IVIG as a Promising Therapy for Methotrexate-induced Life-threatening Neutropenic Enterocolitis in an Elderly Patient With Rheumatoid Arthritis: A Case Report and Literature Review.

BACKGROUND/AIM: Rheumatoid arthritis (RA) is a chronic autoimmune disease associated with the functional impairment of multiple joints and the destruction of bone and cartilage. Methotrexate (MTX) is a first-line drug commonly used to treat RA; however, even low doses of MTX can potentially cause rare but severe adverse reactions, such as neutropenic enterocolitis (NE), a life-threatening disease characterized by intestinal mucosal damage and immunodeficiency. CASE REPORT: Here, we report on an 82-year-old RA patient who developed life-threatening NE after ten years of low-dose MTX treatment. The condition of the patient rapidly worsened, requiring emergency electrical cardioversion and intravenous treatment with immunoglobulin (IVIG). Immunophenotypic responses were analyzed before and after treatment to evaluate therapeutic efficacy. CONCLUSION: This case highlights the importance of monitoring elderly patients with RA receiving low-dose MTX treatment for the potential accumulation of MTX toxicity. Our findings also illustrate the importance of providing timely IVIG therapy for MTX-induced NE.

Risk Factors for Septic Shock After Irinotecan-Containing Chemotherapy: An Exploratory Case-Control Study.

BACKGROUND AND OBJECTIVES: Irinotecan sometimes causes lethal septic shock but the risk factors remain unclear. This retrospective case-control study explored the potential risk factors for septic shock following irinotecan treatment. METHODS: All women who received irinotecan-containing chemotherapy for gynecologic malignancies at Shizuoka General Hospital from October 2014 to September 2020 were investigated. The clinical backgrounds and blood test results of those who developed septic shock after irinotecan-containing chemotherapy were compared with those who did not. Odds ratios (ORs) for developing septic shock after receiving irinotecan were calculated with 95% confidence intervals (CIs), using univariable logistic regression analysis. RESULTS: During the study period, 147 women received irinotecan-containing chemotherapy. Three women developed septic shock due to neutropenic enterocolitis after irinotecan treatment, and 144 did not. The three patients with septic shock had recurrent cervical cancer, heterozygous variants in the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene (two patients had *1/*6, one had *1/*28 variants), a history of concurrent chemoradiation therapy, 50-60 Gy of pelvic irradiation, and platinum-combined chemotherapy. A history of pelvic irradiation was identified as a possible risk factor for developing septic shock after irinotecan-containing chemotherapy (OR 63.0, 95% CI 5.71-8635; p < 0.001). The OR of UGT1A1 polymorphism for septic shock was 9.09 (95% CI 0.86-1233; p = 0.070) in the complete case analysis. CONCLUSION: Medical personnel involved in cancer therapy should consider the possible risk of septic shock developing due to neutropenic enterocolitis when administering irinotecan-containing chemotherapy in patients with a history of pelvic irradiation.

Neutropaenic enterocolitis: A medical/surgical oncological dilemma.

Neutropaenic enterocolitis (NE) is a life-threatening condition characterised by an inflammation of the colon and/or the small bowel in the background of chemotherapy-induced neutropaenia. A 16-year-old girl with acute myeloblastic leukaemia (AML) developed fever, right-sided abdominal pain and tenderness with severe neutropaenia. Initial ultrasound findings suggested acute appendicitis for which she had surgery. She developed recurrent symptoms 3 weeks later. Abdominal computed tomography (CT) scan showed features of NE, but she succumbed to the illness. Another 17-year-old boy with AML developed fever and severe right-sided lower abdominal pain and tenderness, following completion of induction chemotherapy. He was neutropaenic and abdominal CT was typical of NE. He was managed nonoperatively and symptoms resolved. The diagnosis of NE can be a dilemma. A high index of suspicion is needed to avoid a misdiagnosis of acute appendicitis.

