The Ehlers-Danlos syndromes (EDS) are a clinically and genetically heterogeneous group of heritable connective tissue disorders (HCTDs) characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Over the past two decades, the Villefranche Nosology, which delineated six subtypes, has been widely used as the standard for clinical diagnosis of EDS. For most of these subtypes, mutations had been identified in collagen-encoding genes, or in genes encoding collagen-modifying enzymes. Since its publication in 1998, a whole spectrum of novel EDS subtypes has been described, and mutations have been identified in an array of novel genes. The International EDS Consortium proposes a revised EDS classification, which recognizes 13 subtypes. For each of the subtypes, we propose a set of clinical criteria that are suggestive for the diagnosis. However, in view of the vast genetic heterogeneity and phenotypic variability of the EDS subtypes, and the clinical overlap between EDS subtypes, but also with other HCTDs, the definite diagnosis of all EDS subtypes, except for the hypermobile type, relies on molecular confirmation with identification of (a) causative genetic variant(s). We also revised the clinical criteria for hypermobile EDS in order to allow for a better distinction from other joint hypermobility disorders. To satisfy research needs, we also propose a pathogenetic scheme, that regroups EDS subtypes for which the causative proteins function within the same pathway. We hope that the revised International EDS Classification will serve as a new standard for the diagnosis of EDS and will provide a framework for future research purposes. © 2017 Wiley Periodicals, Inc.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/ajmg.c.31552

The 2017 international classification of the Ehlers-Danlos syndromes

Background: At the Third International Workshop on Asymptomatic Primary Hyperparathyroidism (PHPT) in May 2008, recent data on the disease were reviewed. We present the results of a literature review on issues arising from the clinical presentation and natural history of PHPT. Methods: Questions were developed by the International Task Force on PHPT. A comprehensive literature search for relevant studies was reviewed, and the questions of the International Task Force were addressed by the Consensus Panel. Conclusions: 1) Data on the extent and nature of cardiovascular involvement in those with mild disease are too limited to provide a complete picture. 2) Patients with mild PHPT have neuropsychological complaints. Although some symptoms may improve with surgery, available data remain inconsistent on their precise nature and reversibility. 3) Surgery leads to long-term gains in spine, hip, and radius bone mineral density (BMD). Because some patients have early disease progression and others lose BMD after ...

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Diagnosis of asymptomatic primary hyperparathyroidism: proceedings of the third international workshop.

The hypermobile type of Ehlers-Danlos syndrome (hEDS) is likely the most common hereditary disorder of connective tissue. It has been described largely in those with musculoskeletal complaints including joint hypermobility, joint subluxations/dislocations, as well as skin and soft tissue manifestations. Many patients report activity-related pain and some go on to have daily pain. Two undifferentiated syndromes have been used to describe these manifestations-joint hypermobility syndrome and hEDS. Both are clinical diagnoses in the absence of other causation. Current medical literature further complicates differentiation and describes multiple associated symptoms and disorders. The current EDS nosology combines these two entities into the hypermobile type of EDS. Herein, we review and summarize the literature as a better clinical description of this type of connective tissue disorder. © 2017 Wiley Periodicals, Inc.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/ajmg.c.31538

Hypermobile Ehlers-Danlos syndrome (a.k.a. Ehlers-Danlos syndrome Type III and Ehlers-Danlos syndrome hypermobility type): Clinical description and natural history.

Rheumatoid arthritis (RA) is a chronic immuno-mediated disease primarily affecting the joints, characterized by persistent high-grade systemic inflammation. Cardiovascular morbidity and mortality are significantly increased in RA, with >50% of premature deaths attributable to cardiovascular disease. In particular, RA patients were twice as likely to experience sudden cardiac death compared with non-RA subjects, pointing to an increased propensity to develop malignant ventricular arrhythmias. Indeed, ventricular repolarization (QT interval) abnormalities and cardiovascular autonomic nervous system dysfunction, representing two well-recognized risk factors for life-threatening ventricular arrhythmias in the general population, are commonly observed in RA. Moreover, large population-based studies seem to indicate that also the prevalence of atrial fibrillation is significantly higher in RA subjects than in the general population, thus suggesting that these patients are characterized by an abnormal diffuse myocardial electrical instability. Although the underlying mechanisms accounting for the pro-arrhythmogenic substrate in RA are probably intricate, the leading role seems to be played by chronic systemic inflammatory activation, able to promote arrhythmias both indirectly, by accelerating the development of ischaemic heart disease and congestive heart failure, and directly, by affecting cardiac electrophysiology. In this integrated mechanistic view, lowering the inflammatory burden through an increasingly tight control of disease activity may represent the most effective intervention to reduce arrhythmic risk in these patients. Intriguingly, these considerations could be more generally applicable to all the diseases characterized by chronic systemic inflammation, and could help elucidate the link between low-grade chronic inflammation and arrhythmic risk in the general population.

