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.

[Neutropenic enterocolitis in the pediatric cancer patient]. / Enterocolitis neutropénica en el paciente oncológico pediátrico.

Neutropenic enterocolitis (NEC) is a heterogeneous disease of the gastrointestinal tract with systemic response, that corresponds to a severe and life-threatening clinical condition in immunocompromised patients, especially in childhood cancer. The pathologic features are poorly understood, although its multifactorial cause of NEC is well established and it is associated with the cytotoxic effects of the chemotherapy agents used and recognized by the classic triad of fever, neutropenia, and abdominal pain, secondary to gastrointestinal injuries that alters mucosal permeability and helps intramural bacterial invasion. NEC is truly a clinical challenge that requires an early diagnosis and a multidisciplinary approach including basic laboratory and imagological tests in high complexity centers. We present a current review, adding epidemiological aspects, risks factors, diagnostic support elements, therapeutic considerations, and preventive measures in order to provide knowledge of this disease and help to reduce morbidity and mortality associated with it.

Enterocolitis neutropénica en el paciente oncológico pediátrico / Neutropenic enterocolitis in the pediatric cancer patient

Resumen La enterocolitis neutropénica (ECN) es una enfermedad heterogénea de foco digestivo, pero afectación sistémica, que corresponde a una condición clínica grave que amenaza la vida de pacientes inmunocomprometidos, particularmente oncológicos pediátricos. De patogenia aún poco definida y aunque de causa multifactorial, la ECN se asocia a los efectos citotóxicos de la quimioterapia empleada y se caracteriza por la triada clásica que incluye fiebre, neutropenia y dolor abdominal, donde la principal injuria se localiza en la mucosa intestinal, provocando su alteración como barrera y facilitando la invasión bacteriana intramural. La ECN constituye un reto diagnóstico para el equipo tratante, que requiere ser oportuno y contar con apoyo de un óptimo laboratorio general e imagenológico, para iniciar un completo manejo multidisciplinario en unidades y centros de alta complejidad. Se presenta una revisión actualizada del tema incorporando aspectos epidemiológicos, factores de riesgo, elementos de apoyo diagnóstico, consideraciones terapéuticas y medidas de prevención a fin de aportar en el conocimiento de esta patología, y reducir morbimortalidad en estos pacientes.

Abstract Neutropenic enterocolitis (NEC) is a heterogeneous disease of the gastrointestinal tract with systemic response, that corresponds to a severe and life-threatening clinical condition in immunocompromised patients, especially in childhood cancer. The pathologic features are poorly understood, although its multifactorial cause of NEC is well established and it is associated with the cytotoxic effects of the chemotherapy agents used and recognized by the classic triad of fever, neutropenia, and abdominal pain, secondary to gastrointestinal injuries that alters mucosal permeability and helps intramural bacterial invasion. NEC is truly a clinical challenge that requires an early diagnosis and a multidisciplinary approach including basic laboratory and imagological tests in high complexity centers. We present a current review, adding epidemiological aspects, risks factors, diagnostic support elements, therapeutic considerations, and preventive measures in order to provide knowledge of this disease and help to reduce morbidity and mortality associated with it.

Enterocolite Neutropênica em Paciente com Câncer de Mama em Uso de Quimioterapia Adjuvante: Relato de Caso / Neutropenic Enterocolitis in a Breast Cancer Patient using Adjuvant Chemotherapy: Case Report / Enterocolitis Neutropénica en Paciente con Cáncer de Mama que Usa Quimioterapia Adyuvante: Reporte de Caso

Introdução: A enterocolite neutropênica (EN) consiste em ulceração ou necrose da mucosa do ceco, íleo terminal e cólon ascendente, sendo uma condição clínica ocasionada como evento adverso de medicamentos, principalmente em esquemas quimioterápicos. Por ser uma condição com alto índice de mortalidade, o presente relato tem como objetivo contribuir significativamente para discussões que envolvem a EN e a participação da equipe multiprofissional no desfecho clínico. Relato do caso: Paciente do sexo masculino, 75 anos, com diagnóstico de câncer de mama, evoluindo com EN após tratamento com quimioterapia adjuvante. A presença de comorbidades e a idade foram os principais fatores complicadores do quadro de tiflite. Por ser uma toxicidade importante e que pode levar à piora do quadro clínico do paciente com câncer, abordar esse tema é fundamental para um diagnóstico mais rápido, com possibilidade de medidas preventivas. Conclusão: Sendo assim, em virtude do notório aumento dos casos de EN, aponta-se como perspectiva a qualificação da equipe de saúde para a inserção de profissionais ainda mais especializados, capazes de contribuir e identificar os sinais e sintomas relacionados com toxicidades hematológicas, resultado de tratamentos quimioterápicos.

