Ehlers-Danlos Research Articles

Does tenascin-X correlate with adrenal dysfunction in patients with Ehlers-Danlos syndrome?

Does tenascin-X correlate with adrenal dysfunction in patients with Ehlers-Danlos syndrome?

The effects of obesity on bone mineral density in women with Ehlers-Danlos syndrome

The effects of obesity on bone mineral density in women with Ehlers-Danlos syndrome

Can tenascin - X be a marker of bone turnover in patients with Ehlers-Danlos syndrome?

Can tenascin - X be a marker of bone turnover in patients with Ehlers-Danlos syndrome?

Vitamin D deficiency in patients with Ehlers-Danlos syndrome

Vitamin D deficiency in patients with Ehlers-Danlos syndrome

Is autoimmune thyroiditis in females with Ehlers-Danlos syndrome associated with lower bone density?

Is autoimmune thyroiditis in females with Ehlers-Danlos syndrome associated with lower bone density?

Is autoimmune thyroiditis in females with ehlers-danlos syndrome associated with lower bone density?

Is autoimmune thyroiditis in females with ehlers-danlos syndrome associated with lower bone density?

Skin assessment in congenital untreated isolated GH deficiency.

The separation between the inside and outside through the skin was fundamental for the evolution of prevertebrates, which grow through extrapituitary circuits, to vertebrates, which grow through the somatotrophic axis, namely pituitary growth hormone (GH). and circulating IGF1.Individuals with untreated isolated growth hormone (GH) deficiency (IGHD) due to a mutation in the GH-releasing hormone receptor (GHRH) gene, residing in Itabaianinha, Brazil, are vulnerable to skin cancer and have reduced sweating. However other aspects of their skin physiology are still unknown. Our objectives were to evaluate the number of skin cancers, skin aging, and functional aspects of the skin in this IGHD cohort. Twenty-six IGHD individuals and 26 controls matched by age, sex, ethnicity, and occupation were submitted to a biochemical, dermatological and a functional skin assessment by the Multi Probe Adapter Cutometer® MPA 580. There was no difference in the number of skin cancers and in the degrees of photodamage between the groups. The melanin content in the forearm was similar between the groups but was lower in the buttocks (p = 0.005), as well as skin resistance (p < 0.0001) and elasticity (p = 0.003), lower in the IGHD. There was no difference in hydration and sebum content between the two groups. IGHD is apparently associated with a neutral profile in terms of skin cancer and photodamage, with similar melanin on the forearm and lower buttocks, lower skin resistance and elasticity, with hydration and sebum similar to controls.

Intra-Individual Paired Mass Spectrometry Dataset for Decoding Solar-Induced Proteomic Changes in Facial Skin

Photoaging is the premature aging of the skin caused by prolonged exposure to solar radiation. The visual alterations manifest as wrinkles, reduced skin elasticity, uneven skin tone, as well as other signs that surpass the expected outcomes of natural aging. Beyond these surface changes, there is a complex interplay of molecular alterations, encompassing shifts in cellular function, DNA damage, and protein composition disruptions. This data descriptor introduces a unique dataset derived from ten individuals, each with a minimum of 18 years of professional experience as a driver, who are asymmetrically and chronically exposed to solar radiation due to their driving orientation. Skin samples were independently collected from each side of the face using a microdermabrasion-like procedure and analyzed on an Exploris 240 mass spectrometer. Our adapted proteomic statistical framework leverages the sample pairing to provide robust insights. This dataset delves into the molecular differences in exposed skin and serves as a foundational resource for interdisciplinary research in photodermatology, targeted skincare treatments, and computational modelling of skin health.

Lack of Diversity in Research on Females with Ehlers-Danlos Syndromes: Recruitment Protocol for a Quantitative Online Survey.

