RESUMO
Abstract Introduction Hemophagocytic lymphohistiocytosis (HLH) is a rare clinical laboratory condition with high mortality rates, resulting from ineffective overactivation of the immune system. Data in the Brazilian literature is scarce, contributing to the challenge in standardizing conducts and performing an early diagnosis of HLH. Objective To describe the clinical, laboratory, and evolutionary findings on HLH patients treated at a pediatric hospital. Methods This is an observational, cross-sectional and retrospective study on children diagnosed with HLH, hospitalized between 2009 and 2019. The diagnostic criteria were those described in the Histiocyte Society protocol. The authors evaluated HLH patient laboratory tests, myelograms and bone marrow biopsies, clinical characteristics and therapy. Results Twenty-three patients were included, 52.2% of whom were males. The age at diagnosis ranged from one to one hundred and eighty months. Four cases were classified as Primary HLH and nineteen, as Secondary HLH. The main triggers were infections and rheumatological diseases. All children had bicytopenia, and 95.4% had hyperferritinemia. Nineteen patients had liver dysfunction, sixteen had neurological disorders and fourteen had kidney injury. Pulmonary involvement was seen in 61.9%, acting as a worse prognosis for death (p= 0.01). Nine patients underwent the immuno-chemotherapy protocol proposed in the HLH 2004. The time to confirm the diagnosis varied from five to eighty days. The lethality found was 56.3%. Conclusions The present study is the most extensive retrospective exclusively pediatric study published in Brazil to date. Despite the limitations, it was possible to demonstrate the importance of discussing HLH as a pediatric emergency.
Assuntos
Humanos , Masculino , Feminino , Linfo-Histiocitose Hemofagocítica , PediatriaRESUMO
Presentación del caso. Lactante femenina de 14 meses de edad con desarrollo psicomotor normal, sin comórbidos. Con historia de un día de fiebre de 40 °C, intermitente, acompañada de evacuaciones diarreicas y vómitos. Fue llevada por sus padres a una clínica privada sin notar mejoría con el tratamiento médico indicado. Posteriormente, presentó deterioro clínico y fue llevada a un hospital, donde se diagnosticó un síndrome febril agudo, diarrea con deshidratación leve y faringitis. Al cuarto día de evolución inició con máculas y pápulas que progresaron a vesículas y costras. Además, presentó intolerancia a la vía oral, disnea, distensión abdominal, coma y desequilibrio hidroelectrolítico. Intervención terapéutica. Inició el tratamiento con hidratación parenteral, antivirales, esteroides endovenosos y antihistamínicos; se diagnosticó shock séptico con compromiso respiratorio, se proporcionó ventilación mecánica asistida y fue referida al hospital de tercer nivel para atención por medicina crítica. Los estudios reportaron un derrame pleural derecho del 40 % y hepatomegalia. Continuó el tratamiento con antibiótico terapia, hidratación parenteral, antivirales, diuréticos, antipiréticos y hemoderivados, presentó mejoría, continuó el manejo terapéutico. Evolución clínica. El día 18 presentó fiebre, hepatoesplenomegalia, los exámenes reportaron elevación de ferritina, triglicéridos y citopenia se diagnosticó un síndrome hemofagocítico que evolucionó con una falla multisistémica y falleció al siguiente día
Case presentation. A 14-month-old female infant with normal psychomotor development, without comorbidities. With a one-day history of fever of 40 °C, intermittent, accompanied by diarrhea and vomiting. She was taken by her parents to a private clinic without improvement with the indicated medical treatment. Subsequently, she presented clinical deterioration and was taken to a hospital, where she was diagnosed with acute febrile syndrome, diarrhea with mild dehydration, and pharyngitis. On the fourth day of evolution, she started with macules and papules that progressed to vesicles and crusts. In addition, she presented oral intolerance, dyspnea, abdominal distension, coma, and hydro electrolytic imbalance. Therapeutic intervention. She started treatment with parenteral hydration, antivirals, intravenous steroids, and antihistamines; septic shock with respiratory distress was diagnosed, assisted mechanical ventilation was provided, and she was referred to a tertiary hospital for critical care medicine. Studies reported a 40 % right pleural effusion and hepatomegaly. She continued treatment with antibiotic therapy, parenteral hydration, antivirals, diuretics, antipyretics, and hemoderivatives, presented improvement, and continued therapeutic management. Clinical evolution. On day 18 he presented fever and hepatosplenomegaly. Tests reported elevated ferritin, triglycerides, and cytopenia, and was diagnosed with hemophagocytic syndrome that evolved with multisystemic failure and died the following day
Assuntos
Síndrome , Varicela , Linfo-Histiocitose Hemofagocítica , Derrame Pleural , Sepse , Cuidados Críticos , HepatomegaliaRESUMO
INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a rare clinical laboratory condition with high mortality rates, resulting from ineffective overactivation of the immune system. Data in the Brazilian literature is scarce, contributing to the challenge in standardizing conducts and performing an early diagnosis of HLH. OBJECTIVE: To describe the clinical, laboratory, and evolutionary findings on HLH patients treated at a pediatric hospital. METHODS: This is an observational, cross-sectional and retrospective study on children diagnosed with HLH, hospitalized between 2009 and 2019. The diagnostic criteria were those described in the Histiocyte Society protocol. The authors evaluated HLH patient laboratory tests, myelograms and bone marrow biopsies, clinical characteristics and therapy. RESULTS: Twenty-three patients were included, 52.2% of whom were males. The age at diagnosis ranged from one to one hundred and eighty months. Four cases were classified as Primary HLH and nineteen, as Secondary HLH. The main triggers were infections and rheumatological diseases. All children had bicytopenia, and 95.4% had hyperferritinemia. Nineteen patients had liver dysfunction, sixteen had neurological disorders and fourteen had kidney injury. Pulmonary involvement was seen in 61.9%, acting as a worse prognosis for death (p = 0.01). Nine patients underwent the immuno-chemotherapy protocol proposed in the HLH 2004. The time to confirm the diagnosis varied from five to eighty days. The lethality found was 56.3%. CONCLUSIONS: The present study is the most extensive retrospective exclusively pediatric study published in Brazil to date. Despite the limitations, it was possible to demonstrate the importance of discussing HLH as a pediatric emergency.
