Haemophagocytic lymphohistiocytosis (HLH)-associated stress cardiomyopathy secondary to autoimmune conditions successfully treated with anakinra

2021 ◽  
Vol 14 (12) ◽  
pp. e246416
Author(s):  
Muhammad Khalid ◽  
Abuelmagd Abdalla ◽  
Geraldine McCarthy ◽  
John Stack

We describe two young cases of reactive haemophagocytic lymphohistiocytosis (HLH) with the resultant stress cardiomyopathy in the setting of underlying autoimmune diseases, systemic lupus erythematosus (SLE) and Still’s disease. The initial presentation was similar in both cases with fever, hyperinflammatory response, hypotension (vasoplegia), bicytopenia and hyperferritinemia. Despite standard of care and multiple broad-spectrum antibiotics, both cases remained pyrexic and were ultimately admitted to the intensive therapy unit to treat cardiogenic shock. Echocardiogram of both cases showed low ejection fraction, the cause for which was not found until the final diagnosis of HLH was made. Both cases made a complete clinical and cardiac recovery following the initiation of high-dose glucocorticoids and anakinra.

Hematology ◽  
2014 ◽  
Vol 2014 (1) ◽  
pp. 34-43 ◽  
Author(s):  
Konstanze Döhner ◽  
Peter Paschka

Abstract In recent years, research in molecular genetics has been instrumental in deciphering the molecular heterogeneity of acute myeloid leukemia (AML), in particular the subset of patients with “intermediate-risk” cytogenetics. However, at present, only the markers NPM1, CEBPA, and FLT3 have entered clinical practice. Treatment of intermediate-risk AML patients eligible for intensive therapy has not changed substantially. The “3 + 7” induction therapy still represents the standard of care. The addition of the immunoconjugate gemtuzumab ozogamicin to therapy has been shown to improve outcome; however, the drug is not approved for this use. A common standard for postremission therapy is the administration of repeated cycles of intermediate- to high-dose cytarabine. Allogeneic stem cell transplantation may offer a survival benefit for many patients with intermediate-risk AML. Patients are best selected based on the genetic profile of the leukemia cells and the risk associated with the transplantation itself. A myriad of novel agents targeting mutant leukemia drivers or deregulated pathways are in clinical development. In the past, many novel compounds have not met expectations; nonetheless, with the rapid developments in comprehensive molecular profiling and new drug design, there is the prospect of personalizing therapy and improving patient outcome.


2019 ◽  
Vol 3 (4) ◽  
pp. 612-620 ◽  
Author(s):  
Matthew S. Painschab ◽  
Kate D. Westmoreland ◽  
Edwards Kasonkanji ◽  
Takondwa Zuze ◽  
Bongani Kaimila ◽  
...  

Abstract Burkitt lymphoma (BL) is common in sub-Saharan Africa (SSA). In high-income countries, BL is highly curable with chemotherapy. However, there are few prospective studies from SSA describing nonpediatric BL and no regional standard of care. Thirty-five participants age 15 years or older with newly diagnosed BL were enrolled in Malawi from 2013 to 2018. Chemotherapy was administered according to institutional guidelines, with concurrent antiretroviral therapy if HIV infected. Median age was 21 years (range, 15-61) and 15 participants (43%) were HIV infected. Twenty-seven participants (77%) had stage III to IV disease, and 19 (54%) had Eastern Cooperative Oncology Group performance status >1. Among HIV-infected participants, median CD4 count was 130 (range, 29-605) and 10 (67%) had suppressed HIV viral load. Four participants (11%) died before receiving chemotherapy. First-line chemotherapy consisted of: cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (n = 22 [71%]); infusional etoposide, prednisolone, vincristine, cyclophosphamide, and doxorubicin (n = 4 [13%]); high-dose methotrexate-based chemotherapy (n = 4 [13%]); and rituximab plus CHOP (n = 1 [3%]). Among 28 evaluable participants, 14 (50%) achieved a complete response. Median overall survival (OS) was 7 months; 1-year OS was 40% (95% confidence interval [CI], 24%-56%). Sixteen (73%) of 22 deaths were a result of disease progression. Compared with CHOP, more intensive chemotherapy was associated with decreased mortality (hazard ratio, 0.24; 95% CI, 0.05-1.02; P = .05). This is among the best characterized prospective cohorts of nonpediatric BL in SSA. Most deaths resulted from progressive BL. Patients who received more intensive therapy seemed to have better outcomes. Defining optimal approaches is an urgent priority in SSA.


