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1.
BMJ Case Rep ; 15(3)2022 Mar 09.
Article in English | MEDLINE | ID: covidwho-1736043

ABSTRACT

Haemophagocytic lymphohistiocytosis (HLH) is one of the rare haematological syndromes more commonly reported in infants/children than adults. This disease is known for its aggressive dysregulated immune response affecting the host rapidly, causing multiorgan dysfunction and thus carries a high mortality. The disease still remains cryptic in this current decade despite all the developments in the ever-evolving field of haematology. Due to its rare occurrence and being more frequent in infants and the paediatric population, the literature lacks enough data to standardise therapies. Such events in adults and the elderly are invariably related to an underlying insult such as infections, other autoimmune or rheumatological diseases or drugs. We describe an interesting case of a middle-aged Caucasian woman who presented with fever, pancytopenia and hepatitis, who was eventually diagnosed with HLH just in time to receive the life-saving specific treatment as per available guidelines.


Subject(s)
Arthritis, Rheumatoid , Lymphohistiocytosis, Hemophagocytic , Adult , Aged , Anticonvulsants/therapeutic use , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/drug therapy , Child , Female , Fever/complications , Humans , Lamotrigine/therapeutic use , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/drug therapy , Lymphohistiocytosis, Hemophagocytic/etiology , Middle Aged
3.
BMJ Case Rep ; 14(12)2021 Dec 09.
Article in English | MEDLINE | ID: covidwho-1566338

ABSTRACT

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.


Subject(s)
Autoimmune Diseases , Lymphohistiocytosis, Hemophagocytic , Macrophage Activation Syndrome , Takotsubo Cardiomyopathy , Autoimmune Diseases/complications , Autoimmune Diseases/drug therapy , Humans , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Lymphohistiocytosis, Hemophagocytic/complications , Lymphohistiocytosis, Hemophagocytic/drug therapy , Takotsubo Cardiomyopathy/drug therapy
4.
Clin Med (Lond) ; 21(6): e677-e679, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1551863

ABSTRACT

A 36-year-old woman presented to hospital 9 days after receiving her first dose of the ChAdOx1 nCoV-19 vaccine with fever, myalgia and a sore throat. She was previously fit and well with no prior vaccine reactions.There was no clinical response to initial treatment with intravenous (IV) antibiotics. Microbiology tests including for COVID-19 were negative. At day 5, she developed pleuritic pain and a pericardial rub. Echocardiography and subsequent cardiac magnetic resonance imaging showed evidence of constrictive pericarditis. Computed tomography revealed gross hepatomegaly and moderate splenomegaly. Blood tests showed raised inflammatory markers, deranged clotting, low platelets and a marked hyperferritinaemia.A presumptive diagnosis of a multi-system inflammatory disorder secondary to recent COVID-19 vaccination was made and high-dose IV methylprednisolone initiated. Following a high 'H score' of 70%-80% a diagnosis of secondary haemophagocytic lymphohistiocytosis (HLH) was made. She was treated with IV immunoglobulin with subsequent clinical response.HLH is a rare syndrome of acute and rapidly progressive systemic inflammation characterised by cytopenias, excessive cytokine production and hyperferritinaemia. The adult form has multiple triggers, including recent vaccination. This case prompts awareness among clinicians of HLH as a rare complication of COVID-19 vaccination but should not discourage individuals from vaccination.


Subject(s)
COVID-19 , Lymphohistiocytosis, Hemophagocytic , Adult , COVID-19 Vaccines , Female , Humans , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/drug therapy , SARS-CoV-2 , Vaccination
5.
BMC Infect Dis ; 21(1): 811, 2021 Aug 13.
Article in English | MEDLINE | ID: covidwho-1477276

ABSTRACT

BACKGROUND: Hemophagocytic syndrome (HPS) is a severe hyperinflammatory disease, whose diagnosis is based on the HLH-2004 criteria. In secondary forms of HLH (sHLH), the primary goal is treating the triggering factors such as COVID-19 (Coronavirus disease 2019). The link between the cytokine storm related to COVID-19 and development of sHLH has already been reported since the onset of pandemic, but little is known about clinical manifestations of HLH which develop after the patient's recovery from mild symptomatic or asymptomatic Sars-CoV-2 infection. CASE PRESENTATION: We describe the case of a woman diagnosed with sHLH related to previous Sars-CoV-2 infection and successfully treated with steroids, colchicine, etoposide and ruxolitinib. CONCLUSIONS: Our report suggests that HLH-like syndrome might be secondary to Sars-CoV-2 infection, even if the patient utterly recovered from the mildly symptomatic viral infection. In addition, we underline the treatment with low dose ruxolitinib plus etoposide as a potential choice for Sars-CoV-2 infection related HLH.


