RESUMO
Background: Hemophagocytic syndrome or hemophagocytic lymphohistiocytosis (HL) is an immune hyperactivation of multifactorial etiology, characterized by excessive activation of lymphocytes and macrophages, as well as numerous pro-inflammatory cytokines. It has a non-specific and highly variable clinical presentation, with splenomegaly being one of the clinical manifestations. Due to its nature, it can manifest during childhood or adult life, which is why it is a disease of diagnostic and therapeutic complexity. Clinical case: 38-year-old male patient without comorbidities, who presented with abdominal pain, choluria, fever > 38 °C and diaphoresis of more than 10 days of evolution. A bone marrow aspirate was performed as part of the diagnostic approach with data compatible with hemophagocytosis and cytopenias. The immunosuppressive management did not show the expected response, which is why an open splenectomy was performed as the last therapeutic option with adequate hematological control. A documentary review of the disease was carried out, and of the therapeutic options, emphasizing surgical management in case of refractoriness to medical treatment. Conclusions: Splenectomy increases the overall survival rate and the time free of HL progression, even though there are still no studies to determine with certainty the ideal time to perform a splenectomy in patients with pancytopenia without splenomegaly who suffer from hemophagocytic syndrome.
Introducción: el síndrome hemofagocítico o linfohistiocitosis hemofagocítica (LH) es una hiperactivación inmune de etiología multifactorial, caracterizada por activación excesiva de linfocitos y macrófagos, así como por numerosas citocinas proinflamatorias. Tiene una presentación clínica poco específica y muy variable, y la esplenomegalia es una de las manifestaciones clínicas. Debido a su naturaleza puede manifestarse durante la infancia o la vida adulta, por lo que es una enfermedad de complejidad diagnóstica y terapéutica. Caso clínico: paciente del sexo masculino de 38 años sin comorbilidades, quien presentó dolor abdominal, coluria, fiebre > 38 °C y diaforesis de más de 10 días de evolución. Se le hizo aspirado de médula ósea como parte del abordaje diagnóstico con datos compatibles con hemofagocitosis y citopenias. El manejo inmunosupresor no mostró la respuesta esperada, por lo que se hizo esplenectomía abierta como última opción terapéutica con adecuado control hematológico. Se hizo una revisión documental de la enfermedad y de las opciones terapéuticas con énfasis en el manejo quirúrgico en caso de refractariedad al tratamiento médico. Conclusiones: la esplenectomía aumenta la tasa de supervivencia general y el tiempo libre de progresión de la LH, aunque no hay todavía estudios para determinar con certeza el tiempo ideal para hacer una esplenectomía en pacientes con pancitopenia sin esplenomegalia que padezcan síndrome hemofagocítico.
Assuntos
Linfo-Histiocitose Hemofagocítica , Esplenectomia , Linfo-Histiocitose Hemofagocítica/cirurgia , Linfo-Histiocitose Hemofagocítica/diagnóstico , Humanos , Masculino , Adulto , Esplenectomia/métodosRESUMO
OBJECTIVE: Monitoring the disease status of Epstein-Barr virus (EBV)-related hemophagocytic lymphohistiocytosis (HLH) patients is crucial. This study aimed to investigate the different strategies and outcomes of patients with EBV-HLH and re-elevated EBV-DNA. METHOD: A retrospective analysis was conducted on 20 patients diagnosed with EBV-HLH. Clinical features, laboratory tests, treatments, plasma EBV-DNA levels, and outcomes were assessed. Three cases were highlighted for detailed analysis. RESULTS: Nine of the 20 patients had a re-elevation of EBV-DNA during treatment, and 55.5 % (5/9) experienced relapses. Patients with persistently positive plasma EBV-DNA (n = 4) and those with re-elevated EBV-DNA after conversion (n = 9) showed a significantly higher relapse rate compared to those with persistently negative EBV-HLH (n = 7) (p < 0.05). Among the highlighted cases, Case 1 exhibited plasma EBV-DNA re-elevation after four weeks of treatment without relapse, maintaining stability with the original treatment regimen, and eventually, his plasma EBV-DNA turned negative. In Case 2, plasma EBV-DNA was elevated again with a recurrence of HLH after L-DEP. Consequently, she underwent allogeneic hematopoietic stem cell transplantation and eventually achieved complete remission (CR) with negative plasma EBV-DNA. Case 3 experienced plasma EBV-DNA re-elevation after L-DEP but remained in CR, discontinuing chemotherapy without relapse. CONCLUSION: The re-elevation of plasma EBV-DNA during EBV-HLH treatment poses challenges in determining disease status and treatment strategies. Optimal management decisions require a combination of the level of elevated EBV-DNA, the intensity of hyperinflammation, and the patient's immune function.
