Hemosiderosis pulmonar idiopática, caso clínico en México. Importancia de un diagnóstico y tratamiento oportuno / Idiopathic pulmonary hemosiderosis, clinical case in Mexico. The relevance of performed an early diagnosis and treatment

La hemosiderosis pulmonar idiopática (HPI) es una patología poco frecuente; su distribución geográfica, su incidencia y prevalencia se desconocen de manera exacta a nivel mundial. Tiene una fuerte asociación con condiciones autoinmunes y una adecuada respuesta al tratamiento inmunosupresor. A pesar de ser una patología grave, presenta una tasa de morbilidad y mortalidad mediana, siempre que se realice un diagnóstico y tratamiento precoz. Se presenta el caso clínico de una paciente femenina con diagnóstico de HPI quien cursó con la triada clásica de esta enfermedad: hemoptisis, anemia ferropénica e infiltrados pulmonares difusos. Se descartaron otras causas de hemorragia pulmonar difusa y se realizó el diagnóstico por biopsia pulmonar. Se trató con esteroides sistémicos e inhalados y azatioprina. Tras casi 2 años después del diagnóstico, estando sin tratamiento por 3 meses, presentó una exacerbación con hemorragia pulmonar masiva ocasionando el fallecimiento de la paciente.

Idiopathic pulmonary hemosiderosis (IPH) is a rare pathology; its geographic distribution, incidence and prevalence are not accurately known worldwide. It has a strong association with autoimmune conditions and has an adequate response to immunosuppressive treatment. Despite being a serious pathology, it has a medium morbidity and mortality rate, provided that early diagnosis and treatment is performed. We present the clinical case of a female patient diagnosed with IPH who presented with the classic triad of this disease: hemoptysis, iron deficiency anemia and diffuse pulmonary infiltrates. Other causes of diffuse pulmonary hemorrhage were ruled out and the diagnosis was made by lung biopsy. She was managed with systemic and inhaled steroids and azathioprine. After almost 2 years before the diagnosis, being without treatment for 3 month she had a massive pulmonary hemorrhage, causing the death of the patient.

Seroconversion in asymptomatic COVID-19 pediatric patients with rheumatic diseases of one tertiary referral hospital

Abstract Objectives: To evaluate seroconverted asymptomatic COVID-19 in pediatric Autoimmune Rheumatic Diseases (ARDs) patients and to identify the risk factors related to contagion. Methods: A cross-sectional study was conducted in March 2021, before vaccination of children and adolescents in Brazil, including 77 pediatric ARDs patients, followed at a tertiary hospital and 45 healthy controls, all of them without a previous diagnosis of COVID-19. Data was obtained by a questionnaire with demographic data, symptoms compatible with COVID-19 over the previous year, and contact with people with confirmed COVID-19. Patient's medical records were reviewed to access data regarding disease and current medications. A qualitative immunochromatographic SARS-CoV-2 test was performed on all participants. Results: Patients and controls were similar in terms of female gender (70.1% vs. 57.8%, p = 0.173), age (14 vs. 13 years, p = 0.269) and SARS-CoV-2 positive serology (22% vs. 15.5%, p = 0.481). 80.5% of rheumatic patients were in use of immunosuppressive drugs: 27.3% of them used corticosteroids (33.3% in high doses), and 7.8% on immunobiologicals. No statistical differences were found between positive (n = 17) and negative serology (n = 60) patients regarding demographic/socioeconomic data, contact with people with confirmed COVID-19, use and number of immunosuppressive drugs, use and dose of corticosteroids, use of hydroxychloroquine and immunobiological drugs (p > 0.05). Conclusions: Pediatric rheumatic disease patients were infected at the same rate as healthy ones. Neither the underlying pathology nor its immunosuppressive treatment seemed to interfere with contagion risk.

