Case series
893
Authors
Paul Boland, Jennifer Leonard, Michael Saunders, Ford Bursey
Institution
Department of Internal Medicine, Memorial University of Newfoundland, St John’s, Canada
submitted 11. March 2014 accepted after revision 21. May 2014
Idiopathic small-bowel and colonic varices are a rare source of bleeding from the gastrointestinal tract. To date there are only eight published case series of familial idiopathic small-bowel and colonic varices. We present a case series detailing three affected siblings who presented with significant lower gastrointestinal bleeding and had
multiple varices on endoscopy and imaging. Though not confirmed, consanguinity in the parents suggests an autosomal recessive mode of inheritance. We summarize the literature to date and describe our institution’s experience of endoscopy, diagnostic imaging, and treatment in these patients.
Introduction
denum to the proximal jejunum in patient 2. Patient 2 also underwent a capsule endoscopy, which demonstrated varices of the small bowel " Fig. 3). (● Images from contrast-enhanced computed tomography (CT) of the abdomen were striking. In patient 2, there was venous-phase enhancement " Fig. e4). in the gastric fundus and small bowel (● Thickening of the terminal ileum, cecum, and ascending colon was noted, which corresponded to the areas of erythema on colonoscopy. The site of bleeding has been localized in patient 2 only. Tagged red blood cell scans showed bleeding in the distal jejunum/proximal ileum on one occasion and in the cecum on another. In all three patients, bleeding episodes have been self-limiting, lasting 48 – 72 hours. Management has been supportive, with blood transfusions as required, intravenous rabeprazole, and intravenous octreotide.
Bibliography DOI http://dx.doi.org/ 10.1055/s-0034-1377530 Published online: 18.7.2014 Endoscopy 2014; 46: 893–895 © Georg Thieme Verlag KG Stuttgart · New York ISSN 0013-726X Corresponding author Paul Boland, MD Department of Internal Medicine Memorial University of Newfoundland 300 Prince Phillip Drive St. John’s Newfoundland A1B 3V6 Canada Fax: +1-709-777-8377 [email protected]
!
Idiopathic small-bowel and colonic varices are a rare source of bleeding from the gastrointestinal tract. To date there are only eight published case series of familial idiopathic small-bowel and colonic varices. The available cases do not appear to show a difference in incidence with respect to age or sex and are limited to small familial clusters.
Case series !
We present three patients who were siblings and presented in early adulthood with episodes of " Tamelena and hematochezia, summarized in ● ble e1. They do not have any unaffected siblings. Both their parents are healthy without bleeding, though there is anecdotal evidence that they are third cousins. The patients’ mother has four unaffected sisters. The patients’ father has an unaffected son from another relationship. Colonoscopy in all three patients showed extensive involvement of the colon with prominent, ser" Fig. 1 a). In patients 1 and 2, erpiginous varices (● ythematous areas with petechiae were noted " Fig. 1 b). Taking a biopsy from this area resulted (● in brisk bleeding that required hemostatic measures. Pathology showed hyperemia and dilated " Fig. e2). venules without active inflammation (● Upper gastrointestinal endoscopy showed varices of the fundus and proximal stomach in patient 1 and involvement from the second part of the duo-
Discussion !
Lower gastrointestinal bleeding resulting from small-bowel and colonic varices is uncommon with 80 cases reported in the literature. The majority of cases are associated with portal hypertension from cirrhosis or portal vein obstruction. In a case series of patients with cirrhosis, colonic varices were found in 31 % of patients but significant bleeding was found only in 1 % [1]. Other causes include mesenteric vein thrombosis, cardiac insufficiency, extrinsic venous compression,
Boland Paul et al. Familial idiopathic small-bowel and colonic varices … Endoscopy 2014; 46: 893–895
Downloaded by: University of Iowa Libraries. Copyrighted material.
Familial idiopathic small-bowel and colonic varices in three siblings
Case series
Fig. 3 Capsule endoscopy performed in patient 2 showing varices of the small bowel.