Systemic inflammation and arrhythmic risk: lessons from rheumatoid arthritis

Ehlers-Danlos syndrome, hypermobility type, constituting a phenotypic continuum with or, perhaps, corresponding to the joint hypermobility syndrome (JHS/EDS-HT), is likely the most common, though the least recognized, heritable connective tissue disorder. Known for decades as a hereditary condition with predominant rheumatologic manifestations, it is now emerging as a multisystemic disorder with widespread manifestations. Nevertheless, the practitioners' awareness of this condition is generally poor and most patients await years or, perhaps, decades before reaching the correct diagnosis. Among the various sites of disease manifestations, skin and mucosae represent a neglected organ where the dermatologist can easily spot diagnostic clues, which consistently integrate joint hypermobility and other orthopedic/neurologic manifestations at physical examination. In this paper, actual knowledge on JHS/EDS-HT is summarized in various sections. Particular attention has been posed on overlooked manifestations, including cutaneous, mucosal, and oropharyngeal features, and early diagnosis techniques, as a major point of interest for the practicing dermatologist. Actual research progresses on JH/EDS-HT envisage an unexpected link between heritable dysfunctions of the connective tissue and a wide range of functional somatic syndromes, most of them commonly diagnosed in the office of various specialists, comprising dermatologists.

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Ehlers-Danlos Syndrome, Hypermobility Type: An Underdiagnosed Hereditary Connective Tissue Disorder with Mucocutaneous, Articular, and Systemic Manifestations

AIM: To identify the most effective treatment of duodenal stump fistula (DSF) after gastrectomy for gastric cancer.

METHODS: A systematic review of the literature was performed. PubMed, EMBASE, Cochrane Library, CILEA Archive, BMJ Clinical Evidence and UpToDate databases were analyzed. Three hundred eighty-eight manuscripts were retrieved and analyzed and thirteen studies published between 1988 and 2014 were finally selected according to the inclusion criteria, for a total of 145 cases of DSF, which represented our group of study. Only patients with DSF after gastrectomy for malignancy were selected. Data about patients’ characteristics, type of treatment, short and long-term outcomes were extracted and analyzed.

RESULTS: In the 13 studies different types of treatment were proposed: conservative approach, surgical approach, percutaneous approach and endoscopic approach (3 cases). The overall mortality rate was 11.7% for the entire cohort. The more frequent complications were sepsis, abscesses, peritonitis, bleeding, pneumonia and multi-organ failure. Conservative approach was performed in 6 studies for a total of 79 patients, in patients with stable general condition, often associated with percutaneous approach. A complete resolution of the leakage was achieved in 92.3% of these patients, with a healing time ranging from 17 to 71 d. Surgical approach included duodenostomy, duodeno-jejunostomy, pancreatoduodenectomy and the use of rectus muscle flap. In-hospital stay of patients who underwent relaparotomy ranged from 1 to 1035 d. The percutaneous approach included drainage of abscesses or duodenostomy (32 cases) and percutaneous biliary diversion (13 cases). The median healing time in this group was 43 d.

CONCLUSION: Conservative approach is the treatment of choice, eventually associated with percutaneus drainage. Surgical approach should be reserved for severe cases or when conservative approaches fail.

Management of duodenal stump fistula after gastrectomy for gastric cancer: Systematic review

Screening for Celiac Disease in the Joint Hypermobility Syndrome/Ehlers–Danlos Syndrome Hypermobility Type Chiara Danese, Marco Castori,* Claudia Celletti, Silvia Amato, Caterina Lo Russo, Paola Grammatico, and Filippo Camerota Department of Clinical Science, Sapienza University, Umberto I Hospital, Rome, Italy Medical Genetics, Department of Molecular Medicine, Sapienza University, San Camillo-Forlanini Hospital, Rome, Italy Department of Physical Medicine and Rehabilitation, Sapienza University, Umberto I Hospital, Rome, Italy

Screening for celiac disease in the joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type

https://www.internationaljournalofcardiology.com/article/S0167-5273(06)01154-5/pdf

Increased risk of cardiac death in primary hyperparathyroidism: What is a role of electrical instability?

Cardiac involvement has been studied quite extensively in patients affected by inflammatory bowel disease but, as of now, there is no data regarding QT alterations which are well known to be linked to the risk of dangerous arrhythmias. In this study, QT parameters were digitally measured on standard 12-lead ECG in a population of 20 patients affected by inflammatory bowel disease (IBD), with no prior (recent or old) history of cardiac disease and no evidence of electrolyte imbalance. Eighteen healthy subjects formed the control group. The results obtained using non-parametric statistics (Wilcoxon–Mann–Whitney test) showed that heart rate corrected QT interval (QTc) and QTc dispersion (QTc d) values were both significantly higher in IBD patients than in the control group. QTc rank sum values in patients affected by inflammatory bowel disease were 469 versus 311 in healthy subjects (Z = 1.939, p = 0.0263). QTc d rank sum values were 460 in IBD patients versus 320 in controls (Z = 1.686 with p = 0.0459). Regardless of the cause of these QT alterations, it appears evident that accurate monitoring of QT parameters is required in these patients who often experience electrolyte disturbances and who may, in some cases, be undergoing treatment with potentially cardiotoxic drugs such as infliximab.

Silvia Amato

Papers

Management of duodenal stump fistula after gastrectomy for gastric cancer: Systematic review

Screening for celiac disease in the joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type

Increased risk of cardiac death in primary hyperparathyroidism: What is a role of electrical instability?

A study on QT interval in patients affected with inflammatory bowel disease without cardiac involvement.

Parathyroidectomy erase increased myocardial electrical vulnerability in patients with primary hyperparathyroidism.