EP.FRI.719 Gastric Perforation Leading to The Diagnosis of Classic Ehlers Danlos syndrome: A Case Report of an Unusual Presentation

Abstract Background Ehlers-Danlos syndromes (EDS) are clinically and genetically heterogeneous group of heritable connective tissue disorders caused by defective collagen synthesis or structure. Vascular subtype (EDS IV) is reported to be associated with a higher incidence of gastrointestinal ruptures. The Most reported site of perforation was the colon particularly the sigmoid colon followed by small bowel. It is very rare to have stomach perforation. There were no reported cases among classic type I and II. In addition, this patient presented with Marfanoid habitus which may develop acute gastric volvulus in combined with pre-existing EDS, perforation can occur. Case description A 14-year-old girl attended our Emergency Department (ED) with abdominal pain and vomiting. Initially diagnosed with gastroenteritis and discharged once her condition improved. 24 hours later, she developed severe abdominal pain with recurrent vomiting with peritonitis evident on clinical examination. Initial KUB failed to show any free air, however, enhanced Computed Tomography (CT) revealed free air and proximal gut contrast extravasation. During exploratory laparotomy, an ischemia anterior and posterior gastric wall with gastric perforation was encountered. A free-hand partial gastrectomy was done. Her post-operative period was complicated with wound infection that managed successfully with Vacuum-assisted closure (VAC) dressing. She recovered well without gastrointestinal sequelae in 4 years follow up. Conclusions A high level of suspicion must be maintained for heritable systemic connective tissue diseases in any young patient with unusual spontaneous perforation. As these patients can develop life-threatening conditions, immediate intervention is required in addition to prepare for anticipated complications.

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Gastric Perforation Leading to The Diagnosis of Classic Ehlers Danlos syndrome: A Case Report of an Unusual Presentation.

10.21203/rs.3.rs-80043/v1 ◽

2020 ◽

Author(s):

Ahad Eid Aloatibi ◽

Ohood Hamad AlAamer ◽

Mohammed Abdullah Bawazeer ◽

Ali Audah Alzahrani

Keyword(s):

Abdominal Pain ◽

Connective Tissue ◽

Gastric Perforation ◽

Gastric Wall ◽

Gastric Volvulus ◽

Connective Tissue Diseases ◽

Partial Gastrectomy ◽

Type I ◽

Ehlers Danlos Syndrome ◽

Free Air

Abstract Background: Ehlers-Danlos syndromes (EDS) are a clinically and genetically heterogenous group of heritable connective tissue disorders caused by defective collagen synthesis or structure. Vascular subtype (EDS IV) is reported to be associated with higher incidence of gastrointestinal ruptures. The Most reported site of perforation was the colon particularly the sigmoid colon followed by small bowel. It is very rare to have stomach perforation. There were no reported cases among classic type I and II. In addition, this patient presented with Marfanoid habitus which may develop acute gastric volvulus in combined with pre-existing EDS, perforation can occur. Case presentation: We are presenting a 14-year-old girl who attended our Emergency Department (ED) with abdominal pain and vomiting. Initially diagnosed with gastroenteritis and discharged once her condition improved. 24 hours later, she developed severe abdominal pain with recurrent vomiting with peritonitis evident on clinical examination. Initial KUB failed to show any free air, however enhanced Computed Tomography (CT) revealed free air and proximal gut contrast extravasation. During exploratory laparotomy, an ischemia anterior and posterior gastric wall with gastric perforation was encountered. A free-hand partial gastrectomy was done. Her post-operative period was complicated with wound infection that managed successfully with Vacuum assisted closure (VAC) dressing. She recovered well without gastrointestinal sequalae in 4 years follow up. Conclusions: A high level of suspicion must be maintained for heritable systemic connective tissue diseases in any young patient with unusual spontaneous perforation. As these patients can develop life-threatening conditions, immediate intervention is required in addition to prepare for anticipated complications.

