scholarly journals Secondary haemophagocytic lymphohistiocytosis in COVID-19: correlation of the autopsy findings of bone marrow haemophagocytosis with HScore

2021 ◽  
pp. jclinpath-2020-207337
Author(s):  
Claudia Núñez-Torrón ◽  
Ana Ferrer-Gómez ◽  
Esther Moreno Moreno ◽  
Belen Pérez-Mies ◽  
Jesús Villarrubia ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Immune Response ◽  
Immune System ◽  
Multiorgan Failure ◽  
Histological Findings ◽  
Haemophagocytic Lymphohistiocytosis ◽  
Bone Marrow Tissue ◽  
Autopsy Findings ◽  
Specific Finding ◽  
Clinical Records

BackgroundSecondary haemophagocytic lymphohistiocytosis (sHLH) is characterised by a hyper activation of immune system that leads to multiorgan failure. It is suggested that excessive immune response in patients with COVID-19 could mimic this syndrome. Some COVID-19 autopsy studies have revealed the presence of haemophagocytosis images in bone marrow, raising the possibility, along with HScore parameters, of sHLH.AimOur objective is to ascertain the existence of sHLH in some patients with severe COVID-19.MethodsWe report the autopsy histological findings of 16 patients with COVID-19, focusing on the presence of haemophagocytosis in bone marrow, obtained from rib squeeze and integrating these findings with HScore parameters. CD68 immunohistochemical stains were used to highlight histiocytes and haemophagocytic cells. Clinical evolution and laboratory parameters of patients were collected from electronic clinical records.ResultsEleven patients (68.7%) displayed moderate histiocytic hyperplasia with haemophagocytosis (HHH) in bone marrow, three patients (18.7%) displayed severe HHH and the remainder were mild. All HScore parameters were collected in 10 patients (62.5%). Among the patients in which all parameters were evaluable, eight patients (80%) had an HScore >169. sHLH was not clinically suspected in any case.ConclusionsOur results support the recommendation of some authors to use the HScore in patients with severe COVID-19 in order to identify those who could benefit from immunosuppressive therapies. The presence of haemophagocytosis in bone marrow tissue, despite not being a specific finding, has proved to be a very useful tool in our study to identify these patients.

scholarly journals Molecular Insights of Immune Responses Variability in COVID-19 Patients: A Review

2021 ◽  
Vol 10 (3) ◽  
pp. 2402-2413
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Inflammatory Response ◽  
Clinical Symptoms ◽  
Multiorgan Failure ◽  
Innate Immune ◽  
Immune Memory ◽  
System Response ◽  
The Difference ◽  
Novel Coronavirus

Currently, a novel coronavirus disease 2019 (COVID 19) caused by SARS-CoV-2 has emerged worldwide. This chronic viral infection causes an acute respiratory distress syndrome (ARDS) which its pathophysiology is not yet well elucidated. However, ARDS has shown that ARDS causes diffuse alveolar damages induced by an excessive inflammatory response and a lack of anti-inflammatory response to the virus. Furthermore, these pathophysiological characteristics are associated with multiorgan failure and can increase the mortality rate. The difference in immune system response against COVID-19 is not well known. However, variability in innate immune system receptors between patients infected with SARS-CoV-2 as a function of aging and sex can explain this difference. Thus, innate immune memory or trained immunity mediated by epigenetic mechanisms is also involved in the variability response against COVID-19. The action of an adaptative immune response, in particular, antigen presentation via HLA is also a key element in this variability. Finally, each viral strain's capacity in evading the action of the immune response has also been suggested as an important mechanism by which certain patients infected with SARS-CoV-2 develop severity and others did not develop any clinical symptoms.

