Bleeding in Children Caused by Gastrointestinal Vascular Lesions

Bleeding in Children Caused by Gastrointestinal Vascular Lesions By Michael S. Irish, Michael G. Caty, and Richard G. Azizkhan Buffa/o, New York and Cincinnati, Ohio Intestinal vascular malformations in infants and children are rare but must be considered in the differential diagnosis of gastrointestinal bleeding. Many vascular malformation syndromes have associated intestinal lesions. Localization of vascular lesions is essential for successful management. A variety of treatment options including laser photoablation, surgical resection, and other nonoperative therapies have been utilized to treat these disorders. Copyright © 1999 by W.B. Saunders Company

O

NE IN THREE children will have a cutaneous vascular lesion or "birthmark" at birth or early in life, the majority of which will fade or remain dormant and inconsequential. However, intestinal vascular lesions are present only when complications arise, and their prevalence is thus difficult to determine. Although intestinal vascular lesions are rare causes of gastrointestinal bleeding in infants and children, they must be considered in the differential diagnosis of bleeding in these patients. Vascular lesions of the gastrointestinal (GI) tract typically are diagnosed by exclusion of more common causes of bleeding, and, thus, diagnosis of these lesions often is delayed. Because of their diverse nature, an organized approach to their biological classification and potential extraintestinal manifestations is necessary to diagnose and treat them. CLASSIFICATION OF VASCULAR MALFORMATIONS

In 1982 Mulliken and Glowaki 1 prospectively studied 49 vascular lesions encountered in infants and children. By correlating findings on physical examination and natural history with histopathologic and radiographic appearance, they suggested a biological classification composed of 2 major categories of vascular lesions: hemangiomas, and vascular malformations. Hemangiomas

Hemangiomas are vascular tumors characterized by rapid growth, endothelial hyperplasia, increased endothelial turnover, and increased numbers of mast cells. Hemangiomas in the proliferating phase are distinFrom the Division of Pediatric Surgery. Children S Hospital of Buffalo. the Department of Surgery. The State University of New York at Buffalo, Buffalo, NY, and the University of Cincinnati School of Medicine, Children S Hospital Medical Center, Cincinnati, OH. Address reprint requests to Richard G. Azizkhan, MD, Surgeon-inChief, Children S Hospital Medical Center, Department of Surgery, Division of Pediatric Surgery, 3333 Burnet Ave, Cincinnati, OH 45229-3039. Copyright © 1999 by WE. Saunders Company 1055-8586/99/0804-0006$10.00/0 210

guished clinically by a history of rapid growth during early infancy. Histologically, they have endothelial hyperplasia with incorporation of tritiated thymidine, and multilaminated basement membrane formation beneath the endothelium. Hemangiomas in the involuting phase show rapid growth followed by regression. These have histological fibrosis and fat deposition, and low to absent tritiated thymidine labeling of endothelial cells. When discussed in the context of gastrointestinal bleeding, lesions referred as hemangiomas are likely mislabeled and would be better classified as a vascular malformation that does not undergo involution. 2 Vascular Malformations

Vascular malformations usually are noted at birth and grow proportionately as the child grows or expand secondary to hemodynamic alterations. These vascular lesions consist of abnormal and often combined, capillary, arterial, venous, and lymphatic components. They show no tritiated thymidine incorporation, have normal ultrastructural characteristics, and are characterized by a normal endothelial cell cycle and normal numbers of mast cells. For classifying vascular malformations of the gastrointestinal tract, we prefer the classification proposed by Young (Table 1).3 Venous Malformations

Venous malformations (VM) constitute 2% to 12% of all enteric vascular malformations and 0.05% of all intestinal tumors. These low-flow lesions may be either single or multiple and occur throughout the gastrointestinal tract in many forms (phlebectasia, blebs, polypoid lesions, and diffuse forms), although the colon rarely is involved. They may present with either acute or chronic blood loss and are commonly associated with cutaneous vascular lesions (eg, blue rubber bleb nevus syndrome). Other presentations include obstruction and, rarely, intussusception. Rectal venous malformations usually present with bright red blood per rectum in infancy, which may be severe. Other presentations include tenesmus, constipation, and associated hemorrhoids. On proctosigmoidoscopy, rectal VMs may appear as pedunculated vascular lesions, distended vessels within the rectal mucosa, or as a narrowing of the lumen of the rectum. 3 Arteriovenous Malformations

