Chemotherapy-sparing treatment of haemophagocytic lymphohistiocytosis with intravenous immunoglobulins and corticosteroids

2020 ◽  
Vol 13 (5) ◽  
pp. e234490
Author(s):  
Evan C Chen ◽  
Jonathan A Stefely ◽  
Bimalangshu R Dey ◽  
Walter H Dzik

Haemophagocytic lymphohistiocytosis (HLH) can be a rapidly fatal disease. Current treatment in adults is extrapolated from the HLH-2004 protocol that specifies a regimen of etoposide, dexamethasone and cyclosporine. However, HLH presents as a spectrum of disease severity. A therapeutic challenge arises for milder cases where the harms of potent chemotherapy such as etoposide may outweigh its benefit. We present a case of an adult with HLH who developed significant pancytopenia but was otherwise not critically ill and who responded to treatment with a chemotherapy-sparing approach consisting of intravenous immunoglobulins and corticosteroids alone. The case illustrates that tailored therapy may allow effective treatment of the disorder while minimising therapy-related toxicities.

Author(s):  
Isadore Budnick ◽  
Jessica Davis ◽  
Anirudh Sundararaghavan ◽  
Samuel Konkol ◽  
Chelsea Lau ◽  
...  

Background: Fibrinogen (FIB) levels less than 150 mg/dL have been associated with increased rates of bleeding and lower survival in critically ill cirrhosis patients. Objective: We aimed to determine if treatment with cryoprecipitate (CRYO) for low FIB levels were associated with bleeding complications or survival. Patients / Methods: 237 cirrhosis patients admitted to an intensive care unit at a tertiary care liver transplant center with initial FIB levels less than 150 mg/dL were retrospectively assessed for CRYO transfusion, bleeding events, and survival outcomes. Results: The mean MELD score was 27.2 (95% CI 26.0 - 28.3) and CLIF-C Acute on Chronic Liver Failure (ACLF) score was 53.4 (51.9 - 54.8). Ninety-nine (41.8%) were admitted for acute bleeding and the remainder were admitted for non-bleeding illnesses. FIB level on admission correlated strongly with disease severity. After adjusting for disease severity, FIB on admission was not an independent predictor of 30-day survival (HR 0.99, 95% CI 0.99 - 1.01, p = 0.68). CRYO transfusion increased FIB levels but had no independent effect on mortality or bleeding complications (HR 1.10, 95% CI 0.72 - 1.70, p = 0.65). Conclusions: In cirrhosis patients with critical illness, low FIB levels on presentation reflect severity of illness but are not independently associated with 30-day mortality. Treatment of low FIB with CRYO also does not affect survival or bleeding complications suggesting FIB is an additional marker of severity of illness but is not itself a direct factor in the pathophysiology of bleeding in critically ill cirrhosis patients.


2016 ◽  
Vol 44 (6) ◽  
pp. 1034-1041 ◽  
Author(s):  
Jeremy Cohen ◽  
Carel J. Pretorius ◽  
Jacobus P. J. Ungerer ◽  
John Cardinal ◽  
Antje Blumenthal ◽  
...  

BMJ Open ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. e032695 ◽  
Author(s):  
Gunnar Lachmann ◽  
Cornelia Knaak ◽  
Clarissa von Haefen ◽  
Nadine Paeschke ◽  
Christian Meisel ◽  
...  

IntroductionHaemophagocytic lymphohistiocytosis (HLH) in adults is characterised by toxic immune activation and a sepsis-like syndrome, leading to high numbers of undiagnosed cases and mortality rates of up to 68%. Early diagnosis and specific immune suppressive treatment are mandatory to avoid fatal outcome, but the diagnostic criteria (HLH-2004) are adopted from paediatric HLH and have not been validated in adults. Experimental studies suggest biomarkers to sufficiently diagnose HLH. However, biomarkers for the diagnosis of adult HLH have not yet been investigated.Methods and analysisThe HEMICU (Diagnostic biomarkers for adult haemophagocytic lymphohistiocytosis in critically ill patients) study aims to estimate the incidence rate of adult HLH among suspected adult patients in intensive care units (ICUs). Screening for HLH will be performed in 16 ICUs of Charité – Universitätsmedizin Berlin. The inclusion criteria are bicytopaenia, hyperferritinaemia (≥500 µg/L), fever or when HLH is suspected by the clinician. Over a period of 2 years, we expect inclusion of about 100 patients with suspected HLH. HLH will be diagnosed if at least five of the HLH-2004 criteria are fulfilled, together with an expert review; all other included patients will serve as controls. Second, a panel of potential biomarker candidates will be explored. DNA, plasma and serum will be stored in a biobank. The primary endpoint of the study is the incidence rate of adult HLH among suspected adult patients during ICU stay. Out of a variety of measured biomarkers, this study furthermore aims to find highly potential biomarkers for the diagnosis of adult HLH in ICU. The results of this study will contribute to improved recognition and patient outcome of adult HLH in clinical routine.Ethics and disseminationThe institutional ethics committee approved this study on 1 August 2018 (Ethics Committee of Charité – Universitätsmedizin Berlin, EA4/006/18). The results of the study will be disseminated in an international peer-reviewed journal and presented at international conferences.Trial registration numberNCT03510650.


