In a 13‑day post‑allogeneic stem‑cell transplant patient with profound neutropenia (ANC < 0.01 × 10⁹/L), fever, acute abdominal pain, diarrhea, vomiting, hematemesis, acute kidney injury, and severe thrombocytopenia, what are the etiology, typical clinical presentation, and optimal management of typhlitis (neutropenic enterocolitis)?

Typhlitis (Neutropenic Enterocolitis): Etiology, Presentation, and Management

Etiology

Typhlitis results from chemotherapy-induced mucosal damage during profound neutropenia, allowing bacterial invasion of the bowel wall, typically affecting the cecum and terminal ileum. 1

• The condition develops during the second to third week after chemotherapy initiation, coinciding with peak mucosal damage and neutrophil nadir 1
• Pathologic findings include bowel wall ulcerations, necrosis, and bacterial or fungal invasion localized to the cecum, terminal ileum, ascending colon, and occasionally the appendix 2
• The mechanism involves chemotherapy-induced disruption of the intestinal mucosal barrier combined with severe neutropenia (ANC <500 cells/mm³), creating conditions for transmural bacterial invasion 3

Clinical Presentation

Your patient's presentation is classic for typhlitis: occurring 13 days post-transplant with profound neutropenia (ANC <0.01), fever, right lower quadrant abdominal pain, and gastrointestinal symptoms including diarrhea, vomiting, and hematemesis. 4

The characteristic clinical triad consists of:

• Severe neutropenia (ANC <500 cells/mm³ or expected to fall below this threshold) 5
• Fever (present in 48-81% of cases) 1, 5
• Abdominal pain, typically localized to the right lower quadrant but may be diffuse 4, 5

Additional common features include:

• Diarrhea (42.9-80% of cases) 1, 5
• Nausea and vomiting (81.8% in pediatric series) 5
• Gastrointestinal bleeding, which can be severe (present in up to 64% of cases) 1
• Signs of peritoneal irritation in advanced cases 2

Diagnostic Evaluation

Obtain contrast-enhanced CT scan immediately—this is the gold standard and most critical diagnostic step. 4, 6

Imaging Findings

• CT demonstrates bowel wall thickening >4 mm (transversal) or >30 mm (longitudinal) in the cecum and terminal ileum 4
• Wall thickness >10 mm carries dramatically higher mortality (60% vs 4.2% when <10 mm) 1, 4
• Look for complications: free air (perforation), pneumatosis intestinalis, lack of bowel wall enhancement (ischemia), abscess formation, or ascites 1, 6
• Ultrasound can show bowel wall thickening >5 mm but is inferior to CT for excluding complications 1, 7

Laboratory and Microbiologic Workup

• Blood cultures (both peripheral and from central lines if present) 5
• Stool cultures and C. difficile toxin testing must be performed to exclude concurrent infection 4, 6
• Complete blood count showing profound neutropenia and thrombocytopenia 5
• The most commonly isolated organism in blood cultures is Klebsiella pneumoniae 5

Critical pitfall: Do not delay CT imaging based on unremarkable physical examination findings—clinical signs are unreliable in immunocompromised patients. 6, 7

Management

Initial Medical Management (First-Line Approach)

Conservative management is the cornerstone unless complications develop: immediate broad-spectrum antibiotics, bowel rest, IV hydration, and G-CSF to accelerate neutrophil recovery. 4, 3

Antibiotic Therapy

• Start piperacillin-tazobactam or a carbapenem (imipenem-cilastatin or meropenem) immediately as monotherapy with anti-pseudomonal coverage 1, 4, 6
• This follows IDSA guidelines for febrile neutropenia 1
• Continue antibiotics for a median of 13 days (range 8-24 days based on clinical response) 5
• If no improvement after 48-72 hours or if fungemia is suspected, add empirical antifungal therapy (amphotericin B) 1, 6

Supportive Care

• Strict bowel rest (NPO status) 1, 7
• Aggressive IV fluid resuscitation and correction of electrolyte abnormalities 3, 8
• Total parenteral nutrition for nutritional support 1, 3
• Blood product support: transfuse platelets to maintain >50,000/mm³ given bleeding risk; transfuse packed red blood cells for anemia from GI bleeding 8
• Administer G-CSF to accelerate neutrophil recovery—symptom resolution directly correlates with rising neutrophil counts 1, 4, 7

Critical pitfall: Never use antidiarrheal agents—they may worsen ileus and outcomes. 6

Monitoring

• Serial abdominal examinations every 4-6 hours initially 7
• Repeat CT imaging at 48-72 hours if no clinical improvement or if deterioration occurs 7
• Most patients achieve resolution in 6-8 days with conservative management (up to 86% success rate) 1

Surgical Intervention (Reserved for Specific Indications)

Obtain early surgical consultation even while pursuing medical management, but reserve surgery only for documented complications. 1, 6

Absolute Indications for Surgery

• Bowel perforation (free air on imaging) 1, 3
• Intestinal ischemia (lack of bowel wall enhancement on CT) 1, 7
• Persistent GI bleeding despite correction of thrombocytopenia and coagulopathy 1, 3
• Clinical deterioration despite maximal medical therapy 1, 3
• Intestinal obstruction 6, 3
• Abscess formation requiring drainage 1

Surgical Considerations

• Surgery in neutropenic patients carries extremely high mortality (57-81%) 1
• Emergency surgery within 30 days of chemotherapy has mortality rates of 22.4% vs 10.3% in non-chemotherapy patients 1
• When surgery is necessary, right hemicolectomy is the recommended procedure 2
• Premature surgical intervention in stable neutropenic patients dramatically worsens outcomes—operate only for documented perforation or ischemia 7

Prognosis and Mortality

Mortality rates reach 29.5% in patients with positive radiologic findings, emphasizing the critical importance of early CT scanning and aggressive medical management. 4

• Mortality is 60% when bowel wall thickness exceeds 10 mm vs 4.2% when <10 mm 1, 4
• Overall mortality ranges from 5% with optimal medical management to 81% when emergency surgery is required during active chemotherapy 1, 5
• Patients with leukopenia undergoing emergency surgery have 57% mortality 1
• Recovery correlates directly with neutrophil count recovery—rising neutrophil counts predict symptom resolution 1, 7

High-Risk Features Requiring Intensive Monitoring

• Bowel wall thickening >10 mm on imaging 1, 4
• Fluid-filled bowel loops, ascites, or hyperechoic septa (representing necrotic mucosa) on ultrasound 1
• Prolonged duration of neutropenia 5
• Hemodynamic instability or rising lactate 7

Common pitfall: Colonoscopy is absolutely contraindicated—it carries very high risk of perforation in this setting. 1