Sjögren's syndrome combined with cold agglutinin disease: A case report / 北京大学学报(医学版)

Sjögren's syndrome(SS)is a chronic autoimmune disease that affects exocrine glands, especially salivary and lacrimal glands. The main clinical manifestations are dry mouth and dry eyes, but also multi-organ and multi-system can be involved. Cold agglutinin disease(CAD)is an autoimmune disease characterized by red blood cell agglutination in the blood vessels of extremities caused by cold agglutinin at low temperature, resulting in skin microcirculation disturbance, or hemolytic anemia. Cold agglutinin disease is divided into two categories, primary cold agglutinin disease and secondary cold agglutinin disease. Primary cold agglutinin disease is characterized with cold agglutinin titer of 1 ∶4 000 or more and positive Coomb's test. However, the Coomb's test is not necessarily positive and the cold agglutinin titer is between 1 ∶32 and 1 ∶4 000 in secondary cold agglutinin disease. Here, we reported an elderly patient admitted to hospital due to fever. He was diagnosed with respiratory infection, but he showed incompletely response to the anti-infection treatment. Further laboratory tests showed the patient with positive ANA and anti-SSA antibodies. Additionally, the patient complained that he had dry mouth and dry eyes for 1 year. Schirmer test and salivate gland imaging finally confirmed the diagnosis Sjogren's syndrome. During the hospital stay, the blood clots were found in the anticoagulant tubes. Hemolytic anemia was considered as the patient had anemia with elevated reticulocytes and indirect bilirubin. In addition, further examination showed positive cold agglutination test with a titer of 1 ∶1 024, and cold agglutinin disease was an important type of cold-resistant autoimmune hemolytic anemia. Furthermore, the patient developed cyanosis after ice incubating at the tip of the nose. Hence, the patient was diagnosed as CAD and he was successfully treated with glucocorticoids instead of anti-infection treatments. Hence, the patient was diagnosed with SS combined with secondary CAD. SS combined CAD are rarely reported, and they are both autoimmune diseases. The abnormal function of B lymphocytes and the production of autoantibodies might be the common pathogenesis of them. Cold agglutinin disease can lead to severe hemolytic anemia, even life-threatening. In clinical practice, timely recognizing and dealing with CAD might promote the prognosis of the patient.

Cold autoimmune hemolytic anemia with myelodysplastic syndrome: Not just an “Open and Shut case”

Myelodysplastic syndromes (MDSs) are clonal hematopoietic stem cell neoplasms characterized by bone marrow failure leading to ineffective hematopoiesis, dyspoiesis, and cytopenias with a risk of progression to acute leukemia. Immunological syndromes have been reported to occur along with MDS in literature. However, cold autoimmune hemolytic anemia (AIHA) has rarely been reported in association with MDS. Herein, we report a case of an elderly male who presented with fever and cytopenias. He was being treated as a case of megaloblastic anemia in the past with no response to therapy. At present admission, the peripheral blood smear examination revealed red cell agglutination, thrombocytopenia with 4% blasts. Cold agglutinin disease was confirmed by a thermal agglutination test and bone marrow evaluation showed adequate megakaryocytes with 10% blasts; consistent with the diagnosis of MDS with excess blasts (MDS-EB2). Cytogenetic studies revealed multiple abnormalities. This report is being discussed in view of its rarity of presentation of cold AIHA with MDS.

Diagnosis and treatment of 50 children with mycoplasma pneumoniae pneumonia with pseudo-macrocytic erythrocytes / 中国小儿急救医学