Assuntos
DNA Viral , Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Linfo-Histiocitose Hemofagocítica , Recidiva , Humanos , Linfo-Histiocitose Hemofagocítica/terapia , Linfo-Histiocitose Hemofagocítica/sangue , Linfo-Histiocitose Hemofagocítica/virologia , Estudos Retrospectivos , Masculino , Infecções por Vírus Epstein-Barr/sangue , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/terapia , Feminino , DNA Viral/sangue , Pré-Escolar , Criança , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/isolamento & purificação , Lactente , Adolescente , Resultado do Tratamento , Relevância ClínicaRESUMO
Hemophagocytic lymphohistiocytosis (HLH) is a rare genetic hyperinflammatory syndrome that occurs early in life. Macrophage activation syndrome (MAS) usually refers to a secondary form of HLH associated with autoimmunity, although there are other causes of secondary HLH, such as infections and malignancy. In this article, we reviewed the concepts, epidemiology, clinical and laboratory features, diagnosis, differential diagnosis, prognosis, and treatment of HLH and MAS. We also reviewed the presence of MAS in the most common autoimmune diseases that affect children. Both are severe diseases that require prompt diagnosis and treatment to avoid morbidity and mortality.
Assuntos
Doenças Autoimunes , Linfo-Histiocitose Hemofagocítica , Síndrome de Ativação Macrofágica , Criança , Humanos , Síndrome de Ativação Macrofágica/diagnóstico , Síndrome de Ativação Macrofágica/etiologia , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/complicações , Doenças Autoimunes/complicações , Diagnóstico DiferencialRESUMO
Hemophagocytic lymphohistiocytosis (HLH) is a rare condition characterized by a hyperinflammatory state secondary to dysregulated immune activity with multisystem involvement. HLH may be primary or hereditary, or triggered by various diseases. Mortality without a timely treatment reaches 50% of the cases. Here we describe the case of a 1-year and 8-month-old female patient with a recent diagnosis of human immunodeficiency virus infection in the AIDS stage. She was hospitalized for assessment and initiation of antiretroviral therapy during which she developed multiple intercurrent infectious and immune conditions. Two episodes of hemophagocytic lymphohistiocytosis in the setting of uncontrolled acquired immunodeficiency and opportunistic co-infections stand out. The objective of this case report is to highlight the importance of suspecting HLH for a relevant diagnosis and treatment.
La linfohistiocitosis hemofagocítica (LHH) es una entidad rara que se caracteriza por un estado hiperinflamatorio secundario a la activación desregulada del sistema inmune con compromiso multisistémico. Puede ser primaria o hereditaria, o estar desencadenada por diversas enfermedades. La mortalidad sin tratamiento oportuno es del 50 % de los casos. Se presenta el caso de una paciente de 1 año y 8 meses con diagnóstico reciente de infección por virus de inmunodeficiencia humana en estadio sida. Cursó internación para estudio e inicio de tratamiento antirretroviral durante la cual presentó múltiples intercurrencias infectológicas e inmunológicas. Se destacan dos episodios de linfohistiocitosis hemofagocítica en contexto de inmunodeficiencia adquirida no controlada y coinfecciones oportunistas. El objetivo de este reporte es destacar la importancia de la sospecha de LHH para un diagnóstico y tratamiento pertinente.
Assuntos
Coinfecção , Infecções por HIV , Linfo-Histiocitose Hemofagocítica , Humanos , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/etiologia , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Lactente , Infecções Oportunistas Relacionadas com a AIDS/diagnósticoRESUMO
Background: Dengue fever is a mosquito-borne infectious disease endemic in over 100 countries around the world. Among the complications that dengue can cause the Hemophagocytic Lymphohistiocytosis is one of great concern for its severity and complex diagnosis. Case report: Hereby we document a case of this disease expressed on a previously healthy 6-year-old female patient whose dengue infection was so severe that needed intensive care management with vasoactive drugs and diuretics. After a short period of wellness began newly with fever, pancytopenia, hepatitis, and inflammatory response symptoms. Conclusions: A Dengue associated Hemophagocytic Lymphohistiocytosis syndrome was suspected and treated with intravenous corticosteroids on a 3-day scheme at no signs of malignancy with excellent response. The health care professionals must know about this not novel entity in order to reach an efficient diagnosis and treatment mostly, but not only, those in tropical and sub-tropical regions of the word were dengue virus is endemic.
