Use of complement monoclonal antibody eculizumab in Shiga toxin producing <i>Escherichia coli</i> associated hemolytic uremic syndrome: A review of current evidence

Mahat, Upendra; Matar, Raed Bou; Rotz, Seth J.

doi:10.1002/pbc.27913

Cited by 25 publications

(16 citation statements)

References 23 publications

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“…Based on the interaction of Stx2 with the complement system [ 251 ], the C5-complement inhibiting monoclonal antibody Eculizumab was therapeutically employed as rescue therapy for EHEC–HUS patients, which had seizures or were in a stupor or coma [ 490 ]. In a number of studies, Eculizumab showed positive clinical improvement after treatment in severe EHEC-HUS with progressive neurological improvement that often lead to serious long-term disabilities [ 491 ]. In particular, the early use of Eculizumab appeared to improve neurological outcome suggesting that prophylactic antibody therapy before the development of neurological symptoms could be advantageous [ 490 ].…”

Section: Discussionmentioning

confidence: 99%

Valid Presumption of Shiga Toxin-Mediated Damage of Developing Erythrocytes in EHEC-Associated Hemolytic Uremic Syndrome

Detzner

Pohlentz

Müthing

2020

Toxins

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The global emergence of clinical diseases caused by enterohemorrhagic Escherichia coli (EHEC) is an issue of great concern. EHEC release Shiga toxins (Stxs) as their key virulence factors, and investigations on the cell-damaging mechanisms toward target cells are inevitable for the development of novel mitigation strategies. Stx-mediated hemolytic uremic syndrome (HUS), characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal injury, is the most severe outcome of an EHEC infection. Hemolytic anemia during HUS is defined as the loss of erythrocytes by mechanical disruption when passing through narrowed microvessels. The formation of thrombi in the microvasculature is considered an indirect effect of Stx-mediated injury mainly of the renal microvascular endothelial cells, resulting in obstructions of vessels. In this review, we summarize and discuss recent data providing evidence that HUS-associated hemolytic anemia may arise not only from intravascular rupture of erythrocytes, but also from the extravascular impairment of erythropoiesis, the development of red blood cells in the bone marrow, via direct Stx-mediated damage of maturing erythrocytes, leading to “non-hemolytic” anemia.

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Section: Discussionmentioning

confidence: 99%

Valid Presumption of Shiga Toxin-Mediated Damage of Developing Erythrocytes in EHEC-Associated Hemolytic Uremic Syndrome

Detzner

Pohlentz

Müthing

2020

Toxins

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“…Since then, case series and case control studies yielding equivocal results [ 191 ], and two randomized controlled trials completed in 2012 (NCT01410916) and 2018 (NCT02205541) without any publication have cast doubts over the efficacy of complement inhibition in this indication.…”

Section: Managementmentioning

confidence: 99%

Shiga Toxin-Associated Hemolytic Uremic Syndrome: Specificities of Adult Patients and Implications for Critical Care Management

Travert

Rafat

Mariani

et al. 2021

Toxins

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Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC-HUS) is a form of thrombotic microangiopathy secondary to an infection by an enterohemorrhagic E. coli. Historically considered a pediatric disease, its presentation has been described as typical, with bloody diarrhea at the forefront. However, in adults, the clinical presentation is more diverse and makes the early diagnosis hazardous. In this review, we review the epidemiology, most important outbreaks, physiopathology, clinical presentation and prognosis of STEC-HUS, focusing on the differential features between pediatric and adult disease. We show that the clinical presentation of STEC-HUS in adults is far from typical and marked by the prevalence of neurological symptoms and a poorer prognosis. Of note, we highlight knowledge gaps and the need for studies dedicated to adult patients. The differences between pediatric and adult patients have implications for the treatment of this disease, which remains a public health threat and lack a specific treatment.

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“…However, it has been used in some cases of severe STEC-HUS with some efficacy. 15,16 In this case, we had planned to start eculizumab treatment due to brain involvement secondary to severe STEC-HUS.…”

Section: Discussionmentioning

confidence: 99%

Sudden Cardiac Arrest and Malignant Ventricular Tachycardia in an 8-Year-Old Pediatric Patient Who Has Hemolytic Uremic Syndrome Associated with Shiga Toxin-Producing Escherichia coli

Yeşilbaş

Akıncı

Talebazadeh

et al. 2020

J Pediatr Intensive Care

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Gastrointestinal, neurological, pancreatic, hepatic, and cardiac dysfunction are extrarenal manifestations of hemolytic uremic syndrome associated with Shiga toxin-producing Escherichia coli (STEC-HUS). The most frequent cause of death for STEC-HUS is related to the central nervous system and cardiovascular system. Cardiac-origin deaths are predominantly related to thrombotic microangiopathy-induced ischemia and the immediate development of circulatory collapse. STEC-HUS cardiac related deaths in children are rare with only sporadic cases reported. In our literature search, we did not come across any pediatric case report about STEC-HUS causing sudden cardiac arrest and malignant ventricular tachycardia (VT). Herein, we report the case of an 8-year-old female with a typical clinical manifestation of STEC-HUS. On the seventh day of pediatric intensive care unit admission, the patient had a sudden cardiac arrest, requiring resuscitation for 10 minutes. The patient had return of spontaneous circulation with severe monomorphic pulsed malignant VT. Intravenous treatment with lidocaine, amiodarone and magnesium sulfate were promptly initiated, and we administered multiple synchronized cardioversions, but VT persisted. Furthermore, we were not able to ameliorate her refractory circulation insufficiency by advanced cardiopulmonary resuscitation. Thus, inevitably, the patient lost her life. This case illustrates the need for aggressive management and the dilemma that pediatric critical care specialists, cardiologists, and nephrologists have to face when dealing with STEC-HUS that is worsened by a sudden cardiac arrest accompanied with VT.

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Use of complement monoclonal antibody eculizumab in Shiga toxin producing Escherichia coli associated hemolytic uremic syndrome: A review of current evidence

Cited by 25 publications

References 23 publications

Valid Presumption of Shiga Toxin-Mediated Damage of Developing Erythrocytes in EHEC-Associated Hemolytic Uremic Syndrome

Valid Presumption of Shiga Toxin-Mediated Damage of Developing Erythrocytes in EHEC-Associated Hemolytic Uremic Syndrome

Shiga Toxin-Associated Hemolytic Uremic Syndrome: Specificities of Adult Patients and Implications for Critical Care Management

Sudden Cardiac Arrest and Malignant Ventricular Tachycardia in an 8-Year-Old Pediatric Patient Who Has Hemolytic Uremic Syndrome Associated with Shiga Toxin-Producing Escherichia coli

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