Objective:To investigate the clinical characteristics, diagnosis and treatment of mycoplasma pneumoniae(MP) pneumonia in children with pseudo-macrocytic erythrocytes.Methods:The clinical data of 50 children with mycoplasma pneumoniae pneumonia with pseudo-macrocytic erythrocytes in the Department of Pediatrics at Shengjing Hospital of China Medical University from January 2019 to August 2020 were analyzed retrospectively.Results:Among the 50 cases, there were 32 boys and 18 girls.The blood routine examination showed that pseudo-macrocytic erythrocytes, red blood cells decreased significantly, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration increased significantly, as well as MP-IgM was positive.Sixteen cases were complicated with herpes simplex virus infection, one with Epstein Barr virus infection, and six with both herpes simplex virus and Epstein Barr virus infection at the same time.All 50 cases were MP pneumonia, pulmonary imaging showed lobar pneumonia, and 25 cases were complicated with pleural effusion, including 32 cases of refractory MP pneumonia.The clinical symptoms of three cases were extrapulmonary manifestations, hemolytic anemia and diagnosed with cold agglutinin syndrome.In 36 children with D-dimer more than 252 μg/L, one case had femoral vein thrombosis and one case had pulmonary embolism.Conclusion:Pseudo-macrocytic phenomenon may play important roles in clinical etiological diagnosis, severity of disease and refractory MP pneumonia.The children with hemolytic anemia suggest cold agglutinin syndrome, and the hypercoagulable state of MP infection may be related to the aggregation of red blood cells caused by cold agglutinin in MP infection.

Enfermedad por aglutininas frías: proceso diagnóstico, tratamiento y seguimiento de un paciente / Cold agglutinin disease: diagnosis, treatment and follow-up of a patient

La enfermedad por crioaglutininas es una anemia hemolítica autoinmune que se caracteriza, en la gran mayoría de los casos, por la hemólisis mediada por autoanticuerpos de tipo IgM y complemento C3d, contra los antígenos de la membrana del eritrocito, que conduce a hemólisis extravascular con propensión a la trombosis, y que afecta principalmente al sexo femenino y personas mayores. Su diagnóstico se realiza con la prueba de Coombs directo y fraccionado, y la titulación de aglutininas frías >1:64 a 4 °C. Se describe el caso clínico de una mujer de 89 años con un síndrome constitucional y una anemia de 3 años de evolución, en quien se determinó el diagnóstico de enfermedad por aglutininas frías. Asimismo, se describe el abordaje diagnóstico, el tratamiento instaurado, y se hace una breve revisión de la literatura publicada

Cold agglutinin disease (CAD) is an autoimmune hemolytic anemia characterized in the vast majority of cases by hemolysis mediated by IgM autoantibodies and complement C3d against erythrocyte membrane antigens, leading to extravascular hemolysis with propensity to thrombosis, affecting mainly females and older individuals. It is diagnosed by direct and fractionated Coombs test and a cold agglutinin titer >1:64 at 4 °C. We describe the case of an 89-year-old woman with a constitutional syndrome and a 3-year history of anemia, who was diagnosed with cold agglutinin disease. Also, we include the diagnostic and treatment approach, and a brief review of the literature

Cold agglutinin disease related mismatch between hematocrit and hemoglobin values

Autoimmune hemolytic anemia is a disease characterized by destruction of red blood cells (RBC) and anemia, caused by production of antibodies released against the body’s own RBCs. While this condition is more commonly idiopathic, it may accompany autoimmune diseases as well. Cold agglutinin disease (CAD) is a rare subtype of acquired autoimmune hemoliytic anemia, however, is an idiosyncratic clinical and pathological terminology, usually seen in older ages. This condition is caused by IgM antibodies called “cold agglutinins” formed against I antigens on RBC membranes which cause agglutination of RBCs at lower temperatures. In this case, a 56 year old male patient who was diagnosed with CAD secondary to Epstein-Barr virus (EBV) infection is being presented.

Systematic analysis of cases of lymphoma with autoimmune hemocytopenia reported in the Chinese literature in the past 30 years / 中国肿瘤临床

The authors analyzed 140 cases of malignant lymphoma (ML) associated with autoimmune cytopenia (AIC), including autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), pure red cell aplasia (PRCA), and Evans syndrome. The analysis was based on cases reported in the literature as well as the reference lists of papers in this field from 1989 to 2019 by Chinese scholars. The number of cases involving various non-Hodgkin's lymphoma subtypes was small (n=1-28). Nevertheless, interesting and sometimes unexpected differences were noted among different types of ML and AIC. All types of AIC except AIN were seen to coexist with ML, and the increasing order of incidence was as follows: warm antibody-AIHA >ITP >cold antibody-AIHA>PRCA>Evans syndrome. CAS was only seen with B-cell lymphomas, WA-AIHA, and ITP, Evans syndrome was more frequent in B-cell lymphomas and PRCA predominantly occurred with T-cell lymphomas. Anti-lymphoma treatment seemed to be more effective against AIC than conventional therapy with steroids or immunoglobulin. Although based on a literature survey, this compilation of data indicates a complex relation between lymphoma and AIC and warrants more attention and specific studies.