Organ transplantation and parasitic infection / 器官移植

Parasitic infection is manifested with the characteristics of both endemic and infectious diseases, and the onset of parasitic infection is regional and infectious. The incidence of parasitic infection after organ transplantation is relatively low, primarily occurring in single case or case series in developing countries and regions. With the development of social economy and a gradual increasing number of organ transplantation, the risk of parasitic exposure is increased when the recipients travel among different countries or regions. In addition, immunosuppression is the risk factor of parasitic infection. Consequently, the risk of parasitic infection in organ transplant recipients cannot be ignored. In this article, epidemiological characteristics, clinical manifestations, diagnosis, treatment and prevention of parasitic infection after organ transplantation were classified and summarized according to literature review, aiming to provide reference for the prevention and treatment of parasitic infection in organ transplant recipients.

The value of repeat kidney biopsy in lupus nephritis. A systematic review / La utilidad de la biopsia renal repetida en nefritis lúpica. Una revisión sistemática

ABSTRACT A renal biopsy is the 'gold standard' for diagnosis and classification of lupus nephritis (LN). The role of repeat renal biopsy in lupus nephritis (LN) to guide treatment or predict prognosis has been controversial. A systematic literature review was conducted based on retrospective and prospective studies. The studies were identified using English electronic scientific databases, including MEDLINE PUBMED, published between January 1990 and August 2020. The eligibility criteria were studies including adult LN patients with at least one follow-up renal biopsy with appropriate longitudinal information. Case reports, studies with incomplete information or including duplicate patients were excluded. Based on the inclusion and exclusion criteria, a total of 73 publications were identified. This study included a total of 1167 repeat biopsies in LN patients from 15 studies. The primary indication for a repeat biopsy was relapse in 44-78% of the cases, and lack of response in 13-51%. Additionally, several repeat biopsies were done according to the protocol, after induction and maintenance therapy. In terms of histopathological class switches, there was a higher frequency of changes from nonproliferative to proliferative lesions. Only two studies provide a definition of histological response. There were often changes in the therapeutic approach after a repeat biopsy. Repeat kidney biopsies are helpful in patients with LN flare/relapse, and in patients with poor treatment response. Histological transformation was a common finding. The histologic and clinical responses are discordant. A repeat biopsy could be of prognostic value for therapeutic decision-making.

RESUMEN La biopsia renal es el «estándar de oro¼ para el diagnóstico y la clasificación de la nefritis lúpica (NL). El papel de la biopsia renal repetida en nefritis lúpica para orientar el tratamiento o predecir el pronóstico ha sido controversial. Se llevó a cabo una revisión sistemática de la literatura basada en estudios retrospectivos y prospectivos. Los estudios se identificaron a través de bases de datos científicas electrónicas en inglés, incluyendo Medline PubMed, de publicaciones entre enero de 1990 y agosto del 2020. Los criterios de elegibilidad fueron estudios que incluyeran a pacientes adultos con NL, quienes tuvieran al menos una biopsia renal de seguimiento, con información longitudinal apropiada. Se excluyeron informes de casos, estudios con información incompleta o con pacientes duplicados. Basándose en los criterios de inclusión y exclusión, se identificaron 73 publicaciones. En la presente revisión se analizaron un total de 1.167 biopsias repetidas en pacientes con NL en 15 estudios. Las principales indicaciones para la biopsia repetida fueron: recidiva en 44-78% de los casos, y falta de respuesta en 13-51%. Adicionalmente, varias biopsias repetidas se hicieron conforme al protocolo, luego de la terapia de inducción y de mantenimiento. Con respecto a los cambios de clase histopatológica, hubo una mayor frecuencia de cambios de lesiones no proliferativas a lesiones proliferativas. Solamente dos estudios ofrecen una definición de respuesta histológica. Con frecuencia hubo cambios en el abordaje terapéutico después de realizar la biopsia repetida. Las biopsias renales repetidas son útiles en pacientes con exacerbación/recidiva y en pacientes con falta de respuesta a tratamiento. La transformación histológica fue un hallazgo frecuente; las respuestas histológicas y clínicas son discordantes. Una biopsia repetida puede ser de valor pronóstico para la toma de decisiones terapéuticas.