Fig. 1 Colonoscopy of patient 1 showing: a dilated, serpiginous submucosal vessels in the ascending colon; b an area of edema and petechiae in the transverse colon, which bled briskly when a biopsy was taken.
congenital arteriovenous malformations, intra-abdominal adhesions, and chronic pancreatitis [2]. Idiopathic small-bowel and colonic varices are rare. Familial predisposition has been reported in eight case series since 1977 " Table e2). In four of the reported case series, as well as the (● present series, varices are limited to siblings. Several theories have been proposed. Atin at al. [3] hypothesized that occult arteriovenous malformations could raise portal venous pressure or that connective tissue disorders could alter venous structural integrity. Hardy et al. [10] reported three first-degree relatives with an annular aneurysm of the ileocecocolic artery resulting in mesenteric venous hypertension. Klippel–Trenaunay syndrome (KTS) is a non-inherited congenital disorder characterized by cutaneous capillary malformation, varicose veins, and hypertrophy of bone or soft tissue [11]. The association of KTS with gastrointestinal bleeding is increasingly recognized. One case report described a 27-year-old man with KTS who presented with melena and dilated, tortuous veins throughout the sigmoid colon on colonoscopy [12]. Some authors describe these lesions as true varices, while others favor hemangiomas [11, 12]. The lesions in our series have the appearance of varices and there were no other associated vascular abnormalities. Patients 1 and 2 were extensively investigated for secondary causes with negative results. Patient 2 initially had elevations of wedged hepatic venous pressure and hepatic venous pressure gradient. On repeat venography, with no interval therapy, the wedged hepatic venous pressure remained elevated but the hepatic venous pressure gradient was normal. In the initial meas-
urement, the free pressure was measured at the right atrium, while the second measurement used the hepatic vein. This may explain the discrepancy and we are therefore inclined to believe that the hepatic venous pressure gradient is normal. We maintain that these cases represent idiopathic colonic and small-bowel varices. While patient 3 was less extensively investigated for secondary causes of varices, no abnormality was readily apparent, therefore her varices are assumed to be idiopathic. Previous case series have been too small to comment on heritability. In our case series, there was anecdotal evidence of the parents being third cousins. Consanguinity suggests autosomal recessive inheritance. A single affected generation suggests the same. Similarly, the majority of case series only describe affected siblings. Varices in multiple generations in the case series of Bernardini et al. [5], Hawkey et al. [6], and Solis-Herruzo et al. [9] suggest that there may be an alternative mode of inheritance or multiple genetic mutations leading to the same phenotype. In patients 1 and 2, colonoscopy demonstrated areas of erythema and edema mimicking inflammation. Taking a biopsy resulted in significant bleeding that required hemostatic measures. Pathology showed dilated venules suggesting that there is both microvascular and macrovascular involvement. Biopsies of such areas should be avoided. Diagnostic imaging can be equally misleading: other authors have reported barium enemas with an appearance resembling polyposis coli [6]. In patient 2, a CT scan showed dilated, serpiginous vessels throughout the gastrointestinal tract. Interestingly, the CT also showed areas of “thickening” and “fatty infiltration” that possibly corresponded to areas of friable tissue seen on colonoscopy. Kori et al. [7] also reported thickening of the colonic walls on CT scanning. Mortality appears to be low, with no related deaths in any of the reported cases. In our case series, the age of symptom onset was relatively young, with a mean age of 13.7 years. The two brothers appear to have a more severe phenotype. There is no standard therapy for bleeding colonic varices. In the cases presented, the bleeding episodes were treated with octreotide and pantoprazole, with resolution after 48 – 72 hours. Both brothers have been prescribed rabeprazole and nadolol, but have had recurrent bleeding. Other authors have had success with surgical resection for varices limited to the colon [3]. In our patients, diffuse gastrointestinal involvement and multiple foci of bleeding make surgery less attractive. Catheter-based treatment by interventional radiology with embolization or local vasoconstriction is an alternative to surgery in patients refractory to medical therapy.
Boland Paul et al. Familial idiopathic small-bowel and colonic varices … Endoscopy 2014; 46: 893–895
Downloaded by: University of Iowa Libraries. Copyrighted material.
894
Conclusion
References
!
