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.

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.

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.

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.

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.

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.

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.

Mast cell activation and nutritional disorders in patients with hypermobility.

PURPOSE OF REVIEW: Individuals with joint hypermobility disorders are increasingly referred to gastroenterology services for support with the investigation and management of gastrointestinal complaints. Individuals can present with a myriad of complex coexisting diagnoses, the inter-relationship of which is unclear. This review discusses the proposed association between hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorder (HSD) with disorders of mast cell activation and provides an overview of gastrointestinal symptoms and nutritional outcomes in this patient cohort. RECENT FINDINGS: It is unclear whether a true association between hEDS/HSD and mast cell activation disorders exists. There is a high prevalence of nonspecific gastrointestinal symptoms in individuals with hEDS/HSD and patients may be at risk of macro-nutrient and micro-nutrient deficiencies, although the current evidence base is limited. SUMMARY: We advocate a pragmatic approach to the investigation and management of gastrointestinal symptoms in patients with hEDS/HSD. This centres on excluding organic pathology, discussing the overlap with disorders of gut-brain interactions, trialling evidence-based therapies targeting individual symptoms, and supporting nutritional deficiencies where present via the least invasive approach. Engagement with a broad multidisciplinary team is also important to support the holistic needs of this patient cohort.

The use and effectiveness of exercise for managing postural orthostatic tachycardia syndrome in young adults with joint hypermobility and related conditions: A scoping review.

PURPOSE: Postural Orthostatic Tachycardia Syndrome (POTS) is a form of dysautonomia. It may occur in isolation, but frequently co-exists in individuals with hypermobile variants of Ehlers-Danlos Syndrome (EDS) and related conditions (chronic fatigue syndrome [CFS] and fibromyalgia). Exercise is recommended for non-pharmacological POTS management but needs to be individualised. This scoping review explores the current literature on use and effectiveness of exercise-based management for POTS, with specific focus on individuals with joint hypermobility and related conditions who experience hypermobility, and/or pain, and/or fatigue. METHODS: A systematic search, to January 2023, of Medline, EMBASE, AMED, CINAHL and the Cochrane library was conducted. Studies that reported on adolescents and adults who had been diagnosed with POTS using standard criteria and underwent an exercise-based training intervention were included. RESULTS: Following full-text screening, 10 articles were identified (2 randomised control trials, 4 comparative studies and 4 case reports). One comparative study reported a small subset of participants with EDS and one case report included an individual diagnosed with CFS; the remainder investigated a wider POTS population. Overall, 3 months of endurance followed by resistance exercise, graduating from the horizontal-to-upright position reduced POTS symptoms and improved quality-of-life. CONCLUSION: The findings highlight a paucity of higher-level studies documenting exercise for POTS management in people with joint hypermobility and related conditions. Results from the wider POTS population demonstrate exercise is safe and effective. Large, well-designed clinical studies exploring exercise for POTS management adapting to meet the complex musculoskeletal and non-musculoskeletal features of symptomatic joint hypermobility are needed.

The association of pain with gait spatiotemporal parameters in children with hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorder.

BACKGROUND: Children with hypermobility spectrum disorder/hypermobile Ehlers-Danlos syndrome (HSD/hEDS) have a high prevalence of chronic pain, which may influence gait dynamics. However, little is known about pain outcomes and their association with gait spatiotemporal parameters in children with HSD/hEDS. RESEARCH QUESTION: Does pain correlate with gait spatiotemporal parameters in children with HSD/hEDS? METHODS: Eighteen children with HSD/hEDS and eighteen typically developing (TD) children participated in the study. The current level of pain (0-10 on the numeric rating scale), modified Brief Pain Inventory, and Pain Catastrophizing Scale-Child version were implemented to assess pain in children with HSD/hEDS. All children completed a gait analysis at a self-selected speed. Mean and variability (measured using the coefficient of variation) of gait spatiotemporal parameters were analyzed. Gait parameters included stride length, stride time, gait speed, percent stance time, and step width. A Mann-Whitney U-test was used to compare the gait parameters between children with HSD/hEDS and TD children. Spearman correlations were used to examine the relationships between pain and gait spatiotemporal parameters in children with HSD/hEDS. RESULTS: Children with HSD/hEDS had a longer percent stance time compared to TD children (p = 0.03). Lower pain interference in relationships with other people was significantly associated with faster gait speeds (ρ = -0.55, p = 0.03). Children with HSD/hEDS also had greater pain interference during mobility (ρ = 0.5, p = 0.05) and going to school (ρ = 0.65, p = 0.01), which were significantly correlated with greater stride length variability. Greater pain interference during enjoyment of life was significantly associated with greater percent stance time variability (ρ = 0.5, p = 0.05). Greater pain catastrophizing was correlated with decreased step width variability in children with HSD/hEDS (ρ = -0.49, p = 0.05). SIGNIFICANCE: Pain interference and catastrophe were significantly associated with gait spatiotemporal variability. Our findings suggest that assessing pain-associated gait alterations may help understand the clinical features and gait kinematics of children with HSD/hEDS.

