Case of a 33-Year-Old Woman With Hemoptysis and Migrant Nodular Cavitary Lesions.

We describe the case of a young 33-year-old woman that was referred to our clinic for evidence of migrant cavitary nodules at CT scan, dyspnea, and blood sputum. Her physical examination showed translucent and thin skin, evident venous vascular pattern, vermilion of the lip thin, micrognathia, thin nose, and occasional Raynaud phenomenon. We prescribed another CT scan that showed multiple pulmonary nodules in both lungs, some of which had evidence of cavitation. Because bronchoscopy was not diagnostic, we decided to perform surgical lung biopsy. At histologic examination, we found the presence of irregularly shaped, but mainly not dendritic, foci of ossification that often contained bone marrow and were embedded or surrounded by tendinous-like fibrous tissue. After incorporating data from the histologic examination, we decided to perform genetic counseling and genetic testing with the use of whole-exome sequencing. The genetic test revealed a heterozygous de novo missense mutation of COL3A1 gene, which encodes for type III collagen synthesis, and could cause vascular Ehlers-Danlos syndrome.

Diagnosis and treatment of the Ehlers-Danlos syndromes in China: synopsis of the first guidelines.

BACKGROUND: The Ehlers-Danlos syndromes (EDS) are a group of rare hereditary connective tissue disorders. EDS is clinically and genetically heterogeneous and usually involves multiple systems. There are 14 subtypes of EDS with hallmark features including joint hypermobility, skin hyperextensibility, and tissue fragility. The clinical manifestations and their severity differ among the subtypes, encompassing recurrent joint dislocations, scoliosis, arterial aneurysm and dissection, and organ rupture. Challenges in diagnosis and management arise from the complexity of the disease, which is further complicated by its rarity. The development of clinical guidelines and implementation of coordinated multi-disciplinary team (MDT) approaches have emerged as global priorities. MAIN BODY: Chinese Multi-Disciplinary Working Group on the Ehlers-Danlos Syndromes was therefore established. Healthcare professionals were recruited from 25 top hospitals across China. The experts are specialized in 24 fields, including genetics, vascular surgery, dermatology, and orthopedics, as well as nursing care, rehabilitation, psychology, and nutrition. Based on GRADE methodology, the Guidelines were written by the Group supervised by methodologists, following a systemic review of all 4453 articles in PubMed published before August 9, 2023, using the search term "Ehlers Danlos". A coordinated MDT approach for the diagnosis and management of EDS is highly recommended by the Group, along with 29 specific recommendations addressing key clinical questions. In addition to the treatment plan, the Guidelines also emphasize integrating support from nursing care, rehabilitation, psychology, and nutrition. This integration not only facilitates recovery in hospital settings, but most importantly, the transition from an illness-defined life to a more "normalized" life. CONCLUSION: The first guidelines on EDS will shorten the diagnostic odyssey and solve the unmet medical needs of the patients. This article is a synopsis of the full guidelines.

Airway Complications in a Patient With Ehlers-Danlos Syndrome: A Case Report.

A female patient, known to have hypermobile Ehlers-Danlos syndrome (hEDS), underwent several elective gastroscopies under sedation in different hospitals. Except for a single incident of mild laryngospasm during emergence, all procedures were uneventful. On that occasion, following the procedure in the postanesthesia care unit, the patient suffered severe airway obstruction, and standard airway rescue techniques exacerbated adequate ventilation. After the removal of all stimuli and maintaining only an indirect oxygen supply via a mask in front of her face, her airway improved, and the patient fully recovered after 17 minutes. After the gastroscopy, physical examination revealed that the patient had an extremely flexible trachea that could be completely moved outside the midline to the extreme right and left. For the subsequent procedures, an airway plan was developed in conjunction with the patient and resulted in uncomplicated perianesthetic care. This case report serves to alert readers to the risk of adverse airway events in patients with EDS and suggests an alternative approach to avoid such complications. When patients receive care in different hospitals, adequate documentation is essential and adequate preoperative assessment is crucial. This case study demonstrates the value of patient-coproduction care plans.

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

BACKGROUND: 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. OBJECTIVE: This study aims to discuss challenges, strategies, outcomes, and lessons learned from using social media to recruit a large sample of females with EDS. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/53646.

Management of childbearing with hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorders: A scoping review and expert co-creation of evidence-based clinical guidelines.

