Abdominal Compression Syndromes in the Ehlers-Danlos Syndrome
Clinical Genetics and Therapeutics
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Primary Categories:
- Clinical Genetics
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Secondary Categories:
- Clinical Genetics
Introduction:
Abdominal Compression Syndromes [ACS] include Median Arcuate Ligament Syndrome [MALS], Superior Mesenteric Artery Syndrome, May-Thurner Syndrome, and Nutcracker Syndrome. Diagnosis of ACS is challenging and frequently missed in patients with Ehlers-Danlos syndrome [EDS], even with their high prevalence of gastrointestinal symptoms. There is only one report of the frequency of ACS in EDS. This report details our experience with ACS in EDS patients.
Methods:
We have reviewed our records over the past 12 years of 1,568 patients with EDS, including 36 with ACS. Diagnoses were based on the Beighton scoring system and the 2017 revised nosology. About 80% of these patients had insurance enabling analyses of 5 EDS genes (COL1A1, COL1A2, COL3A1, COL5A1, COL5A2) and up to 13 additional connective tissue disorder genes (FBN1, PMEPA1, SMAD2, SMAD3, TGFB2, TGFB3, TGFBR1, TGFBR2). A majority also had additional analyses of up to 19 aneurysm/arterial dissection genes. Clinical diagnosis of ACS was made by clinical suspicion, physical exam, and radiographic imaging.
Results:
Key observations made on our patients with EDS and ACS signs include the following: all but 3/36 (8.3%) were female and almost all Caucasian. The age range at diagnosis was 14-50 years with 22/36 (61.1%) being 20-40 years of age. All patients experienced epigastric and/or left upper quadrant abdominal unremitting pain that lasted from 2-35 years.
Postural pain relief was reported by all but one. Postprandial pain occurred in all patients, with nausea and/or vomiting in all but 1. Significant weight loss occurred in 29/36 (80.6%). Scoliosis and/or lordosis was present in 18/36 (50.0%). All patients had bloating, and all were hyperallergic.
Intravenous fluids via a PORT or PICC line were necessary in 5/36 (13.9%); gastric or jejunal tube were present in 6/36 (16.7%). All patients had MALS and were diagnosed by abdominal CT scans, 3 also had MRAs. Pain relief following celiac ganglion block preceded surgery in all patients.
Concomitant May-Thurner syndrome occurred in 9/36 (25.0%), SMA syndrome 1/36 (2.8%), Thoracic Outlet Syndrome in 3/36 (8.3%), and Nutcracker syndrome in 3/36 (8.3%). A family history of aneurysm was noted in 8/36 (22.2%) [aortic 5, brain 3]. Eagle syndrome was observed in 2/36 (5.6%).
Gene sequencing revealed one patient with a likely pathogenic variant (COL11A2); many others have variants of uncertain significance. All patients have EDS, likely hypermobile EDS, for which gene discovery is awaited.
Conclusion:
The diagnosis of MALS was previously missed in all but one (incidental diagnosis), and frequently not considered despite years of pain. Most patients were initially dismissed by their caregivers with a diagnosis of IBS or a psychosomatic disorder.
Symptoms characteristic of MALS diagnosis include disabling unremitting postprandial epigastric/left upper quadrant abdominal pain, pain reproducible by applying pressure in the epigastrium, postural pain improvement, and sitophobia inducing weight loss.
Resection of MAL with or without resection of celiac plexus was performed in 22/36 patients (61.1%) thus far. Stents were placed in iliac veins for May-Thurner syndrome in 5 of the 9 cases thus far. Diagnostic imaging following clinical suspicion include CT/CTA, MRA, and duplex ultrasound.
Perioperative complications include migration of a celiac artery stent into the left iliac artery (1), clot formation (1), and thrombosis due to PICC (1). EDS-associated comorbidities included intracranial hypertension (1), tethered cord (1), Chiari I malformation (1), and congenital hip dysplasia (2).