Author(s):  
Roberto de la Rica ◽  
Marcio Borges ◽  
María Aranda ◽  
Alberto del Castillo ◽  
Antonia Socias ◽  
...  

ABSTRACTOBJECTIVETo describe the clinical characteristics and epidemiological features of severe (non-ICU) and critically patients (ICU) with COVID-19 at triage, prior hospitalization, in one of the main hospitals in The Balearic Islands health care system.DESIGNRetrospective observational studySETTINGSon Llatzer University Hospital in Palma de Mallorca (Spain)PARTICIPANTSAmong a cohort of 52 hospitalized patients as of 31 March 2020, 48 with complete demographic information and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive test, were analyzed. Data were collected between March 15th, 2020, and March 31th 2020, inclusive of these dates.MAIN OUTCOMESClinical, vital signs and routine laboratory outcomes at the time of hospitalization, including symptoms reported prior to hospitalization. Demographics and baseline comorbidities were also collected. Mortality was reported at the end of the study.RESULTS48 patients (27 non-ICU and 21 ICU) resident in Mallorca, Spain (mean age, 66 years, [range, 33-88 years]; 67% males) with positive SARS-CoV-2 infection were analyzed. There were no differences in age or sex among groups (p >.05). Initial symptoms included fever (100%), coughing (85%), dyspnea (76%), diarrhea (42%) and asthenia (21%). The majority of patients in this case series were hospitalized because of low SpO2 (SpO2 below 90%) and presentation of bilateral pneumonia (94%) at triage. ICU patients had a higher prevalence of dyspnea compared to non-ICU patients (95% vs 61%, p = .022). Acute respiratory syndrome (ARDS) was presented in 100% of the ICU-patients. All the patients included in the study required oxygen therapy. ICU-patients had lymphopenia as well as hypoalbuminemia. Inflammatory markers such as lactate dehydrogenase (LDH), C-reactive protein (CRP), and procalcitonin were significantly higher in ICU patients compared to non-ICU (p < .001).Lower albumin levels were associated with poor prognosis measured as longer hospital length (r= −0.472, p <.001) and mortality (r= −0.424, p=.003). Interestingly we also found, that MCV was lower among of those patients who died (p=.0002). As of April 28, 2020, 10 patients (8 ICU and 2 non-ICU) had died (21% mortality) and while 100% of the non-ICU patients had been discharged, 33% of ICU patients still remained hospitalized (5 in ICU and 2 had been transferred to ward).CONCLUSIONCritically ill patients with COVID-19 present lymphopenia, hypoalbuminemia as well high levels of inflammation. Lower levels of albumin were associated with poorer outcomes in COVID-19 patients. Albumin might be of importance because of its association with disease severity in patients infected with SARS-CoV-2.WHAT IS ALREADY KNOWN IN THIS TOPICSpain has been hit particularly hard by the pandemic. By the time that this manuscript was written more than 25.000 deaths related to COVID-19 have been confirmed. There is limited information available describing the clinical and epidemiological features of Spanish patients requiring hospitalization for COVID-19. Also, it is important to know the characteristics of the hospitalized patients who become critically illWHAT THIS STUDY ADDSThis small case series provides the first steps towards a comprehensive clinical characterization of severe and critical COVID-19 adult patients in Spain. The overall mortality in our patients was 21%. To our knowledge this is the first report with reporting these features in Spain. At triage the majority of patients had lower SpO2 (<90%) and bilateral pneumonia. The most common comorbidities were hypertension (70%), dyslipidemia (62%) and cardiovascular disease (30%). Critically ill patients present hypoalbuminemia and lymphopenia, as well as higher levels of inflammation. Albumin might be of importance because of its association with disease severity and mortality in patients infected with SARS-CoV-2.


Author(s):  
Wandong Hong ◽  
Qin Chen ◽  
Songzan Qian ◽  
Zarrin Basharat ◽  
Vincent Zimmer ◽  
...  