OBJECTIVE: To co-create expert guidelines for the management of pregnancy, birth, and postpartum recovery in the context of hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD). DESIGN: Scoping Review and Expert Co-creation. SETTING: United Kingdom, United States of America, Canada, France, Sweden, Luxembourg, Germany, Italy, and the Netherlands. SAMPLE: Co-creators (n = 15) included expertise from patients and clinicians from the International Consortium on the Ehlers-Danlos syndromes and Hypermobility Spectrum Disorders, facilitated by the Ehlers-Danlos Society. METHODS: A scoping review using Embase, Medline, the Cochrane Central Register of Controlled Trials and CINHAL was conducted from May 2022 to September 2023. Articles were included if they reported primary research findings in relation to childbearing with hEDS/HSD, including case reports. No language limitations were placed on our search, and our team had the ability to translate and screen articles retrieved in English, French, Spanish, Italian, Russian, Swedish, Norwegian, Dutch, Danish, German, and Portuguese. The Mixed Methods Appraisal Tool was used to assess bias and quality appraise articles selected. The co-creation of guidelines was based on descriptive evidence synthesis along with practical and clinical experience supported by patient and public involvement activities. RESULTS: Primary research studies (n = 14) and case studies (n = 21) including a total of 1,260,317 participants informed the co-creation of guidelines in four overarching categories: 1) Preconceptual: conception and screening, 2) Antenatal: risk assessment, management of miscarriage and termination of pregnancy, gastrointestinal issues and mobility, 3) Intrapartum: risk assessment, birth choices (mode of birth and intended place of birth), mobility in labor and anesthesia, and 4) Postpartum: wound healing, pelvic health, care of the newborn and infant feeding. Guidelines were also included in relation to pain management, mental health, nutrition and the common co-morbidities of postural orthostatic tachycardia syndrome, other forms of dysautonomia, and mast cell diseases. CONCLUSIONS: There is limited high quality evidence available. Individualized strategies are proposed for the management of childbearing people with hEDS/HSD throughout pregnancy, birth, and the postpartum period. A multidisciplinary approach is advised to address frequently seen issues in this population such as tissue fragility, joint hypermobility, and pain, as well as common comorbidities, including dysautonomia and mast cell diseases.

Correlation between benign joint hypermobility syndrome and headache in children and adolescents.

BACKGROUND: Benign Joint Hypermobility Syndrome (BJHS) is a most common hereditary connective tissue disorders in children and adolescents. This study aimed to investigate the prevalence and subtypes of headache in children with BJHS. METHODS: This observational-analytical study was conducted in a case-control setting on school children aged 7 to 16 years in 2021-2023 in Isfahan, Iran. Students were examined for BJHS using Beighton criteria by a pediatric rheumatologist. Headache disorder was diagnosed according to the Child Headache-Attributed Restriction, Disability, and Social Handicap and Impaired Participation (HARDSHIP) questionnaires for child and adolescent and International Classification of Headache Disorders (ICHD-III). RESULTS: A total of 4,832 student (mean age 10.3 ± 3.1 years), 798 patients with BJHS and 912 healthy children were evaluated. The probability of headache in children aged 7-11 with hypermobility was 3.7 times lower than in children aged 12-16 with hypermobility (P = 0.001). The occurrence of headache in children with BJHS was more than the control group (P = 0.001), and the probability of headache in children with BJHS was 3.7 times higher than in healthy children (P = 0.001). Migraine was the most common headache type reported of total cases. The probability of migraine in children with BJHS was 4.5 times higher than healthy children ( P = 0.001). CONCLUSION: This study showed a significant correlation between BJHS and headache (especially migraine) in children and adolescents.

Clinical and Molecular Characterization of a Novel Homozygous Frameshift Variant in AEBP1-Related Classical-like Ehlers Danlos Syndrome Type 2 with Comparison to Previously Reported Rare Cases.