Neutropenic enterocolitis-induced sepsis and disseminated intravascular coagulation after chemotherapy: a case report.

BACKGROUND: Neutropenic enterocolitis (NE) is a potentially life-threatening disease that primarily occurs in cancer patients treated with chemotherapy. NE has substantial morbidity and mortality, and its incidence has increased with the widespread use of chemotherapeutic agents such as taxanes, gemcitabine, and leucovorin in patients with lung, breast, gastric, and ovarian cancers. Sometimes NE can be a possible cause of death. Although, conservative approaches are often successful, there are currently no standardized treatment guidelines for NE and it is unclear when such strategies should be implemented. Therefore, we present this report to provide a greater insight into the possible treatment of NE. CASE PRESENTATION: We report the case of a 72-year-old woman with endometrial cancer who was undergoing treatment for hypertension, obesity and diabetes mellitus. The patient initially developed paralytic ileus on the 6th postoperative day (POD) after surgery for endometrial serous carcinoma. Complete recovery was achieved after 4 days of fasting and fluid replacement therapy. On the 27th POD, she received the first cycle of combination chemotherapy consisting of paclitaxel and carboplatin. On day 5 of chemotherapy, she developed the systemic inflammatory response syndrome including febrile neutropenia and sepsis. She then developed disseminated intravascular coagulation (DIC) and septic shock. The patient was subsequently moved to the intensive care unit (ICU). Despite initiating the standard treatment for septic shock and DIC, her overall status worsened. It was assumed that gut distention had led to bowel damage, subsequently leading to bacterial translocation. Thus, she developed NE with severe DIC and septic shock. We decided to reduce the intestinal pressure using an ileus tube to suction the additional air and fluid, even though doing so had a risk of worsening her general condition. The inflammatory reaction subsided, and her general condition improved. The patient recovered after 18 days in the ICU and was discharged alive. CONCLUSIONS: Herein, we describe a patient with suspected chemotherapy-associated NE. Our observations suggest that postoperative ileus may be one of the possible causes of NE. Patients who experience postoperative ileus must be carefully monitored while undergoing chemotherapy.

Good functional outcome following severe neutropenic enterocolitis and perforation in a 48-year-old woman undergoing chemotherapy for breast cancer.

Neutropenic enterocolitis (NEC) is a life-threatening bowel condition, usually resulting from chemotherapy, with a mortality rate thought to be as high as 50%. Markers of poor prognosis include gastrointestinal perforation and bowel wall thickness radiologically detected to be greater than 10 mm. NEC is associated with severe neutropenia and predominantly affects the large bowel; however, we present a case of severe NEC with oesophageal perforation requiring transfer to a specialist upper gastrointestinal unit for corrective stenting. Despite initial bowel wall thickness of 20 mm in the ascending colon, two discrete episodes of bowel perforation and an inpatient stay totalling 89 days, the patient was discharged with full independence, a good quality of life and a plan for curative mastectomy plus axillary clearance.

Fatal neutropenic enterocolitis associated with docetaxel use: A review of cases reported to the United States Food and Drug Administration Adverse Event Reporting System.