Introduction: Neutropenic enterocolitis (NE) consists of ulceration or necrosis of the mucosa of the cecum, terminal ileum, and ascending colon, being a clinical condition caused by an adverse drug event, mainly in chemotherapy regimens. As it is a high mortality rate condition, this report aims to contribute significantly to discussions involving NE and the participation of the multidisciplinary team in the clinical outcome. Case report: This is a 75-year-old male patient diagnosed with Breast Cancer, who developed EN after treatment with adjuvant chemotherapy. The presence of comorbidities and age were the main complicating factors in typhlitis. As it is an important toxicity and can lead to a worsening of the clinical condition of cancer patients, addressing this issue is essential for a faster diagnosis with the possibility of preventive measures. Conclusion: Therefore, in view of the notorious increase of cases of NE, the perspective of the qualification of the health team is pointed out, for the inclusion of even more specialized professionals capable of contributing and identifying the signs and symptoms related to hematological toxicities, result of chemotherapy treatments.

Introducción: La enterocolitis neutropénica (EN) consiste en la ulceración o necrosis de la mucosa del ciego, íleon terminal y colon ascendente, siendo una condición clínica causada por un evento adverso farmacológico, principalmente en regímenes de quimioterapia. Al tratarse de una afección con una alta tasa de mortalidad, este informe tiene como objetivo contribuir de manera significativa a las discusiones que involucran al EN y la participación del equipo multidisciplinario en el resultado clínico. Relato del caso: Paciente masculino, 75 años, diagnosticado de cáncer de mama, que desarrolló EN después del tratamiento con quimioterapia adyuvante. La presencia de comorbilidades y la edad fueron los principales factores de complicación en Tiflite. Como se trata de una toxicidad importante y puede conducir a un empeoramiento de la condición clínica de los pacientes con cáncer, abordar esta cuestión es fundamental para un diagnóstico más rápido con la posibilidad de medidas preventivas. Conclusión: Por tanto, ante el notable incremento de casos de EN, se apunta la perspectiva de la calificación del equipo de salud, para la inclusión de profesionales aún más especializados capaces de aportar e identificar los signos y síntomas relacionados con las toxicidades hematológicas, un resultado de los tratamientos de quimioterapia.

Neutropenic Enterocolitis in Critically Ill Patients: Spectrum of the Disease and Risk of Invasive Fungal Disease.

OBJECTIVES: Neutropenic enterocolitis occurs in about 5.3% of patients hospitalized for hematologic malignancies receiving chemotherapy. Data from critically ill patients with neutropenic enterocolitis are scarce. Our objectives were to describe the population of patients with neutropenic enterocolitis admitted to an ICU and to investigate the risk factors of invasive fungal disease. DESIGN: A multicentric retrospective cohort study between January 2010 and August 2017. SETTING: Six French ICUs members of the Groupe de Recherche Respiratoire en Onco-Hématologie research network. PATIENTS: Adult neutropenic patients hospitalized in the ICU with a diagnosis of enteritis and/or colitis. Patients with differential diagnosis (Clostridium difficile colitis, viral colitis, inflammatory enterocolitis, mesenteric ischemia, radiation-induced gastrointestinal toxicity, and Graft vs Host Disease) were excluded. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: We included 134 patients (median Sequential Organ Failure Assessment 10 [8-12]), with 38.8% hospital mortality and 32.1% ICU mortality rates. The main underlying malignancies were acute leukemia (n = 65, 48.5%), lymphoma (n = 49, 36.6%), solid tumor (n = 14, 10.4%), and myeloma (n = 4, 3.0%). Patients were neutropenic during a median of 14 days (9-22 d). Infection was documented in 81 patients (60.4%), including an isolated bacterial infection in 64 patients (47.8%), an isolated fungal infection in nine patients (6.7%), and a coinfection with both pathogens in eight patients (5.0%). Radiologically assessed enteritis (odds ratio, 2.60; 95% CI, 1.32-7.56; p = 0.015) and HIV infection (odds ratio, 2.03; 95% CI, 1.21-3.31; p = 0.016) were independently associated with invasive fungal disease. CONCLUSIONS: The rate of invasive fungal disease reaches 20% in patients with neutropenic enterocolitis when enteritis is considered. To avoid treatment delay, antifungal therapy might be systematically discussed in ICU patients admitted for neutropenic enterocolitis with radiologically assessed enteritis.