Lupus ◽  
2019 ◽  
Vol 28 (5) ◽  
pp. 591-596
Author(s):  
M Dall’Era ◽  
N Solomons ◽  
R Federico ◽  
M Truman

Lupus nephritis is the most common organ-threatening manifestation of systemic lupus erythematosus. The current standard of care for patients is treatment with a combination of steroids plus either mycophenolate mofetil (MMF) or cyclophosphamide. However, these medications are associated with considerable toxicity and suboptimal efficacy. This retrospective propensity analysis of data from 63 matched patients enrolled in two of the largest active lupus nephritis controlled trials, ALMS and AURA, suggests that the high dose regimen of MMF and steroids as described in the 2012 American College of Rheumatology lupus nephritis guidelines may not be necessary in all lupus nephritis patients. A lower dose regimen may result in better long-term safety, including a reduction in lymphoproliferative disorders, skin cancers and steroid related side effects, without compromising efficacy. An ongoing randomized controlled double-blind phase 3 study, AURORA (NCT03021499), is investigating renal response in 358 patients randomized to receive a low dose regimen containing voclosporin, MMF and steroid therapy as used in the AURA trial. It is anticipated that the AURORA study and its blinded two-year extension will provide important long-term outcome data.


Lupus ◽  
2020 ◽  
Vol 29 (3) ◽  
pp. 324-333 ◽  
Author(s):  
G Lorenz ◽  
L Schul ◽  
F Schraml ◽  
K M Riedhammer ◽  
H Einwächter ◽  
...  

Objective In the context of systemic autoimmunity, that is systemic lupus erythematosus (SLE) or adult-onset Still’s disease (AOSD), secondary haemophagocytic lymphohistiocytosis (HLH; also referred to as macrophage activation syndrome (MAS) or more recently MAS-HLH) is a rare and potentially life-threatening complication. Pathophysiological hallmarks are aberrant macrophage and T cell hyperactivation and a systemic cytokine flare, which generate a sepsis-like, tissue-damaging, cytopenic phenotype. Unfortunately, for adult MAS-HLH we lack standardized treatment protocols that go beyond high-dose corticosteroids. Consequently, outcome data are scarce on steroid refractory cases. Aside from protocols based on treatment with calcineurin inhibitors, etoposide, cyclophosphamide and anti-IL-1, favourable outcomes have been reported with the use of intravenous immunoglobulin (IvIG) and plasma exchange (PE). Methods Here we report a retrospective series of steroid refractory MAS-HLH, the associated therapeutic regimes and outcomes. Results In this single-centre experience, 6/8 steroid refractory patients survived (median follow-up: 54.4 (interquartile range: 23.3–113.3) weeks). All were initially treated with PE, which induced partial response in 5/8 patients. Yet, all patients required escalation of immunosuppressive therapies. One case of MAS-HLH in new-onset AOSD had to be escalated to etoposide, whereas most SLE-associated MAS-HLH patients responded well to cyclophosphamide. Relapses occurred in 2/8 cases. Conclusion Together, early use of PE is at most a supportive measure, not a promising monotherapy of adult MAS-HLH. In refractory cases, conventional cytoreductive therapies (i.e. cyclophosphamide and etoposide) constitute potent and reliable rescue approaches, whereas IvIG, anti-thymoglobulin, and biologic agents appear to be less effective.


Hematology ◽  
2014 ◽  
Vol 2014 (1) ◽  
pp. 34-43 ◽  
Author(s):  
Konstanze Döhner ◽  
Peter Paschka

In recent years, research in molecular genetics has been instrumental in deciphering the molecular heterogeneity of acute myeloid leukemia (AML), in particular the subset of patients with “intermediate-risk” cytogenetics. However, at present, only the markers NPM1, CEBPA, and FLT3 have entered clinical practice. Treatment of intermediate-risk AML patients eligible for intensive therapy has not changed substantially. The “3 + 7” induction therapy still represents the standard of care. The addition of the immunoconjugate gemtuzumab ozogamicin to therapy has been shown to improve outcome; however, the drug is not approved for this use. A common standard for postremission therapy is the administration of repeated cycles of intermediate- to high-dose cytarabine. Allogeneic stem cell transplantation may offer a survival benefit for many patients with intermediate-risk AML. Patients are best selected based on the genetic profile of the leukemia cells and the risk associated with the transplantation itself. A myriad of novel agents targeting mutant leukemia drivers or deregulated pathways are in clinical development. In the past, many novel compounds have not met expectations; nonetheless, with the rapid developments in comprehensive molecular profiling and new drug design, there is the prospect of personalizing therapy and improving patient outcome.


