RESUMEN
Background: Cold agglutinin syndrome (CAS) is a hemolytic anemia mediated by antibodies, mainly IgM, whose maximum activity occurs at 4 °C. It happens secondary to infectious, autoimmune or neoplastic diseases, due to the formation of antibodies that cross-react against erythrocyte antigens, particularly of the I system. Here, we describe a case of CAS associated to Epstein-Barr virus (EBV) reactivation in a patient with primary human immunodeficiency virus (HIV) infection. Clinical case: 22-year old man with no medical history, hospitalized due to mononucleosis and anemic syndrome. Hemoglobin of 3.7 g/dL and elevation of lactate dehydrogenase were documented. In the peripheral blood smear it was observed spherocytosis, polychromasia and nucleated erythrocytes. EBV infection was confirmed with serology and viral load, as well as seronegative HIV infection with positive viral load. The C3d monospecific direct antiglobulin test was positive and an irregular antibody screening revealed the presence of an anti-I antibody. The patient received transfusion support and conservative treatment, with remission of the symptoms 2 weeks after admission. Conclusions: Cold agglutinin syndrome is a rare, potentially fatal complication of infectious mononucleosis, which should be considered in the face of findings suggestive of hemolysis in order to initiate support measures in a timely manner.
Introducción: el síndrome por aglutininas frías (SAF) es una anemia hemolítica mediada por anticuerpos principalmente de tipo IgM, cuya máxima actividad se da a 4 °C. Se presenta en el contexto de enfermedades infecciosas, autoinmunes o neoplásicas por la formación de anticuerpos que tienen reacción cruzada contra antígenos eritrocitarios, particularmente del sistema I. En este trabajo presentamos un caso de SAF asociado a reactivación del virus de Epstein-Barr (VEB) en un paciente con primoinfección por el virus de la inmunodeficiencia humana (VIH). Caso clínico: hombre de 22 años, sin antecedentes patológicos, hospitalizado por síndrome mononucleósico y anémico. Presentó hemoglobina de 3.7 g/dL y elevación de lactato deshidrogenasa. En el frotis de sangre periférica se observó esferocitosis, policromasia y eritrocitos nucleados. Se confirmó infección por VEB con serología y carga viral, así como infección por VIH seronegativa, con carga viral positiva. La prueba de antiglobulina directa monoespecífica a C3d fue positiva y el rastreo de anticuerpos irregulares demostró un anticuerpo anti-I. El paciente recibió soporte transfusional y tratamiento conservador, con remisión del cuadro a las 2 semanas de su ingreso. Conclusiones: el SAF es una complicación poco frecuente de la mononucleosis infecciosa, potencialmente mortal, la cual debe ser considerada ante hallazgos sugestivos de hemólisis con la finalidad de iniciar medidas de soporte de forma oportuna.
Asunto(s)
Anemia Hemolítica Autoinmune , Mononucleosis Infecciosa , Humanos , Masculino , Anemia Hemolítica Autoinmune/etiología , Anemia Hemolítica Autoinmune/diagnóstico , Anemia Hemolítica Autoinmune/terapia , Anemia Hemolítica Autoinmune/virología , Mononucleosis Infecciosa/complicaciones , Mononucleosis Infecciosa/diagnóstico , Adulto JovenRESUMEN
Autoimmune hemolytic anemia (AIHA) is characterized by the accelerated destruction of erythrocytes due to the presence of antibodies and/or complement that bind to antigens on erythrocytes. It can be subdivided into warm, cold or mixed AIHA based on the type of autoantibody and the optimal temperature of antigen-antibody reaction. Glucocorticoid with or without rituximab is the first-line treatment of warm AIHA (wAIHA), and splenectomy was once the preferred second-line treatment for relapsed or refractory wAIHA. However, due to the various complications of splenectomy, rituximab has gradually become the preferred treatment for patients who have failed glucocorticoid therapy. Other available treatments including immunosuppressants and plasma exchange can be chosen. Rituximab with or without bendamustine is generally taken as the first-line regimen for cold autoimmune hemolytic anemia (cAIHA), while glucocorticoid and splenectomy are ineffective. Sutimlimab, a kind of complement inhibitor, has been approved for the treatment of cold agglutinin disease (CAD). In recent years, many new drugs have emerged as treatment options for AIHA. Emerging therapies, including B-cell-directed therapies, plasma cell-directed therapies, complement inhibitors, and phagocytosis inhibition, provide a new perspective for AIHA therapy, showing great potential for clinical applications.