Arteriovenous malformations (AVM) are abnormal communications between arteries and veins, which bySeminars in Pediatric Surgery, Vol 8, No 4 (November), 1999: pp 210-213

GASTROINTESTINAL VASCULAR LESIONS

Table 1. Vascular Malformations of the Gastrointestinal Tract Venous malformation s Arteriovenous malformation s Aneurysms Lymphatic malformations

pass the normal capillary bed. The hemodynamic impact and pathophysiology of large AVMs have been well described. 4 Arteriovenous malformations may present with acute or chronic blood loss, obstruction,5 and, rarely, perforation. 6 AVMs are divided into 3 types. Type I lesions are thought to be an acquired, angiodysplastic, degenerative process and usually present in patients over 55 years of age. These lesions usually are not associated with cutaneous lesions and are multiple and located in the cecum and proximal ascending colon. Fifteen percent of these lesions present with massive hemorrhage.? Type II lesions present before age 50 and are considered developmental anomalies. They are solitary or multiple and often are large and complex involving long segments of bowel. Most are located in the small bowel. Type III AVMs are multiple punctate lesions associated with Rendu-OslerWeber syndrome (hereditary hemorrhagic telangiectasia) and present in middle age. Aneurysms

Aneurysms of the gastrointestinal tract rarely are congenital and occur in the Menkes syndrome. In this disorder, weakening of the arterial wall is caused by a defect in copper absorption, an essential part of the enzyme lysyl amine oxidase, which is needed for cross linkage of collagen. 8 Lymphatic Malformations

Lymphatic malformations of the GI tract such as lymph cysts, chylous ascites, and intestinallymphangiectasia occur along with extraintestinal lymphatic anomalies. As elsewhere in the body, gastrointestinal lymphatic anomalies often are combined with venous malformations. PRESENTATION

Gastrointestinal bleeding caused by congenital vascular malformations may present with either acute or chronic blood loss. Twenty-five percent of intestinal AVMs present in infancy.9 Acute blood loss is seen more commonly than chronic anemia. Other presentations include obstruction and intussusception as well as congestive cardiac failure. Intestinal AVMs should be suspected in patients with gastrointestinal bleeding and known syndromes with extraintestinal vascular lesions. These syndromes include Rendu-Osler-Weber, Klippel-Trenaunay, or Blue Rubber Bleb Nevus.

211

Rendu-Osler-Weber Syndrome

Rendu-Osler-Weber Syndrome or hereditary hemorrhagic telangiectasia (HTT) was originally described at the tum of the 20th century. 10-13 The characteristic lesions that are seen with HTT are discrete maculopapules located on the skin, nail beds, and palmar aspect of the fingers and mucosal surfaces (oral and nasal mucous membranes, tongue, gastrointestinal, bladder, and genital mucosal membranes). Similar lesions also have been described in the liver, spleen, pancreas, kidneys, and brain. HTT is inherited in an autosomal dominant pattern with an incidence of 1 to 2 per 100,000 in Whites. Vascular lesions may appear early in childhood but typically manifest in the third or fourth decade and increase in number with age. Presentations may include neurological symptoms caused by cerebral or spinal bleeding, or pulmonary hypertension or symptoms of substantial pulmonary shunting (cyanosis, clubbing, polycythemia) with pulmonary parenchymal lesions. Gastrointestinal hemorrhage in HTT typically is painless. Klippel-Trenaunay Syndrome

The dominant features of Klippel-Trenaunay Syndrome (KPS) are a cutaneous capillary nevus (birthmark) of a limb with ipsilateral congenital varicose veins and limb hypertrophy (gigantism). Klippel-Trenaunay Syndrome is predominantly a venous lesion and may be associated with intestinal venous and lymphatic malformations and severe GI bleeding. 14.!5 Blue Rubber Bleb Nevus Syndrome