Docetaxel is a microtubule inhibitor indicated for the treatment of multiple cancers as a single agent or in combination with other antineoplastics. The U.S. Food and Drug Administration (FDA) conducted a postmarketing review of fatal neutropenic enterocolitis cases reported with docetaxel using the FDA Adverse Event Reporting System (FAERS) and literature to determine whether the drug was a potential cause. We searched FAERS and the literature for reports of fatal neutropenic enterocolitis with docetaxel-based treatment reported between 14 May 1996 and 13 March 2017. We characterized the clinical course and severity of neutropenic enterocolitis and utilized the World Health Organization-Uppsala Monitoring Centre rubric to assess drug causality. We identified 41 fatal cases of neutropenic enterocolitis with docetaxel from FAERS and the literature. The median time to onset of neutropenic enterocolitis from last docetaxel dose was seven days (range 2-13 days), and median time to death was nine days (range 3-23 days). The cause of death in 83% (34/41) of patients was neutropenic enterocolitis. We determined the drug-event association as probable in seven cases. Neutropenic enterocolitis with docetaxel monotherapy occurred in six cases; however, in 85% (35/41) of cases, neutropenic enterocolitis occurred when docetaxel was used in combination with other cytotoxic chemotherapy. In some cases, neutropenic enterocolitis occurred despite use of granulocyte colony-stimulating factors. Neutropenic enterocolitis is a severe and potentially fatal complication of docetaxel-based treatment, especially when combined with other antineoplastic treatments known to cause neutropenia. Practitioners should be aware of this safety risk to promptly recognize and manage patients.

Neutropenic enterocolitis in patients with FLT3 mutated acute myeloid leukemia undergoing induction chemotherapy with midostaurin.

Neutropenic enterocolitis mostly affects patients with acute myeloid leukemia (AML) who get treated with intensive chemotherapy which is associated with prolonged neutropenia; its pathogenesis is not well understood and the main factors in this life-threatening condition appear to be neutropenia, mucosal injury and a weakened immune system as a consequence of intensive chemotherapeutic agents. Midostaurin in combination with chemotherapy became the standard of care for FLT3 mutant AML since its approval by the United States Food and Drug Administration (FDA) in April 2017. Anecdotally in our institution, we noticed the common occurrence of neutropenic colitis in three out of three patients who were treated with midostaurin as part of induction chemotherapy for AML.

[Fatal neutropenic enterocolitis in a patient with castration-resistant prostate cancer treated with first-line chemotherapy]. / Fatal neutropen enterokolitis hos en patient i kemoterapi med kastrationsresistent prostatacancer.

Neutropenic enterocolitis (NE) is a possible life-threatening complication to chemotherapy. The pathogenesis is multi-factorial with mucosal injury and impaired mucosal defence as contributing factors. Histopathological findings are heterogeneous. Clinical presentation includes neutropenia, fever and abdominal pain. Treatment is not clearly defined. We present a fatal case of NE in a patient with prostate cancer treated with first-line chemotherapy, docetaxel 75 mg/m2 every three weeks and prednisolone 5 mg × 2 daily. The post-mortem examination confirmed NE with prostate cancer cells in bowel wall.

Neutropenic enterocolitis affecting the transverse colon: an unusual complication of chemotherapy.

A 66-year-old woman presented with a 1-day history of sudden onset of generalised abdominal pain associated with fever and vomiting. She was previously diagnosed with left breast cancer 2 months ago and completed a course of chemotherapy 1 week prior to presentation. She was clinically unwell with generalised tenderness in her abdomen. Blood investigations showed severe neutropenia. A CT scan was requested which reported a marked oedematous swelling of the transverse colon with features suggestive of a contained perforation. The decision was made to operate. Intraoperatively, the transverse colon was found to be thickened with omentum adherent focally around the distal third. A right hemicolectomy was performed with an end ileostomy and mucus fistula. The patient made a successful recovery and was discharged within 7 days of presenting. Pathology reported typical features of neutropenic enterocolitis affecting the transverse colon with a normal terminal ileum, caecum and ascending colon.

Neutropenic enterocolitis after high-dose chemotherapy and autologous stem cell transplantation: incidence, risk factors, and outcome.