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Gastric perforation leading to the diagnosis of classic Ehlers–Danlos syndrome: a case report

Journal of Medical Case Reports ◽

10.1186/s13256-021-03108-6 ◽

2021 ◽

Vol 15 (1) ◽

Author(s):

Ahad E. Alotaibi ◽

Ohood H. AlAamer ◽

Mohammed A. Bawazeer ◽

Ali A. Alzahrani

Keyword(s):

Abdominal Pain ◽

Connective Tissue ◽

Bowel Perforation ◽

Connective Tissue Diseases ◽

Young Patients ◽

Partial Gastrectomy ◽

Contrast Extravasation ◽

Ehlers Danlos Syndrome ◽

Free Air ◽

Danlos Syndrome

Abstract Background Ehlers–Danlos syndrome is a clinically and genetically heterogeneous group of heritable connective tissue disorders caused by a defect in collagen synthesis and structure. The vascular subtype (Ehlers–Danlos syndrome IV) is reported to be associated with a higher incidence of gastrointestinal perforations. The most reported site of perforation is the colon, followed by the small bowel. Perforation of the stomach is very rare, and there are no reported cases to date of classic types I and II. Case presentation We present the case of a 14-year-old Saudi girl who visited our emergency department with abdominal pain and vomiting. Initially, she was diagnosed with gastroenteritis and discharged once her condition stabilized. After 48 hours, she developed severe abdominal pain with recurrent vomiting and peritonitis evident on clinical examination. Initial abdominal x-ray failed to show any free air; however, enhanced computed tomography revealed free air and contrast extravasation in the proximal gut. During exploratory laparotomy, a large perforation was found on the anterior wall of the stomach due to the underlying ischemia. The posterior wall had ischemic mucosa with an intact healthy serosa. A free-hand partial gastrectomy was performed to resect all ischemic parts of the stomach. Detailed examinations and laboratory workup were carried out after the surgery to figure out the possible underlying cause. The clinical findings during the physical examination supported marfanoid features. Marfan’s syndrome and related disorders sequencing panel was requested, and Deoxyribonucleic acid (DNA) samples were sent. Given results were supporting the diagnosis of classical Ehlers–Danlos syndrome, the patient was labeled as a case of Ehlers–Danlos syndrome. During the postoperative period, she developed a wound infection that was managed successfully with vacuum-assisted closure dressing. She recovered well without gastrointestinal sequelae in the 4 years of follow-up. Conclusions Heritable systemic connective tissue diseases must be given serious consideration in young patients with unusual spontaneous perforation. Such patients might develop life-threatening conditions that require immediate intervention. Hence, correct and timely diagnosis is important to prepare for the anticipated complications.

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Hereditary Connective Tissue Diseases in Young Adult Stroke: A Comprehensive Synthesis

Stroke Research and Treatment ◽

10.4061/2011/712903 ◽

2011 ◽

Vol 2011 ◽

pp. 1-18 ◽

Cited By ~ 4

Author(s):

Olivier M. Vanakker ◽

Dimitri Hemelsoet ◽

Anne De Paepe

Keyword(s):

Connective Tissue ◽

Metabolic Disorders ◽

Type Iv Collagen ◽

Connective Tissue Diseases ◽

Haemorrhagic Stroke ◽

Monogenic Disease ◽

Connective Tissue Disorders ◽

Ehlers Danlos Syndrome ◽

Type Iv ◽

Danlos Syndrome

Though the genetic background of ischaemic and haemorrhagic stroke is often polygenetic or multifactorial, it can in some cases result from a monogenic disease, particularly in young adults. Besides arteriopathies and metabolic disorders, several connective tissue diseases can present with stroke. While some of these diseases have been recognized for decades as causes of stroke, such as the vascular Ehlers-Danlos syndrome, others only recently came to attention as being involved in stroke pathogenesis, such as those related to Type IV collagen. This paper discusses each of these connective tissue disorders and their relation with stroke briefly, emphasizing the main clinical features which can lead to their diagnosis.

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Genetics of connective tissue diseases

10.1093/med/9780199642489.003.0042 ◽

2013 ◽

Author(s):

Myles Lewis ◽

Tim Vyse

Keyword(s):