ObjectivesThe objective of this study was to investigate the clinical features and laboratory findings of patients with and without critical COVID-19 pneumonia and identify predictors for the critical form of the disease.MethodsDemographic, clinical, and laboratory data of 63 COVID-19 pneumonia patients were retrospectively reviewed. Laboratory parameters were also collected within 3–5 days, 7–9 days, and 11–14 days of hospitalization. Outcomes were followed up until March 12, 2020.ResultsTwenty-two patients developed critically ill pneumonia; one of them died. Upon admission, older patients with critical illness were more likely to report cough and dyspnoea with higher respiration rates and had a greater possibility of abnormal laboratory parameters than patients without critical illness. When compared with the non-critically ill patients, patients with serious illness had a lower discharge rate and longer hospital stays, with a trend towards higher mortality. The interleukin-6 level in patients upon hospital admission was important in predicting disease severity and was associated with the length of hospitalization.ConclusionsMany differences in clinical features and laboratory findings were observed between patients exhibiting non-critically ill and critically ill COVID-19 pneumonia. Non-critically ill COVID-19 pneumonia also needs aggressive treatments. Interleukin-6 was a superior predictor of disease severity.


2021 ◽  
Author(s):  
Maria Schroeder ◽  
Berfin Schaumburg ◽  
Zacharias Mueller ◽  
Ann Parplys ◽  
Dominik Jarczak ◽  
...  

Abstract BACKGROUNDMale sex was repeatedly identified as a risk factor for death and intensive care admission. However, it is yet unclear whether sex hormones are associated with disease severity in COVID-19 patients. We sought to characterize sex differences in hormone levels and cytokine responses in critically ill COVID-19 patients.METHODSWe performed a retrospective cohort study of critically ill COVID-19 patients. Males and females were compared. Multivariate regression was performed to assess the association between sex hormones, cytokine responses and the requirement for extracorporeal membrane oxygenation (ECMO) treatment.RESULTSWe analyzed sex hormone levels (estradiol and testosterone) of n=181 male and female individuals. These consisted of n=50 critically ill COVID-19 patients (n=39 males, n=11 females), n=42 critically ill non-COVID-19 patients (n=27 males, n=15 females), n=39 non-COVID-19 patients with coronary heart diseases (CHD) (n=25 males, n=14 females) and n=50 healthy individuals (n=30 males, n=20 females). We detected highest estradiol levels in critically ill male COVID-19 patients compared to non-COVID-19 patients (p=0.0123), patients with CHD (p=0.0002) or healthy individuals (p=0.0007). Lowest testosterone levels were detected in critically ill male COVID-19 patients compared to non-COVID-19 patients (p=0.0094), patients with CHD (p=0.0068) or healthy individuals (p<0.0001). No statistically significant differences in sex hormone levels were detected in critically ill female COVID-19 patients, albeit similar trends in estradiol levels were observed. In critically ill male COVID-19 patients, cytokine and chemokine responses (IFN-γ, p=0.0301; IL-1RA, p=0.0160; IL-6, p=0.0145; MCP-1, p=0.0052; MIP-1α, p=0.0134) were significantly elevated in those with higher Sequential Organ Failure Assessment (SOFA) scores (8-11). Linear regression analysis revealed that herein IFN-γ levels correlate with estradiol levels in male and female COVID-19 patients (R2=0.216, =0.0009). Male COVID-19 patients with elevated estradiol levels were more likely to receive ECMO treatment in the course of their ICU stay (p=0.0009). CONCLUSIONS We identified high estradiol and low testosterone levels as a hallmark of critically ill male COVID-19 patients. Elevated estradiol levels in critically ill male COVID-19 patients were positively associated with IFN-γ levels and increased risk for ECMO requirement.


2002 ◽  
Vol 13 (5) ◽  
pp. 397-408 ◽  
Author(s):  
Crispian Scully ◽  
Stephen J. Challacombe

Pemphigus is a group of potentially life-threatening diseases characterized by cutaneous and mucosal blistering. There is a fairly strong genetic background to pemphigus with linkage to HLA class II alleles. Certain ethnic groups, such as Ashkenazi Jews and those of Mediterranean origin, are especially liable to pemphigus. Pemphigus vulgaris (PV), the most common and important variant, is an autoimmune blistering disease characterized by circulating pathogenic IgG antibodies against desmoglein 3 (Dsg3), about half the patients also having Dsg1 autoantibodies. Oral lesions are initially vesiculobullous but readily rupture, new bullae developing as the older ones rupture and ulcerate. Biopsy of perilesional tissue, with histological and immunostaining examinations, is essential to the diagnosis. Serum autoantibodies to either Dsg1 or Dsg3 are best detected by both normal human skin and monkey esophagus or by enzyme-linked immunosorbent assay (ELISA). Before the introduction of corticosteroids, pemphigus vulgaris was typically fatal mainly from dehydration or secondary systemic infections. Current treatment is largely based on systemic immunosuppression using systemic corticosteroids, with azathioprine, dapsone, methotrexate, cyclophosphamide, and gold as adjuvants or alternatives, but mycophenolate mofetil and intravenous immunoglobulins also appear promising.


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