Recently, an autosomal recessive subtype of connective tissue disorder within the spectrum of Ehlers-Danlos syndrome (EDS), named classical-like EDS type 2 (clEDS2), was identified. clEDS2 is associated with biallelic variants in the adipocyte enhancer binding protein 1 (AEBP1) gene, specifically, affecting its aortic carboxypeptidase-like protein (ACLP) isoform. We described the 15th patient (13th family) diagnosed with clEDS2. This patient presented with notable similarities in phenotype to the documented cases, along with additional characteristics such as significant prematurity and short stature. An EDS sequencing panel-based analysis revealed homozygous AEBP1: NM_001129.5:c.2923del, p.Ala975Profs*22 likely pathogenic variants, and maternally inherited heterozygous COL11A1: NM_001854.4:c.1160A>G, p.Lys387Arg variant of uncertain significance in our patient. Upon comprehensive review of all previously reported clEDS2 patients, our patient exhibited the following overlapping phenotypes, including cutaneous features: hyperextensibility, atrophic scars/delayed wound healing (100%), easy bruising (100%), excessive skin (93%); skeletal features: generalized joint hypermobility (93%), pes planus (93%), dislocation/subluxation (93%); and cardiovascular features (86%). Our patient did not display symptoms of the critical complications reported in a few individuals, including superior mesenteric artery aneurysms and ruptures, aortic root aneurysm/dissection, spontaneous pneumothoraxes, and bowel ruptures. Together, this case expands the genetic and clinical phenotypic spectrum of AEBP1-related clEDS2.

Joint Hypermobility Syndrome and Membrane Proteins: A Comprehensive Review.

Ehlers-Danlos syndromes (EDSs) constitute a heterogeneous group of connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Asymptomatic EDSs, joint hypermobility without associated syndromes, EDSs, and hypermobility spectrum disorders are the commonest phenotypes associated with joint hypermobility. Joint hypermobility syndrome (JHS) is a connective tissue disorder characterized by extreme flexibility of the joints, along with pain and other symptoms. JHS can be a sign of a more serious underlying genetic condition, such as EDS, which affects the cartilage, bone, fat, and blood. The exact cause of JHS could be related to genetic changes in the proteins that add flexibility and strength to the joints, ligaments, and tendons, such as collagen. Membrane proteins are a class of proteins embedded in the cell membrane and play a crucial role in cell signaling, transport, and adhesion. Dysregulated membrane proteins have been implicated in a variety of diseases, including cancer, cardiovascular disease, and neurological disorders; recent studies have suggested that membrane proteins may also play a role in the pathogenesis of JHS. This article presents an exploration of the causative factors contributing to musculoskeletal pain in individuals with hypermobility, based on research findings. It aims to provide an understanding of JHS and its association with membrane proteins, addressing the clinical manifestations, pathogenesis, diagnosis, and management of JHS.

Otolaryngologic sequelae of Ehlers Danlos Syndrome in pediatric patients.

OBJECTIVE: As outlined by the NIH, Ehlers Danlos Syndrome (EDS) is a group of hereditary connective tissue disorders characterized by skin hyperelasticity, joint hypermobility, atrophic scarring, and blood vessel fragility, with no otolaryngological criteria for diagnosis. We aimed to compare otolaryngological disorders between children with EDS and those not affected by EDS. METHODS: A retrospective chart review was conducted using the US collaborative network within TriNetX. The EDS group was defined by ICD-10 code G47.33, while the non-EDS group excluded any patients with an EDS diagnosis. Cohorts were matched by age, sex, and race using propensity score matching. Pathologies analyzed included hearing loss (ICD-10H90, H91), otitis media (ICD-10H66, H65), allergic rhinitis, acute tonsillitis (ICD-10 J03), sinusitis (ICD-10 J32, J01), and obstructive sleep apnea (OSA) (ICD-10 G47.33). Chi-square and relative risk within a 95 % confidence interval were calculated. RESULTS: Propensity score matching yielded 6440 patients (male: N = 2,523, 39.2 %; female: N = 3,893, 60.5 %; unknown: N = 24, 0.37 %) with a mean age of 9.28 years (SD = 4.38). Children with EDS were 2.04 times more likely to be diagnosed with hearing loss, occurring in 286 (4.4 %) EDS children versus 140 (2.1 %) controls (P < 0.001). Children with EDS were 1.6 times more likely to be diagnosed with allergic rhinitis, occurring in 436 (6.8 %) EDS children versus 274 (4.2 %) controls (P < 0.001). Children with EDS were also 1.52 times (EDS: N = 350, 5.4 %; control: N = 231, 3.6 %) and 4.24 times (EDS: N = 335, 5.2 %; control: N = 79, 1.2 %) more likely to develop sinusitis and be diagnosed with OSA, respectively, compared to children without EDS (P < 0.001). However, children with EDS were only 0.71 times as likely to develop acute tonsillitis, with 101 (1.6 %) of EDS children compared to 142 (2.2 %) of control children being diagnosed (P = 0.009). No statistical difference was found in risk of developing otitis media. CONCLUSIONS: Children with EDS are at higher risk of developing hearing loss, allergic rhinitis, acute sinusitis, and OSA, possibly due to underlying immune dysfunction. Pediatric otolaryngologists should be vigilant about these otolaryngologic sequela in EDS patients.