RESUMO
Sporotrichosis is a fungal disease that causes symptoms similar to those of other infectious and non-infectious diseases, making diagnosis difficult and challenging. Here, we report a case of an HIV-negative patient presenting disseminated sporotrichosis with widespread cutaneous lesions mimicking pyoderma gangrenosum, with bone marrow infection, pancytopenia, and hemophagocytic syndrome. However, all the clinical manifestations and a bacterial coinfection delayed the request for a fungal diagnosis. Therefore, sporotrichosis should always be investigated in patients from endemic areas presenting with widespread cutaneous lesions associated with pancytopenia.
RESUMO
Introducción: El síndrome hemofagocítico se presenta como un cuadro clínico grave, provocado por una respuesta inadecuada del sistema inmunológico a un desencadenante infeccioso, neoplásico, reumatológico o metabólico, que origina una reacción inflamatoria no controlada; presenta una incidencia baja pero la letalidad sin el manejo adecuado es muy elevada. Objetivo: Destacar la importancia de diagnóstico oportuno del síndrome hemofagocítico en pacientes con dengue que presentan evolución tórpida. Presentación del caso: Paciente de 7 años de edad, con dengue grave dado por shock, hepatomegalia con elevación de transaminasas, con mala evolución clínica, quien cumple criterios de Síndrome hemofagocítico. Recibió manejo con inmunomoduladores con evolución satisfactoria. Conclusiones: Es importante considerar el Síndrome hemofagocítico como causa ante enfermedades con evolución tórpida a pesar de tener un manejo médico correcto(AU)
Introduction: Hemophagocytic syndrome is a severe clinical picture with an uncontrolled inflammatory reaction caused by an inadequate immune system response to an infectious, neoplastic, rheumatological, or metabolic trigger. The syndrome has low incidence but high fatality when the management is not adequate. Objective: To highlight the importance of a prompt diagnosis of hemophagocytic syndrome in patients with dengue who present a torpid evolution. Case presentation: Seven-year-old patient with severe dengue caused by shock, hepatomegaly with elevated transaminase levels and poor clinical evolution who meets hemophagocytic syndrome criteria. The patient had satisfactory progression after receiving immunomodulatory treatment. Conclusions: Hemophagocytic syndrome must be considered as a cause of pathologies in dengue patients with torpid evolution, even when correct medical management is made(AU)
Assuntos
Humanos , Masculino , Criança , Evolução Clínica , Dengue Grave , Vírus da Dengue , Linfo-Histiocitose Hemofagocítica , Fatores ImunológicosRESUMO
ABSTRACT Objective: To describe the case of a child who presented hemophagocytic lymphohistiocytosis (HLH) associated with acute monocytic leukemia after chemotherapy, with hemophagocytosis caused by leukemic cells. Case description: In a university hospital in Southern Brazil, a 3-year-old female was diagnosed with acute monocytic leukemia with normal karyotype. The chemotherapy regimen was initiated, and she achieved complete remission six months later, relapsing after four months with a complex karyotype involving chromosomes 8p and 16q. The bone marrow showed vacuolated blasts with a monocytic aspect and evidence of hemophagocytosis. The child presented progressive clinical deterioration and died two months after the relapse. Comments: HLH is a rare and aggressive inflammatory condition characterized by cytopenias, hepatosplenomegaly, fever, and hemophagocytosis in the bone marrow, lymph nodes, spleen, and liver. Although rare, malignancy-associated HLH (M-HLH) is fatal. The patient in this case report met five out of the eight established criteria for HLH. The evolution of the patient's karyotype, regardless of the diagnostic profile, seemed secondary to the treatment for acute monocytic leukemia. In this case, the cytogenetic instability might have influenced the abnormal behavior of leukemic cells. This is a rare case of HLH in a child with acute monocytic leukemia.
