INTRODUCTION

Typhlitis (from the Greek word "typhlon," or cecum) is a life-threatening, necrotizing enterocolitis occurring primarily in neutropenic patients [1]. Other terms that have been used to describe this syndrome include "necrotizing enterocolitis," "neutropenic enterocolitis," and "ileocecal syndrome." Typhlitis occurs most commonly in individuals with hematologic malignancies who are neutropenic and have breakdown of gut mucosal integrity as a result of cytotoxic chemotherapy. “Typhlitis” describes neutropenic enterocolitis of the ileocecal region; the more inclusive term, “neutropenic enterocolitis,” is appropriate when other parts of the small and/or large intestine are involved.

The pathogenesis, clinical manifestations, diagnosis, management, and prognosis of typhlitis are reviewed here.

PATHOGENESIS

The pathogenesis of typhlitis is incompletely understood. It probably involves a combination of factors, including mucosal injury by cytotoxic drugs or other means, profound neutropenia, and impaired host defense to invasion by microorganisms [2]. The microbial infection leads to necrosis of various layers of the bowel wall. The cecum is almost always affected, and the process often extends into the ascending colon and terminal ileum [3]. The predilection for the cecum is possibly related to its distensibility and its diminished vascularization relative to the rest of the colon.

Gross and histologic examinations may reveal bowel wall thickening, discrete or confluent ulcers, mucosal loss, intramural edema, hemorrhage, and necrosis. Various bacterial and/or fungal organisms, including gram-negative rods, gram-positive cocci, anaerobes (eg, Clostridium septicum), and Candida spp, are often seen infiltrating the bowel wall. Polymicrobial infection is frequent. Only rarely are inflammatory or leukemic infiltrates identified [3]. Bacteremia or fungemia is also common, usually with enteric organisms such as Pseudomonas or yeasts such as Candida.

RISK FACTORS AND INCIDENCE

Typhlitis was originally reported in children who underwent induction chemotherapy for acute leukemia [4]. It has subsequently been described in children and adults with acute myeloid leukemia, multiple myeloma, myelodysplastic syndromes, aplastic anemia, acquired immunodeficiency syndrome, cyclic or drug-induced neutropenia, and after immunosuppressive therapy for solid malignancies and transplants [2,3,5-9]. In one study, mucositis [odds ratio (OR) 31], stem cell transplantation (OR 59), and receipt of chemotherapy in the previous two weeks (OR 13) were significantly associated with the occurrence of typhlitis in pediatric patients with cancer [10]. (See "Overview of the complications of acute myeloid leukemia".)