Primera serie de casos reportada en Colombia de la enfermedad por aglutininas frías primaria y secundaria. Experiencia de un centro de referencia en Medellín entre 2010 y 2017 / First case series reported in Colombia of primary and secondary cold agglutinin disease. Experience of a reference center in Medellín between 2010 and 2017

RESUMEN Introducción: la enfermedad por aglutininas frías (EAF) es un trastorno hematológico primario o secundario, caracterizado por la anemia hemolítica autoinmune causada por los anticuerpos IgM a bajas temperaturas. Clínicamente, presenta parestesias y acrocianosis inducidos por frío y fiebre, aunque también puede ser asintomática y solo identificarse por alteraciones en el hemograma. Objetivo: describir las manifestaciones clínicas y de laboratorio, las causas primarias y secundarias de la EAF y compararlas con series de casos descritos en la literatura. Materiales y métodos: análisis retrospectivo de datos clínicos de pacientes del Hospital Universitario San Vicente Fundación de Medellín con resultados positivos para aglutininas frías. Dichos análisis se realizaron en el laboratorio de hematología de la Universidad de Antioquia, consideramos como positivo título ≥ 1: 64 o con la prueba de Coombs directa y positiva para anticuerpos fríos. Resultados: se incluyen los títulos de crioaglutininas de 23 casos con EAF: 6 formas primarias, 4 asociadas con los linfomas no Hodgkin (LNH), 8 secundarias a enfermedades infecciosas y autoinmunes y, 5 asociados con enfermedades misceláneas. Discusión y conclusiones: esta es la primera serie de casos en Colombia de EAF. La edad y género fueron similares a los datos reportados en la literatura. Observamos un mayor número de pacientes que presentaban anemia hemolítica y con síntomas asociados al frío. La relación hemoglobina hematocrito fue 1:2. Dentro de las causas secundarias destacamos las vasculitis, el lupus y la malaria. De las causas primarias las más frecuentes fueron los LNH, específicamente, el linfoplasmocítico. El tratamiento más utilizado para pacientes con EAF primaria incluyo rituximab.

SUMMARY Introduction: Cold agglutinin disease (CAD) is a primary hematologic disorder or can be secondary to another disease. CAD is characterized by autoimmune hemolytic anemia associated with IgM type antibodies, at low temperatures. Clinically CAD is associated with cryoparesthesia and acrocyanosis induced by cold and fever, or it can be asymptomatic and can be detected by abnormalities on cell blood counts. Objective: To describe the clinical and laboratory data and the etiology of CAD. Comparison between this case series and those described in the literature. Materials and Methods: Retrospectively, we analyzed clinical data of patients from Hospital Universitario San Vicente Fundación with positive results for cold agglutinin assays made in the hematology lab from Universidad de Antioquia. We consider patients with titers ≥ 1:64 or Coombs test positive for cold antibodies. Results: We describe clinical and laboratory findings included crioagglutinin titers of 23 cases with CAD: 6 of them with primary CAD, 4 with non-Hodgkin Lymphoma (NHL), 8 patients with CAD associated with infectious and autoimmune disease and 5 with CAD miscellaneous diseases. Discussion and Conclusions: This is the first CAD case series described in Colombia. Age and gender were like others case series. Most of patients presented with hemolityc anemia and cold related symptoms. The hemoglobin/ hematocrit ratio was 1:2. Secondary causes were vasculitis, lupus and malaria. Primary CAD were related to NHL, specifically limphoplasmocytic Most of the treatments of primary CAD included rituximab.