Clinical characteristics of cerebral amyloid angiopathy-related inflammation / 中华神经科杂志

Objective:To investigate the clinical, cerebrospinal fluid (CSF) and neuroimaging characteristics and their associations with prognosis in cerebral amyloid angiopathy(CAA)-related inflammation (CAA-ri).Methods:Seventeen patients with CAA-ri, 59 patients with CAA-related intracerebral hemorrhage (ICH) and 15 patients with CAA-related cognitive decline were recruited from Huashan Hospital, Fudan University from November 2015 to May 2020 and the First Affiliated Hospital of University of Science and Technology of China from January 2018 to May 2020. Vascular risk factors and imaging features of cerebral small vessel disease were compared among three groups. Clinical manifestations, CSF results, lesion features on magnetic resonance imaging, treatment options and follow-up data were collected in patients with CAA-ri. The good prognosis was defined by clinical and radiographic improvement with no disease recurrence. The associations between clinical characteristics and the immunosuppressive therapy or the good prognosis were analyzed by binary Logistic regression models.Results:Patients with CAA-ri showed earlier disease onset [(61.5±11.7) years vs (70.9±8.6) years, t=9.428, P=0.001] and more lobar cerebral microbleeds [69.0 (43.5, 134.3) vs 10.0 (5.0, 59.0), H=3.363, P=0.002] compared to patients with CAA-ICH, and higher prevalence of male (14/17 vs 6/15, χ2=6.099, P=0.014) and lower white matter hyperintensity Fazekas score [4.0 (2.0, 6.0) vs 6.0 (5.0, 6.0), H=2.461, P=0.042] compared to patients with CAA-related cognitive decline. In patients with CAA-ri, the immunosuppressive therapy was positively correlated with CSF protein>600 mg/L (odds ratio 16.50, 95% confidence interval 1.09-250.18, P=0.043), and during a follow-up of (3.0±1.9) years, the good prognosis was positively correlated with CSF protein<1 000 mg/L plus immunosuppressive therapy (odds ratio 20.00, 95% confidence interval 1.39-287.60, P=0.028). Conclusions:CAA-ri is a special subtype of CAA with earlier disease onset and higher prevalence of hemorrhagic imaging makers compared to CAA-ICH and CAA-related cognitive decline. CAA-ri patients with normal or slightly elevated CSF protein receiving immunosuppressive therapy are more likely to have good prognosis.

Tratamiento tardío de la intoxicación por paraquat en pacientes pediátricos: Reporte de dos casos / Late treatment of paraquat poisoning in pediatric patients: Report of two cases

El paraquat (PQ) pertenece al grupo de herbicidas de los bipiridilos. Su presentación es en forma líquida o en granulado, usándose con una concentración al 5 %, para uso en jardinería y al 20 % para uso agrícola. En la intoxicación en humanos el órgano blanco es el pulmón. Los pacientes desarrollan insuficiencia respiratoria que puede explicarse por una inicial actividad que involucra un gran estrés oxidativo, con presencia de radicales libres de oxígeno y peroxidación lipídica, con sus consecuentes daños, además de infiltración por polimorfonucleares que con su reacción de liberación empeoran la neumonitis. Puede haber mejoría de la neumonitis y el daño en algunos órganos, pero pronto la aparición de fibrosis pulmonar lleva a falta de respuesta a la administración de oxígeno y a la muerte por insuficiencia respiratoria en algunos días a semanas. De acuerdo con la cantidad ingerida varía la evolución de la severidad del cuadro clínico. Se presentan dos pacientes pediátricos con intoxicación por PQ, a quienes se les inició tratamiento inmunosupresor después de 48 horas de la exposición. Uno de los pacientes se intoxicó de manera no intencional y otro por suicidio. Los dos pacientes recibieron tratamiento similar, sin embargo, el paciente con intención suicida falleció días después de la exposición. Se hace una revisión de la literatura sobre el tratamiento administrado.