FAMILIAL ERYTHROPHAGOCYTIC LYMPHOHISTIOCYTOSIS

PEDIATRICS ◽  
1963 ◽  
Vol 32 (5) ◽  
pp. 868-879
Author(s):  
H. Edward MacMahon ◽  
Metin Bedizel ◽  
Charles A. Ellis
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
The Body ◽  
Histological Findings ◽  
Autopsy Findings ◽  
Temporary Relief ◽  
Similar Disease ◽  
The Central Nervous System ◽  
Clinical Records ◽  
Histiocytic Infiltration

The clinical records and gross and histological findings are described in the case of two siblings who died at different times and at slightly different ages of an unusual, but apparently similar, disease complex. Letterer-Siwe's disease was suspected clinically, but the autopsy findings characterized by hyperplasia of histiocytic cells, erythrophagocytosis, and an infiltration of lymphocytes and histiocytes into almost every organ in the body, including, in one of the children, the central nervous system, were distinctly different from the disease described by Letterer. Neither the etiology nor the nature of the disease is understood. Little or nothing is known about therapy though splenectomy in one of the two infants led to a temporary relief. Its similarity to other familial diseases of infancy designated by such terms as familial haemophagocytic reticulosis, familial nonlipid reticuloendotheliosis, familial generalized lympho-histiocytic infiltration, and possibly, Chédiak-Higashi syndrome, is so striking as to suggest that these exceptional diseases may themselves comprise a distinct clinical and anatomical category. Until more is known about this group, the descriptive term "familial erythrophagocytic lympho-histiocytosis" is suggested.

Haemophagocytic Lymphohistiocytosis Post Liver Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3822-3822
Author(s):  
Adrian Barnardo ◽  
Z.Y. Lim ◽  
Matthew Foxton ◽  
K. Ramasamy ◽  
Ghulam Mufti
Keyword(s):  
Bone Marrow ◽  
Liver Transplantation ◽  
Liver Disease ◽  
Multiorgan Failure ◽  
Late Complication ◽  
Bone Marrow Examination ◽  
Base Substitution ◽  
Haemophagocytic Lymphohistiocytosis ◽  
Cmv Infection ◽  
Exon 2

Abstract Haemophagocytic syndromes are rare but often-fatal conditions characterised by an inappropriate and sustained activation of the cellular immune system leading to accumulation of activated macrophages and a cytokine storm. Familial haemophagocytic lymphohistiocytosis (FHLH) is an autosomal recessive condition, which presents in infancy and childhood whereas Reactive Haemophagocytic Lymphohistiocytosis (RHLH) occurs at any age and the genetic contribution remains uncertain. Presentation of RHLH is characterised by a sepsis like syndrome with cytopenia, coagulation and lipid abnormalities. We report on the haematological abnormalities and the clinical course of 37 patients who received liver transplantation and developed RHLH between 1998 and 2003. 15/37 patients had been transplanted for acute liver failure(7 drug induced, 7 seronegative hepatitis, 1 Budd Chiari syndrome) and the remaining 22 patients had chronic liver disease(Viral hepatitis 7, Primary bilary cirrhosis 7, Alcohol related liver disease 2, others 7). 34/37 patients presented with thrombocytopenia(< 50x109/l, median 30x109/l), 34/37 were lymphopenic(<1x109/l, median 0.5x109/l), median transfused haemoglobin was 8.3 g/dl, median ferritin was 1294ug/l. Hypertriglyceridemia(>2 mmol/l) and hypofibrinogenemia(<1.5g/l) was noted in 16/37 and 5/37 patients respectively. Median corrected INR was 1.14. Hepatosplenomegaly was a frequent finding in this group but is felt to be associated with the underlying liver disease. 26/37 patients presented within 30 days of transplantation and the remainder developed RHS following either a protracted admission to intensive care or a late complication of transplantation years later(range 33–2737 days). At the time of diagnosis of RHS multiorgan failure was typical with an average 2.4-organ failure. All patients displayed morphological features of RHLH on bone marrow examination, (> 2% macrophages, with tri-lineage histiophagocytosis). Screening for potential infectious triggers revealed contemporaneous positive cytomegalovirus (CMV) serology in 48% (18/37) patients with RHLH compared to annual incidence of CMV post transplant of 4.5% at the same centre. None of these patients received a CMV mismatched organ. Bacterial cultures were positive in 6/18 patients that did not develop CMV. Following PCR amplification and sequencing, one patient was identified as having a single nucleotide base substitution at 272 of exon 2 of PRF1, resulting in an alanine to valine amino acid substitution. This mutation has previously been reported but is felt to be a RFLP. All patients received multiorgan support, targeted anti viral/antibiotic therapy, human immunoglobulin and GM-CSF was reserved for those with severe pancytopenia. In addition all transplant recipients received Tacrolimus and prednisolone. Actuarial one year survival was significantly worse for those who developed RHLH post liver transplant than those that did not (45% vs. 85% p<0.0001; median survival 223 days and 12 month survival 33%). However CMV infection was not associated with length of ITU stay or survival. Our findings suggest that cytopenia post liver transplantation are often associated with RHLH and this population represents a unique group, in whom the histiocyte society criteria for RHLH may not be appropriate and histological diagnosis by bone marrow examination may be required to establish the diagnosis of RHLH. CMV infection is a common trigger of RHLH but is not associated with the poor outcome associated with RHLH.