Childhood pneumonia: read the smear and clinch the diagnosis

Childhood pneumonia has a myriad of disease causing organisms. Identifying the etiology often helps us predict the natural course of the illness. We would like to share an interesting child with pneumonia by the hematological manifestation of the disease. Case report of this study is a 8 year old boy who presented with high grade fever for eleven days associated with cough. History of skin rashes which worsened following therapy with penicillin. On Examination child had maculopapular rashes predominantly over the trunk with decreased air entry in the left hemithorax. Chest x-ray done showed left lower lobe consolidation hence treated with cephalosporins and macrolide. Counts revealed falling trend in haemoglobin with high MCV count. Peripheral smear done showed agglutinated RBC'S and occasional nucleated RBC's. Direct Coombs test was positive. With these haematological manifestations child was diagnosed to have Mycoplasma pneumonia which was proven by positive antibodies against Mycoplasma. Child recovered completely and haematological manifestations became passive after four weeks. Cold agglutinin disease is poorly understood affecting 15% of patients with Autoimmune hemolytic anemia. Respiratory tract involvement and extrapulmonary complications manifest in 3-10% and 25% respectively. Antibodies (IgM) against the I antigen on human erythrocyte membranes appear during the course of M. pneumoniae infection and produce a cold agglutinin response. AIHA typically occurs during 2-3rd week after febrile illness with sudden onset of hemolysis which is self-remitting within 4-6 weeks. The conclusion of this study is extra-pulmonary manifestations in a child with pneumonia help in diagnosing the etiology. This in turn helps us like provide rationale management and Predict the natural course of the illness.

Interference of cold agglutinin autoantibodies in erythrogram interpretation: a case report and literature review / Interferências das crioaglutininas na interpretação do eritrograma: relato de caso com revisão da literatura

ABSTRACT The erythrogram is one of the components of the blood count that includes red blood cell (RBC) quantification and evaluation. A correct interpretation and validation of the results obtained in an erythrogram require experience and critical awareness of health professionals. It is imperative to evaluate the interference of physiological variables, collection procedures, manipulation of samples and endogenous variables (such as the presence of cold agglutinin autoantibodies), since these may falsify the results obtained. Cold agglutinin autoantibodies are predominantly immunoglobulin type M (IgM), which cause agglutination of RBC at temperatures below 37°C, and may appear in cases of autoimmune hemolytic anemia and atypical pneumonia, among other pathologies. The presence of erythrocyte agglutination interferes with RBC and reticulocyte counts, determination of the globular volume and the blood count indices. A set of laboratorial procedures may be performed in order to eliminate the interference of these agglutinins in the results of the erythrogram. If these procedures do not correct the values obtained, the only result of the erythrogram that can be validated is hemoglobin, since the remaining results are falsified due to the presence of cold agglutinin autoantibodies.

RESUMO O eritrograma é um dos componentes do hemograma que inclui a quantificação e a avaliação eritrocitária. Uma correta interpretação e validação dos resultados obtidos em um eritrograma requer experiência e sentido crítico dos profissionais de saúde. Torna-se imperativo avaliar a interferência de variáveis fisiológicas e de colheita, a manipulação das amostras e as variáveis endógenas (como a presença de crioaglutininas), uma vez que estas podem falsear os resultados obtidos. As crioaglutininas são autoanticorpos predominantemente do tipo imunoglobulina da classe M (IgM), as quais provocam aglutinação dos eritrócitos a temperaturas inferiores a 37°C, podendo aparecer em casos de anemia hemolítica autoimune e pneumonias atípicas, entre outras patologias. A presença de aglutinação eritrocitária interfere na contagem de eritrócitos, reticulócitos, determinação do volume globular e dos índices hematimétricos. Laboratorialmente, existe um conjunto de procedimentos que podem ser executados de modo a eliminar a interferência dessas aglutininas nos resultados do eritrograma. Caso esses procedimentos não corrijam os valores obtidos, o único resultado do eritrograma que poderá ser validado é o da hemoglobina, visto que os resultados restantes estão falseados devido à presença de crioaglutininas.

