Hemophagocytic lymphohistiocytosis and miliary tuberculosis in a previously healthy individual: a case report

Abstract Background Hemophagocytic lymphohistiocytosis (HLH) is a rare heterogenous genetic or acquired hyperinflammatory syndrome associated with a high degree of morbidity and mortality. HLH has clinical manifestations related to abnormal prolonged activation of T lymphocytes and macrophages with an excess of proinflammatory cytokines. The main causes of secondary HLH are malignancies and infectious diseases. Case presentation The patient was a 54-year-old man, originally from Eastern Africa, who had lived in Northern Europe for 30 years. Here we describe the clinical features, laboratory parameters, diagnostic workup, management and outcome data of a previously healthy 54-year-old man diagnosed with HLH secondary to tuberculosis. The patient was initially treated for a community-acquired pneumonia. He developed multiorgan failure with acute respiratory distress syndrome, hypertransaminasemia, and kidney and bone marrow dysfunction. The clinical course together with a simultaneous increase in serum ferritin raised the suspicion of HLH. The patient fulfilled seven out of eight diagnostic criteria for HLH. A thorough diagnostic workup with respect to HLH and a potential underlying disease was initiated. Cultivation of bronchoalveolar lavage fluid, stool and urine, and polymerase chain reaction of epithelioid cell granulomas in the bone marrow were all positive for Mycobacterium tuberculosis. He was treated for both HLH and tuberculosis, and he survived without any sequelae. Conclusions We present one of few published cases of a patient who survived HLH triggered by miliary tuberculosis. The current case illustrates the need for awareness of these two diagnoses, and the timely initiation of specific and supportive treatment to reduce mortality.

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Miliary Tuberculosis-Related Acute Respiratory Distress Syndrome Complicated with Hemophagocytic Lymphohistiocytosis Syndrome

Case Reports in Infectious Diseases ◽

10.1155/2019/9501610 ◽

2019 ◽

Vol 2019 ◽

pp. 1-4

Author(s):

Sz-Jiun Shiu ◽

Ting-Ting Li ◽

Bor-Jen Lee ◽

Pin-Kuei Fu ◽

Chen-Yu Wang ◽

...

Keyword(s):

Acute Respiratory Distress Syndrome ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Hemophagocytic Lymphohistiocytosis ◽

Distress Syndrome ◽

Case Reports ◽

Multiorgan Failure ◽

Miliary Tuberculosis ◽

Bone Marrow Aspiration ◽

Underlying Disease

Acute respiratory distress syndrome (ARDS) and hemophagocytic lymphohistiocytosis (HLH) are accompanied with poor outcome and high mortality when miliary tuberculosis is a causative pathogen for both of them. A patient complicated with ARDS and HLH is unusual in critical care, and few case reports are present in PudMed. Besides, the relationship between HLH and ARDS is still unknown and has not been reviewed in the literature. In this report, we present the case of a 74-year-old Taiwanese woman suffering from pulmonary tuberculosis and miliary tuberculosis, and she developed ARDS and HLH on the 3rd day after admission. We arranged serial laboratory examination, various serum markers, bone marrow aspiration, and bronchoscopy with alveolar lavage for survey; we prescribed empirical antibiotics and antituberculosis medication soon after alveolar lavage showing positive acid-fast stain. She was extubated on hospital day 31 and discharged on hospital day 73. In conclusion, early diagnosis and intervention for underlying disease and intensive bundle care for multiorgan failure are crucial for both ARDS and HLH.