Unraveling the genetic collagen connection: clinical and therapeutic insights on genetic connective tissue disorders.

Hereditary connective tissue disorders include more than 200 conditions affecting different organs and tissues, compromising the biological role of the extracellular matrix through interference in the synthesis, development, or secretion of collagen and/or its associated proteins. The clinical phenotype includes multiple signs and symptoms, usually nonspecific but of interest to rheumatologists because of musculoskeletal involvement. The patient´s journey to diagnosis is long, and physicians should include these disorders in their differential diagnoses of diseases with systemic involvement. In this review, insights for the diagnosis and treatment of osteogenesis imperfecta, hypermobility spectrum disorder/Ehlers-Danlos syndrome, Marfan, Loeys-Dietz, and Stickler syndromes are presented.

Visual evoked potential in generalized joint hypermobility: A case-control study.

INTRODUCTION: Generalized joint hypermobility (GJH) can be the result of several hereditary connective tissue disorders, especially Ehlers-Danlos syndrome. Cerebrovascular manifestations are among the most common complications in this disorder, and understanding their extent can help better diagnosis and prevention of hazardous events. We investigated visual evoked potential (VEP) changes in patients with GJH and compared them with healthy individuals. METHODS: Our case-control study included 90 patients who fulfilled the Beighton score (B score) for joint hypermobility and other 90 healthy participants. All of them went under VEP study, and the amplitude and latency of the evoked potential (P100) were compared to each other. RESULTS: The Case group had significantly higher B score (7.18 ± 0.967 vs. 1.18 ± 0.712), P100 latency (110.23 ± 6.64 ms vs. 100.18 ± 4.273 ms), and amplitude (6.54 ± 1.26 mv vs. 6.50 ± 1.29 mv) compared with the Control group, but the difference was only significant regarding B score, and P100 latency (p-value <.0001). Moreover, both latency and amplitude of P100 had significantly positive correlations with the B score in the Case group (p-value <.0001), but such correlations were not found in the Control group (p-value = .059). CONCLUSION: Our study could reveal VEP changes, especially significant P100 latency in GJH patients without previous neurologic or musculoskeletal disorders. Whether these changes are due to GJH itself or are predictive of inevitable neurologic disease or visual pathway involvement, particularly Multiple Sclerosis needs further investigation with longer follow-up periods.

Anaplastic and poorly differentiated thyroid carcinomas: genetic evidence of high-grade transformation from differentiated thyroid carcinoma.

Anaplastic thyroid carcinoma (ATC) is the most advanced and aggressive thyroid cancer, and poorly differentiated thyroid carcinoma (PDTC) lacks anaplastic histology but has lost architectural and cytologic differentiation. Only a few studies have focused on the genetic relationship between the two advanced carcinomas and coexisting differentiated thyroid carcinomas (DTCs). In the present study, we investigated clinicopathologic features and genetic profiles in 57 ATC and PDTC samples, among which 33 cases had concomitant DTC components or DTC history. We performed immunohistochemistry for BRAF V600E, p53, and PD-L1 expression, Sanger sequencing for TERT promoter and RAS mutations, and fluorescence in situ hybridization for ALK and RET rearrangements. We found that ATCs and PDTCs shared similar gene alterations to their coexisting DTCs, and most DTCs were aggressive subtypes harboring frequent TERT promoter mutations. A significantly higher proportion of ATCs expressed p53 and PD-L1, and a lower proportion expressed PAX-8 and TTF-1, than the coexisting DTCs. Our findings provide more reliable evidence that ATCs and PDTCs are derived from DTCs.

Possible involvement of zinc transporter ZIP13 in myogenic differentiation.