Asunto(s)
Anemia Hemolítica Autoinmune , Anemia Hemolítica Autoinmune/terapia , Humanos , Rituximab/uso terapéutico , Esplenectomía , Anticuerpos Monoclonales de Origen Murino/uso terapéuticoRESUMEN
A 19-year-old male patient with high-risk acute B-cell lymphoblastic leukemia received haploidentical stem cell transplantation. He developed anemia repeatedly and parvovirus B19 nucleic acid was positive in blood plasma. The patient was diagnosed with cold agglutinin syndrome and multiple organ dysfunction including respiratory failure and hepatitis. In the conflict between viral infection and the treatment of cold agglutinin syndrome, we provided supportive treatment, complement inhibitors to control hemolysis, and antiviral therapy. After timely glucocorticoid and immunosuppressant therapy, the patient had achieved a good response.
Asunto(s)
Insuficiencia Multiorgánica , Parvovirus B19 Humano , Humanos , Masculino , Adulto Joven , Insuficiencia Multiorgánica/etiología , Insuficiencia Multiorgánica/virología , Infecciones por Parvoviridae/complicaciones , Infecciones por Parvoviridae/diagnóstico , Anemia Hemolítica/etiología , Anemia Hemolítica/diagnóstico , Anemia Hemolítica Autoinmune/terapiaRESUMEN
Evans syndrome is a rare disease marked by a severe clinical course, high relapse rate, infectious and thrombotic complications, and sometimes fatal outcome. Management is highly heterogeneous. There are several case reports but few large retrospective studies and no prospective or randomised trials. Here, we report the results of the first consensus-based expert recommendations aimed at harmonising the diagnosis and management of Evans syndrome in adults. After reviewing the literature, we used a fuzzy Delphi consensus method, with two rounds of a 42-item questionnaire that were scored by a panel of 13 international experts from five countries using a 7-point Likert scale. Panellists were selected by the core panel on the basis of their personal experience and previous publications on Evans syndrome and immune cytopenias; they met virtually throughout 2023. The panellists recommended extensive clinical and laboratory diagnostic tests, including bone marrow evaluation and CT scan, and an aggressive front-line therapy with prednisone (with or without intravenous immunoglobulins), with different treatment durations and tapering for immune thrombocytopenia and autoimmune haemolytic anaemias (AIHAs). Rituximab was strongly recommended as first-line treatment in cold-type AIHA and as second-line treatment in warm-type AIHA and patients with immune thrombocytopenia and antiphospholipid antibodies, previous thrombotic events, or associated lymphoproliferative diseases. However, rituximab was discouraged for patients with immunodeficiency or severe infections, with the same applying to splenectomy. Thrombopoietin receptor agonists were recommended for chronic immune thrombocytopenia and in the case of previous grade 4 infection. Fostamatinib was recommended as third-line or further-line treatment and suggested as second-line therapy for patients with previous thrombotic events. Immunosuppressive agents have been moved to third-line or further-line treatment. The panellists recommended the use of recombinant erythropoietin in AIHA in the case of inadequate reticulocyte counts, use of the complement inhibitor sutimlimab for relapsed cold AIHA, and the combination of rituximab plus bendamustine in Evans syndrome secondary to lymphoproliferative disorders. Finally, recommendations were given for supportive therapy, platelet or red blood cell transfusions, and thrombotic and antibiotic prophylaxis. These consensus-based recommendations should facilitate best practice for diagnosis and management of Evans syndrome in clinical practice.