Subject(s)
COVID-19/complications , Cytokine Release Syndrome/diagnosis , Lymphohistiocytosis, Hemophagocytic/diagnosis , COVID-19/diagnosis , Cytokine Release Syndrome/etiology , Female , Humans , Lymphohistiocytosis, Hemophagocytic/complications , Lymphohistiocytosis, Hemophagocytic/drug therapy , Lymphohistiocytosis, Hemophagocytic/etiology , Middle Aged , Pandemics , SARS-CoV-2
6.
BMJ Case Rep ; 14(9)2021 Sep 17.
Article in English | MEDLINE | ID: covidwho-1416644

ABSTRACT

Haemophagocytic lymphohistiocytosis (HLH) is a rare, often fatal disease, and presents a diagnostic challenge in the pregnant patient. This challenge is particularly relevant during the current COVID-19 pandemic. We present a case of HLH in a pregnant woman presenting with fever predating the COVID-19 pandemic. A 33-year-old, gravida 2, para 1 at 27 weeks' gestation presented with fever, transaminitis, thrombocytopenia and elevated ferritin. After treatment according to the HLH-94 protocol, caesarean delivery and weeks of intensive care, the patient recovered fully. With prompt diagnosis and a multispecialty team at our tertiary care facility, she and her baby overcame a dire prognosis. HLH should be considered in pregnant patients presenting with a febrile illness. Particularly in cases of severe COVID-19, secondary HLH must be considered as an associated diagnosis.


Subject(s)
COVID-19 , Lymphohistiocytosis, Hemophagocytic , Adult , Female , Fever , Humans , Infant , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/drug therapy , Pandemics , Pregnancy , SARS-CoV-2
7.
BMJ Case Rep ; 14(9)2021 Sep 13.
Article in English | MEDLINE | ID: covidwho-1406643

ABSTRACT

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.


Subject(s)
COVID-19 , Lymphohistiocytosis, Hemophagocytic , Adult , Etoposide/therapeutic use , Humans , Lymphohistiocytosis, Hemophagocytic/complications , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/drug therapy , SARS-CoV-2
8.
Pediatr Blood Cancer ; 68(9): e29102, 2021 09.
Article in English | MEDLINE | ID: covidwho-1272230

ABSTRACT

The cytokine storm of secondary haemophagocytic lymphohistiocytosis (sHLH)/macrophage activation syndrome (MAS) can cause life-threatening multiorgan failure. Interleukin-1 (IL-1) receptor blockade with anakinra can be effective in the management of sHLH/MAS. Subcutaneous (SC) dosing regimens are widely described; however, intravenous (IV) dosing is advantageous where time-critical intervention is vital and where SC oedema and/or hypoperfusion limits absorption. We review three critically ill children (aged 9, 11 and 17) with sHLH and rapidly progressive multiorgan dysfunction, successfully treated with continuous IV anakinra infusion. This case series significantly enhances the incipient knowledge regarding the safety and efficacy of IV anakinra for life-threatening sHLH.


Subject(s)
Interleukin 1 Receptor Antagonist Protein/therapeutic use , Lymphohistiocytosis, Hemophagocytic , Macrophage Activation Syndrome , Administration, Intravenous , Child , Critical Illness , Cytokine Release Syndrome , Humans , Interleukin 1 Receptor Antagonist Protein/administration & dosage , Lymphohistiocytosis, Hemophagocytic/drug therapy , Macrophage Activation Syndrome/drug therapy , Multiple Organ Failure/drug therapy , Multiple Organ Failure/etiology
9.
J Hematol Oncol ; 14(1): 87, 2021 06 04.
Article in English | MEDLINE | ID: covidwho-1259207