1 Bresci G, Parisi G, Capria A. Clinical relevance of colonic lesions in cirrhotic patients with portal hypertension. Endoscopy 2006; 38: 830 – 835 2 Miller LS, Barbarevech C, Friedman LS. Less frequent causes of lower gastrointestinal bleeding. Gastroenterol Clin North Am 1994; 23: 21 – 52 3 Atin V, Sabas JA, Cotano JR et al. Familial varices of the colon and small bowel. Int J Colorectal Dis 1993; 8: 4 – 8 4 Beermann EM, Lagaay MB, Van Nouhuys JM et al. Familial varices of the colon. Endoscopy 1988; 20: 270 – 272 5 Bernardini D, Barthet M, Castellani P et al. Familial varices of the colon: report of four cases [In French]. Gastroenterol Clin Biol 1998; 22: 827 – 830 6 Hawkey J, Amar S, Daintith M et al. Familial varices of the colon occurring without evidence of portal hypertension. Br J Radiol 1985; 38: 677 – 679 7 Kori M, Keter D, Grunshpan M et al. Familial Colonic Varices. J Pediatr Gastroenterol Nutr 2000; 30: 447 – 449 8 Morini S, Caruso F, De Angelis P. Familial varices of the small and large Bowel. Endoscopy 1993; 25: 188 – 190 9 Solis-Herruzo JA. Familial varices of the colon diagnosed by colonoscopy. Gastrointest Endosc 1977; 24: 85 – 86 10 Hardy M, Barbin JY, Caroli J. Familial mesenteric hypertension. Rev Med Chir Mal Foie 1967; 42: 237 – 246 11 Deepinder F. GI bleeding, colon varicosities, and visceral enlargement as a manifestation of Klippel-Trenaunay syndrome. Clin Gastroenterol Hepatol 2011; 9: e126 – e127 12 Wang ZK, Wang FY, Zhu RM et al. Klippel-Trenaunay syndrome with gastrointestinal bleeding, splenic hemangiomas and left inferior vena cava. World J Gastroenterol 2010; 16: 1548 – 1552
We present three patients with familial idiopathic small-bowel and colonic varices. There is a suggestion of an autosomal recessive pattern of inheritance. While macrovascular disease is obvious on colonoscopy, areas of microvascular involvement that resemble inflammation can result in significant bleeding if biopsied. Similarly, imaging can be misleading, but in the correct setting can provide insight into the extent of bowel involvement. Bleeding is sporadic and treatment is supportive, with frequent transfusions and presumptive use of octreotide, beta-blockers, and proton pump inhibitors. Interventional radiology or surgery should be considered in refractory cases. Competing interests: None
Acknowledgement !
We are grateful to Dr. Altaf Taher for generously providing the pathology images.
Tables e1 and e2 and Figures e2 and e4 online content viewable at: www.thieme-connect.de
Boland Paul et al. Familial idiopathic small-bowel and colonic varices … Endoscopy 2014; 46: 893–895
895
Downloaded by: University of Iowa Libraries. Copyrighted material.
Case series
893
Authors
Paul Boland, Jennifer Leonard, Michael Saunders, Ford Bursey
Institution
Department of Internal Medicine, Memorial University of Newfoundland, St John’s, Canada
submitted 11. March 2014 accepted after revision 21. May 2014
Idiopathic small-bowel and colonic varices are a rare source of bleeding from the gastrointestinal tract. To date there are only eight published case series of familial idiopathic small-bowel and colonic varices. We present a case series detailing three affected siblings who presented with significant lower gastrointestinal bleeding and had
multiple varices on endoscopy and imaging. Though not confirmed, consanguinity in the parents suggests an autosomal recessive mode of inheritance. We summarize the literature to date and describe our institution’s experience of endoscopy, diagnostic imaging, and treatment in these patients.
Introduction
denum to the proximal jejunum in patient 2. Patient 2 also underwent a capsule endoscopy, which demonstrated varices of the small bowel " Fig. 3). (● Images from contrast-enhanced computed tomography (CT) of the abdomen were striking. In patient 2, there was venous-phase enhancement " Fig. e4). in the gastric fundus and small bowel (● Thickening of the terminal ileum, cecum, and ascending colon was noted, which corresponded to the areas of erythema on colonoscopy. The site of bleeding has been localized in patient 2 only. Tagged red blood cell scans showed bleeding in the distal jejunum/proximal ileum on one occasion and in the cecum on another. In all three patients, bleeding episodes have been self-limiting, lasting 48 – 72 hours. Management has been supportive, with blood transfusions as required, intravenous rabeprazole, and intravenous octreotide.
Bibliography DOI http://dx.doi.org/ 10.1055/s-0034-1377530 Published online: 18.7.2014 Endoscopy 2014; 46: 893–895 © Georg Thieme Verlag KG Stuttgart · New York ISSN 0013-726X Corresponding author Paul Boland, MD Department of Internal Medicine Memorial University of Newfoundland 300 Prince Phillip Drive St. John’s Newfoundland A1B 3V6 Canada Fax: +1-709-777-8377 [email protected]
!
Idiopathic small-bowel and colonic varices are a rare source of bleeding from the gastrointestinal tract. To date there are only eight published case series of familial idiopathic small-bowel and colonic varices. The available cases do not appear to show a difference in incidence with respect to age or sex and are limited to small familial clusters.