Fatal Neutropenic Enterocolitis Caused by Stenotrophomonas maltophilia: A Rare and Underrecognized Entity.

Although Stenotrophomonas maltophilia causes substantial morbidity and mortality in immunocompromised patients, it has not been described as a causal pathogen of neutropenic enterocolitis (NEC). We describe the first case of histologically-confirmed NEC caused by S. maltophilia accompanied by bacteremia and pneumonia after salvage chemotherapy for acute myeloid leukemia relapse following a second hematopoietic stem cell transplantation. S. maltophilia should be included as a pathogenic organism of NEC in severely immunocompromised patients to prevent a delayed diagnosis, which carries a high risk of inappropriate antimicrobial selection and fatal outcome.

Ultrasonography-driven combination antibiotic therapy with tigecycline significantly increases survival among patients with neutropenic enterocolitis following cytarabine-containing chemotherapy for the remission induction of acute myeloid leukemia.

Neutropenic enterocolitis (NEC) is an abdominal infection reported primarily in patients with acute myeloid leukemia (AML) following chemotherapy, especially cytarabine, a notable efficacious cytotoxic agent for AML remission. Specific data regarding the impact of different cytarabine schedules and/or antibacterial regimens for NEC are sparse. The aim of the study was to identify the predictors of outcome within 30 days of NEC onset. NEC episodes were retrospectively pinpointed among 440 patients with newly diagnosed AML hospitalized in our Institution, over a 10-year period, for receiving chemotherapy protocols with 100-6000 mg/m2 daily of cytarabine. Two subgroups, survivors versus nonsurvivors, were compared by using logistic regression analysis. NEC was documented in 100 of 420 (23.8%) analyzed patients: 42.5% had received high-dose cytarabine, whereas 19% and 15% intermediate-dose and standard-dose cytarabine, respectively (P < 0.001). The 30-day NEC attributable mortality rate was 23%. In univariate analysis, antileukemic protocols containing robust dosages of cytarabine were significantly associated with high mortality (P < 0.001); whereas, standard-dose cytarabine and prompt initiation (at the ultrasonographic appearance of intestinal mural thickening) of NEC therapy with antibiotic combinations including tigecycline were significantly associated with low mortality. In multivariate analysis, high-dose cytarabine-containing chemotherapy was the independent predictor of poor outcome (odds ratio [OR]: 0.109; 95% confidence interval [CI]: 0.032-0.364; P < 0.001), whereas ultrasonography-driven NEC therapy with antibiotic regimens including tigecycline was associated with a favorable outcome (OR: 13.161; 95% CI: 1.587-109.17; P = 0.017). Chemotherapy schedules with robust dosages of cytarabine for AML remission are associated with a high rate of NEC incidence and attributable. Vigorous antibacterial therapy, triggered off pathologic ultrasonographic findings, with drug combinations which have broad antimicrobial coverage and good gut penetration, specifically those also including tigecycline, may be effective in improving 30-day survival rate after NEC onset.

Variant neutropenic enterocolitis presenting as acute appendicitis.