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Clinical Characterization of Staphylococcus Septicemia-Associated Hemophagocytic Lymphohistiocytosis

Blood ◽

10.1182/blood.v128.22.4905.4905 ◽

2016 ◽

Vol 128 (22) ◽

pp. 4905-4905

Author(s):

Hongxia Qiu ◽

Meng Song ◽

Fang Ni ◽

Jujuan Wang

Keyword(s):

Bone Marrow ◽

Hemophagocytic Lymphohistiocytosis ◽

Therapeutic Response ◽

Gamma Globulin ◽

Conflicts Of Interest ◽

Laboratory Data ◽

Clinical Manifestations ◽

Hepatic Function ◽

Risk Of Death ◽

Medical University

Abstract Abstract Objective: To analyze the epidemic characters, pathogenesis, clinical manifestations, laboratory data, therapeutic response, and prognosis in patients with staphylococcus septicemia-associated hemophagocytic lymphohistiocytosis(HLH). Methods A r Objective To analyze the epidemic characters, pathogenesis, clinical manifestations, laboratory data, therapeutic response, and prognosis in patients with staphylococcus septicemia-associated hemophagocytic lymphohistiocytosis(HLH). Methods: retrospective study was performed on 7 patients with staphylococcus septicemia-associated HLH who were admitted to The First Affiliated Hospital of Nanjing Medical University from January 2010 to December 2014. Results Seven out of 633patients(1.11%) with staphylococcus septicemia were confirmed to have HLH. The incidence of HLH in staphylococcus subspecies were:S.caprae, 12.50%;S.warneri, 12.50%;Methicillin-resistant Staphylococcusaureus(MRSA), 3.23%;S.hominis, 1.40%;S.haemolyticus, 1.25%;S.epidermidis, 0.59%, respectively. The main clinical manifestations included persistentfever(100%) and splenomegaly(85.71%). The most prominent laboratory abnormalities werehemocytopenia, abnormal hepatic function, and elevated ferritin. Bone marrow aspirations were performed on 6 patients and all of them hadhemophagocytosis shown in bone marrow smears. Among 7 patients, 4 patientssurvived(57.14%) and 3 patients died(42.86%). All the 4 cured patients were treated with antibiotic plus corticosteroid. And 2 of them used gamma globulin, while one used the COP chemotherapy regimen. Treatment with antibiotic plus corticosteroid was effective in our study. Conclusion Treatment with antibiotic plus corticosteroid was recommended for staphylococcus septicemia-associated HLH, and gamma globulin may also be useful in reducing the risk of death. Disclosures No relevant conflicts of interest to declare.

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A Case of Hemophagocytic Lymphohistiocytosis Secondary to Disseminated Histoplasmosis

Case Reports in Hepatology ◽

10.1155/2020/6901514 ◽

2020 ◽

Vol 2020 ◽

pp. 1-4

Author(s):

Ivan Columbus-Morales ◽

Lucas Maahs ◽

Sanam Husain ◽

Stuart C. Gordon ◽

Kedar V. Inamdar ◽

...

Keyword(s):

Liver Function ◽

Autoimmune Diseases ◽

Hemophagocytic Lymphohistiocytosis ◽

Immunocompromised Patient ◽

Multiorgan Failure ◽

Clinical Manifestations ◽

Rare Condition ◽

Immune Dysregulation ◽

Multiorgan Dysfunction ◽

Disseminated Histoplasmosis

Hemophagocytic lymphohistiocytosis (HLH) is a rare condition characterized by a pathologic immune dysregulation resulting in extreme inflammation. Clinical manifestations are varied but can include severe multiorgan failure and death. HLH has been associated with malignancies, autoimmune diseases, and infections, such as histoplasmosis. Histoplasmosis commonly has subclinical manifestations but can also present in its disseminated form. We present the case of an immunocompromised patient with worsening liver function caused by hepatic histoplasmosis that later triggered HLH with severe multiorgan dysfunction.

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Hemophagocytic Lymphohistiocytosis in a Patient With Familial Mediterrean Fever and Miliary Tuberculosis: A Case Report

Modern Rheumatology Case Reports ◽

10.1093/mrcr/rxab026 ◽

2021 ◽

Author(s):

Emir Cerme ◽

Mert Oztas ◽

Ilker Inanc Balkan ◽

Esin Aktas Cetin ◽

Serdal Ugurlu

Keyword(s):