Ehlers-Danlos syndromes (EDS) are a group of connective tissue disorders caused by fragile lax collagen. Current EDS research lacks racial and ethnic diversity. The lack of diversity may be associated with the complexities of conducting a large international study on an underdiagnosed condition and a lack of EDS health care providers who diagnose and conduct research outside of the United States and Europe. Social media may be the key to recruiting a large diverse EDS sample. However, studies that have used social media to recruit have not been able to recruit diverse samples. This study aims to discuss challenges, strategies, outcomes, and lessons learned from using social media to recruit a large sample of females with EDS. Recruitment on social media for a cross-sectional survey examining dyspareunia (painful sexual intercourse) in females was examined. Inclusion criteria were (1) older than 18 years of age, (2) assigned female at birth, and (3) diagnosed with EDS. Recruitment took place on Facebook and Twitter (now X), from June 1 to June 25, 2019. A total of 1178 females with EDS were recruited from Facebook (n=1174) and X (n=4). On Facebook, participants were recruited via support groups. A total of 166 EDS support groups were identified, 104 permitted the principal investigator to join, 90 approved posting, and the survey was posted in 54 groups. Among them, 30 of the support groups posted in were globally focused and not tied to any specific country or region, 21 were for people in the United States, and 3 were for people outside of the United States. Recruitment materials were posted on X with the hashtag #EDS. A total of 1599 people accessed the survey and 1178 people were eligible and consented. The average age of participants was 38.6 (SD 11.7) years. Participants were predominantly White (n=1063, 93%) and non-Hispanic (n=1046, 92%). Participants were recruited from 29 countries, with 900 (79%) from the United States and 124 (11%) from Great Britain. Our recruitment method was successful at recruiting a large sample. The sample was predominantly White and from North America and Europe. More research needs to be conducted on how to recruit a diverse sample. Areas to investigate may include connecting with more support groups from outside the United States and Europe, researching which platforms are popular in different countries, and translating study materials into different languages. A larger obstacle to recruiting diverse samples may be the lack of health care providers that diagnose EDS outside the United States and Europe, making the pool of potential participants small. There needs to be more health care providers that diagnose and treat EDS in countries that are predominantly made up of people of color as well as research that specifically focuses on these populations. RR1-10.2196/53646.

Does sensitive skin lie in epidermal barrier impairment or abnormalities? Results from an observational study assessing biophysical parameters.

The pathophysiology of sensitive skin is largely unknown and no univocal data on the role of the epidermal barrier impairment have been identified. The aim of this study was to assess whether subjects with or without sensitive skin differ for some biophysical skin parameters, which reflect skin barrier integrity or skin hyperactivity. This observational, cross-sectional study included adult volunteers not affected with chronic inflammatory skin diseases who attended the Unit of Dermatology and the Center of Cosmetology of the University of Ferrara, Ferrara, Italy, between March 2021 and November 2022. All subjects, subdivided into those with or without sensitive skin, based on either Lactic Acid Stinging Test (LAST) result or a questionnaire-based skin sensitivity score ≥4, were tested for transepidermal water loss (TEWL), skin elasticity and hydrations and dermographism. One hundred and eighty-seven subjects were included. No significant differences in terms of TEWL, elasticity and hydration levels were recorded between subjects with sensitive skin and those without, subdivided according to both the LAST result and the questionnaire score. Dermographism was elicited more in subjects with sensitive skin than in the others, although without statistical significance. The study failed to find significant biophysical differences between sensitive and non-sensitive skin. Therefore, the role of skin barrier impairment does not appear to be a necessary condition in determining an abnormal skin sensitivity to potentially unpleasant and irritating stimuli. These findings indirectly support the relevance of a peripheral sensory neural hyperactivity in the pathophysiology of sensitive skin.