Bean 16 described Blue Rubber Bleb Nevus Syndrome (BRBN) in 1958. It is a rare entity with an autosomal dominant pattern of inheritance that manifests with soft, sometimes pedunculated, subcutaneous, cavernous, malformed veins presenting as painful blue-purple rubbery lesions and may present with GI bleeding caused by similar lesions found throughout the GI tract, particularly in the small intestine and colon. These lesions also can be found in the liver, spleen, oral cavity, and central nervous system. Unlike hemangiomas, these lesions do not regress.!? Further, they have no malignant potential. BRBN syndrome occurs with a male to female ratio of 14:8 and usually presents in childhood, although a number of reports of its onset and diagnosis in adults have been made. Although most cases are sporadic, an autosomal dominant pattern of inheritance has been suggested. Complications of BRBN include chronic anemia, bleeding (rectal, hematemesis, nasal) and orthopedic pain. Gastrointestinal bleeding from BRBN syndrome usually is occult, but hematochezia and melena have been reported,!8 all resulting in iron-loss anemia. Bone and joint deformities and pain sometimes are caused by extension of lesions into joints and by compression by

212

IRISH, CATV. AND AZIZKHAN

space-occupying lesions. Intussusception caused by BRBN lesions also has been reported. 19 Therapy for BRBN syndrome is largely symptomatic with iron replacement therapy and transfusion for gastrointestinal blood loss. Cutaneous lesions may be treated by laser ablation, orthopedic abnormalities by excision or amputation. Severe or transfusion-dependent gastrointestinal bleeding may require resection of the involved segment of bowel or sclerotherapy. DIAGNOSIS

The most critical aspect of managing intestinal vascular malformations is preoperative localization. When suspected, either by association with other clinical features or by exclusion of more common causes of GI bleeding, investigation for gastrointestinal vascular malformations usually includes painstaking radiographic and endoscopic evaluation: upper or lower gastrointestinal contrast studies and endoscopy,20,21 abdominal and pelvic computed tomography (CT),22 radionuclide scanning,23,24 and angiography.25 Accurate localization of these lesions is imperative to insure effective treatment. 26 ,27 When bleeding from an upper gastrointestinal source is suspected we begin with upper endoscopy, and, if nondiagnostic, we proceed with angiography if the patient's size permits. Our approach to lower gastrointestinal bleeding begins with endoscopy for low-volume bleeding and radionuclide scanning or angiography for highvolume bleeding. 28 Radionuclide scans with technetium (Tc)-99m-labeled sulfur colloid or erythrocytes are particularly helpful for slow bleeding undetectable by angiography (less than 1 mL/min).

with angiomas associated with Von Willebrand's disease, and in patients with numerous lesions.31 Life-threatening hematochezia from rectosigmoid vascular malformations have been palliated successfully using argon laser photocoagulation. 32 Azizkhan 32 reported the use of an argon laser in an adolescent boy with Klippel-Trenaunay syndrome involving the pelvis and left leg. The patient presented with recurrent lifethreatening hematochezia associated with defecation. Angiogram and CT scan showed the extensive nature of the rectal vascular malformation (Fig lA and B). Endoscopy documented that the bleeding originated from the submucosal venous angiomata involving the distal 7cm of the anorectal canal. After laser photocoagulation of this venous plexus, the patient only had one brief episode of hematochezia in 4 years of follow-up. Although this approach provides successful palliation, long-term follow-up and retreatment may be required. When lesions are not able to be located radiographically, and surgery is required for ongoing or recurrent bleeding, intraoperative enteroscopy via the mouth, rectum, or enterotomy may be helpfuJ.33,34 The " pitfalls" of blind resection for GI bleeding have been well described in the adult literature. 26,27 The risk of missing or incompletely resecting the lesion, as well as nutritional and