Paraquat (PQ) belongs to the bipyridyls herbicides. Its presentation is liquid or granulated, being used at concentrations of 5 %, in gardening and 20 % in agricultural use. In human poisoning, the target organ is the lung. The patients develop respiratory insufficiency that can be explained by an initial activity that involves a great oxidative stress, with the presence of oxygen free radicals and lipid peroxidation, with its consequent damages, in addition to polymorphonuclear infiltration that with its liberation reaction worsen pneumonitis. There may be improvement of pneumonitis, but the appearance of pulmonary fibrosis will lead to a lack of response to the administration of oxygen and death due to respiratory failure in a few days to a few weeks. According to the amount ingested, the evolution of the severity of the clinical picture varies. We present two pediatric patients with PQ poisoning, who were started on immunosuppressant treatment after 48 hours of exposure. One of the patients was poisoned incidentally and the other one by suicide. The two patients received similar treatment, however, the patient with suicidal intention died days after the exposure. A review of the literature on the treatment offered is made.

Terapia combinada en enfermedad inflamatoria intestinal: ¿una asociación necesaria? / Combination therapy in inflammatory bowel disease: a necessary association?

The management of inflammatory bowel disease (IBD) is constantly changing due to the arrival of new therapeutic agents. Combined therapy (biological associated with immunosuppressive therapy) has proven to be effective, reducing immunogenicity (antibody formation), optimizing the pharmacokinetics of biological therapy with anti-TNF. This therapeutic strategy has associated risks (neoplasia and intercurrent infections) that are not only explained by the use of drugs but also by the increase of cases in older ages. It is essential for the medical team to be familiar with the optimization and personalization of the therapy to achieve clear therapeutic objectives with the lowest possible risks.

El manejo de la enfermedad inflamatoria intestinal (EII) está en constante cambio, debido a la llegada de nuevos agentes terapéuticos. La terapia combinada (terapia biológica asociada a inmunosupresores) ha demostrado ser efectiva al disminuir la inmunogenicidad (formación de anticuerpos) permitiendo la optimización farmacocinética. Esta estrategia terapéutica tiene riesgos asociados (neoplasias e infecciones intercurrentes) que no sólo se explican por el uso de fármacos sino también por el aumento de casos en edades más avanzadas. Es fundamental que el equipo tratante este familiarizado con la optimización y personalización de la terapia para así lograr objetivos terapéuticos claros con los menores riesgos posibles.

Triple terapia inmunosupresora con el empleo del Tymogam® en la aplasia medular idiopática / Immunosuppressive triple-therapy using Tymogam® in idiopathic aplastic anemia

Introducción: la terapia inmunosupresora con globulina antitimocítica o antilinfocítica y ciclosporina A se considera el tratamiento estándar para pacientes con aplasia medular muy severa o severa, que no tienen posibilidades de trasplante de progenitores hematopoyéticos. Objetivo: evaluar la respuesta del tratamiento inmunosupresor con el empleo de Thymogam® en pacientes adultos con aplasia medular idiopática. Método: se realizó un estudio descriptivo de 26 pacientes mayores de 18 años con diagnóstico de aplasia medular idiopática, atendidos en el Instituto de Hematología e Inmunología entre enero del 2000 y abril del 2012, que recibieron como parte del tratamiento inmunosupresor, la globulina antitimocítica (Thymogam®). Resultados: se clasificaron14 pacientes como aplasia medular muy severa y 12 como severa. La media de edad fue de 36 años (rango 18 - 74 años). En los primeros 6 meses después de iniciado el tratamiento, el 73 por ciento alcanzó algún tipo de respuesta y de ellos, en 15 (57,7 por ciento) la respuesta fue completa, la que fue más frecuente en los menores de 25 años. El porcentaje de recaídas fue del 26,3 por ciento. Las reacciones adversas más frecuentes fueron fiebre, hipertensión arterial, temblores y sudoraciones. Las principales complicaciones fueron las hemorragias graves y la sepsis. Un paciente desarrolló una leucemia mieloide aguda. La sobrevida global a los 5 años fue del 73 por ciento. Conclusiones: el Thymogam® es una opción terapéutica viable en el tratamiento inmunosupresor de pacientes con aplasia medular idiopática severa y muy severa(AU)