BACKGROUND: Neutropenic enterocolitis (NE) is characterized by fever, abdominal pain, and neutropenia. Observed most commonly in relation to solid, hematologic, and lymphoproliferative malignant tumors and their treatment, this disease entity may involve a wide area of the gastrointestinal tract. We report the first case of NE with isolated appendiceal involvement in a non-oncologic neutropenic patient who was managed successfully medically. In addition, we formally recognize neutropenic appendicitis as a variant of NE and differentiate it from acute non-neutropenic appendicitis. METHODS: Case report and review of the pertinent English language literature. CASE REPORT: A 50-year-old man with seronegative large-joint arthritis presented emergently with a one-day history of subjective fever and acute-onset abdominal pain in the setting of recently developed sulfasalazine-induced agranulocytosis. Abdominal examination revealed mild-to-moderate tenderness and rebound tenderness in the right lower quadrant. Computed tomography (CT) of the abdomen demonstrated findings consistent with acute appendicitis. The patient improved clinically with non-operative management including a broad-spectrum antibiotic, with normalization of the white blood cell count four days after initiation of granulocyte-colony stimulating factor therapy. CONCLUSIONS: Given the similarity in clinical presentation and CT imaging in patients with neutropenic and non-neutropenic appendicitis, accurate recognition of neutropenic appendicitis rests on a thorough patient history and a high index of suspicion in febrile neutropenic patients.

Neutropenic enterocolitis: An unusual complication of HCV combination therapy with PEG-IFN and ribavirin.

Drug induced neutropenia as a consequence of intensive chemotherapy for hematological malignancies and solid tumors is known to be associated with severe, life-threatening infections such as neutropenic enterocolitis. However, the neutropenia associated with HCV combination therapy with Pegylated Interferon [PEG-IFN] and ribavirin is considered to be well tolerated in patients without other co-morbidities. We present a case of a severe gastrointestinal complication in a patient receiving HCV combination therapy and advocate caution in continuing therapy in patients with neutropenia, especially in the presence of underlying co-morbidities such as cirrhosis.

Neutropenic enterocolitis in breast cancer patient after taxane-containing chemotherapy.

Neutropenic enterocolitis or typhlitis (from the Greek typhlon, meaning caecum) is defined as a necrotizing colitis with inflammation of the cecum and surrounding tissues. Although this condition occurs primarily in severely myelosuppressed and immunosuppressed patients with leukemia, it may also occur in those with other advanced malignancies receiving myelosuppressive chemotherapy. It has been described most recently in patients with solid tumors who receive taxane-based therapy. A 60-year old woman with medullary breast cancer stage IIIB underwent neoadjuvant chemotherapy with TAC (doxetaxele 100 mg/m2, doxorubicin 50 mg/m2 and cyclophosphamide 600 mg/m2). Sixth day after TAC chemotherapy, she had abdominal pain and vomiting. Abdomen CT scan showed diffuse circumferential thickening of ileum wall typical for ileitis, narrowing of the lumen, disturbance of peristaltic. This abdomen CT scan was thought as abnormality pictures of neutropenic enterocolitis. Neutropenic enterocolitis should be considered in patients with abdominal symptoms especially during the granulocyte nadir following chemotherapy. Increased awareness of this rapidly progressive and potentially fatal disease leads to accurate diagnosis and the prompt treatment that can decrease morbidity and mortality.

[Typhlitis: report of a case and review of the literature]. / Typhlite: à propos d'une observation et revue de la littérature.

INTRODUCTION: Typhlitis is a rare condition, characterized by necrotizing inflammation of the colon. It occurs mainly in neutropenic patients receiving chemotherapy for leukemia. EXEGESIS: We report the case of a 64-year-old woman with T-cell lymphocytic leukaemia, who exhibited asymptomatic reactivation of cytomegalovirus infection and developed subsequently typhlitis. CONCLUSION: The pathological mechanisms of typhlitis remain unclear in neutropenic patients. The role of cytotoxic drugs as well as both bacterial overgrowth and translocation has been postulated. In our patient, asymptomatic reactivation of cytomegalovirus infection may have increased chemotherapeutic-agents-digestive toxicity.

Neutropenic enterocolitis in children with acute leukemia or aplastic anemia.

