[Dynamic functional assessment of internal carotid artery tortuosity in patients with multifocal atherosclerosis]. / Dinamicheskaya funktsional'naya otsenka patologicheskikh izvitostei vnutrennikh sonnykh arterii u bol'nykh s mul'tifokal'nym aterosklerozom. Klinicheskii sluchai.

A personalized approach with attention to anamnesis and specific symptoms is necessary in patients with internal carotid artery tortuosity. Neuroimaging (especially before elective surgery) or functional stress tests following ultrasound of supra-aortic vessels may be necessary depending on medical history and complaints. In addition to standard Doppler ultrasound, these patients should undergo rotational and orthostatic transformation tests. We analyze changes in shape and hemodynamic parameters within the tortuosity area in various body positions. This is especially valuable for patients with concomitant carotid artery stenosis. The article presents a clinical case illustrating the importance of such approach.

[Functional assessment of internal carotid artery tortuosity in patients with multifocal atherosclerosis]. / Vazhnost' dinamicheskoi funktsional'noi otsenki patologicheskoi izvitosti vnutrennikh sonnykh arterii u bol'nykh s mul'tifokal'nym aterosklerozom.

The review is devoted to diagnosis and treatment of internal carotid artery tortuosity. The authors consider modern classification, epidemiology and diagnostic options using neuroimaging or ultrasound-assisted functional stress tests depending on medical history and complaints. In addition to standard Doppler ultrasound, rotational and orthostatic tests are advisable due to possible changes of local shape and hemodynamic parameters following body position changes, especially in patients with concomitant atherosclerotic stenosis. Thus, a personalized approach is especially important for treatment and diagnostics of internal carotid artery tortuosity.

Global intracranial arterial tortuosity is associated with intracranial atherosclerotic burden.

The effect of arterial tortuosity on intracranial atherosclerosis (ICAS) is not well understood. This study aimed to evaluate the effect of global intracranial arterial tortuosity on intracranial atherosclerotic burden in patients with ischemic stroke. We included patients with acute ischemic stroke who underwent magnetic resonance angiography (MRA) and classified them into three groups according to the ICAS burden. Global tortuosity index (GTI) was defined as the standardized mean curvature of the entire intracranial arteries, measured by in-house vessel analysis software. Of the 516 patients included, 274 patients had no ICAS, 140 patients had a low ICAS burden, and 102 patients had a high ICAS burden. GTI increased with higher ICAS burden. After adjustment for age, sex, vascular risk factors, and standardized mean arterial area, GTI was independently associated with ICAS burden (adjusted odds ratio [adjusted OR] 1.33; 95% confidence interval [CI] 1.09-1.62). The degree of association increased when the arterial tortuosity was analyzed limited to the basal arteries (adjusted OR 1.48; 95% CI 1.22-1.81). We demonstrated that GTI is associated with ICAS burden in patients with ischemic stroke, suggesting a role for global arterial tortuosity in ICAS.

Loeys-Dietz syndrome and Goldenhar syndrome unveiled together.

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.

VEXAS syndrome presenting as diffuse alveolar haemorrhage.

We report the case of a man in his late 30s who presented with a history of breathlessness and cough with haemoptysis. Complete blood counts revealed pancytopenia. High-resolution CT showed diffuse bilateral ground glass opacities. Sequential bronchoalveolar lavage confirmed alveolar haemorrhage. Bone marrow aspiration showed vacuoles in erythroid and myeloid precursor cells. The genome was sequenced, and the UBA1 gene revealed a c.121 A>G mutation (p.Met41Val), confirming vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome. The patient was managed with high-dose prednisolone pulse therapy. He improved with the complete resolution of the alveolar haemorrhage and an improvement in lung function and cytopenias.

Medulloblastoma in a child with osteoma cutis - a rare association due to loss of GNAS expression.

OBJECTIVES: Inactivating GNAS mutations result in varied phenotypes depending on parental origin. Maternally inherited mutations typically lead to hormone resistance and Albright's hereditary osteodystrophy (AHO), characterised by short stature, round facies, brachydactyly and subcutaneous ossifications. Paternal inheritance presents with features of AHO or ectopic ossification without hormone resistance. This report describes the case of a child with osteoma cutis and medulloblastoma. The objective of this report is to highlight the emerging association between inactivating germline GNAS mutations and medulloblastoma, aiming to shed light on its implications for tumor biology and promote future development of targeted surveillance strategies to improve outcomes in paediatric patients with these mutations. CASE PRESENTATION: A 12-month-old boy presented with multiple plaque-like skin lesions. Biopsy confirmed osteoma cutis, prompting genetic testing which confirmed a heterozygous inactivating GNAS mutation. At 2.5 years of age, he developed neurological symptoms and was diagnosed with a desmoplastic nodular medulloblastoma, SHH molecular group, confirmed by MRI and histology. Further analysis indicated a biallelic loss of GNAS in the tumor. CONCLUSIONS: This case provides important insights into the role of GNAS as a tumor suppressor and the emerging association between inactivating GNAS variants and the development of medulloblastoma. The case underscores the importance of careful neurological assessment and ongoing vigilance in children with known inactivating GNAS variants or associated phenotypes. Further work to establish genotype-phenotype correlations is needed to inform optimal management of these patients.

Ligneous conjunctivitis: Fresh-frozen plasma and heparin use intra-and postoperatively, a report of two cases.

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.

VEXAS syndrome: A review of cutaneous findings and treatments in an emerging autoinflammatory disease.

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.

[Is hematological cytology outdated at the age of molecular biology and flow cytometry ? Report of a VEXAS syndrome clinical case]. / Cas clinique. La cytologie hématologique désuète à l'heure de la biologie moléculaire et de la cytométrie en flux ? Illustration au travers d'un syndrome de VEXAS.

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.

Case report: Cytopenias in VEXAS syndrome - a WHO 2022 based approach in a single-center cohort.

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.

Macular amyloidosis diagnostic outcomes of skin biopsy: A systematic review.

Macular amyloidosis (MA) is a primary localized cutaneous amyloidosis, characterized by amyloid deposition in the papillary dermis. The clinical presentation includes pruritic hyperpigmented macules and patches with a reticulated or rippled pattern, primarily found on the upper back and extremities. Biopsy is an essential diagnostic tool for confirming MA. This systematic review focused on the biopsy outcomes in patients diagnosed with MA.

Annular Erythematous Eruption in a Pediatric Patient.

An 11-year-old girl presented in autumn with an asymptomatic rash on her arms, face, and legs of a 3-week duration. What is your diagnosis?

Actinic conjunctivitis and its relationship with prurigo in an indigenous population from the Highlands of Chiapas, Mexico.

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.

Vacuoles in bone marrow progenitors: VEXAS syndrome and beyond.

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.

Autoimmunity and Autoinflammation: Relapsing Polychondritis and VEXAS Syndrome Challenge.

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.