Physiological Functions of Aquaporin-3 in Mediating Water and Solutes

Aquaporins (AQP), are a family of membrane channel proteins that facilitate the transmembrane diffusion of water and some small non-charged solutes such as glycerol and urea by osmosis or solute gradient. AQP3, an aquaglyceroporin, is expressed in the kidney, skin, and testes, etc. Mice lacking AQP3 have symptoms of diabetes insipidus. In addition, the absence of AQP3 leads to dry skin in mice. AQP4 is permeable to water only. To understand the specific function of the water permeability and small solute transport mediated by AQP3, we generated AQP3 knock-out (AQP3 KO) mice and AQP4 knock-in mice (AQP4 KI) with AQP4 replacing AQP3 in situ. In the basal condition, knock-out of AQP3 in mice led to increased urine volume, decreased urine osmolality and tubule dilation. Interestingly, in AQP4 KI mice, these phenomena were reversed, showing improved urine concentration and tubular morphology. However, there was no significant difference in non-urea solute concentrations between both genotypes. Subsequently, we conducted acute urea loading tests and high-protein diet experiments to further increase the production and excretion of urea in mice. The experimental results showed that both urea loading and high-protein diet had little impact on urine osmolality and urinary urea concentration in AQP3 KO mice. But the urine osmolality and urinary urea concentration in AQP4 KI mice were altered by exogenous administration of urea. Our data indicates that the absence of AQP3 prevents urea accumulation in the kidney, disrupting urine concentration mechanism. The knock-in of AQP4 can restore AQP3 mediated water channel function and help to regulate the urine concentration ability. The water permeability, other than solute transport, of AQP3 plays important role in urine concentrating mechanism. AQP3 KO mice exhibited significant epidermal thickening, excessive keratinization, decreased skin hydration and elasticity. The replacement of AQP4 in situ did not improve these phenomena, indicating that solute transport mediated by AQP3 may play a role in maintaining normal skin function. Therefore, we constructed a mouse model of psoriasis induced by imiquimod (IMQ). It was found that AQP3 expression was reduced in the lesional skin of wildtype (WT) mice, while AQP3 KO mice and AQP4 KI mice exhibited dry skin, excessive epidermal proliferation, and increased inflammatory response. Local treatment with urea (10%) could alleviate these symptoms. These experimental results confirmed the important role of AQP3 in the pathogenesis of psoriasis and the potential role of urea in the treatment of psoriasis. Our study suggests the diverse physiological functions of AQP3 in different tissues. This research was supported by Beijing Natural Science Foundation (7232249). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A Rare Case of Recurrent Hemopneumothorax

Abstract Hemopneumothorax is most commonly encountered following trauma. Spontaneous hemopneumothorax is rare. Causes of spontaneous hemopneumothorax include congenital cystic lung diseases, bleeding disorders, collagen vascular diseases such as rheumatoid arthritis, systemic lupus erythematosus, and complications of lung malignancies. Vascular Ehlers–Danlos syndrome (vEDS) is a life-threatening rare genetic disorder with a high tendency of arterial and organ rupture. Pulmonary complications in vEDS are rare. This report is of a young male presenting with a history of recurrent hemopneumothorax. He was diagnosed with vEDS by identifying a COL3A1 gene mutation. This report emphasizes the importance of genetic studies when young patients present with unexplained and recurrent hemopneumothorax. Genetic counseling and close monitoring are imperative for the prevention of severe complications.

FIRST COMPREHENSIVE ECHOCARDIOGRAPHIC ASSESSMENT IN PATIENTS WITH VASCULAR EHLERS-DANLOS SYNDROME WITH OR WITHOUT CELIPROLOL THERAPY AT THE MAXIMUM RECOMMENDED DOSE

Objective: Vascular Ehlers-Danlos syndrome (vEDS) is an inherited connective tissue disorder characterized by arterial fragility. Celiprolol is a beta1-adrenoceptor antagonist with partial beta2 agonist activity that has been shown to reduce rates of vascular events in this setting, though the underlying mechanisms are not yet fully understood. Moreover, few data on echocardiographic assessment are available in patients with vEDS. Design and method: Twenty patients with genetically confirmed diagnosis of vEDS followed at our Institution were divided into two groups (10 patients each) according to whether or not they were on celiprolol therapy at the maximum recommended dose (400 mg daily) for at least 12 months. Both groups were compared to 10 healthy individuals matched for sex, age, body mass index (BMI), and office blood pressure values. Each participant underwent transthoracic echocardiography with tissue Doppler analysis for a comprehensive evaluation of cardiac structure and function. Results: Mean age was 35 years and mean BMI was 21.6 kg/m2. Female sex was prevalent (60%). Left ventricular (LV) internal diameter values tended to be lower in patients with untreated vEDS than in healthy controls, though this difference was not statistically significant (4.33 vs 4.74 cm, respectively; p=0.053). Similar data were observed for LV mass index (56.9 vs 68.6 g/m2; p=0.093), stroke volume (56.6 vs 71.6 mL; p=0.068), and E/A ratio (1.26 vs 1.66; p=0.082), whereas an opposite trend was observed for e’ lateral (13.2 vs 12.2; p=0.096). No statistically significant difference was found between groups in terms of other parameters of LV mass, systolic and diastolic function. A normal LV geometry was found in all the cases. Indices of mechano-energetic efficiency and ventricular-arterial coupling were also similar between groups. No patient presented with aortic root dilation, mitral valve prolapse, valve insufficiency of more than mild degree, or valve stenosis of any degree. Conclusions: Our study suggests that patients with vEDS have normal cardiac mass and geometry, as well as normal systolic and diastolic function. Celiprolol therapy does not seem to significantly influence such aspects. Future studies on larger cohort of patients should confirm these aspects.

