Macrophage activation-like syndrome: an immunological entity associated with rapid progression to death in sepsis

Kyriazopoulou, Evdoxia; Leventogiannis, Konstantinos; Norrby‐Teglund, Anna; Dimopoulos, Georgios; Pantazi, Aikaterini; Orfanos, Stylianos E.; Rovina, Nikoletta; Tsangaris, Iraklis; Gkavogianni, Theologia; Botsa, Elektra; Chassiou, Eleftheria; Κοτανίδου, Αναστασία; Kontouli, Christina; Chaloulis, Panagiotis; Velissaris, Dimitrios; Savva, Athina; Cullberg, Jonas-Sundén; Akinosoglou, Karolina; Gogos, Charalambos; Armaganidis, Apostolos; Giamarellos‐Bourboulis, Evangelos J.

doi:10.1186/s12916-017-0930-5

Cited by 143 publications

(144 citation statements)

References 28 publications

Supporting

Mentioning

132

Contrasting

Unclassified

Order By: Relevance

“…If present, hemophagocytosis in tissue and bone marrow can be suggestive of HLH, but hemophagocytosis can be found in critically ill patients with no other HLH features . Beyond patients with clear HLH disease, there is a growing body of evidence to support a macrophage activation syndrome (MAS) like phenotype in some patients with sepsis . Unfortunately, there are multiple definitions that have been used for MAS‐like sepsis, but in general these patients are described as having MODS characterized by hyperferritinemia, hepatobiliary dysfunction, and DIC with or without bone marrow failure .…”

Section: Typical and Unusual Hlh Presentation Phenotypesmentioning

confidence: 99%

Challenges in the diagnosis of hemophagocytic lymphohistiocytosis: Recommendations from the North American Consortium for Histiocytosis (NACHO)

Jordan

Allen

Greenberg

et al. 2019

Pediatric Blood & Cancer

243

232

View full text Add to dashboard Cite

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of pathologic immune activation, often associated with genetic defects of lymphocyte cytotoxicity. Though a distinctive constellation of features has been described for HLH, diagnosis remains challenging as patients have diverse presentations associated with a variety of triggers. We propose two concepts to clarify how HLH is diagnosed and treated: within the broader syndrome of HLH, "HLH disease" should be distinguished from "HLH disease mimics" and HLH subtypes should be categorized by specific etiologic associations, not the ambiguous dichotomy of "primary" and "secondary." We provide expertbased advice regarding the diagnosis and initiation of treatment for patients with HLH, rooted in improved understanding of its pathophysiology.

show abstract

Section: Typical and Unusual Hlh Presentation Phenotypesmentioning

confidence: 99%

Challenges in the diagnosis of hemophagocytic lymphohistiocytosis: Recommendations from the North American Consortium for Histiocytosis (NACHO)

Jordan

Allen

Greenberg

et al. 2019

Pediatric Blood & Cancer

243

232

View full text Add to dashboard Cite

show abstract

“…The Hscore has been recommended but many find it to be insensitive in sepsis especially in the early phase 56 . Macrophage activation-like syndrome has been used as a term to describe the hyper-inflamed state seen in sepsis which does not fulfil the criteria for secondary hemophagocytic lymphohistiocytosis 64 .The same group proposed the use of Ferritin levels of greater than 4000 ng/mL as a sensitive and specific marker for identifying this state but the SARS CoV 2 infection non survivors were found to have a median ferritin level of 1297.6 ng/mL in one case series making the utility of this parameter doubtful 65 . All these highlight the need for finding a more sensitive marker to identify the accompanying inflammatory state in this illness.…”

Section: The Immunological Consequences In Humansmentioning

confidence: 99%

“…All these highlight the need for finding a more sensitive marker to identify the accompanying inflammatory state in this illness. One possibility is using a combination of DIC (disseminated intravascular coagulation) and HBD (hepatobiliary dysfunction) as an indicator of the hyperimmune state 64 . However, the lack of widespread consensus on the cut-offs to denote hepato-biliary dysfunction in this condition and unavailability of tests in many resource poor situations is a drawback.…”

Section: The Immunological Consequences In Humansmentioning

confidence: 99%

Covid-19: Immunological Lessons from Bats, Pangolins and Old Coronaviruses; And How We Can Apply Them in a Timely Way for a Better Outcome

