Case 6 -

Enterocolic (Lymphocytic) Phlebitis Alan G. Rose (Case Courtesy of Dr E. Saraga)

Clinical History The patient was a 67-year-old man who presented with acute abdominal pain, fever and leucocytosis. Clinical signs of an acute abdomen were present for several hours. Past history elicited a one-month history of slight abdominal pain and weight loss. An emergency laparotomy was performed and 2 segments of ileum measuring 70 cm and 30 cm in length respectively were resected. While the resection lines were viable, the central portions of both bowel segments showed hemorrhagic ischemic necrosis. Subsequent postoperative follow-up for 9 years revealed no evidence of systemic disease. A section from a viable portion of the ileum shows recent (? operatively induced) limited intra-serosal hemorrhage. A striking feature is the presence of a widespread lymphocytic venulitis affecting venules within the submucosa as well as the serosa. The adjacent arteries appear normal. A dense lymphocytic infiltrate involves all layers of the venular wall with extension of the infiltrate into the perivenular connective tissue. Fibrin thrombi in various stages of organization are present within some veins. Venular occlusion by agglutinated erythrocytes (red thrombus) is also noted. Both mural and totally occlusive thrombi are present, and some veins show evidence of recanalization. Enterocolic lymphocytic phlebitis{1,2} is a rare cause of intestinal ischemic necrosis{3}. The ischemic bowel lesions tend to be acute or subacute in nature with hemorrhagic infarction, bordered by vascular congestion and marked edema. A few patients may show chronic ischemic ulceration of the bowel. Ischemic lesions have affected the ileum, the right and left colon, and occasionally both small and large bowel. The hemorrhagic nature of the necrosis is consistent with venous occlusion induced infarction of the bowel. Venulitis most extensively affects small submucosal veins and venules less than 2 mm in diameter. Venous channels in the viable resection zones also show a lymphocytic venulitis. Venules in the muscularis and the serosa, as well as the mucosa may also be affected. Necrotizing phlebitis with fibrinoid necrosis and neutrophilic infiltration of the vein, with residual lymphocytic infiltration at the periphery, as well as a granulomatous phlebitis with giant cells, have also been described in some cases.{3} Thrombus organization may result in an appearance of myointimal venular thickening. The etiology of the condition is unknown, but the morphology of the lesion suggests a pathogenesis based upon lymphocyte-mediated venular damage via a hypersensitivity reaction. Some cases have been linked to the administration of the drug hydroxyethyl rutoside. The condition has probably been under-diagnosed. Saraga and Bouzourenne{3} postulate that morphologic variants of the same entity have been previously diagnosed as lymphocytic phlebitis,{4} granulomatous phlebitis,{5} necrotizing phlebitis or myointimal venous hyperplasia.{6} Some cases of mesenteric veno-occlusive disease{7} may also represent the entity under discussion. Saraga and Bouzourenne{3} also point out that, in the absence of venous thrombosis induced infarction, the condition may only cause transitory abdominal pain or discomfort, and/or brief episodes of rectal blood loss. The lesions are essentially located in the submucosa and are rarely present in mucosal biopsies. The differential diagnosis of enterocolic phlebitis (Table 6.1) includes other causes of bowel ischemia such as: (1) Small vessel vasculitis e.g. rheumatoid arthritis associated vasculitis, microscopic polyangiitis (microscopic form of polyarteritis nodosa), Churg-Strauss syndrome, Henoch-Schonlein purpura, systemic lupus erythematosus,{8} and Behcet syndrome.{9,10} (2) Volvulus (which may revert) – may produce venous infarction like that resulting from enterocolic phlebitis. (3) Carcinoid tumor induced small bowel ischemic necrosis due to vascular elastosis of small arteries and veins.{11} (4) Shock induced ischemic ulceration of the bowel. Chronic bowel ischemia may also be associated with re-activation of cytomegalovirus infection. (5) In contrast to systemic vasculitis,{12}in which involvement of the gastrointestinal tract is frequent, isolated intestinal vasculitis is very rare{13} and is more often associated with Crohn's disease.{14 } (6) "Nonocclusive" intestinal infarction is encountered in some patients with systemic hypertension.