2020 ◽  
Vol 26 (28) ◽  
pp. 3468-3496
Author(s):  
Emilio Rodrigo ◽  
Marcio F. Chedid ◽  
David San Segundo ◽  
Juan C.R. San Millán ◽  
Marcos López-Hoyos

: Although acute renal graft rejection rate has declined in the last years, and because an adequate therapy can improve graft outcome, its therapy remains as one of the most significant challenges for pharmacists and physicians taking care of transplant patients. Due to the lack of evidence highlighted by the available metaanalyses, we performed a narrative review focused on the basic mechanisms and current and future therapies of acute rejection in kidney transplantation. : According to Kidney Disease/Improving Global Outcomes (KDIGO) guidelines, both clinical and subclinical acute rejection episodes should be treated. Usually, high dose steroids and basal immunosuppression optimization are the first line of therapy in treating acute cellular rejection. Rabbit antithymocytic polyclonal globulins are used as rescue therapy for recurrent or steroid-resistant cellular rejection episodes. Current standard-of-care (SOC) therapy for acute antibody-mediated rejection (AbMR) is the combination of plasma exchange with intravenous immunoglobulin (IVIG). Since a significant rate of AbMR does not respond to SOC, different studies have analyzed the role of new drugs such as Rituximab, Bortezomib, Eculizumab and C1 inhibitors. Lack of randomized controlled trials and heterogenicity among performed studies limit obtaining definite conclusions. Data about new direct and indirect B cell and plasma cell depleting agents, proximal and terminal complement blockers, IL-6/IL-6R pathway inhibitors and antibody removal agents, among other promising drugs, are reviewed.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 235.2-235
Author(s):  
J. Y. E. Lee ◽  
A. Mendel ◽  
I. Malhamé ◽  
S. Bernatsky ◽  
E. Vinet

Background:Pregnant women with systemic lupus erythematosus (SLE) are at high risk of preeclampsia, leading to substantial maternal and fetal morbidity. Aspirin reduces preeclampsia risk but recent studies suggest aspirin is used only in a minority of SLE pregnancies. There is an urgent need to improve preeclampsia counselling and management in this vulnerable population.Objectives:We are conducting the PREPARE (PREeclamPsia knowledge & Aspirin adheRence in lupus prEgnancies) trial, a randomized controlled trial (RCT) evaluating an educational tool on preeclampsia knowledge and aspirin adherence among pregnant women with SLE. We present preliminary analyses of the effect of this tool on preeclampsia knowledge.Methods:Consecutive pregnant SLE women are recruited until the 16th gestational week at 5Canadian Systemic Lupus International Collaborating Clinics centres (i.e. Montreal, Halifax, Quebec, Winnipeg, and Calgary) since 05/2018. Subjects are randomly assigned to receive either the specifically-designed educational tool (intervention group) or standard of care (control group). At baseline (i.e. first trimester) and second trimester visits, the participants complete self-administered preeclampsia knowledge questionnaires (scored out of 30 by the research team blinded to the intervention). We restricted the current analysis to participants enrolled in Montreal (accounting for nearly half of the total planned sample size). We performed a univariate linear regression analysis to assess the effect of the educational tool on preeclampsia knowledge (i.e. mean score difference between the two groups from baseline to second trimester visit).Results:Thirty-three pregnant SLE women were included in the study, among which 16 were exposed to the intervention and 17 were unexposed. Baseline characteristics were well balanced between the two groups with similar mean maternal age between intervention group (32.2 years, standard deviation, SD, 4.6) and control group (34.1 years, SD 4.2) and identical proportion of subjects with post-secondary education (i.e. 80%). The difference in mean preeclampsia knowledge scores between second trimester and baseline visits in the intervention group was 4.4 points (95% CI -0.1, 9.0) and in the control group was 1.5 points (95% CI -2.7, 5.7). The mean difference in knowledge scores (from baseline to second trimester) for those receiving the educational tool was 2.7 points higher (95% CI -1.5, 6.9) than those receiving standard of care.Conclusion:Approximately midway into the PREPARE trial, we observed a trend for improvement in preeclampsia knowledge from the baseline to the second trimester visit in pregnant women with SLE who received a specifically-designed educational tool compared to the control group, although the CIs included the null. Our RCT is well-poised to provide a new evidence-based approach to improve preeclampsia knowledge in pregnant women with SLE, which could help to optimize aspirin use and outcomes in this vulnerable population.References:[1]Schramm AM, Clowse ME. Aspirin for prevention of preeclampsia in lupus pregnancy. Autoimmune Dis. 2014;2014:920467. doi:10.1155/2014/920467[2]Bujold E, Roberge S, Lacasse Y, et al. Prevention of preeclampsia and intrauterine growth restriction with aspirin started in early pregnancy: a meta-analysis. Obstet Gynecol. 2010;116(2 Pt 1):402-414. doi:10.1097/AOG.0b013e3181e9322a[3]Andreoli L, Bertsias GK, Agmon-Levin N, et al. EULAR recommendations for women’s health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome. Ann Rheum Dis. 2017 Mar;76(3):476–85. doi: 10.1136/annrheumdis-2016-209770.[4]Mendel A, Bernatsky SB, Hanly JG, et al. Low aspirin use and high prevalence of preeclampsia risk factors among pregnant women in a multinational SLE inception cohort. Ann Rheum Dis. 2019;78(7):1010-1012. doi:10.1136/annrheumdis-2018-214434Disclosure of Interests:None declared.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S242-S243
Author(s):  
Sarah I Collens ◽  
Douglas R Wilcox ◽  
Shibani Mukerji ◽  
Farrah J Mateen ◽  
Isaac H Solomon