Case series !
We present three patients who were siblings and presented in early adulthood with episodes of " Tamelena and hematochezia, summarized in ● ble e1. They do not have any unaffected siblings. Both their parents are healthy without bleeding, though there is anecdotal evidence that they are third cousins. The patients’ mother has four unaffected sisters. The patients’ father has an unaffected son from another relationship. Colonoscopy in all three patients showed extensive involvement of the colon with prominent, ser" Fig. 1 a). In patients 1 and 2, erpiginous varices (● ythematous areas with petechiae were noted " Fig. 1 b). Taking a biopsy from this area resulted (● in brisk bleeding that required hemostatic measures. Pathology showed hyperemia and dilated " Fig. e2). venules without active inflammation (● Upper gastrointestinal endoscopy showed varices of the fundus and proximal stomach in patient 1 and involvement from the second part of the duo-
Discussion !
Lower gastrointestinal bleeding resulting from small-bowel and colonic varices is uncommon with 80 cases reported in the literature. The majority of cases are associated with portal hypertension from cirrhosis or portal vein obstruction. In a case series of patients with cirrhosis, colonic varices were found in 31 % of patients but significant bleeding was found only in 1 % [1]. Other causes include mesenteric vein thrombosis, cardiac insufficiency, extrinsic venous compression,
Boland Paul et al. Familial idiopathic small-bowel and colonic varices … Endoscopy 2014; 46: 893–895
Downloaded by: University of Iowa Libraries. Copyrighted material.
Familial idiopathic small-bowel and colonic varices in three siblings
Case series
Fig. 3 Capsule endoscopy performed in patient 2 showing varices of the small bowel.
Fig. 1 Colonoscopy of patient 1 showing: a dilated, serpiginous submucosal vessels in the ascending colon; b an area of edema and petechiae in the transverse colon, which bled briskly when a biopsy was taken.
congenital arteriovenous malformations, intra-abdominal adhesions, and chronic pancreatitis [2]. Idiopathic small-bowel and colonic varices are rare. Familial predisposition has been reported in eight case series since 1977 " Table e2). In four of the reported case series, as well as the (● present series, varices are limited to siblings. Several theories have been proposed. Atin at al. [3] hypothesized that occult arteriovenous malformations could raise portal venous pressure or that connective tissue disorders could alter venous structural integrity. Hardy et al. [10] reported three first-degree relatives with an annular aneurysm of the ileocecocolic artery resulting in mesenteric venous hypertension. Klippel–Trenaunay syndrome (KTS) is a non-inherited congenital disorder characterized by cutaneous capillary malformation, varicose veins, and hypertrophy of bone or soft tissue [11]. The association of KTS with gastrointestinal bleeding is increasingly recognized. One case report described a 27-year-old man with KTS who presented with melena and dilated, tortuous veins throughout the sigmoid colon on colonoscopy [12]. Some authors describe these lesions as true varices, while others favor hemangiomas [11, 12]. The lesions in our series have the appearance of varices and there were no other associated vascular abnormalities. Patients 1 and 2 were extensively investigated for secondary causes with negative results. Patient 2 initially had elevations of wedged hepatic venous pressure and hepatic venous pressure gradient. On repeat venography, with no interval therapy, the wedged hepatic venous pressure remained elevated but the hepatic venous pressure gradient was normal. In the initial meas-
urement, the free pressure was measured at the right atrium, while the second measurement used the hepatic vein. This may explain the discrepancy and we are therefore inclined to believe that the hepatic venous pressure gradient is normal. We maintain that these cases represent idiopathic colonic and small-bowel varices. While patient 3 was less extensively investigated for secondary causes of varices, no abnormality was readily apparent, therefore her varices are assumed to be idiopathic. Previous case series have been too small to comment on heritability. In our case series, there was anecdotal evidence of the parents being third cousins. Consanguinity suggests autosomal recessive inheritance. A single affected generation suggests the same. Similarly, the majority of case series only describe affected siblings. Varices in multiple generations in the case series of Bernardini et al. [5], Hawkey et al. [6], and Solis-Herruzo et al. [9] suggest that there may be an alternative mode of inheritance or multiple genetic mutations leading to the same phenotype. In patients 1 and 2, colonoscopy demonstrated areas of erythema and edema mimicking inflammation. Taking a biopsy resulted in significant bleeding that required hemostatic measures. Pathology showed dilated venules suggesting that there is both microvascular and macrovascular involvement. Biopsies of such areas should be avoided. Diagnostic imaging can be equally misleading: other authors have reported barium enemas with an appearance resembling polyposis coli [6]. In patient 2, a CT scan showed dilated, serpiginous vessels throughout the gastrointestinal tract. Interestingly, the CT also showed areas of “thickening” and “fatty infiltration” that possibly corresponded to areas of friable tissue seen on colonoscopy. Kori et al. [7] also reported thickening of the colonic walls on CT scanning. Mortality appears to be low, with no related deaths in any of the reported cases. In our case series, the age of symptom onset was relatively young, with a mean age of 13.7 years. The two brothers appear to have a more severe phenotype. There is no standard therapy for bleeding colonic varices. In the cases presented, the bleeding episodes were treated with octreotide and pantoprazole, with resolution after 48 – 72 hours. Both brothers have been prescribed rabeprazole and nadolol, but have had recurrent bleeding. Other authors have had success with surgical resection for varices limited to the colon [3]. In our patients, diffuse gastrointestinal involvement and multiple foci of bleeding make surgery less attractive. Catheter-based treatment by interventional radiology with embolization or local vasoconstriction is an alternative to surgery in patients refractory to medical therapy.