Awareness of ACS in EDS will enable prompt diagnosis and treatment with avoidance of years of pain and unnecessary suffering.
Abdominal Compression Syndromes [ACS] include Median Arcuate Ligament Syndrome [MALS], Superior Mesenteric Artery Syndrome, May-Thurner Syndrome, and Nutcracker Syndrome. Diagnosis of ACS is challenging and frequently missed in patients with Ehlers-Danlos syndrome [EDS], even with their high prevalence of gastrointestinal symptoms. There is only one report of the frequency of ACS in EDS. This report details our experience with ACS in EDS patients.
Methods:
We have reviewed our records over the past 12 years of 1,568 patients with EDS, including 36 with ACS. Diagnoses were based on the Beighton scoring system and the 2017 revised nosology. About 80% of these patients had insurance enabling analyses of 5 EDS genes (COL1A1, COL1A2, COL3A1, COL5A1, COL5A2) and up to 13 additional connective tissue disorder genes (FBN1, PMEPA1, SMAD2, SMAD3, TGFB2, TGFB3, TGFBR1, TGFBR2). A majority also had additional analyses of up to 19 aneurysm/arterial dissection genes. Clinical diagnosis of ACS was made by clinical suspicion, physical exam, and radiographic imaging.
Results:
Key observations made on our patients with EDS and ACS signs include the following: all but 3/36 (8.3%) were female and almost all Caucasian. The age range at diagnosis was 14-50 years with 22/36 (61.1%) being 20-40 years of age. All patients experienced epigastric and/or left upper quadrant abdominal unremitting pain that lasted from 2-35 years.
Postural pain relief was reported by all but one. Postprandial pain occurred in all patients, with nausea and/or vomiting in all but 1. Significant weight loss occurred in 29/36 (80.6%). Scoliosis and/or lordosis was present in 18/36 (50.0%). All patients had bloating, and all were hyperallergic.
Intravenous fluids via a PORT or PICC line were necessary in 5/36 (13.9%); gastric or jejunal tube were present in 6/36 (16.7%). All patients had MALS and were diagnosed by abdominal CT scans, 3 also had MRAs. Pain relief following celiac ganglion block preceded surgery in all patients.
Concomitant May-Thurner syndrome occurred in 9/36 (25.0%), SMA syndrome 1/36 (2.8%), Thoracic Outlet Syndrome in 3/36 (8.3%), and Nutcracker syndrome in 3/36 (8.3%). A family history of aneurysm was noted in 8/36 (22.2%) [aortic 5, brain 3]. Eagle syndrome was observed in 2/36 (5.6%).
Gene sequencing revealed one patient with a likely pathogenic variant (COL11A2); many others have variants of uncertain significance. All patients have EDS, likely hypermobile EDS, for which gene discovery is awaited.
Conclusion:
The diagnosis of MALS was previously missed in all but one (incidental diagnosis), and frequently not considered despite years of pain. Most patients were initially dismissed by their caregivers with a diagnosis of IBS or a psychosomatic disorder.
Symptoms characteristic of MALS diagnosis include disabling unremitting postprandial epigastric/left upper quadrant abdominal pain, pain reproducible by applying pressure in the epigastrium, postural pain improvement, and sitophobia inducing weight loss.
Resection of MAL with or without resection of celiac plexus was performed in 22/36 patients (61.1%) thus far. Stents were placed in iliac veins for May-Thurner syndrome in 5 of the 9 cases thus far. Diagnostic imaging following clinical suspicion include CT/CTA, MRA, and duplex ultrasound.
Perioperative complications include migration of a celiac artery stent into the left iliac artery (1), clot formation (1), and thrombosis due to PICC (1). EDS-associated comorbidities included intracranial hypertension (1), tethered cord (1), Chiari I malformation (1), and congenital hip dysplasia (2).
Awareness of ACS in EDS will enable prompt diagnosis and treatment with avoidance of years of pain and unnecessary suffering.