Functional neurological signs in hypermobile Ehlers-Danlos syndrome and hypermobile spectrum disorders with suspected neuropathic pain.

BACKGROUND: The hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD) are connective tissue disorders characterized by generalized joint hypermobility, associated with chronic pain and several symptoms, such as fatigue, dysautonomia, as well as psychiatric co-morbidities. Clinical observations of unusual manifestations during systematic sensory testing raised the question of a possible co-existence with a functional neurological disorder (FND). Hence, this study aimed to assess the presence of positive functional neurological signs (FNS) in a cohort of patients with hEDS/HSD. METHODS: The clinical data of hEDS/HSD patients (N = 24) were retrospectively analyzed and compared to a prospectively recruited age-/sex-matched healthy control group (N = 22). Four motor- and three sensory-positive FNS were assessed. RESULTS: Twenty-two patients (92%) presented at least one motor or sensory FNS. Five patients (21%) presented only a single FNS, 14 presented between 2 and 4 FNS (58%), and 3 patients presented 5 or more FNS (12%). None of the healthy controls presented motor FNS, and only two presented a sensory FNS. CONCLUSIONS: The presence of FNS in hEDS/HSD deserves better clinical detection and formal diagnosis of FND to offer more adequate care in co-morbid situations. In fact, FND can severely interfere with rehabilitation efforts in hEDS/HSD, and FND-targeted physical therapy should perhaps be combined with EDS/HSD-specific approaches.

Craniocervical instability in patients with Ehlers-Danlos syndromes: outcomes analysis following occipito-cervical fusion.

Craniocervical instability (CCI) is increasingly recognized in hereditary disorders of connective tissue and in some patients following suboccipital decompression for Chiari malformation (CMI) or low-lying cerebellar tonsils (LLCT). CCI is characterized by severe headache and neck pain, cervical medullary syndrome, lower cranial nerve deficits, myelopathy, and radiological metrics, for which occipital cervical fusion (OCF) has been advocated. We conducted a retrospective analysis of patients with CCI and Ehlers-Danlos syndrome (EDS) to determine whether the surgical outcomes supported the criteria by which patients were selected for OCF. Fifty-three consecutive subjects diagnosed with EDS, who presented with severe head and neck pain, lower cranial nerve deficits, cervical medullary syndrome, myelopathy, and radiologic findings of CCI, underwent open reduction, stabilization, and OCF. Thirty-two of these patients underwent suboccipital decompression for obstruction of cerebral spinal fluid flow. Questionnaire data and clinical findings were abstracted by a research nurse. Follow-up questionnaires were administered at 5-28 months (mean 15.1). The study group demonstrated significant improvement in headache and neck pain (p < 0.001), decreased use of pain medication (p < 0.0001), and improved Karnofsky Performance Status score (p < 0.001). Statistically significant improvement was also demonstrated for nausea, syncope (p < 0.001), speech difficulties, concentration, vertigo, dizziness, numbness, arm weakness, and fatigue (p = 0.001). The mental fatigue score and orthostatic grading score were improved (p < 0.01). There was no difference in pain improvement between patients with CMI/LLCT and those without. This outcomes analysis of patients with disabling CCI in the setting of EDS demonstrated significant benefits of OCF. The results support the reasonableness of the selection criteria for OCF. We advocate for a multi-center, prospective clinical trial of OCF in this population.

Diagnosis and treatment of cardiovascular disease in patients with heritable connective tissue disorders or heritable thoracic aortic diseases.

Patients with heritable connective tissue disorders (HCTDs), represented by Marfan syndrome, can develop fatal aortic and/or arterial complications before age 50. Therefore, accurate diagnosis, appropriate medical treatment, and early prophylactic surgical treatment of aortic and arterial lesions are essential to improve prognosis. Patients with HCTDs generally present with specific physical features due to connective tissue abnormalities, while some patients with heritable thoracic aortic diseases (HTADs) have few distinctive physical characteristics. The development of genetic testing has made it possible to provide accurate diagnoses for patients with HCTDs/HTADs. This review provides an overview of the diagnosis and treatment of HCTDs/HTADs, including current evidence on cardiovascular interventions for this population.

Treating pain in patients with Ehlers-Danlos syndrome : Multidisciplinary management of a multisystemic disease.

BACKGROUND: The clinical picture of people with Ehlers-Danlos syndromes (EDS) is complex and involves a variety of potential causes of pain. This poses major challenges to patients and healthcare professionals alike in terms of diagnosis and management of the condition. OBJECTIVES: The aim of the article was to provide an overview of the specific pain management needs of patients with EDS and address their background. MATERIAL AND METHODS: A selective literature search was performed to highlight the current state of research on pain management in EDS patients. RESULTS: Affected patients require multimodal pain management considering their individual needs, disease-specific features, and comorbidities. CONCLUSION: Medical awareness and evidence need to be further improved to enhance the medical care situation of these patients with complex needs.

Healthcare experiences among adults with hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorder in the United States.