Introduction: immunosuppressive treatment with antithymocyte or antilymphocyte globulin and cyclosporin A is considered the standard treatment for patients with very severe or severe idiopathic aplastic anemia who do not have the possibility of progenitor hematopoietic transplantation. Objective: to evaluate the responses to immunosuppressive treatment using Thymogam® in adult patients with idiopathic aplastic anemia. Methods: A descriptive study was performed in 26 patients older than 18 years with diagnosis of idiopathic aplastic anemia, attended at the Institute of Hematology and Immunology from January 2000 to April 2012, who received antithymocyte globulin (Thymogam®) as part of immunosuppressive treatment. Results: patients were classified as very severe (14) and severe ( 12). The median age was 36 years old (range 18 - 74 years). In the first six months after the start of treatment, 73 percent of patients obtained some kind of response and 15 of them (57,6 percent) had a complete response, which was more frequent in the group of patients with less of 25 years of age. The percentage of relapse was 26,3 percent. The more frequent adverse reactions were fever, arterial hypertension, tremors and sweatiness. The main adverse reactions were severe bleeding and infections. One patient developed acute myeloid leukemia. Overall survival at 5 years was 73 percent. Conclusion: thymogam® is one therapeutic option in the immunosuppressive treatment in patients with very severe or severe idiopathic aplastic anemia(AU)

Recent advances in treatment of aplastic anemia

Recent advances in the treatment of aplastic anemia (AA) made most of patients to expect to achieve a long-term survival. Allogeneic stem cell transplantation (SCT) from HLA-matched sibling donor (MSD-SCT) is a preferred first-line treatment option for younger patients with severe or very severe AA, whereas immunosuppressive treatment (IST) is an alternative option for others. Horse anti-thymocyte globuline (ATG) with cyclosporin A (CsA) had been a standard IST regimen with acceptable response rate. Recently, horse ATG had been not available and replaced with rabbit ATG in most countries. Subsequently, recent comparative studies showed that the outcomes of patients who received rabbit ATG/CsA were similar or inferior compared to those who received horse ATG/CsA. Therefore, further studies to improve the outcomes of IST, including additional eltrombopag, are necessary. On the other hand, the upper age limit of patients who are able to receive MSD-SCT as first-line treatment is a current issue because of favorable outcomes of MSD-SCT of older patients using fludarabine-based conditioning. In addition, further studies to improve the outcomes of patients who receive allogeneic SCT from alternative donors are needed. In this review, current issues and the newly emerging trends that may improve their outcomes in near futures will be discussed focusing the management of patients with AA.

S-Fas Urinary Excretion Helps to Predict the Immunosuppressive Treatment Outcomes in Patients with Proliferative Primary Glomerulonephritis