Antecedentes: La fiebre por dengue es una enfermedad infecciosa transmitida por mosquitos, endémica en más de 100 países alrededor del mundo. La Linfohistiocitosis Hemofagocítica, dentro de las complicaciones que puede ocasionar el dengue, es una de las más preocupantes por su complejidad diagnostica y gravedad. Reporte de caso: Femenino de 6 años de edad, previamente sana, cuya infección por dengue fue tan grave que requirió manejo en cuidados intensivos. Después de un breve período de bienestar recrudeció la fiebre, además de pancitopenia, hepatitis y síntomas de respuesta inflamatoria. Conclusiones: Se sospechó síndrome de Linfohistiocitosis Hemofagocítica asociada a Dengue y se trató con corticoides intravenosos en un esquema de 3 días con excelente respuesta. Los profesionales de la salud deben conocer esta entidad no novedosa para poder llegar a un diagnóstico y tratamiento eficaz en su mayoría, pero no solo, en las regiones tropicales y subtropicales del mundo donde el virus del dengue es endémico.
Assuntos
Dengue , Hepatite , Linfo-Histiocitose Hemofagocítica , Feminino , Humanos , Criança , Linfo-Histiocitose Hemofagocítica/etiologia , Hepatite/complicações , Dengue/complicaçõesRESUMO
BACKGROUND: Patients with Coronavirus Disease 2019 (COVID-19) frequently experience a hyperinflammatory syndrome leading to unfavorable outcomes. This condition resembles Secondary Hemophagocytic Lymphohistiocytosis (sHLH) described in neoplastic, rheumatic and other infectious diseases. A scoring system (HScore) that evaluates underlying immunosuppression, temperature, organomegaly, cytopenias, ferritin, triglycerides, fibrinogen and AST was validated for sHLH, and recently proposed to evaluate hyperinflammation in COVID-19. AIM: To assess the presence of sHLH among patients with COVID-19 admitted for hospitalization and to evaluate Hscore as a prognostic tool for poor outcomes. MATERIAL AND METHODS: One hundred forty-three patients aged 21-100 years (64% males) admitted because of COVID-19 were enrolled in a prospective study. HScore was calculated within 72 hours admission. The incidence of sHLH during hospitalization was evaluated. Additionally, the relationship between a HScore ≥ 130 points and either the requirement of mechanical ventilation or 60-days mortality was explored. RESULTS: The median HScore was 96 (33-169). A SHLH was diagnosed in one patient (incidence 0.7%), whose HScore was 169. After adjusting for age, sex, comorbidities and obesity, HScore ≥ 130 was independently associated with the composite clinical outcome (Hazard rartio 2.13, p = 0.022). CONCLUSIONS: sHLH is not frequent among COVID-19 patients. HScore can be useful to predict the risk for poor outcomes.
Assuntos
COVID-19 , Linfo-Histiocitose Hemofagocítica , Masculino , Humanos , Feminino , COVID-19/complicações , Estudos Prospectivos , Linfo-Histiocitose Hemofagocítica/etiologia , Comorbidade , HospitalizaçãoRESUMO
A female patient in her 30s presented to the emergency department with a 10-day history of fever, weakness and diaphoresis. Subsequent investigations revealed a diagnosis of haemophagocytic syndrome, secondary to disseminated non-tuberculous mycobacterial infection affecting the bone marrow, lungs, lymph nodes and skin. The bone marrow culture confirmed the presence of Mycobacterium avium infection. The patient's haemophagocytic syndrome was managed using the HLH-2004 chemoimmunotherapy, and M. avium infection was treated with a combination of clarithromycin, ethambutol, rifampicin, ciprofloxacin and amikacin. Throughout her hospitalisation, the patient faced several serious complications arising from both the medications and the prolonged hospital stay (lasting 12 months). However, these complications were promptly identified and effectively managed through a multidisciplinary and comprehensive approach. This approach was crucial in achieving a favourable patient outcome and successful recovery.