ABSTRACT

Cases of thrombotic thrombocytopenia induced by coronavirus disease 2019 (COVID-19) vaccines have been reported recently. Herein, we describe the first case of another critical disorder, hemophagocytic lymphohistiocytosis (HLH), in a healthy individual after COVID-19 vaccination. A 43-year-old Chinese farmer developed malaise, vomiting, and persistent high fever (up to 39.7 °C) shortly after receiving the first dose of the inactivated SARS-CoV-2 vaccine. The initial evaluation showed pancytopenia (neutrophil count, 0.70 × 109/L; hemoglobin, 113 g/L; platelet, 27 × 109/L), elevated triglyceride (2.43 mmol/L), and decreased fibrinogen (1.41 g/L). Further tests showed high serum ferritin levels (8140.4 µg/L), low NK cell cytotoxicity (50.13%-60.83%), and positive tests for Epstein-Barr virus (EBV) DNA. Hemophagocytosis was observed in the bone marrow. Therefore, HLH was confirmed, and dexamethasone acetate (10 mg/day) was immediately prescribed without etoposide. Signs and abnormal laboratory results resolved gradually, and the patient was discharged. HLH is a life-threatening hyperinflammatory syndrome caused by aberrantly activated macrophages and cytotoxic T cells, which may rapidly progress to terminal multiple organ failure. In this case, HLH was induced by the COVID-19 vaccination immuno-stimulation on a chronic EBV infection background. This report indicates that it is crucial to exclude the presence of active EBV infection or other common viruses before COVID-19 vaccination.


Subject(s)
COVID-19 Vaccines/adverse effects , COVID-19/prevention & control , Lymphohistiocytosis, Hemophagocytic/etiology , Adult , Anti-Inflammatory Agents/therapeutic use , Bone Marrow/pathology , Dexamethasone/analogs & derivatives , Dexamethasone/therapeutic use , Humans , Lymphohistiocytosis, Hemophagocytic/blood , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/drug therapy , Male , SARS-CoV-2/isolation & purification
10.
BMJ Case Rep ; 14(5)2021 May 19.
Article in English | MEDLINE | ID: covidwho-1236429

ABSTRACT

Haemophagocytic lymphohistiocytosis has been reported as an uncommon complication of severe COVID-19 disease while thrombotic thrombocytopenic purpura has been rarely reported. Here, we are reporting a 21-year-old man who developed a combination of these complications during the hospital stay in the post-COVID-19 recovery period. He presented with fever and bilateral COVID-19-related pneumonia requiring invasive ventilation. His hospital course was complicated by the development of pneumothorax, ventilator-associated pneumonia, thrombotic thrombocytopenic purpura and haemophagocytic lymphohistiocytosis. He received remdesivir, IVIG, steroid, fresh frozen plasma and supportive care but had a fatal outcome.


Subject(s)
COVID-19 , Lymphohistiocytosis, Hemophagocytic , Purpura, Thrombotic Thrombocytopenic , Adult , Humans , Lymphohistiocytosis, Hemophagocytic/complications , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/drug therapy , Male , Purpura, Thrombotic Thrombocytopenic/complications , Purpura, Thrombotic Thrombocytopenic/diagnosis , Purpura, Thrombotic Thrombocytopenic/therapy , SARS-CoV-2 , Young Adult
11.
J Pediatric Infect Dis Soc ; 10(4): 543-546, 2021 Apr 30.
Article in English | MEDLINE | ID: covidwho-1211412

ABSTRACT

Down syndrome (DS) predisposes to severe immunologic reaction secondary to infectious triggers. Here, we report a pediatric DS patient with coronavirus disease 2019 (COVID-19) who developed a hyperinflammatory syndrome, severe acute respiratory distress syndrome, and secondary hemophagocytic lymphohistiocytosis requiring pediatric intensive care unit admission and treatment with steroids, intravenous immunoglobulin, and remdesivir. Investigations into genetic susceptibilities for COVID-19 and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-associated complications warrant systematic clinical and scientific studies. We report a pediatric Down syndrome patient with coronavirus disease 2019 (COVID-19) who developed secondary hemophagocytic lymphohistiocytosis requiring treatment with steroids, intravenous immunoglobulin, and remdesivir. Investigations into genetic susceptibilities for COVID-19-associated complications warrant systematic clinical and scientific studies.


Subject(s)
COVID-19/complications , Down Syndrome/complications , Lymphohistiocytosis, Hemophagocytic/virology , Systemic Inflammatory Response Syndrome/virology , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/virology , COVID-19 Testing , Child, Preschool , Critical Care , Genetic Predisposition to Disease , Glucocorticoids/therapeutic use , Humans , Immunoglobulins, Intravenous/therapeutic use , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/drug therapy , Male , Prednisolone/therapeutic use , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/drug therapy
13.
Medicine (Baltimore) ; 100(12): e25170, 2021 Mar 26.
Article in English | MEDLINE | ID: covidwho-1150007

