , Humanos , Masculino , Dor Abdominal , Mutação , Pacientes , Idoso
19.
Am J Med Genet A ; 194(3): e63465, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37916856

RESUMO

Loeys-Dietz syndrome (LDS) is an autosomal connective tissue disorder commonly presenting with hypertelorism, bifid uvula, aortic aneurysms, and arterial tortuosity. The aim of the present study was to investigate differences in tortuosity index (TI) between genotypes of LDS, possible progression over time and its use as an adjunctive prognostic tool alongside aortic dimensions to aid timely surgical planning in pediatric patients. A retrospective observational study of pediatric LDS patients referred to our center (November 2012-February 2021) was conducted. Using magnetic resonance angiography (MRA) with 3D maximum intensity projection volume-rendered angiogram, arterial TI was measured. Twenty three patients had genetically confirmed LDS with at least one head and neck MRA and 19 had no less than one follow-up MRA available. All patients presented arterial tortuosity. Patients with TGFBR2 variants had greater values of TI compared to patients with TGFB2 variants (p = 0.041). For patients who did not undergo surgery (n = 18), z-scores at the level of the sinus of Valsalva showed a significant correlation with vertebral TI (rs = 0.547). There was one death during follow-up. This study demonstrates that patients with LDS and TGFBR2 variants have greater values of TI than patients with TGFB2 variants and that greatest values of TI are associated with increased aortic root z-scores. Furthermore, as TI decreases over time, less frequent neuroimaging follow-up can be considered. Nevertheless, additional studies are needed to better define more accurate risk stratification and long-term surveillance in these patients.


Assuntos
Artérias/anormalidades , Instabilidade Articular , Síndrome de Loeys-Dietz , Dermatopatias Genéticas , Malformações Vasculares , Criança , Humanos , Receptor do Fator de Crescimento Transformador beta Tipo II/genética , Síndrome de Loeys-Dietz/diagnóstico , Síndrome de Loeys-Dietz/genética , Síndrome de Loeys-Dietz/complicações , Dermatopatias Genéticas/complicações , Aorta/patologia
20.
Pediatr Dermatol ; 41(1): 16-22, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37864376

RESUMO

BACKGROUND/OBJECTIVE: Stiff skin syndrome (SSS) is a rare disorder characterized by "rock hard" indurated skin affecting different body parts. The localized variant poses a diagnostic challenge, as it is frequently mistaken for other inflammatory connective tissue disorders. The aim of this study is to provide insightful clinical, radiologic and diagnostic data that might prove useful for the evaluation, management and treatment of pediatric patients with segmental SS. METHODS: This single-center cohort study included patients ≤18 years diagnosed with localized SSS from 1988 to 2021 in a quaternary pediatric healthcare center in Toronto, Canada. Data included demographics, clinical, histopathologic and radiologic features, treatments, and clinical course. Data were summarized with descriptive statistics (mean, standard deviation, medians, interquartile ranges [IQRs]) and frequencies. RESULTS: A total of 11 patients were included. The sclerotic changes were measured clinically and radiologically, by a total of 16 imaging studies: 13 magnetic resonance imaging (MRI) and 3 ultrasound. MRI readings showed abnormal high signal intensity of the affected tissue correlating with the anatomical site of involvement in all cases, specifically, in the shoulder/pelvic girdle with limb extension. Shear wave ultrasound elastography (SWE) demonstrated higher values within the dermis compared to the control site. CONCLUSION: The presence of segmental sclerotic changes that affects the pelvic/shoulder girdle with extension to the extremities, in the absence of inflammation on biopsy and abnormal signaling intensity on imaging is suggestive of SSS. Skin SWE is a feasible, noninvasive, and objective instrument to evaluate and monitor sclerotic changes overtime, it could be potentially extrapolated to other pediatric skin sclerotic conditions.


Assuntos
Contratura , Dermatopatias Genéticas , Humanos , Criança , Estudos Retrospectivos , Estudos de Coortes , Centros de Atenção Terciária
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