Asunto(s)
Anemia Hemolítica Autoinmune , Trombocitopenia , Humanos , Anemia Hemolítica Autoinmune/diagnóstico , Anemia Hemolítica Autoinmune/terapia , Trombocitopenia/diagnóstico , Trombocitopenia/terapia , Trombocitopenia/etiología , Adulto , Consenso , Manejo de la Enfermedad , Rituximab/uso terapéutico , Inmunoglobulinas Intravenosas/uso terapéuticoRESUMEN
We present a case of a man in his 40s with pulmonary-renal syndrome due to myeloperoxidase-positive antineutrophil cytoplasmic antibodies-associated vasculitis and concurrent cold agglutinin disease, a combination that has not yet been described in the literature. The fulminant course of the disease, including the need for kidney replacement therapy and mechanical ventilation posed a significant treatment challenge due to haemolytic complications.
Asunto(s)
Anemia Hemolítica Autoinmune , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Humanos , Masculino , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicaciones , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/diagnóstico , Anemia Hemolítica Autoinmune/complicaciones , Anemia Hemolítica Autoinmune/terapia , Anemia Hemolítica Autoinmune/diagnóstico , Adulto , Enfermedades Pulmonares/complicaciones , Glomerulonefritis/complicaciones , Glomerulonefritis/diagnóstico , HemorragiaRESUMEN
Cold agglutinin disease (CAD), an immune hemolytic disease mediated by the classical complement-dependent pathway, accounts for approximately 8% of autoimmune hemolytic anemia (AIHA) cases. Primary CAD is a clonal B-cell lymphoproliferative disease of the bone marrow that produces IgM type-M protein, while conventional secondary CAD is cold agglutinin syndrome (CAS). Clinical findings are broadly classified into chronic anemia due to hemolysis and symptoms associated with peripheral circulatory failure due to erythrocyte aggregation under cold exposure. Not all patients require drug therapy, but monoclonal antibody therapy against complement C1s is preferred for the former presentation and B-cell suppressors for the latter. As cold AIHA is treated differently than warm AIHA, misdiagnosis can significantly impact the outcome of treatment. The most important aspect of blood testing is temperature control of specimens. Cold agglutinin titer, IgM quantification, electrophoresis, and immunofixation methods may produce false-negative results if the serum is not temperature-controlled at 37-38°C until serum separation. Correct handling of specimens, along with knowledge of the various clinical features of CAD, will lead to correct diagnosis and appropriate treatment.
Asunto(s)
Anemia Hemolítica Autoinmune , Humanos , Anemia Hemolítica Autoinmune/diagnóstico , Anemia Hemolítica Autoinmune/terapiaRESUMEN
BACKGROUND AND OBJECTIVE: Autoimmune hemolytic anemia (AIHA) is a rare but important cause of morbidity in pediatric hematology patients. Given its rarity, there is little high-quality evidence on which to base the investigation and management of pediatric AIHA. This scoping review aims to summarize the current evidence and highlight key gaps to inform future studies. METHODS: This review searched MEDLINE and the Cochrane CENTRAL Trials Register from 2000 to November 03, 2023. Experimental and observational studies reporting AIHA diagnostic criteria, laboratory workup, or treatment/management in populations with at least 20% of patients ≤18 years were included. RESULTS: Forty-three studies were included, with no randomized controlled trials identified. AIHA diagnostic criteria, diagnostic tests, and treatments were highly variable. First-line treatment approaches include corticosteroids, intravenous immunoglobulin, or both. Approaches to AIHA resistance to first-line therapy were widely variable between studies, but most commonly included rituximab and/or cyclosporine. CONCLUSIONS: We identify a heterogenous group of observational studies into this complex, immune-mediated disorder. Standardized definitions and classifications are needed to guide collaborative efforts needed to study this rare disease. The work done by the CEREVANCE group provides an important paradigm for future studies.
