Pediatric Evans Syndrome: A 20-year experience from a tertiary center in Brazil

Abstract Introduction The Evans syndrome (ES) is a rare, often chronic, relapsing and treatment-refractory hematological disorder. We described the clinical features, diagnostic workup, treatment and outcome in patients with ES. Method We performed a retrospective chart review of patients aged < 18 years with ES admitted to a tertiary center in Brazil from 2001 to 2021. The analysis of the data was primarily descriptive, using median, interquartile range and categorical variables presented in absolute frequencies. Main results Twenty patients (12 female, 8 male) were evaluated in this study. The median age at the initial cytopenia was 4.98 years (1.30-12.57). The ES was secondary in nine cases (45%), of which six patients (30%) showed autoimmune disease (AID) or primary immunodeficiencies (PID) and one presented a spontaneous recovery. Steroids and intravenous immunoglobulin were first-line therapy in 19 cases. Twelve patients (63%) required second-line treatments (rituximab, cyclosporine, splenectomy, sirolimus, cyclophosphamide, mycophenolate mofetil, azathioprine and eltrombopag). The median follow-up period was 2.41 years (1.4 -7.52). One patient (5%) died of underlying neuroblastoma, one case (5%) was lost to follow-up and four patients (20%) received a medical discharge. The median age for the 14 remaining cases was 12.6 years. Twelve patients (85.7%) were in complete response (CR) with no therapies. Two patients (14.3%) were in CR with chronic therapy. Conclusion As ES may be a symptom of AID and PID, a thorough rheumatological, immunologic and genetic workup and a careful follow-up are essential. The second-line treatment remains a dilemma. Further prospective studies are needed to address the optimal therapeutic combinations, morbidity and mortality in this disorder.

Diagnoses, outcomes, and chronicity predictors of patients with secondary immune thrombocytopenia: ten-year data from a hematology referral center

ABSTRACT Background: Secondary immune thrombocytopenia (ITP) is a heterogeneous and unpredictable disease associated with various underlying conditions. Objective: The objective of the study was to investigate clinical evolution and chronicity predictors in secondary ITP. Methods: Patients treated at an academic medical center during 2008-2019 were stratified by age as children <16 years and adults >16 years. Responses to steroids, intravenous immunoglobulin G (IVIG), rituximab, and eltrombopag were classified as response (R) and complete response (CR). Risk factors for chronic ITP were determined by multiple regression with uni- and multi-variate analysis. Results: Eighty-three patients were included, 37 children and 46 adults. The most frequent associated conditions were infections 53%, systemic lupus erythematosus (SLE) 24%, thyroid disease 9.6%, and Evans syndrome 3.6%. Response to first-line treatment in the whole cohort was 94%; CR 45.7%; and R 50.6%. Initial response to steroids alone was 91.3% (n = 21/23), rituximab plus high-dose dexamethasone (HDD) 93.3% (n = 14/15); children receiving IVIG alone 100% (n=12/12); and eltrombopag in adults 100% (n = 3/3). Relapse was documented in 19.4% of children and 34% of adults, at a median time of 15 and 2 months, respectively; 30.4% of adults (15.2% from the miscellaneous group, 10.9% SLE-associated, and 4.3% infection-associated) and 18.9% of children followed a chronic course; age ≥10 years and platelets ≥20 × 109/L were risk factors for chronic ITP in children. Conclusion: Evolution was heterogeneous: a better and more sustained response was documented in the infections group compared to SLE or the miscellaneous group. (REV INVEST CLIN. 2021;73(1):31-8)

Maternal and perinatal outcome of Evan’s syndrome: a 5 years study in a tertiary care centre