RESUMO Objetivo: Descrever um caso de um paciente pediátrico que apresentou linfo-histiocitose hemofagocítica (LHH) associada à leucemia monocítica aguda pós-quimioterapia, com hemofagocitose causada pelas próprias células leucêmicas. Descrição do caso: Em um hospital universitário do Sul do Brasil, uma menina de três anos foi diagnosticada com leucemia monocítica aguda com cariótipo normal. Após receber protocolo quimioterápico, atingiu remissão seis meses depois do início do tratamento, recaíndo quatro meses após com um cariótipo complexo envolvendo ambos os cromossomos, 8p e 16q. A medula óssea mostrava-se infiltrada por células blásticas vacuolizadas com aspecto monocítico, com evidências de hemofagocitose. A criança apresentou um declínio clínico progressivo e dois meses após a recaída foi a óbito. Comentários: A LHH é uma condição inflamatória rara e agressiva caracterizada por citopenias, hepatoesplenomegalia, febre e hemofagocitose na medula óssea, linfonodos, baço e fígado. A LHH associada a doenças malignas, embora seja uma condição rara, é potencialmente fatal. A paciente deste caso apresentou cinco dos oito critérios estabelecidos para o diagnóstico de LHH. A evolução do cariótipo do paciente, independentemente do perfil do diagnóstico, pareceu ser secundária ao tratamento da leucemia monocítica aguda, sendo que a instabilidade citogenética pode ter influenciado o comportamento atípico observado nas células leucêmicas. Este é um dos raros casos de LHH em uma criança com leucemia monocítica aguda.
Assuntos
Humanos , Feminino , Pré-Escolar , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Leucemia Monocítica Aguda/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/etiologia , Brasil , Leucemia Monocítica Aguda/diagnóstico , Leucemia Monocítica Aguda/genética , Leucemia Monocítica Aguda/patologia , Evolução Fatal , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/imunologia , Linfo-Histiocitose Hemofagocítica/patologiaRESUMO
Resumen: El síndrome hemofagocítico es una enfermedad infrecuente y de alta mortalidad. El término hemofagocitosis describe la presencia de macrófagos activados que incorporan dentro de su citoplasma eritrocitos, leucocitos y plaquetas. Cuando esto ocurre en el contexto de una respuesta inmune exagerada e ineficaz, se denomina síndrome hemofagocítico. Se clasifica en primario cuando se asocia a alteraciones genéticas generalmente hereditarias, y secundario, más frecuente en adultos, cuando se desencadena por alguna enfermedad o condición subyacente. El diagnóstico requiere de un alto grado de sospecha y se realiza según criterios diagnósticos establecidos, siendo la sepsis el principal diagnóstico diferencial. Se comentan dos casos de hombres jóvenes con infección por virus de la inmunodeficiencia humana en estadío avanzado, que se presentan con fiebre y fallo multiorgánico, en los que se hace el diagnóstico de síndrome hemofagocítico secundario.
Abstract: The hemophagocytic syndrome is an infrequent and fatal disease. The concept of hemophagocytosis describes the presence of activated macrophages that incorporate within their cytoplasms erythrocytes, leukocytes and platelets. When it occurs in the context of an exaggerated and inefficient immune response, it is called hemophagocytic syndrome. It is classified in primary when it is associated with genetic alterations generally hereditary, and secondary, more frequent in adults, when it is triggered by a disease or an underlying condition. The diagnosis requires a high grade of suspicion and is based on established diagnostic criteria, being sepsis the main differential diagnosis. We present two cases of young men with advanced infection by the human immunodeficiency virus, who developed fever and multiorgan failure, arriving at the diagnosis of secondary hemophagocytic syndrome.
Resumo: A síndrome hemofagocítica é uma doença rara e com alta mortalidade. O termo hemofagocitose descreve a presença de macrófagos ativados que incorporam eritrócitos, leucócitos e plaquetas em seu citoplasma. Quando ocorre no contexto de uma resposta imune exagerada e ineficaz, é chamada de síndrome hemofagocítica. É classificada como primária quando é associada a alterações genéticas geralmente hereditárias, e secundária quando é desencadeada por uma doença ou condição de base, mais frequente em adultos. O diagnóstico exige alto grau de suspeita e é feito de acordo a critérios com diagnósticos estabelecidos, sendo a sepse o principal diagnóstico diferencial. São discutidos dois casos de homens jovens com infecção pelo vírus da imunodeficiência humana em estágio avançado, apresentando febre e falência de múltiplos órgãos, fazendo o diagnóstico de síndrome hemofagocítica secundária.
RESUMO
Introduction: Haemophagocytic Lymphohistiocytosis (HLH), during HIV infection is a rare complication with a poor prognosis. There are few data on HLH within the Amazon region. The objective was to describe epidemiological, clinical and therapeutic features of HIV-related HLH in French Guiana. Methods: A retrospective analysis of adult HIV patients at Cayenne hospital with HLH between 2012 and 2015. A diagnosis of HLH was given if the patient presented at least 3 of 8 criteria of the HLH-2004 classification. Results: Fourteen cases of HLH were tallied during the study period. The mean age was 46 years with a sex ratio of 1.8. The most frequent etiology of HLH was an associated infection (12/14). Confirmed disseminated histoplasmosis, was found in 10 of 14 cases, and it was suspected in 2 other cases. The CD4 count was below 200/mm3 in 13/14 cases. An HIV viral load >100,000 copies/ml was observed in 13/14 cases. An early treatment with liposomal amphotericin B was initiated in 12/14 cases. The outcome was favorable in 12/14 of all cases and in 10/12 cases involving histoplasmosis. Case fatality was 2/14 among all cases (14.3%) et 1/10 among confirmed disseminated histoplasmosis with HLH (10%). During the study period 1 in 5 cases of known HIV-associated disseminated histoplasmosis in French Guiana was HLH. Conclusion: Histoplasmosis was the most frequent etiology associated with HLH in HIV-infected patients in French Guiana. The prognosis of HLH remains severe. However, a probabilistic empirical first line treatment with liposomal amphotericin B seemed to have a favorable impact on patient survival.