scholarly journals Haemophagocytic lymphohistiocytosis after heart transplantation: a case report

2020 ◽  
Vol 4 (3) ◽  
pp. 1-4
Author(s):  
Christian Danielsson ◽  
Kristjan Karason ◽  
Göran Dellgren
Keyword(s):  
Bone Marrow ◽  
Inflammatory Response ◽  
Heart Transplantation ◽  
Multiorgan Failure ◽  
Favourable Outcome ◽  
Infectious Agents ◽  
Haemophagocytic Lymphohistiocytosis ◽  
Bone Marrow Biopsies ◽  
History Of ◽  
Autoimmune Reactivity

Abstract Background Haemophagocytic lymphohistiocytosis (HLH) is an uncommon but serious systemic inflammatory response with high mortality rates. It can be triggered by malignancy or infectious agents, often in the context of immunosuppression. Literature covering HLH in heart transplantation (HTx) is scarce. Case summary A 25-year-old male with a history of celiac disease underwent HTx at Sahlgrenska Hospital in 2011 due to giant cell myocarditis and was treated with tacrolimus, mycophenolate mofetil (MMF), and prednisolone. He developed several episodes of acute cellular rejections (ACR) during the first 3 post-HTx years, which subsided after addition of everolimus. In May 2017, the patient was admitted to the hospital due to fever without focal symptoms. He had an extensive inflammatory reaction, but screening for infectious agents was negative. Haemophagocytic lymphohistiocytosis was discussed early, but first dismissed since two bone marrow biopsies revealed no signs of haemophagocytosis. Increasing levels of soluble IL-2 were considered confirmative of the diagnosis. Even with intense immunosuppressant treatment, the patient deteriorated and died in progressive multiorgan failure within 2 weeks of the symptom onset. Discussion A 25-year-old HTx recipient with an extensive inflammatory response, fulfilled criteria for HLH, but the diagnosis was delayed due to normal bone marrow biopsies. A background with autoimmune reactivity and immunosuppressive therapy may have contributed to HLH, but the actual trigger was not identified. Haemophagocytic lymphohistiocytosis can occur in HTx recipients in the absence of malignancy, identifiable infectious triggers and signs of haemophagocytosis. Early diagnosis and intervention are likely to be of importance for a favourable outcome.

scholarly journals Haemophagocytic lymphohistiocytosis in an adult with postacute COVID-19 syndrome

2021 ◽  
Vol 14 (9) ◽  
pp. e245031
Author(s):  
Daniel Wiseman ◽  
John Lin ◽  
Jean-Pierre Routy ◽  
Gordan Samoukovic
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Aspirate ◽  
Clinical Presentation ◽  
Healthy Adult ◽  
Multiorgan Failure ◽  
Haemophagocytic Lymphohistiocytosis ◽  
Initial Infection ◽  
First Case ◽  
Life Threatening

Haemophagocytic lymphohistiocytosis (HLH) causing multiorgan failure has been reported as an acute clinical presentation of COVID-19. However, the literature surrounding HLH in the context of a postacute COVID-19 syndrome is limited. This report presents a case of a life-threatening HLH occurring 6 weeks after a pauci-symptomatic COVID-19 infection in a previously healthy adult. A bone marrow aspirate confirmed the HLH and the patient was successfully treated with dexamethasone and etoposide. To our knowledge, this is the first case of HLH occurring as a postacute COVID-19 syndrome following a pauci-symptomatic initial infection.