Background: Evans syndrome is a rare autoimmune disorder characterized by simultaneous or sequential presence of a positive antiglobulin test, autoimmune haemolytic anemia (AIHA), and immune thrombocytopenia (ITP). It is characterised by frequent exacerbations and remissions within a chronic course. It was first described by Robert Evans in 1951.  Incidence of AIHA is 1 per 75 - 80,000 and ITP is 5.5 /100000 per general adult population.  Incidence of Evans syndrome is 1.8% to 10% of patients with ITP. Objective was to study the maternal and perinatal outcome of women with Evans syndrome (E).Methods: About 4 antenatal mothers were identified with Evans syndrome at St. Johns medical college and hospital, Bengaluru during the study period of 5 years from July 2013-July 2017. They were followed up during their antenatal, intra natal and postnatal period and outcomes were studied. All patients included in the study fulfilled the criteria for Evans syndrome.Results: There were 4 cases of Evans syndrome, with a total number of deliveries of 11859, during this 5 year study. Incidence was 0.09 per 1000 births. All patients presented with bleeding manifestations ranging from mucosal haemorrhage to subarachnoid haemorrhage (SAH) at the time of diagnosis. All patients were on treatment with either 1st or 2nd line of management with corticosteroids/ azathioprine. None had bleeding during pregnancy after the initiation of treatment. Patients had antenatal complications like preeclampsia 25%, IUGR 25%, oligohydraminos 50%, IUD 25%. 2 patients received platelet transfusions intrapartum. None had intrapartum or postpartum haemorrhage. There were no maternal and neonatal mortality.Conclusions: Evans syndrome in pregnancy is a rare condition and requires multi disciplinary approach involving specialists from obstetrics, neonatology, and hematology. Close maternal and fetal surveillance and management during pregnancy is essential to increase the possibility of a favourable pregnancy outcome in these women.

Advances in pathogenesis of children with chronic refractory immune thrombocytopenia / 中华实用儿科临床杂志

Chronic refractory autoimmune thrombocytopenia (C/RITP) comprises complex and heterogeneous pathogenesis.Beyond the classic immune disorders such as platelet autoantibodies and cellular immune imbalance,other important considerations that can cause acquired C/RITP include infection,drug,vaccines,autoimmune diseases,tumor,or platelet function disorder.In addition,advances in the molecular mechanism and genetic correlations of C/RITP for children are also discussed.

A Case of Immune Thrombocytopenic Purpura Associated with Scrub Typhus / 대한내과학회지

Thrombocytopenia is a common manifestation of rickettsial disease. However, the pathogenesis of thrombocytopenia in many rickettsial diseases is poorly understood. Thrombocytopenia may be associated with consumption due to widespread endothelial damage or disseminated intravascular coagulation, hypersplenism, decreased marrow production, and immune-mediated platelet destruction. Some reports have found anti-platelet antibodies detected in thrombocytopenic patients with rickettsial disease. In addition to thrombocytopenia, facial palsy and Guillain-Barre syndrome were also reported as immune-mediated phenomena in scrub typhus. Here we report a case diagnosed as immune-mediated thrombocytopenia associated with scrub typhus. This is the first report of immune thrombocytopenic purpura (ITP) associated with scrub typhus in Korea. The patient exhibited eschar with a high titer of anti-tsutsugamushi antibody, thrombocytopenia, severe gastrointestinal hemorrhage, and purpura on the lower region of both legs. After steroid treatment, the sustained thrombocytopenia recovered.

Asociación de la púrpura trombocitopénica inmunológica y el síndrome de Guillain-Barré: a propósito de un caso / Association of immunologic thrombocytopenia and the Guillain-Barré syndrome: with regard to a case

La púrpura trombocitopénica inmunológica es una enfermedad autoinmune, benigna, de aparición frecuente, caracterizada por la presencia de anticuerpos dirigidos contra las glicoproteínas de la membrana plaquetaria que producen una disminución del recuento plaquetario y manifestaciones hemorrágicas cutáneo-mucosas. El diagnóstico de esta entidad se realiza por exclusión de otras causas de trombocitopenia. El síndrome de Guillain-Barré es también una enfermedad de naturaleza autoinmune donde la pérdida de la tolerancia inmunológica trae como consecuencia la aparición de anticuerpos dirigidos contra los gangliósidos de los nervios periféricos. Se presenta una paciente femenina de 40 años con diagnóstico de una púrpura trombocitopénica inmunológica crónica que comenzó con una parálisis motora ascendente, sin toma respiratoria, parálisis facial y dolor intenso en las regiones dorsal y lumbar. Fue diagnosticada como un síndrome de Guillain-Barré e inmediatamente se comenzó tratamiento con vitaminoterapia y esteroides a altas dosis. Después de varios meses de seguimiento y rehabilitación presentó una evolución satisfactoria con remisión de todos los síntomas neurológicos