ABSTRACT

RATIONALE: The immunologic syndrome induced by severe acute coronavirus disease 2019 (COVID-19) is yet not fully understood. Typical patterns of clinical and laboratory features match secondary hemophagocytic lymphohistiocytosis (sHLH). However, the optimal approach to COVID-19 patients testing positive for sHLH is still unclear. PATIENT CONCERNS: Three patients with COVID-19 are reviewed. All showed hyperinflammation and cytokine storm, necessitating intensive care treatment including mechanical ventilation. DIAGNOSIS: Secondary hemophagocytic lymphohistiocytosis due to severe COVID-19; diagnosed via HScore. INTERVENTIONS: A treatment regimen of methylprednisolone, pentaglobin, and anakinra was developed and administered. OUTCOMES: One patient survived the ICU stay. Two other patients, in whom sHLH was diagnosed too late, deceased. LESSONS: A routine screening of COVID-19 patients for secondary HLH by using the HScore is feasible; especially those patients deteriorating clinically with no sufficient response to shock management might be at particular high risk. A stepwise therapeutic approach comprising corticosteroids, immunoglobulins and anakinra, accompanied by immunoadsorption, may dampen cytokine storm effects, and potentially reduce mortality.


Subject(s)
COVID-19/complications , Lymphohistiocytosis, Hemophagocytic/drug therapy , Lymphohistiocytosis, Hemophagocytic/etiology , Aged , Anti-Inflammatory Agents/therapeutic use , COVID-19/physiopathology , COVID-19/therapy , Combined Modality Therapy , Critical Care , Cytokine Release Syndrome/drug therapy , Delayed Diagnosis , Fatal Outcome , Female , Humans , Immunoglobulin A/therapeutic use , Immunoglobulin M/therapeutic use , Immunoglobulins, Intravenous/therapeutic use , Immunosuppressive Agents/therapeutic use , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Lymphohistiocytosis, Hemophagocytic/diagnosis , Male , Methylprednisolone/therapeutic use , Middle Aged , Respiration, Artificial , SARS-CoV-2
15.
Blood Rev ; 45: 100707, 2021 01.
Article in English | MEDLINE | ID: covidwho-1064893

ABSTRACT

A subset of patients with severe COVID-19 develop profound inflammation and multi-organ dysfunction consistent with a "Cytokine Storm Syndrome" (CSS). In this review we compare the clinical features, diagnosis, and pathogenesis of COVID-CSS with other hematological CSS, namely secondary hemophagocytic lymphohistiocytosis (sHLH), idiopathic multicentric Castleman disease (iMCD), and CAR-T cell therapy associated Cytokine Release Syndrome (CRS). Novel therapeutics targeting cytokines or inhibiting cell signaling pathways have now become the mainstay of treatment in these CSS. We review the evidence for cytokine blockade and attenuation in these known CSS as well as the emerging literature and clinical trials pertaining to COVID-CSS. Established markers of inflammation as well as cytokine levels are compared and contrasted between these four entities in order to establish a foundation for future diagnostic criteria of COVID-CSS.


Subject(s)
COVID-19/immunology , Castleman Disease/immunology , Cytokine Release Syndrome/immunology , Immunologic Factors/therapeutic use , Lymphohistiocytosis, Hemophagocytic/immunology , SARS-CoV-2/pathogenicity , Adrenal Cortex Hormones/therapeutic use , Antibodies, Monoclonal/therapeutic use , Biomarkers/blood , C-Reactive Protein/immunology , C-Reactive Protein/metabolism , COVID-19/drug therapy , COVID-19/pathology , COVID-19/virology , Castleman Disease/drug therapy , Castleman Disease/pathology , Clinical Trials as Topic , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/pathology , Cytokine Release Syndrome/virology , Ferritins/blood , Ferritins/immunology , Gene Expression Regulation , Humans , Immunotherapy, Adoptive/adverse effects , Interleukin-1/antagonists & inhibitors , Interleukin-1/blood , Interleukin-1/immunology , Interleukin-6/antagonists & inhibitors , Interleukin-6/blood , Interleukin-6/immunology , Lymphohistiocytosis, Hemophagocytic/drug therapy , Lymphohistiocytosis, Hemophagocytic/pathology , Signal Transduction
16.
Eur J Haematol ; 106(5): 654-661, 2021 May.
Article in English | MEDLINE | ID: covidwho-1057986