Neutropenic enterocolitis (NE) and acute appendicitis are life-threatening conditions that develop in children with severe or prolonged neutropenia secondary to acute leukemia and lymphoma. The medical records of 118 patients who were treated for acute lymphoblastic leukemia (69 patients), acute myelogenous leukemia (22 patients), or aplastic anemia (27 patients) between 1997 and 2006 in our hospital pediatric hematology department were examined retrospectively. NE was diagnosed in 11 patients (age range, 2.5-16 years) on the basis of clinical and laboratory features. Two of these 11 patients had appendicitis in addition to NE. Conservative treatment was favored for all patients, but 1 patient with acute appendicitis underwent surgery. Neutropenic patients with a hematologic malignancy and abdominal pain should receive their diagnoses immediately and undergo treatment. NE and acute appendicitis should always be considered in the differential diagnosis of abdominal pain. Conservative treatment must be chosen initially for patients with NE, and these patients should be evaluated carefully for surgery. The criteria for the surgical process are the same as those for immunocompetent children. In addition, the close monitoring of hematologic factors is necessary.

[Neutropenic enterocolitis in adult patients with acute leukemia or stem cell transplant recipients: study of 7 cases]. / Enterocolitis neutropénica en adultos con leucemia aguda o receptores de un trasplante de progenitores hematopoyéticos: estudio de 7 casos.

BACKGROUND AND OBJECTIVE: Neutropenic enterocolitis (NE) is a complication arising in neutropenic patients with acute leukemia or solid tumours while treated with intensive chemotherapy. The optimal therapeutic procedures have not been well established. PATIENTS AND METHOD: Seven cases of NE diagnosed and treated in a tertiary hospital between 2000 and 2007 are described. Their clinico-biological characteristics, therapeutic procedures and evolution were analysed retrospectively. RESULTS: Five of the patients were males, their median age was 39 years. Acute myeloblastic leukemia was the most frequent diagnosis (5 cases). Two other patients had received an stem cell transplantation. Abdominal pain was present in all patients, diarrhoea in 6, and fever in 5. Microorganisms were isolated from blood cultures in 4 cases (Clostridium septicum, Escherichia coli, Pseudomonas aeruginosa and Aeromonas hydrophila). Abnormal mural thickening of the caecum was observed in the 6 cases in which a computed tomography scan could be performed. The median mural thickness at its maximum section was 11 mm (range: 8-16). All patients first received medical treatment with wide spectrum antibiotics and intestinal rest, and abdominal surgery was indicated in 6 cases after a median time from first symptom of 4 days (range: 0-12). NE was confirmed histologically in all 6 patients. Five patients required admission in Intensive Care Unit and 2 (29%) died as a result of NE. CONCLUSIONS: NE is a severe complication of patients with hematologic malignancies submitted to intensive chemotherapy or receiving stem cell transplantation. Abdominal computed tomography scan is the most valuable diagnostic tool. Prompt surgical intervention may improve the prognosis in patients with NE.

Neutropenic enterocolitis: is there a right timing for surgery? Assessment of a clinical case.

Neutropenic enterocolitis is a severe and potentially life-threatening complication that may affect patients undergoing chemotherapy for acute leukemia or lymphoma. These patients may develop systemic sepsis through bacterial or fungal translocation across the intestinal wall. In many cases neutropenic enterocolitis is confined to the cecum, but the entire colon is sometimes involved. Most patients are treated conservatively because an improvement occurs when the absolute neutrophil count rises. However, a surgical approach consisting of resection of the colon may sometimes be necessary, even in patients with complete aplasia and a high risk of complications. The right time to perform surgery is hard to define. Intestinal wall thickness, evaluated by ultrasound, is an important prognostic factor which could act as a guide to surgical indication. We analyze a case of neutropenic enterocolitis which occurred in a patient with acute myeloid leukemia during chemotherapy and we suggest that, as well as intestinal wall thickness, hemodynamic worsening should be considered an indication for surgery.

Neutropenic enterocolitis in lung cancer: a report of two cases and a review of the literature.

The first patient, a 68-year-old woman, presented neutropenic fever and hemorrhagic diarrhea on the sixth day of a combination chemotherapy of carboplatin and paclitaxel. The second patient, a 30-year-old man, presented neutropenia and diarrhea on the tenth day of the second cycle of a combination chemotherapy of cisplatin and vinorelbine. In both patients, abdominal computed tomography scan showed thickening of the colon wall and pericolic edema, and the ultrasonography revealed echogenic thickening of the colon walls. These findings confirmed the diagnosis of neutropenic enterocolitis. After the treatments, we changed the anticancer drug regimen; and successfully achieved partial responses.