PURPOSE: This cross-sectional mixed-method study examined healthcare experiences among individuals in the US with hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorder (HSD), genetic connective tissue disorders. We hypothesized that many individuals with these conditions would report low satisfaction with healthcare and low health-related quality of life, and that lower healthcare satisfaction would be related to lower health-related quality of life and self-efficacy for symptom management. METHODS: Adults living in the US with hEDS or HSD (N= 2125) completed an online survey assessing satisfaction with healthcare, health-related quality of life, and symptom management self-efficacy. Qualitative data also were gathered on desired changes to improve healthcare. RESULTS: Participants reported low satisfaction with healthcare and lower health-related quality of life and symptom management self-efficacy than norm groups. Lower satisfaction with healthcare was associated with lower health-related quality of life and lower symptom management self-efficacy, ps <.001. The most common desired change to improve healthcare was more knowledge about hEDS and HSD among healthcare professionals. CONCLUSIONS: U.S. adults with joint hypermobility report negative healthcare experiences and poor health-related quality of life. Future research should explore ways to improve the healthcare experiences and quality of care for individuals with hEDS and HSD.Implications for RehabilitationIndividuals with hypermobility spectrum disorder (HSD) and hypermobile Ehlers-Danlos syndrome (hEDS) score worse than the U.S. population on most health-related quality of life domains and symptom management self-efficacy.Individuals with HSD and hEDS report low levels of satisfaction with healthcare compared to norm groups.Participants particularly wanted to see improvements in the level of awareness and education about HSD and hEDS among healthcare professionals, provider attitudes about HSD and hEDS, and healthcare accessibility and convenience.Individuals who were less satisfied with their healthcare reported lower health-related quality of life and lower symptom management self-efficacy, underscoring the importance of improving healthcare experiences.

Patients' strategies for numeric pain assessment: a qualitative interview study of individuals with hypermobile Ehlers-Danlos Syndrome.

PURPOSE: Chronic pain is a common feature of hypermobile Ehlers-Danlos Syndrome (hEDS), yet how patients assess and communicate their pain remains poorly understood. The objective of the present study was to explore the use of numeric pain assessment in individuals with hEDS, from a patient-centered perspective. MATERIALS AND METHODS: Our analysis is based on in-depth qualitative interviews. The interviews were conducted over the phone. Our participants were patients living with hEDS (N = 35). Interviews were recorded, transcribed, and analyzed to identify factors related to their use of these pain assessment instruments. RESULTS: Three primary themes emerged from these data, namely, (1) confusion around the quantification of multidimensional pain, (2) the subjectivity of pain experience, and (3) a strategic use of assessments for practical purposes beyond the accurate representation of pain.These results demonstrate the need for caution in relying exclusively on numeric pain assessment instruments. We conclude with a brief proposal for a clinical communication strategy that may help to address the limitations of numeric pain assessment that were identified in our interviews.

Chronic pain is a common feature of hypermobile Ehlers­Danlos Syndrome (hEDS), yet how patients assess and communicate their pain remains poorly understood.Clinicians should be aware that patients have difficulties with the Numeric Rating Scale (NRS) for at least three reasons: (1) confusion around the quantification of multidimensional pain, (2) the subjectivity of pain experience, and (3) a strategic use of assessments for practical purposes beyond the accurate representation of pain.Clinicians should use caution in relying exclusively on NRS instruments.Clinicians may benefit from using clinical communication strategies outlined in our paper, which may help to address the limitations of the NRS that were identified in our interviews.

Psychological interventions to improve pain, fatigue, anxiety, depression, and quality of life in children and adults with hypermobility spectrum disorders and Ehlers-Danlos syndrome: a systematic review.

Hypermobility spectrum disorders (HSD) affect individuals across physical, psychological and social domains, making assessment and management difficult. Management for this condition primarily focuses on addressing the musculoskeletal complaints using physiotherapy rather than the additional manifestations such as fatigue, anxiety and depression. This systematic review aims to identify psychological interventions and assess whether they improve the lived experiences of individuals with HSD. It also aims to assess which psychological interventions were most effective, which symptoms were most effectively managed by a psychological intervention, and whether there were differences between children and adults. Studies were included if they were a randomised controlled trial or pre/post-test design, a sample of any age and clinical diagnosis of HSD (including Ehlers-Danlos syndrome), used a psychological intervention and assessed the effect of the intervention on lived experiences using appropriate outcome measures. Risk of bias was assessed using the Mixed Methods Appraisal Tool. The results were narratively synthesised. Six studies were included in the review, one isolated psychological intervention and five incorporated a psychological intervention within a multidisciplinary programme. The interventions predominantly aimed to reduce pain including intensity, interference, pain-related fear and catastrophising, with anxiety and depression, affect, daily living, fatigue also being evaluated. The most beneficial psychological interventions were those delivered alongside physiotherapy in an outpatient or community setting, improving both the physical and psychological aspects of pain, subsequently improving quality of life. However, there lacks randomised controlled trials with larger samples to definitively confirm the significant findings discussed in this review.