ABSTRACT

INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a cytokine storm syndrome associated with mortality rates of up to 88%. Standard therapy with high-dose glucocorticoids and etoposide used in adults is extrapolated from pediatric trials, with significant toxicity in older patients and those with poor performance status. The JAK1/2 inhibitor ruxolitinib has recently gained attention as a treatment option for HLH due to its broad cytokine-modulating abilities and safety profile. Herein we report our center's experience using ruxolitinib in the treatment of adult-onset secondary HLH. CASE SERIES: We report four patients with profound secondary HLH provoked by diverse triggers, including invasive pulmonary aspergillosis on background systemic lupus erythematosus, disseminated tuberculosis, and T-cell lymphoma treated with ruxolitinib as monotherapy or combination therapy in upfront and salvage settings. RESULTS: All four patients had rapid, sustained improvement in clinical status, inflammatory markers, and hematological cell counts followed by durable remission. Three patients developed manageable infectious complications postruxolitinib. CONCLUSIONS: This series demonstrates the effective use of JAK inhibition with ruxolitinib to control pathological immune activation in critically ill patients with secondary HLH and otherwise limited therapeutic options. JAK inhibition is also an area of urgent investigation for the treatment of cytokine storm associated with COVID-19.


Subject(s)
Janus Kinases/antagonists & inhibitors , Lymphohistiocytosis, Hemophagocytic/drug therapy , Protein Kinase Inhibitors/therapeutic use , Pyrazoles/therapeutic use , Adult , COVID-19/complications , Combined Modality Therapy , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/etiology , Cytokines/blood , Female , Humans , Invasive Pulmonary Aspergillosis/complications , Lupus Erythematosus, Systemic/complications , Lymphohistiocytosis, Hemophagocytic/etiology , Lymphoma, T-Cell/complications , Male , Middle Aged , Nitriles , Pyrimidines , SARS-CoV-2 , Salvage Therapy , Tuberculosis/complications , Young Adult
18.
Front Immunol ; 11: 1665, 2020.
Article in English | MEDLINE | ID: covidwho-945649

ABSTRACT

We report a case of an 8-year-old girl who underwent a SARS-CoV-2 infection manifesting with atypical symptoms spearheaded by abdominal discomfort and systemic inflammation and partially mimicking hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS), which however did not fulfill the HLH/MAS diagnostic criteria. In this case of what has since been described as Pediatric Inflammatory Multisystem Syndrome Temporally associated with SARS-COV-2 (PIMS-TS) we documented excellent clinical response to immunosuppression with systemic corticosteroids and intravenous immunoglobulins. We show a detailed longitudinal development of neutrophil immunophenotype which suggests activation and engagement of neutrophils during PIMS-TS with compensatory contraction of the response and contra-regulation of neutrophil phenotype during recovery.


Subject(s)
Adrenal Cortex Hormones/administration & dosage , Betacoronavirus , Coronavirus Infections , Immunoglobulins, Intravenous/administration & dosage , Lymphohistiocytosis, Hemophagocytic , Macrophage Activation Syndrome , Pandemics , Pneumonia, Viral , Betacoronavirus/immunology , Betacoronavirus/metabolism , COVID-19 , Child , Coronavirus Infections/blood , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Coronavirus Infections/immunology , Female , Humans , Inflammation/diagnosis , Inflammation/drug therapy , Inflammation/immunology , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/drug therapy , Lymphohistiocytosis, Hemophagocytic/immunology , Macrophage Activation Syndrome/diagnosis , Macrophage Activation Syndrome/drug therapy , Macrophage Activation Syndrome/immunology , Neutrophils , Pneumonia, Viral/blood , Pneumonia, Viral/diagnosis , Pneumonia, Viral/drug therapy , Pneumonia, Viral/immunology , SARS-CoV-2
20.
Clin Lymphoma Myeloma Leuk ; 21(1): e66-e75, 2021 01.
Article in English | MEDLINE | ID: covidwho-718689

ABSTRACT

Histiocytic disorders are an exceptionally rare group of diseases with diverse manifestations and a paucity of approved treatments, thereby leading to various challenges in their diagnosis and management. With the discovery of novel molecular targets and the incorporation of targeted agents in the management of various adult histiocytic disorders, their management has become increasingly complex. In an attempt to improve the understanding of the clinical features and management of common adult histiocytic disorders (Langerhans cell histiocytosis, Erdheim-Chester disease, Rosai-Dorfman disease, and hemophagocytic lymphohistiocytosis), we created this document based on existing literature and expert opinion.


Subject(s)
Erdheim-Chester Disease/drug therapy , Histiocytosis, Langerhans-Cell/drug therapy , Histiocytosis, Sinus/drug therapy , Lymphohistiocytosis, Hemophagocytic/drug therapy , Adult , Drug Therapy, Combination , Erdheim-Chester Disease/diagnosis , Histiocytosis, Langerhans-Cell/diagnosis , Histiocytosis, Sinus/diagnosis , Humans , Lymphohistiocytosis, Hemophagocytic/diagnosis , Treatment Outcome
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