Assuntos
Linfo-Histiocitose Hemofagocítica , Infecções por Mycobacterium não Tuberculosas , Infecções Oportunistas , Feminino , Humanos , Linfo-Histiocitose Hemofagocítica/complicações , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/complicações , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Amicacina , CiprofloxacinaRESUMO
Hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are life-threatening hyperinflammatory syndromes. Familial HLH is caused by genetic impairment of granule-mediated cytotoxicity (eg, perforin deficiency). MAS is linked to excess activity of the inflammasome-activated cytokine interleukin-18 (IL-18). Though individually tolerated, mice with dual susceptibility (Prf1â»/â»Il18tg; DS) succumb to spontaneous, lethal hyperinflammation. We hypothesized that understanding how these susceptibility factors synergize would uncover key pathomechanisms in the activation, function, and persistence of hyperactivated CD8 T cells. In IL-18 transgenic (Il18tg) mice, IL-18 effects on CD8 T cells drove MAS after a viral (lymphocytic choriomeningitis virus), but not innate (toll like receptor 9), trigger. In vitro, CD8 T cells also required T-cell receptor (TCR) stimulation to fully respond to IL-18. IL-18 induced but perforin deficiency impaired immunoregulatory restimulation-induced cell death (RICD). Paralleling hyperinflammation, DS mice displayed massive postthymic oligoclonal CD8 T-cell hyperactivation in their spleens, livers, and bone marrow as early as 3 weeks. These cells increased proliferation and interferon gamma production, which contrasted with increased expression of receptors and transcription factors associated with exhaustion. Broad-spectrum antibiotics and antiretrovirals failed to ameliorate the disease. Attempting to genetically "fix" TCR antigen-specificity instead demonstrated the persistence of spontaneous HLH and hyperactivation, chiefly on T cells that had evaded TCR fixation. Thus, drivers of HLH may preferentially act on CD8 T cells: IL-18 amplifies activation and demand for RICD, whereas perforin supplies critical immunoregulation. Together, these factors promote a terminal CD8 T-cell activation state, combining features of exhaustion and effector function. Therefore, susceptibility to hyperinflammation may converge on a unique, unrelenting, and antigen-dependent state of CD8 T-cell hyperactivation.
Assuntos
Linfo-Histiocitose Hemofagocítica , Camundongos , Animais , Linfo-Histiocitose Hemofagocítica/etiologia , Perforina/genética , Perforina/metabolismo , Interleucina-18/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismoRESUMO
Hemophagocytic lymphohistiocytosis (HLH) is a rare multisystemic hyperinflammatory disease commonly associated with hepatic dysfunction. Liver injury is mediated by unchecked antigen presentation, hypercytokinemia, dysregulated cytotoxicity by natural killer and CD8 T cells, and disruption of intrinsic hepatic metabolic pathways. Over the past decade, there have been significant advances in diagnostics and expansion in therapeutic armamentarium for this disorder allowing for improved morbidity and mortality. This review discusses the clinical manifestations and pathogenesis of HLH hepatitis in both familial and secondary forms. It will review growing evidence that the intrinsic hepatic response to hypercytokinemia in HLH perpetuates disease progression and the novel therapeutic approaches for patients with HLH-hepatitis/liver failure.
Assuntos
Linfo-Histiocitose Hemofagocítica , Humanos , Linfo-Histiocitose Hemofagocítica/complicações , Linfo-Histiocitose Hemofagocítica/diagnóstico , Síndrome da Liberação de Citocina/complicações , Fígado/metabolismo , Linfócitos T CD8-Positivos/metabolismoRESUMO
Sickle cell disease (SCD) is an inherited blood disorder caused by a ß-globin gene point mutation that results in the production of sickle hemoglobin that polymerizes upon deoxygenation, causing the sickling of red blood cells (RBCs). RBC deformation initiates a sequence of events leading to multiple complications, such as hemolytic anemia, vaso-occlusion, chronic inflammation, and tissue damage. Macrophages participate in extravascular hemolysis by removing damaged RBCs, hence preventing the release of free hemoglobin and heme, and triggering inflammation. Upon erythrophagocytosis, macrophages metabolize RBC-derived hemoglobin, activating mechanisms responsible for recycling iron, which is then used for the generation of new RBCs to try to compensate for anemia. In the bone marrow, macrophages can create specialized niches, known as erythroblastic islands (EBIs), which regulate erythropoiesis. Anemia and inflammation present in SCD may trigger mechanisms of stress erythropoiesis, intensifying RBC generation by expanding the number of EBIs in the bone marrow and creating new ones in extramedullary sites. In the current review, we discuss the distinct mechanisms that could induce stress erythropoiesis in SCD, potentially shifting the macrophage phenotype to an inflammatory profile, and changing their supporting role necessary for the proliferation and differentiation of erythroid cells in the disease. The knowledge of the soluble factors, cell surface and intracellular molecules expressed by EBI macrophages that contribute to begin and end the RBC's lifespan, as well as the understanding of their signaling pathways in SCD, may reveal potential targets to control the pathophysiology of the disease.