Ehlers-Danlos Syndrome with Classical Subtype in a Cat

Ehlers-Danlos Syndrome with Classical Subtype in a Cat

A Clinical Study of Orally Collagen Intake and Evaluation of the Effects on Human Skin Physiological Properties

Today, food supplements have become an indispensable part of a healthy and balanced life, and one of them, collagen supplements especially support the healthy skin structure and have many positive effects on it. The present study is aimed that evaluating the effects of PROFIN® Collagen on healthy skin conditions such as skin hydration, wrinkles, and elasticity. With this aim, we conducted a prospective, single-center, double-blind, randomized, placebo-controlled, 2-arm, parallel-design study to evaluate the effect of 12-week consumption of PROFIN® Collagen Hydrolysate on skin health. A total of 72 healthy female adults, aged between 40 and 65 with at least moderate eye wrinkles were randomized to receive 10 g of PROFIN® Collagen or placebo, once daily for 12 weeks. The majority (73(%)) of participants who took ‘Profin Collagen Hydrolysate’ had a statistical improvement (decrease) (p&lt;0,05) in mean wrinkle length at Day 42, this improvement continued at the end of the intervention. Furthermore, compared with the placebo group, in placebo group transepidermal water loss results show that there was a significant increase after 6, and 12 weeks of administration, but not in PROFIN® Collagen group. In conclusion, this study demonstrates that PROFIN® Collagen has a positive effect on skin wrinkles and water loss.

The WD Domain of Atg16l1 Crucial for LC3-Associated Phagocytosis Is Not Required for Preserving Skin Barrier Function in Mice

The skin is a multifunctional organ, forming a barrier between the external and internal environment, thereby functioning as a safeguard against extrinsic factors. Autophagy has been implicated in epidermal differentiation and in preserving skin homeostasis. LC3-associated phagocytosis (LAP) uses some but not all components of autophagy. The Atg16l1 ( WD) mouse model lacks the WD40 domain required for LAP and has been widely used to study the effects of LAP deficiency and autophagy on tissue homeostasis and response to infection. In this study, the WD model was used to study the relationship between LAP and skin homeostasis by determining whether LAP-deficient mice display a cutaneous phenotype. Skin histology of wild-type and WD mice aged 1 year revealed minor morphological differences in the tail skin dermal layer. RT-qPCR and western blot analysis showed no differences in key keratin expression between genotypes. Skin barrier formation, assessed by dye permeation assays, demonstrated full and proper formation of the skin barrier at embryonic day 18.5 in both genotypes. Biomechanical analysis of the skin showed decreased skin elasticity in aged WD but not wild-type mice. In summary, the LAP-deficient WD mice displayed subtle alterations in dermal histology and age-related biomechanical changes.

DISEASES OF THE AORTA IN PREGNANT WOMEN

Aortopathy in pregnant women is caused by genetically determined connective tissue dysplasia (Marfan, Ehlers–Danlos, Loyes–Dietz syndromes, etc.). The most severe complication is aortic aneurysm and its dissection with a probability of fatal outcome. The key to preventing this complication is frequent repeat imaging (ultrasound is the method of choice) and interdisciplinary collaboration, planning and coordination of antenatal care, labor management and postnatal care.