Clinical features and prognosis of 17 patients with primary cold agglutinin disease / 中华血液学杂志

Objective@#To explore the clinical characteristics, treatment and prognosis in 17 patients with primary cold agglutinin disease (CAD) .@*Methods@#Clinical data, treatment and survival status of 17 patients diagnosed with primary cold agglutinin disease in Peking Union Medical College Hospital during April 2007 to October 2016 were retrospectively analyzed. The MYD88L265P mutation was tested in 4 patients.@*Results@#The median age of 17 patients was 67 years (range, 51-86 years) , and male- to female ratio was 1.1∶1. Seven patients were diagnosed with indolent lymphoma, including 3 Waldenstrom macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL) , 2 small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL) , and 2 splenic marginal zone lymphoma (SMZL) . 15 patients experienced anemia. The median HGB level was 67 (35-127) g/L. 11 patients had cold agglutinin (CA) titers ≥1∶64, with median CA of 1∶1 024. MYD88L265P mutation was detected in 1 patient. 12 patients received drug therapy: 7 were treated with glucocorticoid-based therapy and 1 patient responded to treatment; 5 received rituximab-based therapy and 3 patients responded to treatment. With a median follow-up of 14 (0.5-96) months, the median overall survival was not reached.@*Conclusion@#Clinical manifestations of CAD are various, and diagnosis is dependent on CA testing. The efficacy of glucocorticoid-based therapy is limited, and rituximab is recommended for CAD treatment.

Clinical characteristics and treatment outcomes of primary autoimmune hemolytic anemia: a single center study from South India

BACKGROUND: Autoimmune hemolytic anemia (AIHA) is a less recognized, potentially fatal condition. There is a scarcity of data on clinicoserological characteristics and response to therapy concerning this disease from South India. METHODS: Data for 33 patients with primary AIHA recorded from July 2009 to June 2015 were retrospectively analyzed for clinical presentation, response to frontline therapy, durability of response, time to next treatment (TTNT), and response to second-line agents. RESULTS: The median follow-up period was 50 months. Among 33 patients, 48% of the cases were warm autoimmune hemolytic anemia (WAIHA), 46% were cold agglutinin disease (CAD), and 6% were atypical. Three-fourth of patients had severe anemia (<8 g/dL hemoglobin [Hb]) at onset; younger patients (age <40 yr) had more severe anemia. All of the patients who required treatment received oral prednisolone at 1.5 mg/kg/d as a frontline therapy, and the response rate was 90% (62% complete response [CR] and 28% partial response [PR]). The overall response to corticosteroids in WAIHA and CAD was 87% and 92%, respectively. The median corticosteroid duration was 14 months, and 50% of the patients required second-line agents. Fourteen patients received azathioprine as a second-line agent, and 11 of these patients responded well, with half of them not requiring a third agent. Four patients developed severe infections (pneumonia, sepsis, and soft tissue abscess) and two had life-threatening venous thrombosis. One case of death was recorded. CONCLUSION: AIHA is a heterogeneous disease that requires care by physicians experienced in treating these patients.

Crioglobulina con propiedad crioaglutinina en un paciente con linfoma esplénico de zona marginal / Cryoglobulin with cold agglutinin properties in a patient with splenic marginal zone lymphoma / Crioglobulina com propriedade crioaglutinina em um paciente com linfoma esplênico de zona marginal

El objetivo del trabajo fue describir un caso de linfoma esplénico de zona marginal (LEZM) con un componente monoclonal que posee propiedades de crioglobulina y crioaglutinina, un hallazgo de muy baja frecuencia. Una paciente con LEZM padeció una anemia hemolítica autoinmune 5 años después del diagnóstico, con hematocrito de 0,15 L/L, hemoglobina 49 g/L, lactato deshidrogenasa 16,82 μkat/L, prueba de Coombs directa positiva con anti- IgG/C3d, bilirrubina total 90,6 μmol/L e indirecta de 58,1 μmol/L. No presentó evidencia clínica ni serológica de infección por VIH, hepatitis B ni C. El proteinograma sérico presentó un pico monoclonal de 14 g/L, con crioglobulinemia positiva a las 24 h, y un criocrito de 30%. La crioglobulina purificada fue de tipo I con un componente monoclonal IgM-lambda, coincidente al observado en suero. El suero, el eluato a 37 °C y la crioglobulina purificada de la paciente presentaron actividad de crioaglutinina con especificidad anti-I, fenómeno producido por la misma inmunoglobulina. El hallazgo de una crioglobulina con propiedades de crioaglutinina en pacientes con LEZM no ha sido descrito previamente en la bibliografía.

