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Objective: Hemophagocytic lymphohistiocytosis is a hyperinflammatory syndrome that often requires critical care support and remains difficult to diagnose. These guidelines are meant to aid in the early recognition, diagnosis, supportive care, and treatment of patients with hemophagocytic lymphohistiocytosis in ICUs.Data Sources: The literature searches were performed with PubMed (MEDLINE).Study Selection: Keywords and medical subject headings terms for literature search included "macrophage activation syndrome," hemophagocytic lymphohistiocytosis," and "hemophagocytic syndrome."Data Extraction: The Histiocyte Society developed these consensus recommendations on the basis of published reports and expert opinions with level of evidence provided for each recommendation. They were endorsed by the Society of Critical Care Medicine.Data Synthesis: Testing for hemophagocytic lymphohistiocytosis should be initiated promptly in all patients admitted to ICUs with an unexplained or disproportionate inflammatory response, especially those with rapid clinical deterioration. Meeting five or more of eight hemophagocytic lymphohistiocytosis 2004 diagnostic criteria serves as a valuable diagnostic tool for hemophagocytic lymphohistiocytosis. Early aggressive critical care interventions are often required to manage the multisystem organ failure associated with hemophagocytic lymphohistiocytosis. Thorough investigation of the underlying triggers of hemophagocytic lymphohistiocytosis, including infections, malignancies, and autoimmune/autoinflammatory diseases, is essential. Early steroid treatment is indicated for patients with familial hemophagocytic lymphohistiocytosis and is often valuable in patients with acquired hemophagocytic lymphohistiocytosis (i.e., secondary hemophagocytic lymphohistiocytosis) without previous therapy, including macrophage activation syndrome (hemophagocytic lymphohistiocytosis secondary to autoimmune/autoinflammatory disease) without persistent or relapsing disease. Steroid treatment should not be delayed, particularly if organ dysfunction is present. In patients with macrophage activation syndrome, whose disease does not sufficiently respond, interleukin-1 inhibition and/or cyclosporine A is recommended. In familial hemophagocytic lymphohistiocytosis and severe, persistent, or relapsing secondary macrophage activation syndrome, the addition of prompt individualized, age-adjusted etoposide treatment is recommended.Conclusions: Further studies are needed to determine optimal treatment for patients with hemophagocytic lymphohistiocytosis in ICUs, including the use of novel and adjunct therapies. [ABSTRACT FROM AUTHOR]

Response to mitogen-activated protein kinase inhibition of neurodegeneration in Langerhans cell histiocytosis monitored by cerebrospinal fluid neurofilament light as a biomarker: a pilot study Keywords: Langerhans cell histiocytosis; central nervous system; neurodegeneration; mitogen-activated protein kinase inhibition; neurofilament light chain protein EN Langerhans cell histiocytosis central nervous system neurodegeneration mitogen-activated protein kinase inhibition neurofilament light chain protein 248 254 7 12/27/21 20220101 NES 220101 Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia with highly variable clinical presentation.1 Granulomatous lesions of bone, skin, and lungs (particularly in adults) are most common, but the liver, spleen, bone marrow, and central nervous system (CNS) may also be affected.1 CNS involvement (CNS LCH) often causes endocrinopathies, most commonly diabetes insipidus (DI), but may also cause a debilitating slowly-progressive neurodegeneration.1,2 Notably, a population-based study reported that at least 24% of all children with LCH develop signs of neurodegenerative CNS LCH (ND-CNS-LCH) on magnetic resonance imaging (MRI).3 Thus, a strategy for early detection, treatment, and monitoring of ND-CNS-LCH is imperative. Central nervous system, neurodegeneration, Langerhans cell histiocytosis, mitogen-activated protein kinase inhibition, neurofilament light chain protein GLO:1XW/01jan22:bjh17781-fig-0001.jpg PHOTO (COLOR): 1 Neurofilament (NFL) levels in the cerebrospinal fluid (CSF) in the five children with central nervous system (CNS) affection of Langerhans cell histiocytosis (LCH) before and after initiation of treatment with mitogen-activated protein kinase pathway inhibitors (MAPKi). [Extracted from the article]

Aim: To present the first case series of patients with Langerhans cell histiocytosis (LCH) also affected by Crohn's disease (CD), both of which are granulomatous diseases, and in LCH investigate the role of interleukin (IL)‐23, which is a well‐described disease mediator in CD. Methods: A case series of three patients with LCH and CD were described; a cohort of LCH patients (n = 55) as well as controls (n = 55) were analysed for circulating IL‐23 levels; and the relation between the percentage of LCH cells in lesions and circulating IL‐23 levels was analysed in seven LCH patients. Results: Differential diagnostic challenges for these two granulomatous diseases were highlighted in the case series, and it took up to 3 years to diagnose CD. Elevated IL‐23 levels were found in LCH patients. The amount of lesional LCH cells correlated with the levels of circulating IL‐23. Conclusion: Both CD and LCH should be considered in patients with inflammatory gastrointestinal involvement. The IL‐23 pathway is a common immunological trait between these two granulomatous diseases. [ABSTRACT FROM AUTHOR]