BACKGROUND: Neutropenic enterocolitis (NE) is a life-threatening complication occurring after intensive chemotherapy; however, no data are available on NE development after hematopoietic stem cell transplantation (SCT). The aim of this study was to determine the incidence, risk factors, and outcome of NE after high-dose chemotherapy and autologous SCT (autoSCT). METHODS: A total of 297 adult patients who qualified for autoSCT with non-Hodgkin's lymphoma (NHL), Hodgkin's disease, multiple myeloma, and acute myeloid leukemia were analyzed. Patients were conditioned with carmustine, etoposide, cytarabine, melphalan (BEAM); melphalan alone; or busulfan and cyclophosphamide (BuCy2), and transplanted with peripheral blood or bone marrow CD34(+) cells. Diagnosis of NE was established in case of neutropenic fever, abdominal pain or diarrhea, and bowel wall thickening >4 mm on abdominal sonography. RESULTS: Neutropenic infections occurred in 262 patients (88%). NE was diagnosed in 32 patients (12%), a median +3 (1-5) days after SCT. Bloodstream infections were present in 18 patients, with gram-negative bacteria in 11 patients. All patients were treated conservatively with carbapenems and total parenteral nutrition with bowel rest. The course of disease was complicated by ileus or septic shock in 9 patients, and was fatal for 3 (9.6%) patients. In univariate analysis, the initial diagnosis of NHL (P = 0.017) and conditioning with BEAM (P = 0.043) had prognostic value. In multivariate analysis, only initial diagnosis of NHL (P = 0.017) had prognostic significance. CONCLUSIONS: NE is a rare but severe complication in patients undergoing autoSCT. Gram-negative bacteria remain the main causative pathogen. Abdominal sonography allows early diagnosis and treatment, effective in most of patients without surgery. In our analysis, NE was seen more often in NHL patients treated with a BEAM regimen.

Neutropenic enterocolitis, a growing concern in the era of widespread use of aggressive chemotherapy.

Neutropenic enterocolitis (NEC) is a life-threatening disease with substantial morbidity and mortality, seen primarily in patients with hematologic malignancies. The frequency of NEC has increased with the widespread use of chemotherapeutic agents such as the taxanes, which cause severe gastrointestinal mucositis. Neutropenic patients with fever and abdominal symptoms (cramping, pain, distention, diarrhea, GI bleeding), should undergo evaluation of the abdomen for bowel wall thickening of >4 mm, the hallmark of NEC. Clostridium difficile infection should be ruled out, as well as other etiologies such as graft-versus-host disease. Complications include bacteremia, which is often polymicrobial, hemorrhage, and bowel wall perforation/abscess formation. Management includes bowel rest, correction of cytopathies and coagulopathies, and broad spectrum antibiotics and antifungal agents. Surgical intervention may be necessary to manage complications such as hemorrhage and perforation and should be delayed, if possible, until recovery from neutropenia.

Rectal involvement in neutropenic enterocolitis.

Neutropenic enterocolitis is a common gastrointestinal complication in children undergoing chemotherapy for a variety of malignancies. It usually involves ileum and caecum, and involvement of rectum has rarely been reported. The authors report neutropenic enterocolitis in a child undergoing chemotherapy for acute lymphoblastic lymphoma which presented with ileus along with a mass like lesion in the rectum.

Chemotherapy-induced neutropenic necrotizing enterocolitis: a review.

Neutropenia is a common toxicity of systemic cytotoxic therapy. Neutropenic enterocolitis (NE) is a rare occurrence but can be fatal, subsequent to neutropenia. The exact incidence and frequency is difficult to establish, but is usually underestimated. It is often missed but has recently been appreciated with increasing frequency in solid tumours. NE was initially reported with taxenes but now an increasing number of chemotherapeutic drugs are implicated. NE incidence is expected to increase with the use of dose dense regimens, myeloablative cytotoxic protocols, tissue transplants, and emerging newer molecules. The usual presentation is often non-specific and often over shadowed by the symptomatology of primary malignant disease and toxicity symptoms of chemotherapy. The basis of diagnosis is clinical, radiological (ultra sound/CT scan), per operative findings, and eventually post mortem. Treatment options of this highly fatal phenomenon varies from conservative to early surgical intervention. NE is expected to be diagnosed with increasing frequency. The factors leading to it are mucosal injury, caecal distension with resultant ischaemia, cytotoxic drugs, and microbiological agents. A high index of clinical suspicion and an early diagnosis is paramount for better outcome. Irrespective of management employed, conservative or upfront surgical intervention, it has a poor out come with high mortality. A clinical suspicion, early diagnosis, and prompt management are the key to a better result. There is need to identify people at high risk by prognostic factors, large scale studies, and formulating consensus management guidelines. At present individualized risk assessment based strategy is advocated.