The aim of this paper is to describe a case of splenic marginal zone lymphoma (SMZL) with monoclonal component having properties of cryoglobulin and cold agglutinin, a finding of very low frequency. A patient with SMZL suffered autoimmune hemolytic anemia five years after diagnosis, with hematocrit 0.15 L/L, hemoglobin 49 g/L, lactate dehydrogenase 16.82 μkat/L, direct Coombs test with anti-IgG/C3d positive, total bilirubin 90.6 μmol/L and indirect 58.1 μmol/L. She presented no clinical or serological evidence of HIV, hepatitis B or C infection. Serum protein electrophoresis showed a monoclonal peak of 14 g/L, with positive cryoglobulinemia at 24 hours, and 30% cryocrit. Purified cryoglobulin was type I with a monoclonal IgM-lambda component coincident with that observed in serum. The patient serum, eluate at 37 °C and purified cryoglobulin showed cold agglutinin activity with anti-I specificity, phenomenon produced by the same immunoglobulin. The finding of a cryoglobulin with cold agglutinin properties in patients with SMZL has not been previously described in the literature.

O objetivo do trabalho foi descrever um caso de linfoma esplênico de zona marginal (LEZM) com um componente monoclonal com propriedades do crioglobulina e crioaglutinina, um achado de muito baixa frequência. Um doente com LEZM sofreu uma anemia hemolítica autoimune cinco anos após o diagnóstico, com hematócrito de 0,15 L/L, hemoglobina 49 g/L, lactato desidrogenase de 16,82 μkat/L, teste de Coombs direto positivo com anti-IgG/C3d, bilirrubina total 90,6 μmol/L e indireta 58,1 μmol/L. Não apresentou evidência clínica ou sorológica de infecção por HIV, hepatite B ou C. O proteinograma sérico mostrou um pico monoclonal de 14 g/L, com crioglobulinemia positiva 24 horas, e um criocrito de 30%. Crioglobulina purificada foi tipo I com o componente monoclonal IgM-lambda, coincidente com a observada no soro. O soro, o eluato a 37 ° C e a crioglobulina purificada do paciente mostraram atividade de crioaglutinina com especificidade anti-I, fenômeno produzido pela mesma imunoglobulina. O achado de uma crioglobulina com propriedades de crioaglutinina em pacientes com LEZM não foi previamente descrito na literatura.

Therapeutic Plasma Exchange for a Patient with Severe Cold Agglutinin Disease / 대한수혈학회지

Cold agglutinin disease is a kind of autoimmune hemolytic anemia, caused by cold agglutinin, serum autoantibodies activated at reduced body temperatures to produce red blood cell agglutination and hemolysis. In this paper we described a case of severe hemolytic anemia in a cold agglutinin disease patient treated with therapeutic plasma exchange. Therapeutic plasma exchanges were performed four times every other day. Over the same period, a total of 8 units of washed red blood cells were transfused. Then hemoglobin was increased from 4.0 g/dL to 7.8 g/dL. On the 12th hospital day hemoglobin level was decreased again to 4.2 g/dL and fludarabine chemotherapy was started on the 14th hospital day. The patient's symptoms were relieved and she was discharged on the 30th hospital day. As in this case, therapeutic plasma exchange could be considered as secondary therapy for temporary improvement of acute severe hemolytic anemia in cold agglutinin disease.

A Case of Cold Agglutinin Disease Accompanied by Bacterial Pneumonia That Was Treated with Rituximab / 대한수혈학회지

Cold agglutinin disease (CAD) is a small group of disorders that is characterized by cold-reactive autoantibodies that bind to erythrocyte carbohydrate antigens, and this causes hemagglutination and complement-mediated hemolysis. Autoimmune hemolytic anemia (AIHA) is an immune disorder that is mediated via auto-antibodies produced by lymphoid B cells against red blood cells. The disorder may be a primary (idiopathic) or secondary disease with an underlying autoimmune disease, a lymphoproliferative disorder or infection. The mainstay of initial treatment is immunosuppression with glucocorticosteroids. For those who do not have satisfactory response to initial glucocorticosteroids or they have a relapse after initially successful treatment, splenectomy or other immunosuppressive agents such as azathioprine, cyclosporine and intravenous immunoglobulin (IVIG) could be the next available options. More recently, rituximab, which is a human-murine chimeric monoclonal antibody specific for the CD20 antigen found on the surface of B lymphocytes, is also available. We report here on the successful use of rituximab for the treatment of a Korean elderly patient with CAD and the patient presented with recurrent AIHA.