Systemic Sclerosis ◽

Connective Tissue ◽

Large Scale ◽

Apoptotic Cell ◽

Association Studies ◽

Group Analysis ◽

Connective Tissue Diseases ◽

Susceptibility Genes ◽

Type I ◽

Genome Wide Association Studies

The advent of genome-wide association studies (GWAS) has been an exciting breakthrough in our understanding of the genetic aetiology of autoimmune diseases. Substantial overlap has been found in susceptibility genes across multiple diseases, from connective tissue diseases and rheumatoid arthritis (RA) to inflammatory bowel disease, coeliac disease, and psoriasis. Major technological advances now permit genotyping of millions of single nucleotide polymorphisms (SNPs). Group analysis of SNPs by haplotypes, aided by completion of the Hapmap project, has improved our ability to pinpoint causal genetic variants. International collaboration to pool large-scale cohorts of patients has enabled GWAS in systemic lupus erythematosus (SLE), systemic sclerosis and Behçet's disease, with studies in progress for ANCA-associated vasculitis. These 'hypothesis-free' studies have revealed many novel disease-associated genes. In both SLE and systemic sclerosis, identified genes map to known pathways including antigen presentation (MHC, TNFSF4), autoreactivity of B and T lymphocytes (BLK, BANK1), type I interferon production (STAT4, IRF5) and the NFκ‎B pathway (TNIP1). In SLE alone, additional genes appear to be involved in dysregulated apoptotic cell clearance (ITGAM, TREX1, C1q, C4) and recognition of immune complexes (FCGR2A, FCGR3B). Future developments include whole-genome sequencing to identify rare variants, and efforts to understand functional consequences of susceptibility genes. Putative environmental triggers for connective tissue diseases include infectious agents, especially Epstein-Barr virus; cigarette smoking; occupational exposure to toxins including silica; and low vitamin D, due to its immunomodulatory effects. Despite numerous studies looking at toxin exposure and connective tissue diseases, conclusive evidence is lacking, due to either rarity of exposure or rarity of disease.

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Unusual Differential Diagnosis of Upper Abdominal Pain

Diagnostic and Therapeutic Endoscopy ◽

10.1155/2009/817052 ◽

2009 ◽

Vol 2009 ◽

pp. 1-3

Author(s):

Lanthaler Monika ◽

Grissmann Thomas ◽

Schwentner Lukas ◽

Nehoda Hermann

Keyword(s):

Abdominal Pain ◽

Liver Abscess ◽

Unusual Case ◽

Foreign Bodies ◽

Gastric Perforation ◽

Gastric Wall ◽

Endoscopic Removal ◽

Quadrant Pain ◽

Anterior Gastric Wall ◽

Upper Abdominal

We here present an interesting unusual case of upper abdominal pain. The patient was a 38-year-old man, who was admitted to our hospital complaining of right upper quadrant pain caused by a toothpick that perforated the anterior gastric wall and penetrated segment I of the liver. After endoscopic removal and an initially uneventful course, computed tomography revealed a perigastric abscess that was treated by repeated gastroscopic rinsing via an endoscopically placed catheter. After another three uneventful weeks, a liver abscess with minor tendency to constrict the portal vein was diagnosed, and a segment I liver resection together with abscess drainage was performed. The peculiarity of this case is the rarity of toothpick ingestion and gastric perforation in a young and healthy white Caucasian followed by development of a liver abscess after primary uneventful endoscopic removal. In light of this case, gastric perforation due to ingested foreign bodies such as toothpicks can be considered a rare cause of upper abdominal pain.

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Neurovascular manifestations of connective-tissue diseases: A review

Interventional Neuroradiology ◽

10.1177/1591019916659262 ◽

2016 ◽

Vol 22 (6) ◽

pp. 624-637 ◽

Cited By ~ 31

Author(s):

Sarasa T Kim ◽

Waleed Brinjikji ◽

Giuseppe Lanzino ◽

David F Kallmes

Keyword(s):

Connective Tissue ◽

Treatment Options ◽

Connective Tissue Diseases ◽

Neurofibromatosis Type ◽

Cerebrovascular Diseases ◽

Connective Tissue Disorders ◽

Ehlers Danlos Syndrome ◽

Danlos Syndrome ◽

Heritable Connective Tissue Disorders

Patients with connective tissue diseases are thought to be at a higher risk for a number of cerebrovascular diseases such as intracranial aneurysms, dissections, and acute ischemic strokes. In this report, we aim to understand the prevalence and occurrences of such neurovascular manifestations in four heritable connective tissue disorders: Marfan syndrome, Ehlers-Danlos syndrome, Neurofibromatosis Type 1, and Loeys-Dietz syndrome. We discuss the fact that although there are various case studies reporting neurovascular findings in these connective tissue diseases, there is a general lack of case-control and prospective studies investigating the true prevalence of these findings in these patient populations. Furthermore, the differences observed in the manifestations and histology of such disease pathologies encourages future multi-center registries and studies in better characterizing the pathophysiology, prevalence, and ideal treatment options of neurovascular lesions in patents with connective tissue diseases.