Assuntos
Infecções por HIV , Histoplasmose , Linfo-Histiocitose Hemofagocítica , Adulto , Guiana Francesa , Infecções por HIV/complicações , Histoplasmose/complicações , Histoplasmose/diagnóstico , Histoplasmose/tratamento farmacológico , Hospitais , Humanos , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/epidemiologia , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Hodgkin lymphoma is a malignant neoplasm of B lymphoid cells whose histologic characteristic is the presence of Reed-Sternberg cells in an inflammatory environment. CASE REPORT: A 37-year-old woman with a history of up to 40°C fever for four months, progressive and bilateral decrease in hearing acuity, weight loss of up to 6 kg, cervical lymphadenopathy, hepatosplenomegaly, and pancytopenia. Auditory sensory neuropathy was confirmed. The patient developed hemophagocytic syndrome, therefore, infectious and autoimmune etiologies were ruled out. The CT scan revealed hepatosplenomegaly with thoracic and abdominal cervical nodes, with loss of fatty hilum. The laboratory tests showed evidence that suggested the reactivation of the Epstein-Barr virus. Through a submandibular node biopsy, the diagnostic conclusion was that lymphocyte-rich classical Hodgkin's lymphoma was present. CONCLUSION: This is the first report in Latin American literature about a patient with hemophagocytic syndrome that is secondary to classic Hodgkin lymphoma and associated with Epstein-Barr infection.
Antecedentes: El linfoma de Hodgkin es una neoplasia maligna de células linfoides tipo B cuya característica histológica es la presencia de células de Reed-Sternberg en un medio inflamatorio. Caso clínico: Mujer de 37 años, con fiebre de hasta 40 °C desde cuatro meses atrás, disminución bilateral y progresiva de la agudeza auditiva, pérdida ponderal de 6 kg, linfadenopatía cervical, hepatoesplenomegalia y pancitopenia. Se corroboró neuropatía sensorial auditiva. La paciente desarrolló síndrome hemofagocítico, por lo que se descartaron procesos infecciosos o autoinmunes. La tomografía reveló hepatoesplenomegalia, ganglios cervicales torácicos y abdominales con pérdida del hilio graso; en los estudios de laboratorio se evidenciaron datos sugerentes de reactivación del virus de Epstein-Barr. Mediante biopsia de ganglio submandibular se concluyó que se trataba de linfoma de Hodgkin tipo clásico rico en linfocitos. Conclusión: La paciente descrita con síndrome hemofagocítico secundario a linfoma de Hodgkin clásico asociado a infección por Epstein-Barr constituye el primero caso reportado en la literatura latinoamericana.
Assuntos
Infecções por Vírus Epstein-Barr/complicações , Doença de Hodgkin/complicações , Linfo-Histiocitose Hemofagocítica/etiologia , Adulto , Feminino , HumanosRESUMO
BACKGROUND: The hemophagocytic syndrome is a serious complication of several systemic illnesses. OBJECTIVE: To define the characteristics of the hemophagocytic syndrome at a pediatric specialty hospital in Tuxtla Gutiérrez, Chiapas, Mexico; incidences, underdiagnosis and overdiagnosis, associated conditions, treatment, and prognosis were included. METHODS: 214 cases of probable hemophagocytic syndrome that were seen between January 2011 and May 2019 were analyzed. 26 patients diagnosed with hemophagocytic syndrome and 188 cases with suspicion of this entity and/or ferritin > 500 ug/L were included. The cases that met four or more criteria of the HFS (Histiocyte Society, 2004) were included in this study. RESULTS: Thirty-five cases were validated (fourteen were previously diagnosed, nine had suspicion, and twelve had ferritin > 500 µg/L). Neither twelve out of 26 of the cases that were previously diagnosed (46.2 % overdiagnosed). Of the 35 validated cases, 21 hadn't been diagnosed (60 % underdiagnosed) met the diagnostic criteria of the HFS. The annual occurrence was of 2.0/1000 egresses. The Epstein-Barr virus was involved in 42 % of the cases. The overall mortality was of 80 %. CONCLUSIONS: Hemophagocytic syndrome had been significantly underdiagnosed and overdiagnosed at the analyzed hospital. The clinical features allow early suspicion, diagnosis, and treatment. Specific and non-specific illnesses that were associated to hemophagocytic syndrome were identified.