Deregulation of soluble apoptosis stimulating fragment (sFas) plays an important role in glomerulonephritis (GN). The study assed the influence of immunosuppressive treatment on serum and urine sFas in patients with proliferative (PGN) and non-proliferative (NPGN) GN, and evaluated the potential of sFas measurements in predicting outcomes. Eighty-four patients with GN (45 males and 39 females) were included. Serum concentration (ng/mL) and urinary excretion (ng/mg of urinary creatinine) of sFas were measured before and after the treatment. After 12 months of therapy with steroids and cyclophosphamide, patients were divided into two subgroups according to the treatment results: Responders (R) and Non-Responders (NR). The sFas urinary excretion was reduced after treatment in both PGN and NPGN (from 17.12 +/- 15 to 5.3 +/- 4.2, P = 0.008 and from 10.11 +/- 6.1 to 3.4 +/- 3.0, P = 0.039; respectively) whereas the sFas serum concentration remained unchanged. In PGN, pre-treatment urinary sFas concentration was significantly lower in the Responders than in Non-Responders (2.3 +/- 3.1 vs 19.4 +/- 14.1, P = 0.003), and was lower still than in both R (P = 0.044) and NR (P = 0.042) subgroups with NPGN. The immunosuppressive treatment reduced sFas urinary excretion in proliferative and non-proliferative GN and results suggest that the lower urinary sFas may be linked with favorable therapy outcomes in patients with PGN.

Predictive Value of Conjointly Examined IL-1ra, TNF-R I, TNF-R II, and RANTES in Patients with Primary Glomerulonephritis

Interleukin-1 receptor antagonist (IL-1ra), tumor necrosis factor soluble receptors (sTNF-R) type I and II, and regulated upon activation, normal T-cell expressed and secreted (RANTES) play an important role in the modulation of primary glomerulonephritis (GN) course. The aim of the study was to assess whether pre-treatment measurements of IL-1ra, sTNF-R, and RANTES assessed conjointly may be useful as predicting factors in patients with GN. In 84 patients (45 males and 39 female) serum concentration (pg/mL) and urinary excretion (pg/mgCr) of cytokines were measured. After 12 months of therapy with steroids and cyclophosphamide the patients were divided into two subgroups: Responders (R) and Non-Responders (NR) according to the treatment results. The urinary IL-1ra, TNF-RI and RII were significantly higher in R than NR (1,732 vs 646 with P < 0.001, 13.1 vs 6.3 with P = 0.005, and 33.6 vs 14.4 with P = 0.012). The urinary RANTES excretion was increased in NR (79.6 vs 28.5; P < 0.001). The multivariable analysis showed that if conjointly assessed, only urinary IL-1ra, TNF-R I and R II, RANTES with 85% probability pointed the feature remission (R). In conclusion, the urinary excretion of IL-1ra, TNF-R I and R II, and RANTES examined conjointly are effective in predicting favorable response to immunosuppressive treatment in patients with GN.

The efficacy of medium-and long-term immunosuppressive therapy in Crohn's disease / 中华消化杂志

ObjectiveTo investigate the clinical features and the efficacy of medium-and long-term immune suppression in the treatment of Crohn's disease (CD) in Chinese Han nationality.MethodsThe clinical data and diagnosis methods of 178 CD patients between 2003 and 2010 were analyzed.All patients received predinisone and immune suppression (azathioprine) treatment.The patients were followed up every 2 weeks.Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were reviewed every 4 weeks.CD activity index (CDAI) was scored every 3 to 6 months.ResultsThe peak age for onset of CD was between 18 to 30 years old,and the mean time from the appearance of symptoms to diagnosis was (8.3±3.7) months.About 34.8％ (62/178 cases) patients had corresponding complications at time of diagnosis due to the progress of the disease.The average dosage of azathioprine was (1.24±0.16) mg/kg,and the total withdrawal rate due to adverse effect was 15％ (25/167 cases).The surgical intervention rate was 15.1％ (22/146 cases) during long-term follow-up.ESR and CRP of patients decreased obviously and tended to normal after 3 months treatment.The CDAI score significantly decreased after 6 months treatment.Conclusions Most Chinese patients had a good tolerance of immune suppression and achieved better medium- and long-term clinical efficacy at the dosage lower than that recommended by European and United States guidelines.