{11,15} Table 1: Differential Diagnosis of Enterocolic Lymphocytic Phlebitis Small Vessel Vasculitis Microscopic polyangiitis Rheumatoid vasculitis Churg-Strauss syndrome Henoch-Schonlein purpura Behcet syndrome Volvulus Ischemia Shock Thromboembolism Hypertension related mesenteric artery narrowing and "nonocclusive" intestinal infarction ? chronic ischemia Isolated Intestinal Vasculitis Crohn disease Carcinoid Induced Vascular Elastosis Short notes on various conditions that come into the differential diagnosis of Enterocolic Lymphocytic Phlebitis: Microscopic polyangiitis: This microscopic form of polyarteritis nodosa is characterized by a small vessel necrotizing vasculitis affecting arterioles, capillaries and venules with few if any immune deposits. Associated necrotizing arteritis of medium sized arteries may occur, together with necrotizing glomerulonephritis and pulmonary capillaritis. Rheumatoid vasculitis: Rheumatoid arthritis may affect all parts of the vascular system including peripheral arteries where it may cause gangrene of digits, a limb, or it may lead to bowel infarction and perforation. Venular involvement is rare. Churg-Strauss syndrome (Allergic granulomatosis and angiitis): Eosinophils permeate granulomatous inflammation in the respiratory tract and necrotizing vasculitis is observed in small to medium-sized arteries and veins, arterioles and veins in a wide variety of organs including the gut. Asthma is common in these patients. Henoch-Schonlein (Anaphylactoid) Purpura: Vasculitis characterized by IgA-dominant immune deposits within small vessels (arterioles, capillaries, and venules) may be caused by hypersensitivity to drugs (e.g. aspirin or quinidine) or a b-hemolytic streptococcal infection. Typically affects skin, gut and glomeruli with arthralgias/arthritis. Behcet syndrome: A systemic illness characterized by recurrent oral and genital mucosal aphthous ulcers, and ocular inflammation. It may also affect the CNS, genitourinary, gastrointestinal and cardiovascular systems. The basic lesion is a vasculitis affecting predominantly venules with perivascular infiltration by lymphocytes, monocytes and scanty plasma cells. Frank necrosis of small blood vessels is rare. The condition is believed to be a delayed hypersensitivity reaction to an unknown antigenic stimulus. Volvulus: Twisting of the bowel on its mesentery initially occludes the venous circulation, while the arterial circulation is maintained. Later the arterial flow is also compromised. The gross and microscopic appearance of the bowel is that of venous infarction of the gut. Secondary venous thrombosis is often evident in the bowel wall and mesentery, but the distinctive lymphocytic infiltrate seen in lymphocytic phlebitis is not evident. Ischemia: Shock may produce skip lesions of infarction throughout the gut, with wide variation in both the depth of the necrosis (varies from superficial mucosal to transmural) and its lateral extent. Secondary thrombosis and inflammation may be noted in the microvasculature of affected areas. Embolism: Thromboembolism of bland or infected thrombi may produce bowel infarction by occluding the arterial system either proximal or distal to the mesenteric anastomotic arcades. Small emboli that occlude the vasa recta close to the bowel wall will produce much smaller zones of infarction than occlusion of a major vessel such as the superior mesenteric artery. There is no difficulty in distinguishing this condition from lymphocytic phlebitis. Nonocclusive intestinal infarction: Hypertension may play a role in the pathogenesis of intimal fibromuscular proliferation and medial hypertrophy that produces obstruction in terminal mesenteric arteries. Such lesions may be implicated in so-called "nonocclusive" intestinal infarction. Typically there is no significant atherosclerosis in larger mesenteric vessels, but in the presence of narrowed small distal arteries a critical reduction in mesenteric blood flow with resultant infarction can readily occur with dehydration, splanchnic vasoconstriction, or low cardiac output. Bowel infarction induced by vascular elastogenic factor released from carcinoid tumor has already been discussed in Case 1. References Chergui MH, Vandeperre J, van Eeckhout P. Enterocolic lymphocytic phlebitis: a case report. Acta Chir Belg 1997; 97: 293-296. Saraga E, Costa J. Idiopathic entero-colic lymphocytic phlebitis. A cause of ischemic intestinal necrosis. Am J Surg Pathol 1989; 13: 303-308. 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