Boland Paul et al. Familial idiopathic small-bowel and colonic varices … Endoscopy 2014; 46: 893–895
Downloaded by: University of Iowa Libraries. Copyrighted material.
894
Conclusion
References
!
1 Bresci G, Parisi G, Capria A. Clinical relevance of colonic lesions in cirrhotic patients with portal hypertension. Endoscopy 2006; 38: 830 – 835 2 Miller LS, Barbarevech C, Friedman LS. Less frequent causes of lower gastrointestinal bleeding. Gastroenterol Clin North Am 1994; 23: 21 – 52 3 Atin V, Sabas JA, Cotano JR et al. Familial varices of the colon and small bowel. Int J Colorectal Dis 1993; 8: 4 – 8 4 Beermann EM, Lagaay MB, Van Nouhuys JM et al. Familial varices of the colon. Endoscopy 1988; 20: 270 – 272 5 Bernardini D, Barthet M, Castellani P et al. Familial varices of the colon: report of four cases [In French]. Gastroenterol Clin Biol 1998; 22: 827 – 830 6 Hawkey J, Amar S, Daintith M et al. Familial varices of the colon occurring without evidence of portal hypertension. Br J Radiol 1985; 38: 677 – 679 7 Kori M, Keter D, Grunshpan M et al. Familial Colonic Varices. J Pediatr Gastroenterol Nutr 2000; 30: 447 – 449 8 Morini S, Caruso F, De Angelis P. Familial varices of the small and large Bowel. Endoscopy 1993; 25: 188 – 190 9 Solis-Herruzo JA. Familial varices of the colon diagnosed by colonoscopy. Gastrointest Endosc 1977; 24: 85 – 86 10 Hardy M, Barbin JY, Caroli J. Familial mesenteric hypertension. Rev Med Chir Mal Foie 1967; 42: 237 – 246 11 Deepinder F. GI bleeding, colon varicosities, and visceral enlargement as a manifestation of Klippel-Trenaunay syndrome. Clin Gastroenterol Hepatol 2011; 9: e126 – e127 12 Wang ZK, Wang FY, Zhu RM et al. Klippel-Trenaunay syndrome with gastrointestinal bleeding, splenic hemangiomas and left inferior vena cava. World J Gastroenterol 2010; 16: 1548 – 1552
We present three patients with familial idiopathic small-bowel and colonic varices. There is a suggestion of an autosomal recessive pattern of inheritance. While macrovascular disease is obvious on colonoscopy, areas of microvascular involvement that resemble inflammation can result in significant bleeding if biopsied. Similarly, imaging can be misleading, but in the correct setting can provide insight into the extent of bowel involvement. Bleeding is sporadic and treatment is supportive, with frequent transfusions and presumptive use of octreotide, beta-blockers, and proton pump inhibitors. Interventional radiology or surgery should be considered in refractory cases. Competing interests: None
Acknowledgement !
We are grateful to Dr. Altaf Taher for generously providing the pathology images.
Tables e1 and e2 and Figures e2 and e4 online content viewable at: www.thieme-connect.de
Boland Paul et al. Familial idiopathic small-bowel and colonic varices … Endoscopy 2014; 46: 893–895
895
Downloaded by: University of Iowa Libraries. Copyrighted material.
Case series