Formulation development of nanostructured lipid carrier-based nanogels encapsulating tacrolimus for sustained therapy of psoriasis

The goal of this study was to formulate tacrolimus nanogel based on nanostructured lipid carrier (NLC) in order to improve the efficacy, aesthetic, and patient compliance for the treatment of psoriasis. The microemulsion method was used to create phase diagrams and NLCs were prepared using points obtained from the microemulsion region and characterized. The gelling agent carbopol was used to develop an NLC-based nanogel. The pH, drug assay, viscosity, spreadability, and in vitro release of the nanogel, were evaluated. Ex vivo cytotoxicity of the formulation was assessed in murine fibroblast cells. Oxazolone and imiquimod models of psoriasis were used to assess the effectiveness of the nanogel. The NLCs exhibited a submicron particle size of 320 ± 10 nm, a low polydispersity index (<0.3), and a zeta potential of −19.4 mV. Morphological analysis revealed spherical nanoparticles with an encapsulation efficiency of 60 ± 3 %. The nanogel maintained a pH of 6.0 ± 0.5 and possessed a remarkable drug content of 99.73 ± 1.4 %. It exhibited pseudoplastic flow behaviour, ensuring easy spreadability, and demonstrated sustained drug release exceeding 90 % over a 24-hr period. Ex vivo cytotoxicity assessments revealed that the nanogel was safe because no cell death was induced. Nanogel resolved psoriatic blisters, was non-irritating and improved skin elasticity. The favorable properties, safety profile, and remarkable efficacy show the potential of the nanogel as a patient-friendly and effective therapeutic option for psoriasis treatment.

Risk factors associated with symptoms of temporomandibular disorders among women with hypermobile Ehlers-Danlos syndrome: Questionnaire-based study in Finland and Sweden.

Generalized joint hypermobility as a characteristic feature of Ehlers-Danlos syndromes (EDS) is among the factors contributing to temporomandibular disorders (TMD). To evaluate the prevalence of TMD symptoms and their risk factors among women born in Sweden or Finland who were 27- to 78-year-olds with diagnosed hypermobile EDS (hEDS). A cohort of women with confirmed hEDS (n = 185) was constructed from the members of the National EDS Associations in both countries. Based on questionnaire data, frequency of independent variables in terms of socio-demographic, general health and oral health-related factors, comorbid symptoms and psychological distress for self-reported TMD symptoms as the dependent variables, were calculated first. Prevalence ratios (PR) and their 95% confidence interval (95% CI) were estimated for the association between independent and dependent variables. Nearly all participants reported TMD symptoms (98%) with TMD pain (95%), TMJ clicking (90%) and jaw fatigue (80%) as the most common symptoms and TMJ crepitation (63%) and luxation (44%) as the least common symptoms. Risk factors for TMD among 27- to 50-year-olds participants were Finland as a country of birth, living alone and self-reported worst pain in the body (not the joints). The respective risk factors among the 51- to 78-year-olds were Finland as a country of birth, family history of EDS, tinnitus and regularly taking contraceptives. Among adult women with confirmed hEDS, socio-demographic and health-related factors and comorbid symptoms were significantly associated with TMD but with differences regarding age group. Therefore, management of TMD requires a multidisciplinary approach among the affected.

Amino Acids Oral Treatment for the Amelioration of Skin, Hair, and Nails Conditions: An Open-Label Study

This study aimed at investigating the effect of a food supplement in ameliorating the skin, hair, and nails conditions. An open-label study on 21 women with mild-to-moderate aging all over the face (including wrinkles/fine lines, loss of skin firmness/elasticity, and normal to dry skin), acute telogen effluvium, and brittle/fragile nails was conducted. Skin (moisturization, elasticity, profilometry, and skin thickness), hair (pull test and phototricogram), and nails (clinical analysis of nail plate status) parameters were measured at baseline, and after 28 and 84 days of intake. The clinical analysis carried out by a board-certified dermatologist and the self-evaluation integrated the instrumental measurements. After 28 (D28) and 84 (D84) days of product intake the skin moisturization (superficial moisturization: +6.0% at D28 and +9.2% at D84; deep moisturization: +4.2% at D28 and +7.6 at D84), elasticity (R0 parameter: -11.5% at D28 and -19.3% at D84; R2 parameter: +7.8% at D28 and +11.9 at D84), profilometry (wrinkle depth: -9.5% at D28 and -14.5% at D84; skin smoothness: -4.9% at D28 and -7.7% at D84) and thickness (+0.11 mm at D28 and +0.24 mm at D84) were improved. At D84 the density of telogen hair was reduced by 9.5%; while at day 28 pull test was not indicative for telogen effluvium. The nail status was improved in most of the enrolled subjects. The instrumental measured effects were perceived by both the dermatologist and the enrolled subjects. Our results highlight the test product efficacy in improving the skin, hair, and nails conditions.