Asunto(s)
Anemia Hemolítica Autoinmune , Manejo de la Enfermedad , Humanos , Anemia Hemolítica Autoinmune/diagnóstico , Anemia Hemolítica Autoinmune/terapia , Niño , Corticoesteroides/uso terapéutico , Inmunoglobulinas Intravenosas/uso terapéutico , Susceptibilidad a Enfermedades , Rituximab/uso terapéuticoRESUMEN
INTRODUCTION: During the last decades, the pathogenesis of cold agglutinin disease (CAD) has been well elucidated and shown to be complex. Several documented or investigational therapies have been made available. This development has resulted in major therapeutic advances, but also in challenges in choice of therapy. AREAS COVERED: In this review, we address each step in pathogenesis: bone marrow clonal lymphoproliferation, composition and effects of monoclonal cold agglutinin, non-complement mediated erythrocyte agglutination, complement-dependent hemolysis, and other effects of complement activation. We also discuss the heterogeneous clinical features and their relation to specific steps in pathogenesis, in particular with respect to the impact of complement involvement. CAD can be classified into three clinical phenotypes with consequences for established treatments as well as development of new therapies. Some promising future treatment approaches - beyond chemoimmunotherapy and complement inhibition - are reviewed. EXPERT OPINION: The patient's individual clinical profile regarding complement involvement and hemolytic versus non-hemolytic features is important for the choice of treatment. Further development of treatment approaches is encouraged, and some candidate drugs are promising irrespective of clinical phenotype. Patients with CAD requiring therapy should be considered for inclusion in clinical trials.
Asunto(s)
Anemia Hemolítica Autoinmune , Hemólisis , Humanos , Anemia Hemolítica Autoinmune/diagnóstico , Anemia Hemolítica Autoinmune/terapia , Anemia Hemolítica Autoinmune/etiología , Activación de Complemento , Proteínas del Sistema Complemento/metabolismo , Proteínas del Sistema Complemento/inmunología , CrioglobulinasRESUMEN
BACKGROUND: Autoimmune hemolytic anemia disease often produces a large number of various autoantibodies, and some autoantibodies may be related to Rh blood group. In rare cases, autoantibodies can specifically target Rh antigen, thus interfering with the identification of Rh blood group. METHODS: A case of systemic lupus erythematosus (SLE) with inconsistent RhD blood group identification results in different periods was reported and the reasons were analyzed. RESULTS: Some autoantibodies can completely block D antigen on red blood cells, resulting in no redundant D sites on red blood cells binding to reagent anti D. In addition, the immunity of the body is extremely low, and the expression of red blood cell blood group antigens in part of the body is inhibited, which will cause the weakening of the expression of Rh antigen in red blood cells. Therefore, when testing the RhD blood type of the patient, the reagent anti D does not agglutinate with the patient's red blood cells, and a false negative result of the initial screening appears. Through the RhD negative confirmation test, the patient's blood type is a serologically weak D phenotype. CONCLUSIONS: If the result of serological preliminary screening test is RhD negative or RhD variant, the recipient should be treated as RhD negative, and RhD negative red blood cells should be transfused during blood transfusion. Conditional laboratories can implement RHD genotyping, which is conducive to improving the precise blood transfusion management level of RhD negative blood recipients, saving rare blood resources and improving the treatment efficiency of patients.
Asunto(s)
Anemia Hemolítica Autoinmune , Lupus Eritematoso Sistémico , Sistema del Grupo Sanguíneo Rh-Hr , Humanos , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/diagnóstico , Sistema del Grupo Sanguíneo Rh-Hr/inmunología , Sistema del Grupo Sanguíneo Rh-Hr/genética , Femenino , Anemia Hemolítica Autoinmune/inmunología , Anemia Hemolítica Autoinmune/diagnóstico , Anemia Hemolítica Autoinmune/sangre , Anemia Hemolítica Autoinmune/terapia , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Eritrocitos/inmunología , Adulto , Tipificación y Pruebas Cruzadas Sanguíneas/métodosRESUMEN
INTRODUCTION: Cold agglutinin disease (CAD) is driven by IgM autoantibodies reactive at <37°C and able to fix complement. The activation of the classical complement pathway leads to C3-mediated extravascular hemolysis in the liver and to intravascular hemolytic crises in case of complement amplifying conditions. C3 positivity at direct Coombs test along with high titer agglutins are required for the diagnosis. Treatment is less standardized. AREAS COVERED: This review recapitulates CAD diagnosis and then focus on the evolving management of the disease. Both current approach and novel targeted drugs are discussed. Literature search was conducted in PubMed and Scopus from 2000 to 2024 using 'CAD' and 'autoimmune hemolytic anemia' as keywords. EXPERT OPINION: Rituximab represents the frontline approach in patients with symptomatic anemia or disabling cold-induced peripheral symptoms and is effective in 50-60% of cases. Refractory/relapsing patients are an unmet need and may now benefit from complement inhibitors, particularly the anti-C1s sutimlimab, effective in controlling hemolysis thus improving anemia in >80% of patients, but not active on cold-induced peripheral symptoms. Novel drugs include long-acting complement inhibitors, plasma cells, and B-cell targeting agents (proteasome inhibitors, anti-CD38, BTKi, PI3Ki, anti-BAFF). Combination therapy may be the future answer to CAD unmet needs.