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The TLRs and IFNs in patients with connective tissue diseases

Postępy Polskiej Medycyny i Farmacji ◽

10.5604/01.3001.0014.1583 ◽

2020 ◽

Vol 7 ◽

pp. 1-10

Author(s):

Agnieszka Paradowska-Gorycka ◽

Anna Wajda ◽

Barbara Stypińska ◽

Ewa Walczuk ◽

Marcela Walczyk ◽

...

Keyword(s):

Immune System ◽

Connective Tissue ◽

Immune Complexes ◽

Connective Tissue Diseases ◽

Serum Levels ◽

Protective Role ◽

Type I ◽

Complement Components ◽

Ifn Γ ◽

Stimulation Of

Autoimmune connective tissue diseases (ACTD) are characterized by spontaneous stimulation of the immune system and the production of autoantibodies. Some autoantibodies may create an immune complex with DNA and/or RNA and promote tissue inflammation. Immune complexes that contain nucleic acids can act as ligands for endosomal Toll-like receptors (TLR), which activation induces secretion of the type I and type III interferons. The present study aimed to determine whether TLRs and IFNs genes could be considered as potential ACTD biomarkers. IFN-A and IFN-G showed a relationship with a predisposition to the development of SLE and MCTD, and IFN-B with a predisposition to the development of SLE. The TLR7 rs5743305 T allele and rs5743316 A allele may play a protective role against the development of MCTD, and the TLR7 rs1731479 T allele and TLR8 rs17256081 C allele may be predictors of MCTD development. mRNA expression of the IFN-α, IFN-β, IFN-γ, TLR3, TLR8 and TLR7 was significantly higher in patients with SLE compared to patients with MCTD and SSc. MCTD patients with anti-U1-70k (+) had higher IFN-γ and lower IFN-β serum levels than patients without this antibody. In patients with SLE, serum levels of IFN-α and IFN-γ correlate with the concentration of complement components, and serum levels of IFN-α with disease activity. The study confirmed that the TLR-IFN pathway may be considered as an important pathogenic mechanism for ACTD.

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Psoriasis and Connective Tissue Diseases

International Journal of Molecular Sciences ◽

10.3390/ijms21165803 ◽

2020 ◽

Vol 21 (16) ◽

pp. 5803 ◽

Cited By ~ 1

Author(s):

Toshiyuki Yamamoto

Keyword(s):

Connective Tissue ◽

Genetic Background ◽

Type I Interferon ◽

Connective Tissue Diseases ◽

Neutrophil Extracellular Trap ◽

Type I ◽

T Helper ◽

T Helper 17 ◽

Psoriatic Disease ◽

Systemic Inflammatory Disease

Psoriasis is a chronic systemic inflammatory disease with various co-morbidities, having been recently considered as a comprehensive disease named psoriatic disease or psoriatic syndrome. Autoimmune diseases are one form of its co-morbidities. In addition to the genetic background, shared pathogenesis including innate immunity, neutrophil extracellular trap (NETs), and type I interferon, as well as acquitted immunity such as T helper-17 (Th17) related cytokines are speculated to play a significant role in both psoriasis and connective tissue diseases. On the other hand, there are definite differences between psoriasis and connective tissue diseases, such as their pathomechanisms and response to drugs. Therefore, we cannot expect that one stone kills two birds, and thus caution is necessary when considering whether the administered drug for one disease is effective or not for another disease. In this review, several connective tissue diseases and related diseases are discussed from the viewpoint of their coexistence with psoriasis.

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The Roles of Tenascins in Cardiovascular, Inflammatory, and Heritable Connective Tissue Diseases

Frontiers in Immunology ◽

10.3389/fimmu.2020.609752 ◽

2020 ◽

Vol 11 ◽

Author(s):

Ken-ichi Matsumoto ◽

Hiroki Aoki

Keyword(s):