Comparison of Diagnostic Methods and the Changes of IgG Subclasses in Children with Mycoplasma pneumoniae pneumonia / 소아알레르기및호흡기학회지

PURPOSE: This study aimed to investigate the positive rate of 3 serologic methods and polymerase chain reaction (PCR) and the changes of IgG and IgG subclasses in children with Mycoplasma pneumoniae pneumonia (MP). METHODS: Fifty children with pneumonia admitted to Daejeon St. Mary's Hospital, Korea, during MP outbreaks were evaluated for the diagnostic antibody status using 3 serologic methods: indirect micro-particle agglutinin assay (MAA, Serodia-Myco II, Fujirebio, Tokyo, Japan), cold agglutinins and enzyme-linked immunoassay (EIA, Platelia M. pneumoniae IgM & IgG BIO-RAD, Marnes-la-Coquette, France) and PCR. The levels of antibody for MP in each method were measured 2 times during hospitalization: at presentation and at discharge (mean interval, 6.5 days). The levels of IgG and IgG subclasses (IgG1, IgG2, IgG3 and IgG4) were also analyzed 2 times (at presentation and at discharge) using stored sera. RESULTS: At presentation, the positive rates of the diagnostic methods were 52%, 38%, 30% and 12% for MAA, cold agglutinins, EIA and PCR assay, respectively. Following analysis of the repetitive measurement of the antibody, the positive rates of the diagnostic methods were 76%, 60% and 56% for MAA, cold agglutinins and EIA, respectively. The mean IgG level of MP patients increased during hospitalization (973+/-184 vs. 1,040+/-205 mg/dL; P=0.008). Among the IgG subclasses, the levels of IgG1 and IgG3 showed a significant increase during hospitalization (553+/-129 vs. 611+/-151 mg/dL, P=0.003 for IgG1; 43+/-27 vs. 47+/-30 mg/dL, P=0.005 for IgG3). CONCLUSION: For the accurate and relatively rapid diagnosis of MP, a paired sample examination is mandatory, especially within a short-time period. The sensitivity of serologic tests for the diagnosis of MP may differ among commercially available kits. IgG1 and IgG3 appear to be the main IgG subclasses that show an increase after MP infection.

Cold agglutinin disease (CAD)with autoimmune haemolytic anaemia: a case report of a coronary artery disease patient

Cold agglutinin disease (CAD) with autoimmune haemolytic anemia is characterized by the production of harmful cold autoantibodies associated with increased red cell destruction during exposure to cold. The treatment of CAD is very difficult and a great effort is required to obtain therapeutic success. Cyclophosphamide is a potent immunosuppressive agent which is widely used in all bone marrow transplantation conditioning regimens for patients with acquired severe aplastic anemia. In this report, we describe the case of a coronary artery disease patient with severe CAD, but without lymphoproliferative disease, in which general measures and immunosuppressive therapies were adopted, there by avoiding blood transfusions.

A doença por aglutininas a frio (CAD) cursando com anemia hemolítica auto-imune (AHAI) é decorrente da produção de autoanticorpos que reagem muito bem a baixas temperaturas, dirigidos contra hemácias autólogas. A habilidade desses anticorpos em destruir as hemácias encontra-se diretamente relacionada à sua capacidade em fixar complemento durante a exposição do paciente a baixas temperaturas. A AHAI por anticorpos frios pode ser idiopática - ausência de doença de base - ou secundária, geralmente associada a desordens linfoproliferativas de células B ou determinados processos infecciosos. A hemólise é intravascular, através de aglutininas da classe IgM, com teste direto da antiglobulina humana positivo para complemento. O tratamento da CAD é difícil, exigindo um esforço contínuo, necessário para se obter sucesso terapêutico. A ciclofosfamida é um agente imunossupressor potente, amplamente utilizado em transplantes de medula óssea, particularmente nos portadores de anemia aplástica. Descrevemos o caso de um coronariopata portador de CAD severa, cuja exploração diagnóstica excluiu doença linfoproliferativa. Adotamos medidas gerais de suporte e terapia imunossupressora, coibindo o uso de hemotransfusões.