Antecedentes: El síndrome hemofagocítico es una complicación grave que se observa en diversos padecimientos sistémicos. Objetivo: Conocer las características del síndrome hemofagocítico en el Hospital de Especialidades Pediátricas de Tuxtla Gutiérrez, Chiapas, México; se incluyó incidencia, subdiagnóstico y sobrediagnóstico, padecimientos asociados, tratamiento y pronóstico. Métodos: Se analizaron 214 casos probables de síndrome hemofagocítico atendidos entre enero de 2011 y mayo de 2019. Se incluyeron 26 pacientes con diagnóstico de síndrome hemofagocítico y 188 en los que se sospechaba esta entidad o con ferritina > 500 µg/L. Los casos en los que se cumplieron cuatro o más criterios de la Sociedad del Histiocito fueron incluidos en el estudio. Resultados: Se validaron 35 casos (14 con diagnóstico previo, nueve con sospecha y 12 con ferritina > 500 µg/L). No cumplieron con los criterios de la Sociedad del Histiocito, 12 casos diagnosticados previamente (sobrediagnóstico de 46.2 %). De los 35 validados, 21 no habían sido diagnosticados (subdiagnóstico de 60 %). La incidencia anual fue de 2.0/1000 egresos. El virus Epstein-Barr estuvo involucrado en 42 % de los casos. La mortalidad representó 80 %. Conclusiones: El síndrome hemofagocítico fue subdiagnosticado y sobrediagnosticado en el hospital estudiado. Las características clínicas permiten sospecharlo, diagnosticarlo y tratarlo oportunamente. Se identificaron padecimientos específicos y no específicos asociados a síndrome hemofagocítico.
Assuntos
Infecções por Vírus Epstein-Barr , Linfo-Histiocitose Hemofagocítica , Criança , Herpesvirus Humano 4 , Hospitais , Humanos , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/epidemiologia , Uso Excessivo dos Serviços de SaúdeRESUMO
Abstract INTRODUCTION Visceral leishmaniasis (VL) is an ill-studied disease that is endemic to several regions of Brazil. It is often complicated by hemophagocytic lymphohistiocytosis (HLH), a potentially fatal disorder resulting from excessive non-malignant activation/proliferation of T lymphocytes and macrophages. Considering the overlapping clinical and laboratory characteristics of these diseases, diagnosing HLH is a challenge. Therefore, tracking the association between VL and HLH is necessary in endemic areas. Although HLH can be inapparent and resolve with antileishmanicides, this may not always occur. HLH causes high lethality; therefore, immunosuppressive therapy should be instituted immediately in order to avoid a fatal outcome. METHODS: We described the epidemiological, clinical, laboratory, and therapeutic profile of this association in a region of Brazil endemic for VL. RESULTS We presented 39 patients with this association in a retrospective cohort of 258 children who were admitted from January 2012 to June 2017. Of the 39 patients, 31 were from urban areas (79.5%), and 21 (53%) were males. The mean age and weight were 2.86 (2.08) years and 14.03 (5.96) kg, respectively. The main symptoms were fever (100%), hepatosplenomegaly (100%), pallor of the skin and mucosa (82.5%), edema (38.5%), bleeding (25%), and jaundice (7.5%). Hemophagocytosis was identified in 16/37 (43.24%) patients, and direct examination revealed that 26/37 (70.27%) patients were positive for VL. The patients were treated as recommended by the Ministry of Health. CONCLUSIONS It was observed that HLH is a common complication in endemic areas, and its diagnosis must consider the overlapping of clinical characteristics and pancytopenia.
Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Linfo-Histiocitose Hemofagocítica/etiologia , Leishmaniose Visceral/complicações , Brasil , Estudos Retrospectivos , Linfo-Histiocitose Hemofagocítica/terapiaRESUMO
Resumen El síndrome hemofagocítico es una enfermedad caracterizada por fiebre, citopenias, esplenomegalia y otras alteraciones en laboratorios debido a una activación excesiva de los macrófagos, debido a mutaciones genéticas o secundario a infecciones, malignidad o enfermedades reumatológicas. Debido a la poca especificidad de los síntomas, el diagnóstico usualmente se realiza de manera tardía. Su manejo requiere el tratamiento de la causa subyacente, y de ser necesario, medicamentos que disminuyan la respuesta inflamatoria.
Abstract Hemophagocytic syndrome is a disease characterized by fever, cytopenia, splenomegaly and other alterations in laboratories due to excessive activation of macrophages, by genetic mutations or secondary to infections, malignancy or rheumatological diseases. Because of the low specificity of the symptoms, the diagnosis is usually late. Its management requires the treatment of the underlying cause and, if necessary, medications that decrease the inflammatory response.
