P063 Loeys-Dietz syndrome presenting with inflammatory bowel disease symptoms
Authors: Lybil Mendoza Alvarez , Genie Beasley 
Published: July 2019

BACKGROUND:

Loeys-Dietz syndrome (LDS) is a rare autosomal dominant disorder of connective tissue caused by mutations in the genes encoding receptor subunits for TGFβ, TGFBR1 and TGFBR2. It is characterized by arterial aneurysms and dissections, skeletal abnormalities, joint laxity and craniofacial abnormalities. There is an increased risk of immunologic diseases including allergic and eosinophilic gastrointestinal disorders, as well as inflammatory bowel disease (IBD). TGF-β signaling plays an important role in regulating mucosal immune responses likely leading to increased propensity for development of IBD. This case highlights a rare presentation of LDS, with symptoms of IBD presenting in advance of cardiac symptoms, leading to diagnosis of this rare connective tissue disorder.

CASE:

A 14 yo Male presented with 1 year of intermittent bloody stools, diarrhea and fatigue. Physical exam was only positive for a bifid uvula and marfanoid body habitus. Laboratory testing showed microcytic anemia, elevated C-reactive protein, erythrocyte sedimentation rate, and hypoalbuminemia. Stool tests were negative for infectious causes of diarrhea. Esophagogastroduodenoscopy and colonoscopy showed gross findings of duodenal ulcer and mucosal ulceration throughout the colon. Histology showed chronic focal active duodenitis with intramucosal granuloma, and chronic active pancolitis. No eosinophils were observed. Findings were thought to be consistent with diagnosis of IBD, so patient was initially treated with Mesalamine and Prednisone. After treatment failure, therapy was switched to infliximab plus oral methotrexate, and responded well, clinically. Approximately 6 months after diagnosis of IBD, the patient developed chest pain, tachycardia, and shortness of breath. Due to new elevation of CRP and ESR, there was a suspicion for myocarditis. Echocardiogram, however, showed bicuspid aortic valve with dilated aortic root. Given this finding, the cardiologists suspected a collagen disorder and subsequently started patient on Losartan. After being seen by Genetics, a next generation sequencing panel demonstrated mutation of the TGFBR2 (p.C61Y) gene. He was diagnosed with LDS. Three years after diagnosis, patient has remained in deep remission of his IBD with combination of infliximab and methotrexate. One year after diagnosis of LDS, the patient’s aortic root dilation reached critical limits and he successfully underwent ascending aortic graft and aortic root replacement with On-X 25 valve. He tolerated this procedure well and remains on lifelong anticoagulation therapy.

DISCUSSION:

It is thought that patients with LDS are 10 times more likely to have IBD than the general population. However, the occurrence of non-eosinophilic chronic IBD in patients with LDS has been reported but has been poorly documented. Typical cases of LDS described in literature present with eosinophilic gastrointestinal disorders, food allergies and rarely IBD. Typically, cardiac and skeletal disorders precede the GI manifestations. Our case is remarkable in that the patient first diagnosed with IBD and then later presented with cardiac symptoms finally leading to diagnosis of LDS. Currently, there is no established protocol for the evaluation and management of IBD in LDS patients. This case highlights life-threatening aortic or cardiovascular conditions linked with LDS. As such, a low index of suspicion is needed when managing IBD in patients with features suggestive of LDS.