scholarly journals Immunologic Aberrations in the Di Guglielmo Syndrome

Blood ◽  
1966 ◽  
Vol 28 (5) ◽  
pp. 634-649 ◽  
Author(s):  
HARVEY E. FINKEL ◽  
MARK J. BRAUER ◽  
ROBERT N. TAUB ◽  
WILLIAM DAMESHEK
Keyword(s):  
Bone Marrow ◽  
Immune System ◽  
Antibody Response ◽  
Neoplastic Transformation ◽  
Myeloproliferative Disorders ◽  
Immune Reactivity ◽  
Systemic Lupus ◽  
Bone Marrow Tissue ◽  
Self Recognition ◽  
Neoplastic Process

Abstract Immunologic studies were performed in 49 patients with the Di Guglielmo syndrome. Although altered immune reactivity has not been previously thought to be a feature of myeloproliferative disorders, more than one-third of the cases showed immunologic aberrations. The abnormalities encountered included overproduction of antibody protein (hypergammaglobulinemia) and an increased tendency to form rheumatoid factor, LE factor (including one case with overt systemic lupus), positive serologic tests for syphilis, and erythrocyte autoantibodies and isoantibodies. Possible pathogenetic mechanisms are considered. The underlying neoplastic process might directly involve the immunocytes, resulting in exaggerated and nonspecific responses, or in defective self-recognition and thus in the production of autoantibodies. Alternatively, preexisting but "hidden" antigens might be exposed by the proliferative disorder, thus stimulating an antibody response. Finally, and perhaps most likely, antigenic alteration of bone marrow tissue might accompany its neoplastic transformation. Such tissue could be recognized as "not-self" or "foreign" by a qualitatively normal immune system. This would result in the production of abnormal proteins, some of which would be immunologically effective.

Hemophagocytic Lymphohistiocytosis in a Extremely Low Birth Weight Infant Presenting with a Neonatal Thrombocytopenia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3890-3890
Author(s):  
Mee Jeong Lee ◽  
Young Won An ◽  
Young Pyo Chang ◽  
Won Ae Lee ◽  
Joowan Park ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Biopsy ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Parvovirus B19 ◽  
Multiorgan Failure ◽  
Extremely Low Birth Weight ◽  
Suspected Sepsis ◽  
Abdominal Ultrasonography ◽  
Autopsy Findings ◽  
Neonatal Thrombocytopenia

Abstract INTRODUCTION: Hemophagocytic lymphohistiocytosis(HLH) is a potentially fatal disease presenting at an young children. Symptoms and physical findings include fever, rash and pancytopenia associated with histiocytic infiltration of bone marrow, liver and spleen. Its occurrence in neonates is very rare. We describe a female infant diagnosed with HLH, who was born at 24 week 3 days of gestational age(GA) weighing 666 gm. The infant expired due to aggravating thrombocytopenia and hepatosplenomegaly leading to multiple organ failure associated with suspected sepsis. Autopsy findings lead to a confirmation of HLH. CASE: The baby, weighing 666gm, was born from a 36 year-old mother at GA 24 weeks 3 days, by emergency cesarian section due to vaginal bleeding. The mother came from the Republic of Kyrgystan and didn’t receive any antenatal care. The mother had a history of 8 prior abortions due to incompetence of internal os cervix (0–5–3/0–0). CBC on the first day was normal, but on the third day itg showed thrombocytopenia (Hb 11.2 g/dL, WBC 11,700/mm3, Platelet 78x103/mm3). Antibiotics were administered for suspected sepsis. On the 47th day, abdominal ultrasonography was performed due to abdominal distension and TPN-induced conjugated hyperbilirubinemia. GB wall edema and hepatomegaly were noted. Thrombocytopenia persisted and on the 55th day the patient became hypotensive and develped metabolic acidosis. Laboratory work up for persistent thrombocytopenia included anti-platelet antibody(−), TORCH(−), parvovirus-B19 PCR(-), CMV PCR (−), EBV infection(−). Bone marrow biopsy was not done. The patient expired from sepsis and multiorgan failure on the 61st day. Autopsy findings showed histiocyte infiltration of all tissue including the liver, spleen and brain. Bone marrow biopsy also showed infiltration of abundant hemophagocytic histiocytes consistent with a diagnosis of HLH. CONCLUSION: A premature newborn with HLH described here presented with thrombocytopenia. Therefore, HLH should be included in the differential diagnosis of neonatal thrombocytopenia.