Asunto(s)
Algoritmos , Anemia Hemolítica Autoinmune , Rituximab , Humanos , Anemia Hemolítica Autoinmune/diagnóstico , Anemia Hemolítica Autoinmune/terapia , Anemia Hemolítica Autoinmune/tratamiento farmacológico , Rituximab/uso terapéutico , Manejo de la Enfermedad , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Inmunoglobulina M/sangreRESUMEN
Primary cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia caused by cold-reactive antibodies that bind to red blood cells and lead to complement-mediated hemolysis. Patients with primary CAD experience the burden of increased health resource utilization and reduced quality of life. The standard-of-care (SOC) in patients with primary CAD has included cold avoidance, transfusion support, and chemoimmunotherapy. The use of sutimlimab, a humanized monoclonal antibody that selectively inhibits C1-mediated hemolysis, was shown to reduce transfusion-dependence and improve quality of life across two pivotal phase 3 studies, further supported by 2-year extension data. Using data from the transfusion-dependent patient population that led to sutimlimab's initial FDA approval, we performed the first-ever cost-effectiveness analysis in primary CAD. The projected incremental cost-effectiveness ratio (ICER) in our Markov model was $2 340 000/QALY, significantly above an upper-end conventional US willingness-to-pay threshold of $150 000/QALY. These results are consistent across scenarios of higher body weight and a pan-refractory SOC patient phenotype (i.e., treated sequentially with bendamustine-rituximab, bortezomib, ibrutinib, and eculizumab). No parameter variations in deterministic sensitivity analyses changed our conclusion. In probabilistic sensitivity analysis, SOC was favored over sutimlimab in 100% of 10 000 iterations. Exploratory threshold analyses showed that significant price reduction (>80%) or time-limited treatment (<18 months) followed by lifelong clinical remission off sutimlimab would allow sutimlimab to become cost-effective. The impact of sutimlimab on health system costs with longer term follow-up data merits future study and consideration through a distributional cost-effectiveness framework.
Asunto(s)
Anemia Hemolítica Autoinmune , Anticuerpos Monoclonales Humanizados , Análisis Costo-Beneficio , Humanos , Anemia Hemolítica Autoinmune/terapia , Anemia Hemolítica Autoinmune/tratamiento farmacológico , Anemia Hemolítica Autoinmune/economía , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/economía , Femenino , Masculino , Persona de Mediana Edad , Cadenas de Markov , Años de Vida Ajustados por Calidad de Vida , AncianoRESUMEN
We report here the case of a 50-year-old man who was first diagnosed with myelodysplastic syndrome with excess blasts-2 (MDS-EB-2) and underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 2019, resulting in complete remission. However, he was diagnosed in 2021 with several autoimmune disorders, including autoimmune hepatitis (AIH), Hashimoto's thyroiditis (HT), and autoimmune hemolytic anemia (AIHA). This is referred as multiple autoimmune syndrome (MAS), which is a rare occurrence after allo-HSCT, as previously noted in the literature. Despite being treated with glucocorticoids, cyclosporine A, and other medications, the patient did not fully recover. To address the glucocorticoid-refractory MAS, a four-week course of rituximab (RTX) at a weekly dose of 100mg was administered, which significantly improved the patient's condition. Thus, this case report underscores the importance of implementing alternative treatments in patients with post-transplant autoimmune diseases, who are glucocorticoid-refractory or glucocorticoid-dependent, and highlights the effectiveness of RTX as second-line therapy.