Dua¹,

Yadav²,

Jetley³

et al. 2020

Preprint

View full text Add to dashboard Cite

Introduction: The COVID-19 pandemic is a global crisis, the number of cases and deaths are on a steep incline. This article reviews the possible immunological mechanisms which underlie the disease pathogenesis by looking at the behaviour of previous coronaviruses not only in humans but also other mammals which possibly act as reservoir hosts. Observations: A key aspect of this coronavirus as well as the previous SARS CoV seems to be the importance of host immune response in the pathology and clinical severity of illness caused by them. A hyperactive innate immune state in combination with an exhausted adaptive immune response are possible determinants of severe illness. Conclusion: There is a possibility that the current SARS CoV 2 has immune evasive tactics similar to SARS CoV in its repertoire, since they share a 76% homology. These might have been learnt behaviour from long periods of persistence in their reservoir hosts and they may be the reason behind the dysregulated immune response evoked in humans. That in turn is highly likely to be one of the factors which govern disease severity. With this in mind we want to bring the medical community’s attention to a ‘hit early, hit hard’ intervention as a possible strategy to modify the course of the disease and bring down the numbers of severe sufferers.

show abstract

“…A macrophage activation-like syndrome (MALS) has been described in patients with sepsis who have an HScore of >151 and/or had evidence of disseminate intravascular coagulation and hepatobiliary dysfunction [41]. Presence of MALS was associated with an increased risk of death within the first 10 days of sepsis.…”

Section: Treatmentmentioning

confidence: 99%

Hemophagocytic Lymphohistiocytosis and Other Culture Negative Sepsis-Like Syndromes in the ICU

Denstaedt

Singer

2020

Evidence-Based Critical Care

View full text Add to dashboard Cite

A 57 year old man with history of idiopathic panniculitis on long-term steroid treatment presented to the hospital with a 1 month history of dyspnea, malaise, nausea and vomiting. He was hypotensive and tachycardic with an acute kidney injury. Prior to this presentation, he had been hospitalized for 2 weeks at a nearby hospital with similar symptoms and had been found to have multifocal ground glass opacities on CT of the chest. His condition after admission improved with fluid resuscitation, stress-dose steroids, and treatment for presumed sepsis. Infectious and rheumatologic workups were negative. He was noted to have bilateral pulmonary infiltrates ( Fig. 79.1a, b). One week after discharge, however, he presented again with systemic inflammatory response syndrome (SIRS). A bronchoscopy revealed only acute and chronic organizing pneumonia, with no evidence of infection. A bone marrow biopsy was performed, which demonstrated a hypercellular marrow. Pulse dose steroids were initiated for organizing pneumonia and he improved significantly over the next week with continuation of empiric antimicrobials and tapering of steroids. After 1 week of this regimen, however, he again decompensated with hypoxia and hypotension. Worsening infiltrates were noted on his chest radiograph ( Fig. 79.1c). Ferritin was elevated at 7652 ng/mL, and sIL-2R was elevated at 3432 U/ mL. Trigylcerides were normal and fibrinogen was elevated. Given his unremarkable bone marrow biopsy 7 days before and elevated fibrinogen, the possibility of hemophagocytic lymphohistiocytosis (HLH) was dismissed as his hyperferritinemia and elevated sIL-2R were attributed to history of blood transfusion and occult infection. He continued to improve with empiric antimicrobials and steroids, and was discharged from the hospital 5 days after admission to the ICU to complete a course of levofloxacin on 40 mg of prednisone daily.He presented to the hospital for the third time 2 days after discharge with hypotension and hypoxia requiring endotracheal intubation and vasopressors, and antibiotics and steroids were restarted. He was admitted to the ICU and his pulmonary status rapidly improved. After 3 days, however, he again decompensated with hypotension and an elevated lactate. He received intravenous fluids and intravenous steroids. Given the unclear association between changes in his antimicrobial regimen, steroid dosing, and clinical condition, his steroid dose was decreased from 40 mg prednisone daily by 10 mg each day. A repeat bone marrow biopsy was performed, which showed rare hemophagocytic macrophages but no evidence of malignancy. The next day, in the setting of reducing his steroid dose, he again had an episode of hypoxia and hypotension. Ferritin was measured at that time and was 9148 ng/mL, increased from 4074 ng/mL the day before ( Fig. 79.2). sIL2-R was measured and was elevated at 3494 U/mL. A diagnosis of HLH was made, and he was started on chemotherapy with etoposide and high dose dexamethasone. Eight weeks had elapsed since his initial presentati...

show abstract

Macrophage activation-like syndrome: an immunological entity associated with rapid progression to death in sepsis

Cited by 143 publications

References 28 publications

Challenges in the diagnosis of hemophagocytic lymphohistiocytosis: Recommendations from the North American Consortium for Histiocytosis (NACHO)

Challenges in the diagnosis of hemophagocytic lymphohistiocytosis: Recommendations from the North American Consortium for Histiocytosis (NACHO)

Covid-19: Immunological Lessons from Bats, Pangolins and Old Coronaviruses; And How We Can Apply Them in a Timely Way for a Better Outcome

Hemophagocytic Lymphohistiocytosis and Other Culture Negative Sepsis-Like Syndromes in the ICU

Contact Info

Product

Resources

About