TREATMENT

Nonsurgical management options for intestinal vascular malformations include vasopressin infusion, estrogen therapy, gelfoam embolization, and, more commonly, endoscopic electrocoagulation, or epinephrine injection. These nonoperative measures are used in patients with endoscopically accessible malformations such as Dieulafoy lesions of the stomach, duodenum,29 and rectum. 30 Other management options that have been used include intraoperative bipolar coagulation and Nd:YAG laser ablation.3 ! Rutgeerts et aPl reviewed the effect of Nd: YAG laser photocoagulation gastrointestinal vascular malformations in 59 patients with a total of 482 lesions. After a mean follow-up period of 11.5 months (range, 1 to 48 months), 17 of the 57 patients available for follow-up had rebleeding episodes. The investigators found statistically significant reductions of the bleeding rate at 1, 6, 12, and 18 months of follow-up, and transfusion rates at 1, 6, and 12 months. They also noted that results were worse in patients with Osler-Weber-Rendu syndrome, in patients

Fig 1. (A) Pelvic CT shows a rectosigmoid malformation in an adolescent with Klippel-Trenaunay syndrome. (B) Selective visceral angiography (capillary-venous phase) shows a markedly dilated venous plexus in the rectosigmoid colon. (Reprinted with permission.32)

GASTROINTESTINAL VASCULAR LESIONS

213

malabsorption issues, make this approach unfavorable in infants and children. Management of rectal vascular malformations poses the challenge of anatomic resection and preservation of continence. Historically, these lesions were managed by abdominoperineal resection or ineffectually by sclerotherapy. Recently Telander et aI'5 and Jeffrey et aP5 have described mucosectomy, endorectal pull-through, and coloanal anastamosis in the management of these lesions. Telander et aI'5 describe the persistence of the surgical plane between the submucosa and underlying muscularis during mucosectomy, and, although the muscular cuff contains the vascular lesion,

the normal pulled-through segment of colon provides an effective barrier avoiding intraluminal bleeding. Intestinal vascular malformations in infants and children are rare but must be considered in the differential diagnosis of gastrointestinal bleeding. Several extraintestinal vascular malformation syndromes may have associated intestinal lesions. Localization of the lesion is essential to successful management. Nonoperative and laser ablation may provide adequate palliation. When required, guided and limited resection with preservation of intestinal length and continence remain the goals of surgical management of these lesions.

REFERENCES 1. Mulliken JB , Glowacki J: Hemangiomas and vascular malformations in infants and children: A classification based on endothelial characteristics. Plast Reconstr Surg 69:412-422,1982 2. Enjolras 0 , Wassef M, Mazoyer E, et al: Infants with KassabachMerritt syndrome do not have "true" hemangiomas. J Pediatrics 130:631-640, 1997 3. Young AE: Arteriovenous Malformations, in Mulliken JB, Young AE, (eds.): Vascular Birthmarks: Hemangiomas and Malformations, Philadelphia, PA, WB Saunders, 1988 pp 228-245 4. Young AE, Senapati A: Intra-abdominal and pelvic vascular malformations, in Mulliken JB, Young AE, (eds): Vascular Birthmarks: Hemangiomas and Malformations, Philadelphia, PA, WB Saunders, 1988 pp 381-399 5. Graivier L: Ileal stenosis due to arteriovenous malformation in a newborn infant. J Pediatr Surg 17:78-79, 1982 6. Munn J, Hussain A, Castelli M, et al: Ileal perforation due to arteriovenous malformation in a premature infant. J Pediatr Surg 25:701-703, 1990 7. Freud E, Kidron D, Gornish M, et al: The value of precise preoperative localization of colonic arteriovenous malformation in childhood. Am J Gastroenterol 88:443-446, 1993 8. Smith DW: Menke's Syndrome, in Smith DW, (eds.): Recognizable Patterns of Human Malformations (ed. 3). Philadelphia, PA, Saunders, 1982 p 150 9. Enjolras 0, Riche MC , Merland JJ, et al: Management of alarming hemangiomas in infancy: A review of 25 cases [see comments]. Pediatrics 85:491-498,1990 10. Hanes FM: Multiple hereditary telangiectases causing hemorrhage (hereditary hemorrhagic telangiectasia. Am J Dermatol GenitoUrinary Dis 13:249, 1909 11. Osler W: On a family form of recurring epistaxis associated with mUltiple telangiectases of skin and mucous membrane. Bull Johns Hopkins Hosp 12:333, 1901 12. Parkes Weber F: Multiple hereditary developmental angiomata of the skin and mucous membranes associated with recurring haemorrhages. Lancet 2: 160, 1907 13. Rendu M: Epistaxix repetees chez un sujet porteu de petits angiomes cutanes et muqueux. Bull Societe Medical des Hopitaux de Paris 13 :731 , 1896 14. Mondragon L, Vargas Gomez M, Tiscarreno M, et al: Angiodysplasia of the colon in children. J Pediatr Surg 30:72-75,1995 15. Telander R, Ahlquist D, B1aufuss M: Rectal mucosectomy: A definitive approach to extensive hemangiomas of the rectum. J Pediatr Surg 28:379-381, 1993 16. Bean WB: Vascular spiders and related lesions of the skin. Springfield, IL, Charles C. Thomas, 1958 pp 178-185 17. Oranje AP: Blue rubber bleb nevus syndrome. Pediatric Dermatology 3:304-310,1986