CT features of neutropenic enterocolitis in adult patients with hematological diseases undergoing chemotherapy.

PURPOSE: This study investigates the features of neutropenic enterocolitis (NE) in adults. MATERIALS AND METHODS: Chart and radiology report reviews were used to identify neutropenic patients with hematological diseases undergoing chemotherapy, who had CT scans for the clarification of abdominal symptoms between October 2003 and October 2009. Patients with any cause for enteritis other than NE were excluded. The scans were analyzed with respect to imaging features and location. Morphological findings were correlated with clinical data. RESULTS: Thirty-one patients with NE (median age 46 years; range 20 - 75) could be identified. Wall thickening and hyperemia could be found in all bowel segments from jejunum to rectum. The right hemicolon was the most frequent location in 19 patients (61%). Involvement was generalized in 6 patients (19%) and segmental in 25 cases (81%). The longer the duration of neutropenia, the more likely generalized involvement of the bowel was. In 8 patients who underwent CT follow-up, the appearance of bowel segments had completely (n = 5) or partially (n = 3) returned to normal at the latest 14 days after the initial diagnosis. Eight patients (26%) died 1 - 78 days after NE, 7 of who had previously recovered from NE. CONCLUSION: CT findings are useful for the diagnosis of NE and should be considered even in the presence of isolated small bowel involvement. The terms NE and typhlitis should thus no longer be used synonymously.

The gastrointestinal complications of oncologic therapy.

A spectrum of oncologic treatments including chemotherapy, radiotherapy, and molecular targeted therapies is available to combat cancer. These treatments are associated with adverse effects in several organ systems including the gastrointestinal (GI) tract. The immunocompromised state induced by oncologic therapy is also an important contributing factor underlying GI complications. This review discusses common GI complications that can result from cancer therapy. The pathologic mechanisms underlying each complication and the pharmacology of the agents used to treat these complications are discussed.

[Treatment of neutropenic enterocolitis]. / Behandling av nøytropen enterokolitt.

BACKGROUND: Neutropenic enterocolitis is a life-threatening complication that usually occurs in connection with chemotherapy for acute leukemias. Our experience with diagnosis and treatment of these patients is presented. MATERIAL AND METHODS: Medical records from patients treated for neutropenic enterocolitis at Ullevaal University Hospital in the period 2000-2008 were retrospectively reviewed. RESULTS: 16 patients with median age 33 years were treated for neutropenic enterocolitis. Induction chemotherapy was given for acute myelogenic (n = 9) or lymphatic (n = 4) leukemia, myelomatosis (n = 2) or lymphoma (n = 1). The patients developed aplasia five days (median) after start of chemotherapy. All patients were first treated conservatively with broad-spectrum antibiotics, fluids and electrolyte supplementation; nine of them recovered without complications. Four underwent surgery for perforation or ileus and these had the longest period with aplasia (median 31 days). Surgery for perforation is mainly limited resection and construction of ileostomy reservoirs (one or two). Three patients died. These were only treated conservatively; aplasia occurred quicker in these patients (after median two days) and they had the largest number of affected bowel segments (median nine). INTERPRETATION: Neutropenic enterocolitis is a heterogeneous condition and the treatment is mainly conservative. Surgical intervention is mandatory in patients with free intraabdominal air, ileus and intractable intestinal bleeding. The prognosis seems to worsen when aplasia develops after a short time and when there is a large number of affected bowel segments.