Bone Marrow ◽

Hemophagocytic Lymphohistiocytosis ◽

Case Reports ◽

Miliary Tuberculosis ◽

Biopsy Material ◽

Viral Origin ◽

Acute Phase Reactants ◽

Positron Emission ◽

Caseating Granuloma ◽

Fdg Pet Ct

Abstract Hemophagocytic Lymphohistiocytosis (HLH) is a lethal complication of several infections especially viral origin. M.Tuberculosis infection can also lead HLH, yet it is an uncommon trigger. Considering role of increased cytokines in HLH, autoinflammatory conditions as Familial Mediterrean Fever (FMF) might contribute to development of it. Nevertheless, possible relationship between FMF and HLH has only suggested in some case reports. We present a case with FMF was admitted to hospital with the complaints of constitutional symptoms and chest pain regarding to recurrent pericarditis. On blood test, pancytopenia and elevated acute phase reactants were seen. FDG Positron Emission Tomography/Computed Tomography (FDG PET/CT) demonstrated positive FDG uptake sites on both right and left surrenal glands, visseral layer of pericard and reactive lymphadenomegalies at multipl mediastinal regions. Bone marrow biopsy revealed hemophagocytosis. Methylprednisolone treatment was initiated. Despite immunosupressive treatment, clinical and biochemical parameters deteriorated thus a thorax CT was executed. Findings were consistent with miliary tuberculosis (TB) infection. M.Tuberculosis was detected in blood culture and bronchoalveolar lavage culture material. Also bone marrow and surrenal biopsy material revealed necrotising caseating granuloma.

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

Blood ◽

10.1182/blood.v106.11.3890.3890 ◽

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.

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

BMJ Case Reports ◽

10.1136/bcr-2020-238317 ◽

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.

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

Journal of Clinical Pathology ◽

10.1136/jclinpath-2020-207337 ◽

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.

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Managing the combined consequences of COVID-19 infection and lock-down policies on athletes: narrative review and guidelines proposal for a safe return to sport

BMJ Open Sport & Exercise Medicine ◽

10.1136/bmjsem-2020-000849 ◽

2020 ◽

Vol 6 (1) ◽

pp. e000849

Author(s):

Jean-Bernard Fabre ◽

Laurent Grelot ◽

William Vanbiervielt ◽

Julien Mazerie ◽

Raphael Manca ◽

...

Keyword(s):

Sports Medicine ◽

Acute Myocarditis ◽

Multiorgan Failure ◽

Clinical Manifestations ◽

Return To Sport ◽

Disease Spread ◽

Cardiac Complications ◽

Professional Soccer ◽

Physical Abilities ◽

Fitness And Health

COVID-19 pandemic is a global health matter. The disease spread rapidly across the globe and brought the world of sports to an unprecedented stoppage. Usual symptoms of the disease are fever, cough, myalgia, fatigue, slight dyspnoea, sore throat and headache. In more severe cases, dyspnoea, hypoxaemia, respiratory failure, shock and multiorgan failure occur. This appears to be a self-limiting phenomenon related to individuals with coexisting medical conditions, such as hypertension, diabetes and cardiovascular disorders. Nevertheless, cases have been reported in professional soccer players in extremely good fitness condition, demonstrating that athletes are not spared by the disease. Despite COVID-19 clinical manifestations are mainly respiratory, major cardiac complications are being reported, leading to acute myocarditis. One difficulty is that symptoms of COVID-19 vary among individuals, with athletes being affected with no apparent sign of the disease. This could be a real danger for amateur or professional athletes when returning to their usual training and thus to play. Another threat is that the lock-down policies did not allow most athletes to follow their usual training routines. There is thus a need for a careful approach by the sports medicine community to ensure safety of all athletes before they return to sport. Here, we propose evaluation guidelines of fitness and health of athletes to (1) reduce any lethal risk of practice, especially myocarditis and sudden cardiac death; (2) evaluate the combined consequences of the disease and detraining on the physical abilities and biological profile of athletes; and (3) monitor postinfection fatigue symptoms.