RESUMO
Introducción: El síndrome hemofagocítico, llamado también linfohistiocitosis hemofagocítica o síndrome de activación macrofágica, es una grave enfermedad que se caracteriza por la activación exagerada del sistema inmune y aumento de la actividad linfocítica citotóxica y macrofágica, que puede ser potencialmente fatal. Objetivo: Describir un caso con este síndrome poco frecuente pero de alta mortalidad. Presentación del caso: Paciente de 10 meses, nacido de parto eutócico, a término, normopeso, con antecedentes de ingreso a los dos meses por sepsis, con aumento de las transaminasas y adenopatías cervicales. Se realizó biopsia del ganglio cervical y se diagnosticó adenitis granulomatosa. En esta ocasión, cuatro días antes del ingreso comenzó con fiebre y decaimiento; al examen físico presentó tiraje intercostal bajo, polipnea superficial, hepatomegalia y esplenomegalia. Exámenes complementarios, presentó anemia, transaminasas, albúmina y proteínas totales elevadas; orina con pigmentos biliares y cuerpos cetónicos positivos; plaquetas 100 x 109. Los especialistas de gastroenterología plantearon una colestasis del lactante. El paciente falleció y en la necropsia se constató una hepatoesplenomegalia, hígado amarillento, adenopatías mesentéricas y peripancreáticas, pulmones hemorrágicos con aumento de consistencia; en el estudio microscópico se encontró en hígado, bazo, médula ósea, y ganglios linfáticos, histiocitos con hemofagocítosis. Conclusiones: El síndrome hemofagocítico es una enfermedad poco frecuente que muchas veces no se sospecha y pasa inadvertido, por lo tanto hay que pensar en dicha entidad porque tiene implicaciones pronósticas graves para el paciente, como puede ser un desenlace fatal(AU)
Introduction: The hemophagocytic syndrome, also called hemophagocyticlymphohistiocytosis or macrophage activation´s syndrome is a serious disease characterized by exaggerated activation of the immune system and increased cytotoxic lymphocytic and macrophage activity, which can be potentially fatal. Objective: To describe a case with this rare syndrome with a high mortality rate, and the diagnosis was made postmortem in our hospital. Case presentation: A 10-month-old patient, born by natural delivery, with normal weight, with a history of admission at 2 months due to sepsis, with increased transaminases levels and cervical adenopathies. A cervical lymph node biopsy was performed, and granulomatous adenitis was diagnosed. On this occasion, four days before admission, he presented fever and weakness; physical examination revealed low intercostals retraction, superficial polypnea, hepatomegaly and splenomegaly. The complementary tests showed anemia, transaminases, albumin and total proteins with high levels; urine had bile pigments and positive ketone bodies; platelets 100 x 109. Gastroenterology specialists set out cholestasis of the infant. The patient died and at necropsy there were evidences of hepato splenomegaly, yellowish liver, mesenteric and peripancreatic adenopathies, hemorrhagic lungs with increased consistency. In the microscopic study, histiocytes with hemophagocytosis were found in liver, spleen, bone marrow, and lymph nodes. Conclusions: The hemophagocytic syndrome is a rare disease that often goes unnoticed. It has serious prognostic implications for the patient with a fatal outcome(AU)
Assuntos
Humanos , Masculino , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/patologia , Relatos de CasosRESUMO
Various infectious diseases can hyper-stimulate the immune system, causing hemophagocytic syndrome (HPS). Little is known regarding the accuracy of diagnostic criteria and epidemiological triggering factors in the acquired immunodeficiency syndrome (AIDS) setting. We investigated the major infectious disease triggers of HPS in patients living with human immunodeficiency virus (HIV)/AIDS and determined the accuracy of bone marrow aspiration (BMA). The inclusion criteria were (i) confirmed HIV diagnosis, (ii) bone marrow aspiration, and (iii) a minimum of four HPS criteria. Patients were further classified into those with four presumed HPS criteria, or ≥ 5 confirmed criteria. The disease triggers, accuracy of bone marrow aspiration, and prognosis markers were examined. Presumed HPS was observed in 15/36 patients (41%), and confirmed HPS in 58% (n = 21). The major etiological triggers were infection with Mycobacterium (34%), Cytomegalovirus (14%), Cryptococcus neoformans (11%), and hematological or tumoral disease (11%). BMA demonstrated 93% specificity on screening diagnosis (odds ratio [OR] 12.7, 95% confidence interval [CI] 1.4-115.1, P = 0.01). Ferritin > 5000 ng/mL correlated with probability of death in univariate analysis (OR 6.00, 95% CI 1.33-27.05, P = 0.02). Ferritin performance as test of death probability presented area under the curve as 0.74 (95% CI 0.56-0.91, P = 0.016). However, neither cluster of differentiation for lymphocyte count nor HIV viral load correlated with patient deaths. Mycobacterium spp. and Cytomegalovirus were the main factors triggering HPS, followed by Cryptococcus neoformans, and hematological and tumoral diseases. High ferritin levels were associated with increased death probability. High specificity was noted with BMA
Assuntos
Humanos , HIV , Infecções Oportunistas Relacionadas com a AIDS , Linfo-Histiocitose HemofagocíticaRESUMO
Various infectious diseases can hyper-stimulate the immune system, causing hemophagocytic syndrome (HPS). Little is known regarding the accuracy of diagnostic criteria and epidemiological triggering factors in the acquired immunodeficiency syndrome (AIDS) setting. We investigated the major infectious disease triggers of HPS in patients living with human immunodeficiency virus (HIV)/AIDS and determined the accuracy of bone marrow aspiration (BMA). The inclusion criteria were (i) confirmed HIV diagnosis, (ii) bone marrow aspiration, and (iii) a minimum of four HPS criteria. Patients were further classified into those with four presumed HPS criteria, or ≥ 5 confirmed criteria. The disease triggers, accuracy of bone marrow aspiration, and prognosis markers were examined. Presumed HPS was observed in 15/36 patients (41%), and confirmed HPS in 58% (n = 21). The major etiological triggers were infection with Mycobacterium (34%), Cytomegalovirus (14%), Cryptococcus neoformans (11%), and hematological or tumoral disease (11%). BMA demonstrated 93% specificity on screening diagnosis (odds ratio [OR] 12.7, 95% confidence interval [CI] 1.4-115.1, P = 0.01). Ferritin > 5000 ng/mL correlated with probability of death in univariate analysis (OR 6.00, 95% CI 1.33-27.05, P = 0.02). Ferritin performance as test of death probability presented area under the curve as 0.74 (95% CI 0.56-0.91, P = 0.016). However, neither cluster of differentiation for lymphocyte count nor HIV viral load correlated with patient deaths. Mycobacterium spp. and Cytomegalovirus were the main factors triggering HPS, followed by Cryptococcus neoformans, and hematological and tumoral diseases. High ferritin levels were associated with increased death probability. High specificity was noted with BMA.