Key Clinical Message We report a case of several autoimmune disorders eventually presenting as severe multi organ dysfunction syndrome caused by adult hemophagocytic lymphohistiocytosis ( HLH). Clinical and laboratory tests might lead to fatal misinterpretation without awareness of its diagnostic evaluation, as HLH shares common features with sepsis and immune-mediated systemic inflammatory response syndromes. [ABSTRACT FROM AUTHOR]

Background: Severe pandemic influenza has been associated with the hyperinflammatory condition secondary haemophagocytic lymphohistiocytosis (HLH)., Objectives: To determine the frequency, degree, character and possible cause of influenza-associated HLH in critically ill patients with severe acute respiratory distress syndrome due to influenza A (H1N1) infection requiring extracorporeal membrane oxygenation (ECMO) support at our hospital., Design: A retrospective observational study., Patients and Setting: Medical data were retrieved retrospectively from 11 consenting patients of thirteen adults infected with pandemic influenza A (H1N1) 2009 requiring ECMO between July 2009 and January 2010 at the ECMO Centre of Karolinska University Hospital, Stockholm, Sweden. All patients were evaluated for HLH using HLH-2004 criteria and HScore., Results: Eleven patients (median age 31 years) were included in the study and all survived. All patients showed signs of multiple organ dysfunction and pronounced inflammation, more severe in the four patients with HLH who had significantly higher peak serum concentrations of ferritin (P = 0.024), alkaline phosphatase (P = 0.012) and gamma-glutamyl transferase (P = 0.024), lower concentration of albumin (P = 0.0086) and more frequently hepatomegaly (P = 0.048). Abnormal lymphocyte cytotoxicity (lytic units <10) and a low proportion of natural killer (NK) cells were observed in three of four patients with HLH. Notably, we found a significant inverse correlation between serum ferritin concentration and NK cell and cytotoxic T lymphocyte percentages (rs = -0.74, P = 0.0013 and rs = -0.79, P = 0.0025, respectively). One HLH patient received HLH-directed cytotoxic therapy, another intravenous immunoglobulin and the other two no specific HLH-directed therapy., Conclusion: Critically ill patients, including healthy young adults, with pandemic influenza may develop HLH and should be monitored for signs of hyperinflammation and increasing organ dysfunction, and evaluated promptly for HLH because HLH-directed therapy may then be beneficial. The association of low NK percentages with hyperferritinaemia may suggest a role for reduced NK cell numbers, possibly also cytotoxic T lymphocytes, and subsequently reduced lymphocyte cytotoxicity, in the pathogenesis of hyperinflammation and secondary HLH., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Society of Anaesthesiology.)

Background: Globally, ~500 000 people with severe dengue (SD) require hospitalization yearly; ~12 500 (2.5%) die. Secondary hemophagocytic lymphohistiocytosis (sHLH) is a potentially fatal hyperinflammatory condition for which HLH-directed therapy (as etoposide and dexamethasone) can be life-saving. Prompted by the high mortality in SD and the increasing awareness that patients with SD may develop sHLH, our objectives were to (1) determine the frequency of dengue-HLH in SD, (2) describe clinical features of dengue-HLH, (3) assess mortality rate in SD and dengue-HLH, and (4) identify mortality-associated risk factors in SD., Methods: A 5-year retrospective single-center study in all adult patients with SD admitted to a tertiary intensive care unit in Malaysia., Results: Thirty-nine of 180 (22%) patients with SD died. Twenty-one of 180 (12%) had HLH defined as an HLH probability ≥70% according to histo score (HScore); 9 (43%) died. Similarly, 12 of 31 (39%) fulfilling ≥4 and 7 of 9 (78%) fulfilling ≥5 HLH-2004 diagnostic criteria died. Peak values of aspartate aminotransferase (AST), alanine aminotransferase, lactate dehydrogenase, and creatinine correlated to fatality (odds ratios [ORs], 2.9, 3.4, 5.8, and 31.9; all P < .0001), as did peak ferritin (OR, 2.5; P = .0028), nadir platelets (OR, 1.9; P = .00068), hepatomegaly (OR, 2.9; P = .012), and increasing age (OR, 1.2; P = .0043). Multivariable logistic regression revealed peak AST (OR, 2.8; P = .0019), peak creatinine (OR, 7.3; P = .0065), and SOFA (Sequential Organ Failure Assessment) score (OR, 1.4; P = .0051) as independent risk factors of death., Conclusions: Be observant of dengue-HLH due to its high mortality. A prospective study is suggested on prompt HLH-directed therapy in SD patients with hyperinflammation and evolving multiorgan failure at risk of developing dengue-HLH., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)