Connective Tissue ◽

Inflammatory Diseases ◽

Expression Patterns ◽

Connective Tissue Diseases ◽

Connective Tissue Disorder ◽

Tissue Homeostasis ◽

Dependent Manner ◽

Specific Expression ◽

Ehlers Danlos Syndrome ◽

Tenascin C

Tenascins are a family of multifunctional extracellular matrix (ECM) glycoproteins with time- and tissue specific expression patterns during development, tissue homeostasis, and diseases. There are four family members (tenascin-C, -R, -X, -W) in vertebrates. Among them, tenascin-X (TNX) and tenascin-C (TNC) play important roles in human pathologies. TNX is expressed widely in loose connective tissues. TNX contributes to the stability and maintenance of the collagen network, and its absence causes classical-like Ehlers-Danlos syndrome (clEDS), a heritable connective tissue disorder. In contrast, TNC is specifically and transiently expressed upon pathological conditions such as inflammation, fibrosis, and cancer. There is growing evidence that TNC is involved in inflammatory processes with proinflammatory or anti-inflammatory activity in a context-dependent manner. In this review, we summarize the roles of these two tenascins, TNX and TNC, in cardiovascular and inflammatory diseases and in clEDS, and we discuss the functional consequences of the expression of these tenascins for tissue homeostasis.

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Syndrome of occipitoatlantoaxial hypermobility, cranial settling, and Chiari malformation Type I in patients with hereditary disorders of connective tissue

Journal of Neurosurgery Spine ◽

10.3171/spi-07/12/601 ◽

2007 ◽

Vol 7 (6) ◽

pp. 601-609 ◽

Cited By ~ 113

Author(s):

Thomas H. Milhorat ◽

Paolo A. Bolognese ◽

Misao Nishikawa ◽

Nazli B. McDonnell ◽

Clair A. Francomano

Keyword(s):

Connective Tissue ◽

Chiari Malformation ◽

Upright Position ◽

Paraxial Mesoderm ◽

Type I ◽

Pannus Formation ◽

Chiari Malformation Type I ◽

Ehlers Danlos Syndrome ◽

Hereditary Disorders ◽

Healthy Control

Object Chiari malformation Type I (CM-I) is generally regarded as a disorder of the paraxial mesoderm. The authors report an association between CM-I and hereditary disorders of connective tissue (HDCT) that can present with lower brainstem symptoms attributable to occipitoatlantoaxial hypermobility and cranial settling. Methods The prevalence of HDCT was determined in a prospectively accrued cohort of 2813 patients with CM-I. All patients underwent a detailed medical and neuroradiological workup that included an assessment of articular mobility. Osseous structures composing the craniocervical junction were investigated morphometrically using reconstructed 3D computed tomography and plain x-ray images in 114 patients with HDCT/CM-I, and the results were compared with those obtained in patients with CM-I (55 cases) and healthy control individuals (55 cases). Results The diagnostic criteria for Ehlers–Danlos syndrome and related HDCT were met in 357 (12.7%) of the 2813 cases. Hereditability was generally compatible with a pattern of autosomal dominant transmission with variable expressivity. The diagnostic features of HDCT/CM-I were distinguished from those of CM-I by clinical stigmata of connective tissue disease, a greater female preponderance (8:1 compared with 3:1, p < 0.001), and a greater incidence of lower brainstem symptoms (0.41 compared with 0.11, p < 0.001), retroodontoid pannus formation (0.71 compared with 0.11, p < 0.001), and hypoplasia of the oropharynx (0.44 compared with 0.02, p < 0.001). Measurements of the basion–dens interval, basion–atlas interval, atlas–dens interval, dens–atlas interval, clivus–atlas angle, clivus–axis angle, and atlas–axis angle were the same in the supine and upright positions in healthy control individuals and patients with CM-I. In patients with HDCT/CM-I, there was a reduction of the basion–dens interval (3.6 mm, p < 0.001), an enlargement of the basion–atlas interval (3.0 mm, p < 0.001), and a reduction of the clivus–axis angle (10.8°, p < 0.001), clivus–atlas angle (5.8°, p < 0.001), and atlas–axis angle (5.3°, p < 0.001) on assumption of the upright position. These changes were reducible by cervical traction or returning to the supine position. Conclusions The identification of HDCT in 357 patients with CM-I establishes an association between two presumably unrelated mesodermal disorders. Morphometric evidence in this cohort—cranial settling, posterior gliding of the occipital condyles, and reduction of the clivus–axis angle, clivus–atlas angle, and atlas–axis angle in the upright position—suggests that hypermobility of the occipitoatlantal and atlantoaxial joints contributes to retroodontoid pannus formation and symptoms referable to basilar impression.

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