Ehlers-Danlos syndrome spondylodysplastic type 3 (EDSSPD3, OMIM 612350) is an inherited recessive connective tissue disorder that is caused by loss of function of SLC39A13/ZIP13, a zinc transporter belonging to the Slc39a/ZIP family. We previously reported that patients with EDSSPD3 harboring a homozygous loss of function mutation (c.221G > A, p.G64D) in ZIP13 exon 2 (ZIP13G64D) suffer from impaired development of bone and connective tissues, and muscular hypotonia. However, whether ZIP13 participates in the early differentiation of these cell types remains unclear. In the present study, we investigated the role of ZIP13 in myogenic differentiation using a murine myoblast cell line (C2C12) as well as patient-derived induced pluripotent stem cells (iPSCs). We found that ZIP13 gene expression was upregulated by myogenic stimulation in C2C12 cells, and its knockdown disrupted myotubular differentiation. Myocytes differentiated from iPSCs derived from patients with EDSSPD3 (EDSSPD3-iPSCs) also exhibited incomplete myogenic differentiation. Such phenotypic abnormalities of EDSSPD3-iPSC-derived myocytes were corrected by genomic editing of the pathogenic ZIP13G64D mutation. Collectively, our findings suggest the possible involvement of ZIP13 in myogenic differentiation, and that EDSSPD3-iPSCs established herein may be a promising tool to study the molecular basis underlying the clinical features caused by loss of ZIP13 function.

Temporomandibular disorders among Ehlers-Danlos syndromes: a narrative review.

This narrative review aims to demonstrate and summarize the complex relationship between Ehlers-Danlos syndromes (EDS) and temporomandibular disorders (TMD) by reviewing the results of observational studies and case reports. EDS are a set of hereditary connective tissue disorders, where generalized joint hypermobility (GJH), especially in the hypermobile subtype (hEDS), is a key symptom. Mutations have been identified in genes that impact the production or assembly of collagen for all subtypes except hEDS. While the correlation between GJH and TMD has been analysed in various studies, fewer studies have examined TMD in patients with EDS, with most showing an increased prevalence of TMD. In case-control studies, an elevated prevalence of myalgia, arthralgia and disc-related disorders was found in individuals with EDS. Various therapeutic interventions have been reported within the literature in the form of case reports and observational studies, but there are no long-term clinical trials with results on the efficacy of different therapeutic approaches to date. This review demonstrates the high prevalence of different TMDs in different subtypes of EDS, but also shows that little is known about the success of treatment thus far. Further clinical research is necessary to provide adequate guidance on targeted treatment.

Impairment of lung volume perception and breathing control in hypermobile Ehlers-Danlos syndrome.

Breathing difficulties and exertional dyspnea are frequently reported in hypermobile Ehlers-Danlos syndrome (hEDS); however, they are not clearly explained. An impaired proprioception or the addition of a cognitive task could influence ventilatory control. How can the perception of lung volume be measured? Is lung volume perception impaired in hEDS patients? Is the breathing control impaired during a cognitive task in hEDS patients? A device was developed to assess the accuracy of lung volume perception in patients with hEDS and matched control subjects. In the second step, ventilation was recorded in both groups with and without a cognitive task. Two groups of 19 subjects were included. The accuracy of lung volume perception was significantly (P < 0.01) lower at 30% of inspired vital capacity in patients with hEDS in comparison to the control group, and they showed erratic ventilation (based on spatial and temporal criteria) when performing a cognitive task. These data support the influence of the proprioceptive deficit on ventilatory control in hEDS patients. These elements may help to understand the respiratory manifestations found in hEDS. Future research should focus on this relationship between lung volume perception and ventilation, and could contribute to our understanding of other pathologies or exercise physiology.Trial registration number: ClinicalTrials.gov, NCT05000151.

Hyperhidrosis and Hypermobility Spectrum Disorders Among Adolescents.

This cross-sectional study assesses the prevalence and risk of excessive sweating and joint hypermobility in Israeli adolescents aged 16 to 19 years.

Heterozygous THBS2 pathogenic variant causes Ehlers-Danlos syndrome with prominent vascular features in humans and mice.