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A Case of COVID-19-Related Thrombocytopenia and Leukopenia in an Adolescent with Mild Symptoms

Children ◽

10.3390/children8060509 ◽

2021 ◽

Vol 8 (6) ◽

pp. 509

Author(s):

Lydia Kossiva ◽

Athanasios Thirios ◽

Eleni Panagouli ◽

Alexandros Panos ◽

Stavroula Lampidi ◽

...

Keyword(s):

Bone Marrow ◽

Viral Infection ◽

Nasal Congestion ◽

Pediatric Population ◽

Clinical Manifestations ◽

Bone Marrow Aspiration ◽

White Blood Count ◽

Chronic Obstructive ◽

First Case ◽

The Impact

Since the beginning of the COVID-19 pandemic, there have been numerous reports and reviews on the complications caused by the disease, analyzing the acute and chronic consequences. The main symptoms of SARS-CoV-2 are dry cough, fever, and fatigue. COVID-19 appears to affect all systems, including renal, cardiovascular, circulatory, and respiratory systems, causing chronic obstructive pulmonary disease. We report on a 14-year-old male adolescent, who presented with thrombocytopenia (platelet count 92 × 109 /L) and leukopenia (white blood count 4.2 × 103 /μL) that was observed two months ago. Ten days before the first blood test, a viral infection with nasal congestion and runny nose was reported, without other accompanying symptoms. Viral antibodies screening revealed positivity for all the three specific COVID-19 antibodies. Further haematological evaluation with bone marrow aspiration revealed non-specific dysplastic features of the red cell and megakaryocyte progenitors. Although haematological alterations due to COVID-19 infection are available from adult patients’ reports, the effect of COVID-19 infection in the pediatric population is underestimated and this is the first case with such haematological involvement. Noteworthy, in the current case, the impact of the COVID-19 infection was not related to the severity of the disease, as the symptoms were mild. In similar cases, bone marrow aspiration would not be performed as a part of routine work-up. Thus, it is important when evaluating pediatric patients with COVID-19 infection to search and report those alterations in order to better understand the impact and the spectrum of clinical manifestations of the specific viral infection in children and adolescents.

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Conditioning with Fludarabine-Busulfan versus Busulfan-Cyclophosphamide Is Associated with Lower aGVHD and Higher Survival but More Extensive and Long Standing Bone Marrow Damage

BioMed Research International ◽

10.1155/2016/3071214 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Xin He ◽

YongBin Ye ◽

XiaoJun Xu ◽

Jing Wang ◽

YuXian Huang ◽

...

Keyword(s):

Bone Marrow ◽

Bone Marrow Cells ◽

Conditioning Regimen ◽

Clinical Manifestations ◽

Major Complication ◽

Clinical Situation ◽

Hematopoietic Stem ◽

T Cell Infiltration ◽

Bone Marrow Damage ◽

The Impact

Acute graft-versus-host disease (aGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and a major cause of nonrelapse mortality after allo-HSCT. A conditioning regimen plays a pivotal role in the development of aGVHD. To provide a platform for studying aGVHD and evaluating the impact of different conditioning regimens, we established a murine aGVHD model that simulates the clinical situation and can be conditioned with Busulfan-Cyclophosphamide (Bu-Cy) and Fludarabine-Busulfan (Flu-Bu). In our study, BALB/c mice were conditioned with Bu-Cy or Flu-Bu and transplanted with 2×107 bone marrow cells and 2×107 splenocytes from either allogeneic (C57BL/6) or syngeneic (BALB/c) donors. The allogeneic recipients conditioned with Bu-Cy had shorter survivals (P<0.05), more severe clinical manifestations, and higher hepatic and intestinal pathology scores, associated with increased INF-γ expression and diminished IL-4 expression in serum, compared to allogeneic recipients conditioned with Flu-Bu. Moreover, higher donor-derived T-cell infiltration and severely impaired B-cell development were seen in the bone marrow of mice, exhibiting aGVHD and conditioned with Flu-Bu. Our study showed that the conditioning regimen with Bu-Cy resulted in more severe aGVHD while the Flu-Bu regimen was associated with more extensive and long standing bone marrow damage.

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