Assuntos
Síndrome da Imunodeficiência Adquirida , Linfo-Histiocitose Hemofagocítica , Síndrome da Imunodeficiência Adquirida/epidemiologia , Síndrome da Imunodeficiência Adquirida/microbiologia , Síndrome da Imunodeficiência Adquirida/patologia , Síndrome da Imunodeficiência Adquirida/virologia , Adulto , Medula Óssea/metabolismo , Medula Óssea/microbiologia , Medula Óssea/patologia , Medula Óssea/virologia , Criptococose/epidemiologia , Criptococose/microbiologia , Criptococose/patologia , Criptococose/virologia , Cryptococcus neoformans , Citomegalovirus , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/microbiologia , Infecções por Citomegalovirus/patologia , Infecções por Citomegalovirus/virologia , Feminino , HIV-1 , Humanos , Linfo-Histiocitose Hemofagocítica/epidemiologia , Linfo-Histiocitose Hemofagocítica/microbiologia , Linfo-Histiocitose Hemofagocítica/patologia , Linfo-Histiocitose Hemofagocítica/virologia , Masculino , Mycobacterium , Infecções por Mycobacterium/epidemiologia , Infecções por Mycobacterium/microbiologia , Infecções por Mycobacterium/patologia , Infecções por Mycobacterium/virologia , Estudos RetrospectivosRESUMO
La infección por el virus del dengue constituye un problema de salud pública mundial. Causada por un virus de la familia Flaviviridae, presenta un amplio espectro clínico, desde formas asintomáticas frecuentes hasta las formas graves de fiebre hemorrágica y shock por fuga capilar. Existen cuatro serotipos; los serotipos 2 y 3 están asociados a las formas graves de la enfermedad. El diagnóstico definitivo de infección por dengue depende del aislamiento del virus en sangre, de la detección del antígeno viral o el ARN viral en suero o tejido, o detección de anticuerpos específicos. El síndrome hemofagocítico se produce ante la desregulación del sistema inmune que lleva a la activación macrofágica descontrolada, y se manifiesta con alteraciones clínicas, hematológicas, bioquímicas e histológicas. La asociación entre ambas entidades se encuentra descripta como una forma inusual y grave de presentación que responde a la tormenta de citocinas liberadas durante la enfermedad. Presentamos el caso de un paciente adulto con dengue, hemofagocitosis y valores inusualmente elevados de ferritina en sangre que evolucionó favorablemente con tratamiento de soporte.
Dengue virus infection constitutes a major public health problem worldwide. It is caused by a virus belonging to the Flaviviridae family. It produces a wide range of clinical presentations, from asymptomatic infection to severe forms of the disease with hemorrhagic fever or shock secondary to capillary leak syndrome. Four serotypes have been described; serotype 2 and serotype 3 are associated with the most severe forms of the disease. The diagnosis is based on laboratory tests aimed to detect antibodies, viral RNA, or antigens in serum. The hemophagocytic syndrome is generated by a dysfunction of the immune system with clinical, hematological, biochemical and histological manifestations. The association between these two entities is described as an unusual and severe presentation of dengue fever. We present a case of an adult patient with this association and very high blood levels of ferritin, who responded favorably to supportive care.
Assuntos
Humanos , Masculino , Idoso , Dengue/complicações , Insuficiência Renal/etiologia , Linfo-Histiocitose Hemofagocítica/etiologia , Índice de Gravidade de Doença , Insuficiência Renal/diagnóstico , Linfo-Histiocitose Hemofagocítica/diagnósticoRESUMO
Dengue virus infection constitutes a major public health problem worldwide. It is caused by a virus belonging to the Flaviviridae family. It produces a wide range of clinical presentations, from asymptomatic infection to severe forms of the disease with hemorrhagic fever or shock secondary to capillary leak syndrome. Four serotypes have been described; serotype 2 and serotype 3 are associated with the most severe forms of the disease. The diagnosis is based on laboratory tests aimed to detect antibodies, viral RNA, or antigens in serum. The hemophagocytic syndrome is generated by a dysfunction of the immune system with clinical, hematological, biochemical and histological manifestations. The association between these two entities is described as an unusual and severe presentation of dengue fever. We present a case of an adult patient with this association and very high blood levels of ferritin, who responded favorably to supportive care.