Asunto(s)
Enfermedades Autoinmunes , Glucocorticoides , Trasplante de Células Madre Hematopoyéticas , Trasplante Homólogo , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Masculino , Persona de Mediana Edad , Glucocorticoides/uso terapéutico , Enfermedades Autoinmunes/etiología , Enfermedades Autoinmunes/terapia , Rituximab/uso terapéutico , Anemia Hemolítica Autoinmune/etiología , Anemia Hemolítica Autoinmune/terapia , Anemia Hemolítica Autoinmune/tratamiento farmacológico , Resistencia a MedicamentosRESUMEN
Autoimmune hemolytic anemias (AIHAs) are conditions involving the production of antibodies against one's own red blood cells (RBCs). These can be primary with unknown cause or secondary (by association with diseases or infections). There are several different categories of AIHAs recognized according to their features in the direct antiglobulin test (DAT). (1) Warm-antibody AIHA (wAIHA) exhibits a pan-reactive IgG autoantibody recognizing a portion of band 3 (wherein the DAT may be positive with IgG, C3d or both). Treatment involves glucocorticoids and steroid-sparing agents and may consider IVIG or monoclonal antibodies to CD20, CD38 or C1q. (2) Cold-antibody AIHA due to IgMs range from cold agglutinin syndrome (CAS) to cold agglutin disease (CAD). These are typically specific to the Ii blood group system, with the former (CAS) being polyclonal and the latter (CAD) being a more severe and monoclonal entity. The DAT in either case is positive only with C3d. Foundationally, the patient is kept warm, though treatment for significant complement-related outcomes may, therefore, capitalize on monoclonal options against C1q or C5. (3) Mixed AIHA, also called combined cold and warm AIHA, has a DAT positive for both IgG and C3d, with treatment approaches inclusive of those appropriate for wAIHA and cold AIHA. (4) Paroxysmal cold hemoglobinuria (PCH), also termed Donath-Landsteiner test-positive AIHA, has a DAT positive only for C3d, driven upstream by a biphasic cold-reactive IgG antibody recruiting complement. Although usually self-remitting, management may consider monoclonal antibodies to C1q or C5. (5) Direct antiglobulin test-negative AIHA (DAT-neg AIHA), due to IgG antibody below detection thresholds in the DAT, or by non-detected IgM or IgA antibodies, is managed as wAIHA. (6) Drug-induced immune hemolytic anemia (DIIHA) appears as wAIHA with DAT IgG and/or C3d. Some cases may resolve after ceasing the instigating drug. (7) Passenger lymphocyte syndrome, found after transplantation, is caused by B-cells transferred from an antigen-negative donor whose antibodies react with a recipient who produces antigen-positive RBCs. This comprehensive review will discuss in detail each of these AIHAs and provide information on diagnosis, pathophysiology and treatment modalities.
Asunto(s)
Anemia Hemolítica Autoinmune , Anemia Hemolítica Autoinmune/diagnóstico , Anemia Hemolítica Autoinmune/terapia , Anemia Hemolítica Autoinmune/inmunología , Humanos , Autoanticuerpos/inmunología , Autoanticuerpos/sangre , Manejo de la Enfermedad , Prueba de Coombs/métodosRESUMEN
Introduction: Over the past decade, immune checkpoint inhibitors such as antibodies against cytotoxicity T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) have become an important armamentarium against a broad spectrum of malignancies. However, these specific inhibitors can cause adverse autoimmune reactions by impairing self-tolerance. Hematologic side effects of immune checkpoint inhibitors, including autoimmune hemolytic anemia (AIHA), are rare but can be life-threatening. Case report: Herein, we report two patients on immune checkpoint inhibitors for metastatic melanoma who developed AIHA with symptoms of dyspnea and fatigue. In the first patient, symptoms alleviated after discontinuation of combined anti CTLA-4 and anti-PD-1 therapy, initiation of corticosteroids and application of a single red blood cell transfusion. Due to subsequent progress of melanoma, combinational anti-PD-1 and tyrosine kinase inhibitor therapy was initiated based on multidisciplinary tumor board decision. After two months, she again developed the described hematological and clinical signs of AIHA leading to cessation of anti-PD-1 therapy and initiation of corticosteroids, which again resulted in an alleviation of her symptoms. Due to further progression, the patient received dacarbazine for several months before she decided to stop any therapy other than palliative supportive care. In the second patient, discontinuation of anti-PD-1 therapy and initiation of corticosteroids entailed a complete alleviation of his symptoms. After refusing chemotherapy due to subsequent melanoma progression, he received radiotherapy of bone metastases and is currently enrolled in a clinical trial. The patient did not develop AIHA ever since. Conclusion: Hematologic immune-related adverse events due to treatment with immune checkpoint inhibitors are rare but can have life-threatening consequences. If dyspnea and other clinical symptoms are present, AIHA should be considered as a potential cause and treated promptly in a multidisciplinary setting. An expanded comprehension of risk factors and pathogenesis of AIHA is needed to identify high-risk patients beforehand, leading to more effective predictive and reactive treatment approaches.