Abstract Background Eastern equine encephalitis (EEE) is a mosquito-borne viral infection with significant neurological morbidity and mortality. The clinical presentation and patient outcomes after treatment with IVIG, high-dose steroids, or standard of care alone in EEE remains unclear. Methods A retrospective observational study of patients admitted to two tertiary academic medical centers in Boston, Massachusetts with EEE from 2005 to 2019. Results Of 17 patients (mean [SD] age, 50 [26] years; 10 (59%) male, and 16 (94%) White race), 17 patients had fever (100%), 15 had encephalopathy (88%), and 12 had headache (71%). Eleven of 14 patients with cerebrospinal fluid (CSF) cell count differential had a neutrophil predominance (mean [SD], 60.6% of white blood cells [22.8]) with an elevated protein level (mean [SD], 112 mg/dL [48.8]). Affected neuroanatomical regions included the basal ganglia (n=9/17), thalamus (n=7/17), and mesial temporal lobe (n=7/17). A total of 11 patients (65%) received IVIG; 8 (47%) received steroids. Of the patients who received IVIG, increased time from hospital admission to IVIG administration correlated with worse long-term disability as assessed by modified Rankin Score (mRS) (r=0.72, p=0.02); steroid use was not associated with mRS score. The mortality was 12%. Figure 1. Imaging Characteristics: Typical Pattern of MRI Involvement and Affected Neuroanatomical Regions in Patients with Eastern Equine Encephalitis. All images displayed are the T2-FLAIR sequence. (A) Representative images of pattern of typical neuroanatomical region involved in one patient with demonstrated involvement of the temporal lobe and pons, temporal lobe and midbrain, and basal gangial by T2-FLAIR hyperintensity (panels left to right). (B) Representative images of patients with mild (mRS 0–2), moderate (mRS 3–4), and severe (mRS 5–6) disability score at discharge. (C) Representative images of one patient over course of hospitalization at days 1, 4, and 10 after admission. (D) Quantification of neuroanatomical region involvement in initial MRI of patients with EEE as determined by T2-FLAIR hyperintensity. An area was scored as abnormal only once per patient. Figure 2. Outcomes in Patients with Eastern Equine Encephalitis. Patient disability by modified Rankin Score (mRS) of EEE patients at admission to the hospital, discharge from the hospital, and last recorded follow-up (A). Time to IVIG administration compared to mRS at discharge (B), and most recent clinical follow-up (C). Table 1. Demographics, Clinical Characteristics, and Laboratory Data in Patients with Eastern Equine Encephalitis. Abbreviations: CSF = cerebrospinal fluid, WBC = white clood count, EEG = electroencephalogram, ALT = alanine aminotransferase, AST = aspartate transaminase. Demographic data was collected for all patients with confirmed EEE. Altered mental status included any description of encephalopathy, confusion, or difficulty with attention. Seizures were defined as clinical events with a high-degree of suspicion to be true seizures, and were entirely comprised of generalized tonic-clonic seizures. Conclusion Clinicians should suspect EEE in immunocompetent patients with early subcortical neuroimaging abnormalities and CSF neutrophilic predominance. This study suggests a lower mortality than previously reported, but a high morbidity rate in EEE. IVIG as an adjunctive to standard of care may be considered early during hospitalization. Disclosures All Authors: No reported disclosures


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