18. Morris SJ, Kaplan SR, Balian K, et al: Blue rubber-bleb nevus syndrome. Jama 239:1978 19. Browne AF, Katz S, Miser J, et al: Blue Rubber Bleb Nevi as a cause of intussusception. J Pediatr Surg 18:7-9, 1983 20. Miller V, Doig CM: Upper gastrointestinal tract endoscopy. Arch Dis Child 59:1100-1102, 1984 21. Tarn PK, Saing H : Pediatric surgeons can and should perform colonoscopy. J Pediatr Surg 22:332-334, 1987 22. Bank ER, Hernandez RJ, Byrne WJ: Gastrointestinal hemangiomatosis in children: Demonstration with CT. Radiology 165:657-658, 1987 23. Majd M : Radionuclide imaging in pediatrics. Pediatr Clin North Am 32:1559-1579,1985 24. Majd M: Radionuclide imaging in clinical pediatrics. Pediatr Ann 15:396-402,407-398, 1986 25. Moore AV, Kirks DR, Mills SR, et al: Pediatric abdominal angiography: Panacea or passe? AJR. Am J Roentgenol 138:433-443, 1982 26. Spechler S, Schimmel E: Gastrointestinal tract bleeding of unknown origin. Arch Intern Med 142:236-240, 1982 27. Gianfrancisco J, Abcarian H: Pitfalls in the treatment of massive lower gastrointestinal bleeding with " blind" subtotal colectomy. Dis Colon Rectum 25:441-445, 1982 28. Pearl RH, Irish MS, Caty MG, et al: The approach to common abdominal diagnosis in infants and children. Part II. Pediatr Clin North Am 45:1287-1326, 1998 29. Goldenberg S, DeLuca V, Marignani P: Endoscopic treatment of Dieulafoy's lesion of the dueodenum. Am J Gastroenterol 85:452-454, 1990 30. Abdelmalek M, Pockaj B, Leighton J: Rectal bleeding from a mucous fistula secondary to a Dieulafoy's lesion. J Clin Gastroenterol 24:259-261,1997 31. Rutgeerts P, Van Gompel F, Geboes K, et al: Long term results of treatment of vascular malformations of the gastrointestinal tract by neodymium Yag laser photocoagulation. Gut 26:586-593,1985 32. Azizkhan RG: Life-threatening hematochezia from a rectosigmoid vascular malformation in Klippel-Trenaunay syndrome: Longterm palliation using an argon laser. J Pediatr Surg 26: 1125-1128, 1991 33. Benaroch LM, Rudolph CD: Introduction to pediatric esophagogastroduodenoscopy and enteroscopy. Gastrointest Endosc Clin North Am 4:121-142, 1994 34. Tada M, Misaki F, Kawai K: Pediatric enteroscopy with a sonde-type small intestinal fiberscope (SSIF-type VI). Gastrointest Endosc 29:44-47,1983 35. Jeffery P, Hawley P, Parks A: Colo-anal sleeve anastomosis in the treatment of diffuse cavernous haemangioma involving the rectum. Br J Surg 63:678-682, 1976