A Case of Childhood Pernio Treated with Nifedipine / 대한피부과학회지

Pernio, or chilblains, are a localized inflammatory lesion of the skin resulting from an abnormal response to cold. The condition is characterized by cutaneous lesions located on the distal parts, such as the fingers, toes, nose and ears. Pernio develops among susceptible individuals who are exposed to non-freezing condition and most commonly occurs among young women and children. However, reports on childhood pernio are rarely found. Several conditions have been described as predisposing factors to pernio, including excessive cold exposure, low-grade vasculitis, the presence of cryoproteins, anorexia nervosa, systemic lupus erythematous and antiphospholipid antibodies. It is important, therefore, when evaluating a patient with chronic pernio who is resistant to conservative management, to exclude an underlying condition and also to determine whether additional testing is necessary. Herein, we present an uncommon case of a 5-year-old female patient with chronic pernio that may be associated with the presence of cold agglutinin. She received topical steroids prior to evaluation but no improvement was seen. Howere, treatment with calcium channel blocker, nifedipine, was of benefit to our patient.

A Case of Acute Respiratory Distress Syndrome by Nosocomial Mycoplasma Pneumonia Associated with Cold Agglutinin Disease in Primary CNS Lymphoma / 감염과화학요법

Although Mycoplasma pneumonia is frequently observed in immunocompromized patient if, rarely results in acute respiratory distress syndrome (ARDS). The cold agglutinin is positive in 33-76% of patients with M. pneumonia infection. We experienced a case of ARDS due to mycoplasma pneumonia associated with cold agglutinin disease in primary CNS lymphoma. He was a 60-year old primary CNS lymphoma patient with mycoplasma pneumonia and cold agglutinin disease who rapidly progressed to ARDS after 1 cycle of chemotherapy. He completely recovered with roxithromycin, levofloxacin, and ventilator supports. After recovery 2nd cycle of combination chemotherapy and brain radiation therapy was given and, CNS lymphoma is in complete remission until now.

A Case of Acute Respiratory Distress Syndrome by Nosocomial Mycoplasma Pneumonia Associated with Cold Agglutinin Disease in Primary CNS Lymphoma / 감염과화학요법

Although Mycoplasma pneumonia is frequently observed in immunocompromized patient if, rarely results in acute respiratory distress syndrome (ARDS). The cold agglutinin is positive in 33-76% of patients with M. pneumonia infection. We experienced a case of ARDS due to mycoplasma pneumonia associated with cold agglutinin disease in primary CNS lymphoma. He was a 60-year old primary CNS lymphoma patient with mycoplasma pneumonia and cold agglutinin disease who rapidly progressed to ARDS after 1 cycle of chemotherapy. He completely recovered with roxithromycin, levofloxacin, and ventilator supports. After recovery 2nd cycle of combination chemotherapy and brain radiation therapy was given and, CNS lymphoma is in complete remission until now.

Cold Agglutinin Disease due to Anti-Pr Cold Autoantibody in a Patient with Bone Marrow Transplantation / 대한수혈학회지

Cold agglutinin disease (CAD) is a most common autoimmune hemolytic anemia (AIHA) induced by cold antibody. CAD represents approximately 16-32% of AIHA cases and causative cold autoantibodies commonly show specificity against the I antigen. We report a case of cold agglutinin disease with anti-Pr cold autohemolysin. A 20 year old woman with a history of bone marrow transplantation was admitted with nausea, vomiting, and pallor. Direct antiglobulin tests were positive with IgG and C3d specific AHG reagents. Cold agglutinin titer was as high as 1:1024 at 4degrees C, 1:16 at room temperature, negative at 37degrees C. The agglutinin titer was diminished after treatment with protease, ficin and immunohematologic results of cold agglutinin was compatible with anti-Pr specificity. In unexpected antibody identification test, anti-M which showed reactivity at anti-human globulin phase was identified. Washed and prewarmed 16 units of A+, M antigen negative red blood cells were transfused. After two weeks, patient was improved with steroid therapy and experienced relief of fever and hemolysis, and she was discharged.