Asunto(s)
Anemia Hemolítica Autoinmune , Melanoma , Neoplasias Primarias Secundarias , Humanos , Masculino , Femenino , Melanoma/tratamiento farmacológico , Melanoma/etiología , Anemia Hemolítica Autoinmune/inducido químicamente , Anemia Hemolítica Autoinmune/terapia , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inmunoterapia/efectos adversos , Inmunoterapia/métodos , Neoplasias Primarias Secundarias/etiología , Disnea/etiología , Corticoesteroides/uso terapéuticoRESUMEN
Autoimmune cytopenias are defined by autoantibodies' immune destruction of one or more blood elements. Most often it is autoimmune hemolytic anemia or immune thrombocytopenia or both that define Evans syndrome. It may be secondary to infection or to underlying pathology such as systemic autoimmune disease or primary immunodeficiency, especially when it becomes chronic over several years. Primary Immunodeficiencies or inborn errors of immunity (IEI) are no longer defined solely by infections: autoimmunity is part of the clinical features of several of these diseases. It is dominated by autoimmune cytopenias, in particular, immune thrombocytopenia (ITP) and autoimmune hemolytic anaemia (AIHA). The challenges for the clinician are the situations where autoimmune cytopenias are chronic, recurrent and/or refractory to the various long-term therapeutic options. Most of these therapies are similar in action and generally consist of non-mediated immune suppression or modulation. In these situations, primary Immunodeficiencies must be diagnosed as soon as possible to allow the initiation of a targeted treatment and to avoid several ineffective therapeutic lines.
Asunto(s)
Anemia Hemolítica Autoinmune , Citopenia , Púrpura Trombocitopénica Idiopática , Trombocitopenia , Niño , Humanos , Púrpura Trombocitopénica Idiopática/terapia , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Anemia Hemolítica Autoinmune/terapia , Anemia Hemolítica Autoinmune/tratamiento farmacológico , Trombocitopenia/diagnóstico , Trombocitopenia/terapiaRESUMEN
Kabuki syndrome (KS) is now listed in the Human Inborn Errors of Immunity (IEI) Classification. It is a rare disease caused by KMT2D and KDM6A variants, dominated by intellectual disability and characteristic facial features. Recurrently, pathogenic variants are identified in those genes in patients examined for autoimmune cytopenia (AIC), but interpretation remains challenging. This study aims to describe the genetic diagnosis and the clinical management of patients with paediatric-onset AIC and KS. Among 11 patients with AIC and KS, all had chronic immune thrombocytopenic purpura, and seven had Evans syndrome. All had other associated immunopathological manifestations, mainly symptomatic hypogammaglobinaemia. They had a median of 8 (5-10) KS-associated manifestations. Pathogenic variants were detected in KMT2D gene without clustering, during the immunological work-up of AIC in three cases, and the clinical strategy to validate them is emphasized. Eight patients received second-line treatments, mainly rituximab and mycophenolate mofetil. With a median follow-up of 17 (2-31) years, 8/10 alive patients still needed treatment for AIC. First-line paediatricians should be able to recognize and confirm KS in children with ITP or multiple AIC, to provide early appropriate clinical management and specific long-term follow-up. The epigenetic immune dysregulation in KS opens exciting new perspectives.