Assuntos
Dengue/complicações , Linfo-Histiocitose Hemofagocítica/etiologia , Insuficiência Renal/etiologia , Idoso , Dengue/diagnóstico , Humanos , Linfo-Histiocitose Hemofagocítica/diagnóstico , Masculino , Insuficiência Renal/diagnóstico , Índice de Gravidade de DoençaRESUMO
Aggressive natural killer (NK)-cell leukemia (ANKL) is a very rare oncohematological disease among youngsters in Latin America. Its clinical picture imitates a variety of syndromes and diseases due to its pathophysiology. Its diagnosis is relatively simple due to the prominence of NK malignant cells in peripheral blood and its clinical aggressiveness. In certain circumstances though, the presence of blast NK cells and the natural course of the disease can be so modified by the treatment of one of the imitated diseases, especially when using steroids, that it becomes very difficult to diagnose early in its course. We present a case of a 16-year-old Mexican male who initiated symptoms imitating dengue to severe dengue for which he received steroids, apparently inducing a partial remission; he was then diagnosed as having community acquired pneumonia, then sepsis, septic shock w/disseminated intravascular coagulation, primary hemophagocytic syndrome, severe hepatitis, lupus and finally hyper IgE. It was not until 1 day before dying of hemorrhagic shock, a month after initiating symptoms, when the (re)emergence of blast NK cells in peripheral blood allowed the correct diagnosis to be made. Knowledge of ANKL pathophysiology may raise awareness of this multifaceted malignancy and may open up possibilities for its therapy. Gained knowledge can also be used for guiding NK cell evident aggressiveness against other malignancies.
RESUMO
El síndrome hemofagocítico está caracterizado por la activación anómala del sistema inmune. De etiología primaria o secundaria a enfermedades infecciosas, metabólicas, inmunitarias o neoplásicas. Con incidencia de 0,12 a 1 casos por cada 100 000 niños y una sobrevida de dos meses de no recibir tratamiento. Se diagnostica con 5 de 8 criterios propuestos por la Asociación Internacional de Histocitosis, y tratamiento según etiología. . Se presenta el caso de un paciente masculino de 15 meses de edad, procedente una zona endémica de leishmaniasis (Choluteca, Honduras), que ingresó al Hospital Escuela Universitario con cuadro clínico de fiebre prolongada y hepatoesplenomegalia. En los exámenes auxiliares de detectó: pancitopenia, serología positiva para leishmania, hipertrigliceridemia y valor de ferritina aumentada. Se hizo el diagnóstico de leishmaniasis visceral y síndrome hemofagocítico. Se trató con antimoniato de meglumina por 28 días, metilprednisolona y prednisona; con evolución favorable. El síndrome hem ofagocítico podría ocurrir secundario a leishmaniasis visceral por lo que su diagnóstico debería sospecharse tempranamente para un tratamiento oportuno y mejor pronóstico
The hemophagocytic syndrome is characterized by an abnormal activation of the immune system. This condition may be primary or secondary to infectious, metabolic, immunological, or malignant conditions. Its incidence is 0.12 to 1 case per 100,000 children, and the survival time is around two months with no therapy. The condition is diagnosed with the occurrence of 5 of 8 criteria proposed by the International Histiocytosis Association, and its therapy is according the original etiology. We present the case of a 15-month old male patient, who was brought from Choluteca (an endemic area for leishmaniasis), who was admitted to the University Hospital with prolonged fever and hepatosplenomegaly. Laboratory tests showed pancytopenia, positive serology for Leishmania, hypertriglyceridemia, and increased ferritin levels. Visceral leishmaniasis and hemophagocytic syndrome were diagnosed. The patient received meglumine antimoniate for 28 days, and also methylprednisolone and prednisone; and he had a favorable outcome. The hemophagocytic syndrome may be secondary to visceral leishmaniasis, and its diagnosis should be promptly suspected in order to have timely therapy and a better prognosis
RESUMO
OBJECTIVE: To develop and validate a diagnostic score that assists in discriminating primary hemophagocytic lymphohistiocytosis (pHLH) from macrophage activation syndrome (MAS) related to systemic juvenile idiopathic arthritis. STUDY DESIGN: The clinical, laboratory, and histopathologic features of 362 patients with MAS and 258 patients with pHLH were collected in a multinational collaborative study. Eighty percent of the population was assessed to develop the score and the remaining 20% constituted the validation sample. Variables that entered the best fitted model of logistic regression were assigned a score, based on their statistical weight. The MAS/HLH (MH) score was made up with the individual scores of selected variables. The cutoff in the MH score that discriminated pHLH from MAS best was calculated by means of receiver operating characteristic curve analysis. Score performance was examined in both developmental and validation samples. RESULTS: Six variables composed the MH score: age at onset, neutrophil count, fibrinogen, splenomegaly, platelet count, and hemoglobin. The MH score ranged from 0 to 123, and its median value was 97 (1st-3rd quartile 75-123) and 12 (1st-3rd quartile 11-34) in pHLH and MAS, respectively. The probability of a diagnosis of pHLH ranged from <1% for a score of <11 to >99% for a score of ≥123. A cutoff value of ≥60 revealed the best performance in discriminating pHLH from MAS. CONCLUSION: The MH score is a powerful tool that may aid practitioners to identify patients who are more likely to have pHLH and, thus, could be prioritized for functional and genetic testing.