A Case of Autoimmune Hemolytic Anemia Complicating Hematopoietic Cell Transplantation / 대한진단검사의학회지

A 32-yr-old male diagnosed with myelodysplastic syndrome underwent an unmanipulated, unrelated, HLA matched, peripheral blood stem cell transplantation. The patient and donor were both blood type O, CcDEe. Twelve weeks post-transplantation, he developed acute autoimmune hemolytic anemia (AIHA). He was transfused multiple times with washed O red cells. High-dose steroid therapy was initiated and he underwent splenectomy; however, AIHA was refractory to therapy. The patient was further treated with combined treatment modalities including immunosuppressive therapy with mycophenolate mofetil and cyclosporine and three cycles of plasma exchange, and AIHA responded to treatment. This is the third case of AIHA complicating hematopoietic stem cell transplantation reported in Korea. Since AIHA is relatively common after hematopoietic stem cell transplantation, accurate and timely diagnosis of the disease and treatment strategies with multiple modalities are necessary.

Antithymocyte Globulin Combining Cyclosporin in Treatment of Pediatric Severe Aplastic Anemia / 实用儿科临床杂志

Objective To analyze the effectiveness of antithymocyte globulin(ATG) combined with cyclosporin(CSA)in treatment of pediatric severe aplastic anemia(SAA).Methods Seven children with SAA were treated with ATG and CSA,ATG 4-5 mg/(kg?d),5 days,methyprednisone 2-3 mg/(kg?d) to reduce anaphylaxis,CSA 3-5 mg/(kg?d),assisting with transfusion and G-CSF.Results The complete remission rate was 28.57%(2/7),the partial remission rate was 14.29%(1/7),and the obvious improvement rate was 28.57%(2/7),1 child died.The overall response rate was 71.43%.Transfusion volumes in 4 to 6 months post treatment decreased obviously comparing to the first 3 months(P

A Clinical Study on Hemophagocytic Lymphohistiocytosis / 대한소아혈액종양학회지

BACKGROUND: Hemophagocytic lymphohistiocytosis(HLH) is a rare and fatal disorder in children. Recently its clinical characteristics and etiology of uncontrolled activation of cellular immune system in genetically predirected patients have keen elucidated. The authors analyzed the clinical characteristics and response to immunosuppressive agents of HLH patients in single institute. METHODS: The authors retrospectively analyzed various clinical data including CSF and bone marrow examination at diagnosis and follow up period in the 6 patients who were diagnosed as HLH at Asan Medical Center during last 2 years. Antithymocyte globulin(ATG : 10 mg/kg/day) and methylprednisolone(methyl-PD: 5 mg/kg/day) for 5 consecutive days as induction treatment and cyclosporin A(CsA) as maintenance treatment after induction with weekly intrathecal methotrexate for 5-6 weeks were given to the recently diagnosed 3 patients. RESULTS: All the patients except one were infants. Persistent fever, hepatosplenomegaly and pancytopenia were observed in all the patients. Family history of suspicious HLH was observed in 4 patients(67%). The characteristic elevated serum triglyceride(TG) level and/or decreased fibrinogen level were noted in all. Mild to moderate CSF pleocytosls with increased lymphocytes and monocytes was also observed in all during the disease course. Variable degree of nonqr-Langerhans cell histiocytic infiltration and hemophagocytosis were observed in all the cases. Of the 3 patients treated with ATG and methyl-PD, one achieved complete remission and the others achieved partial remission within 2 weeks of treatment, but all expired after 5 months, remission with CsA. Regardless of treatment regimen, all the 6 patients expired due to CNS sequelae of HLH. CONCLUSIONS: HLH mainly developed in infants. Persistant fever, hepatosplenomegaly and pancytopenia were observed in most cases with the characteristic change of serum TG and/or fibrinogen level. HLH should be included in the differential diagnosis in patients with these features especially when the family history of suspicious HLH is present, and histologic comfirmation of HLH could be easily accomplished with bone marrow study in most cases. Remission induction of HLH could be achieved with immunosuppressive treatment but it was difficult to maintain long term remission.