Bone marrow necrosis and fat embolism syndrome: a near fatal complication in previously undiagnosed sickle beta + thalassaemia

2021 ◽  
Vol 14 (1) ◽  
pp. e238317
Author(s):  
Nibash Budhathoki ◽  
Sunita Timilsina ◽  
Bebu Ram ◽  
Douglas Marks
Keyword(s):  
Bone Marrow ◽  
Multiorgan Failure ◽  
Rare Condition ◽  
Altered Mental Status ◽  
Fat Embolism ◽  
Bone Marrow Necrosis ◽  
Embolism Syndrome ◽  
Hb S ◽  
High Index Of Suspicion ◽  
Specific Symptoms

Prevalence of haemoglobin sickle-β+ thalassaemia (Hb S/β+thal) is variable with geography ranging from 0.2% to 10% among sickle cell patients. Clinical presentation of Hb S/β+thal patients depends on HbA level, with milder disease often going undiagnosed. However, rarely these patients can present with a fulminant vaso-occlusive crisis (VOC). Given VOC can present with non-specific symptoms, the diagnosis and treatment is often delayed. Here, we present a patient who initially developed altered mental status, pancytopenia and multiorgan failure due a critical VOC resulting in bone marrow necrosis and fat embolism. Subsequent workup confirmed that our patient had Sickle-β+ thalassaemia, which had gone undiagnosed, despite subclinical evidence of haemolysis on routine lab work for years. Following diagnosis and initiation of RBC exchange, he improved significantly and was discharged home. High index of suspicion and bone marrow biopsy is vital for early diagnosis and management of this rare condition.

scholarly journals The immune response of T cells and therapeutic targets related to regulating the levels of T helper cells after ischaemic stroke

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Tian-Yu Lei ◽  
Ying-Ze Ye ◽  
Xi-Qun Zhu ◽  
Daniel Smerin ◽  
Li-Juan Gu ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune System ◽  
Immune Responses ◽  
Ischaemic Stroke ◽  
Immune Cells ◽  
Tissue Injury ◽  
Recovery Period ◽  
Vital Functions ◽  
Anti Inflammatory

AbstractThrough considerable effort in research and clinical studies, the immune system has been identified as a participant in the onset and progression of brain injury after ischaemic stroke. Due to the involvement of all types of immune cells, the roles of the immune system in stroke pathology and associated effects are complicated. Past research concentrated on the functions of monocytes and neutrophils in the pathogenesis of ischaemic stroke and tried to demonstrate the mechanisms of tissue injury and protection involving these immune cells. Within the past several years, an increasing number of studies have elucidated the vital functions of T cells in the innate and adaptive immune responses in both the acute and chronic phases of ischaemic stroke. Recently, the phenotypes of T cells with proinflammatory or anti-inflammatory function have been demonstrated in detail. T cells with distinctive phenotypes can also influence cerebral inflammation through various pathways, such as regulating the immune response, interacting with brain-resident immune cells and modulating neurogenesis and angiogenesis during different phases following stroke. In view of the limited treatment options available following stroke other than tissue plasminogen activator therapy, understanding the function of immune responses, especially T cell responses, in the post-stroke recovery period can provide a new therapeutic direction. Here, we discuss the different functions and temporal evolution of T cells with different phenotypes during the acute and chronic phases of ischaemic stroke. We suggest that modulating the balance between the proinflammatory and anti-inflammatory functions of T cells with distinct phenotypes may become a potential therapeutic approach that reduces the mortality and improves the functional outcomes and prognosis of patients suffering from ischaemic stroke.

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