Ehlers-Danlos syndromes (EDS) are a group of connective tissue disorders caused by mutations in collagen and collagen-interacting genes. We delineate a novel form of EDS with vascular features through clinical and histopathological phenotyping and genetic studies of a three-generation pedigree, displaying an apparently autosomal dominant phenotype of joint hypermobility and frequent joint dislocations, atrophic scarring, prolonged bleeding time and age-related aortic dilatation and rupture. Coagulation tests as well as platelet counts and function were normal. Reticular dermis displayed highly disorganized collagen fibers and transmission electron microscopy (TEM) revealed abnormally shaped fibroblasts and endothelial cells, with high amount and irregular shape of extracellular matrix (ECM) substance, especially near blood vessels. Genetic analysis unraveled a heterozygous mutation in THBS2 (NM_003247.5:c.2686T>C, p.Cys896Arg). We generated CRISPR/Cas9 knock-in (KI) mice, bearing the heterozygous human mutation in the mouse ortholog. The KI mice demonstrated phenotypic traits correlating with those observed in the human subjects, as evidenced by morphologic, histologic, and TEM analyses, in conjunction with bleeding time assays. Our findings delineate a novel form of human EDS with classical-like elements combined with vascular features, caused by a heterozygous THBS2 missense mutation. We further demonstrate a similar phenotype in heterozygous THBS2Cys896Arg KI mice, in line with previous studies in Thbs2 homozygous null-mutant mice. Notably, THBS2 encodes Thrombospondin-2, a secreted homotrimeric matricellular protein that directly binds the ECM-shaping Matrix Metalloproteinase 2 (MMP2), mediating its clearance. THBS2 loss-of-function attenuates MMP2 clearance, enhancing MMP2-mediated proteoglycan cleavage, causing ECM abnormalities similar to those seen in the human and mouse disease we describe.

Heavy Menstrual Bleeding in Adolescents with Joint Hypermobility Syndrome/Hypermobile-Type Ehlers-Danlos: A Review.

Heavy menstrual bleeding has a high prevalence and is well documented in adult patients with hypermobile-type Ehlers-Danlos syndrome, but there is limited research surrounding work-up and treatment for the adolescent population. Excessive menstrual blood loss can significantly interfere with emotional and physical quality of life. A provider should acquire a comprehensive medical and menstrual history and focused physical examination, as well as baseline laboratory studies, to determine the presence of anemia or underlying bleeding disorder. Use of a pictorial blood assessment chart may be considered to help quantify the amount of bleeding. Treatment to reduce heavy menstrual flow and referral to specialty care should be initiated swiftly to improve quality of life for this population. [Pediatr Ann. 2024;53(3):e104-e108.].

Web-based survey investigating cardiovascular complications in hypermobile Ehlers-Danlos syndrome after COVID-19 infection and vaccination.

BACKGROUND: Hypermobile Ehlers-Danlos syndrome is a heritable connective tissue disorder associated with generalized joint hypermobility but also other multisystem comorbidities, many of which may be exacerbated during a viral illness or after a vaccination. We sought to determine whether individuals with hypermobile Ehlers Danlos syndrome report an increase in adverse events, including cardiovascular events, after COVID-19 illness or vaccination. METHODS: A cross-sectional web-based survey was made available from November 22, 2021, through March 15, 2022. 368 respondents primarily from the United States self-reported data including diagnosis. We used a Cox proportional hazards model with time varying indicators for COVID-19 illness or vaccination in the previous 30 days. RESULTS: We found a significantly increased rate of new abnormal heart rhythms reported in the 30 days following COVID-19 illness. No additional cardiovascular events were reported after COVID-19 illness. 2.5% of respondents with COVID-19 illness were hospitalized. We did not find a statistically significant increased rate of cardiovascular events in the 30 days following any COVID-19 vaccination dose. Post COVID-19 vaccination, 87.2% of hypermobile Ehlers-Danlos syndrome respondents endorsed an expected adverse event (EAE), and 3.1% reported an emergency department visit/hospitalization, of those who received at least one vaccine dose. Events possibly reflecting exacerbation of orthostasis/dysautonomia were common. CONCLUSION: Respondents did not report an increased rate of any cardiovascular events in the 30 days following COVID-19 vaccination; however, those with hypermobile Ehlers-Danlos syndrome experienced a high rate of expected adverse events after vaccination consistent with a high baseline prevalence of similar symptoms. No cardiovascular events other than new abnormal heart rhythms were reported at any point after a COVID-19 illness.