Asunto(s)
Anomalías Múltiples , Proteínas de Unión al ADN , Cara , Enfermedades Hematológicas , Histona Demetilasas , Proteínas de Neoplasias , Enfermedades Vestibulares , Humanos , Enfermedades Vestibulares/genética , Enfermedades Vestibulares/diagnóstico , Niño , Cara/anomalías , Femenino , Masculino , Preescolar , Anomalías Múltiples/genética , Adolescente , Histona Demetilasas/genética , Proteínas de Neoplasias/genética , Enfermedades Hematológicas/genética , Proteínas de Unión al ADN/genética , Púrpura Trombocitopénica Idiopática/genética , Púrpura Trombocitopénica Idiopática/terapia , Púrpura Trombocitopénica Idiopática/diagnóstico , Lactante , Trombocitopenia/genética , Trombocitopenia/diagnóstico , Trombocitopenia/etiología , Trombocitopenia/terapia , Anemia Hemolítica Autoinmune/genética , Anemia Hemolítica Autoinmune/diagnóstico , Anemia Hemolítica Autoinmune/terapia , Enfermedades Autoinmunes/genética , Enfermedades Autoinmunes/diagnóstico , Rituximab/uso terapéutico , Mutación , CitopeniaRESUMEN
Cold agglutinins produced in the setting of B cell neoplasms, such as lymphoplasmacytic lymphoma and plasma cell myeloma, can mediate autoimmune haemolytic anemia. Transfusion of these patients can exacerbate cold agglutinin-mediated haemolysis. Moreover, the workup for these reactions represents a diagnostic challenge due in part to false negative direct antiglobulin tests (DATs). Here, we report an anaemic patient who after a red blood cell (RBC) transfusion performed without blood warming, experienced a DAT-negative haemolytic transfusion reaction, and was later diagnosed with IgA-multiple myeloma, which showed an uncommon granular pattern by CD138 immunohistochemistry. Extensive workup excluded other diagnostic possibilities, including the presence of Donath-Landsteiner antibodies and cryoglobulins. Successful treatment with CyBorD (cyclophosphamide, bortezomib and dexamethasone) achieved complete remission, and additional RBC transfusions using warmers were completed uneventfully.
Asunto(s)
Anemia Hemolítica Autoinmune , Mieloma Múltiple , Reacción a la Transfusión , Humanos , Mieloma Múltiple/complicaciones , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/terapia , Crioglobulinas , Anemia Hemolítica Autoinmune/diagnóstico , Anemia Hemolítica Autoinmune/etiología , Anemia Hemolítica Autoinmune/terapia , Inmunoglobulina ARESUMEN
The histo-blood group antigens P, P1 and Pk are a closely related set of glycosphingolipid structures expressed by red blood cells and other tissues. None of these three characters is expressed on p cells, a null phenotype that arises in the context of homozygous mutation of the A4GALT gene. Subjects with p phenotype spontaneously develop a natural alloantibody named anti-PP1Pk, which is a mixture of IgG and IgM against P1, P and Pk. While anti-P1 is a weak cold antibody with poor clinical significance, anti-P and anti-Pk antibodies are potent haemolysins responsible for severe hemolytic transfusion reactions. The rare anti-PP1Pk alloantibodies are associated with recurrent spontaneous abortion in the first trimester of gestation. P and Pk antigens are expressed at high levels on the placenta and antibodies directed against both these structures are deleterious to placental trophoblasts. Here we describe the use of plasma exchange (PEX) in a nulliparous 39-year-old woman with anti-PP1Pk antibodies and a history of repeated spontaneous early abortions and hypofertility. The patient underwent apheresis starting from the third week throughout the pregnancy and a healthy child was delivered by cesarean section at 35 WG. The newborn required only phototherapy within a few days of life. We can state that an early treatment with the only PEX has proven to be effective and safe in the management of a fetomaternal P-incompatibility caused by a high anti-PP1Pk titer (256).