The immunologic thrombocytopenic purpura is an autoimmune, benign, of frequent appearance disease characterized by the presence of antibodies directed to glycoproteins of platelet membrane producing a decrease of platelet count and cutaneous-mucosal hemorrhagic manifestations. The Guillain-BarrÚ syndrome is also a disease autoimmune by origin where the loss of immunological tolerance causes the appearance of antibodies directed to gangliosides of peripheral nerves. This is the case of female patient aged 40 diagnosed with a chronic immunologic thrombocytopenic purpura beginning with an ascendant motor paralysis, without respiratory compromise, facial paralysis and intense pain in dorsal and lumbar regions and also a diagnosis of Guillain-BarrÚ syndrome with immediate treatment based on vitamin-therapy and high dose of steroids. After some months of follow-up and rehabilitation there was a satisfactory evolution with remission of all neurological symptoms

Detection of Platelet Specific Antibodies by Modified Antigen Capture ELISA Test / 대한진단검사의학회지

BACKGROUND: Autoimmune thrombocytopenia (AITP) is characterized by autoantibody-induced platelet destruction. Although several studies have shown that pathogenic autoantibodies are mainly IgG directed platelet glycoproteins (GP), a platelet GP specific test is not available in clinical laboratories. The aim of this study was to evaluate the clinical usefulness of a Modified Antigen Capture Enzyme-linked immunosorbent assay (MACE) test in the diagnosis of AITP. METHODS: We investigated fifty-seven patients who showed a platelet count lower than 100 x 10(9)/L and underwent a bone marrow examination. They were classified into primary AITP (P-AITP) (n=21), secondary AITP (S-AITP) (n=15), and non-immune thrombocytopenia (NITP) (n=21) by bone marrow findings and clinical diagnosis. Platelet GP (IIb/IIIa, Ia/IIa, Ib/IX, IV)-specific antibodies and anti-HLA class I antibody were detected by MACE test. RESULTS: Among 57 samples, platelet GP specific antibodies were detected in 8 (22.2%) of 36 patients with AITP and 1 (4.8%) of 21 patients with NITP. The specificities were as follows: GP IIb/IIIa (n=4), GP Ia/IIa (n=5), GP Ib/IX (n=3) and GPIV (n=2). Of the nine patients with platelet GP specific antibodies, four (44.4%) had more than two platelet GP specific antibodies. The sensitivity, specificity, positive predictive value and negative predictive values of the MACE test for AITP were 22.2%, 95.2%, 88.9%, 41.7%, respectively. A previous transfusion history was associated with a higher detection rate of anti-HLA class I antibodies (P<0.05). CONCLUSIONS: The MACE test is a convenient method to detect platelet GP specific antibody and is very specific to diagnose AITP. In clinical practice, even though it is not sensitive, the MACE test would be useful in differentiating AITP from NITP.

Outcome of refractory autoimmune thrombocytopenia purpura treated with autologous peripheral blood stem cell transplantation / 基础医学与临床

Objective To explore the efficacy and immune reconstitution of autologous peripheral blood stem cell transplantation (APBSCT) in the treatment of refractory autoimmune thrombocytopenia purpura (ITP). MethodsOne patient with refractory ITP was treated with APBSCT, the effectiveness and the process of immune reconstitution were analyzed retrospectively. Results The case was mobilized by cyclophosphamide (CY) plus G-CSF and 4.7?106/kg CD34+ cell was gained totally. Neutrophil and platelet were engrafted at 11th and 12th day without severe complications following the conditioning of TBI and CY. Although the each phenotype of the peripheral blood lymphocytes recovered gradually 6 months after the transplant,inverted CD4/CD8 ratio exited and memory T cell was improved much earlier than naive T cell. The platelete count was constantly over 100?109/L and the patient was in complete remission after a follow-up of 31 months.Conclusion APBSCT is a potential approach in the treatment of refractory ITP.

A Case of Successful Danazol Therapy in Autoimmune Thrombocytopenia Associated with Systemic Lupus Erythematosus

Autoimmune thrombocytopenia and autoimmune hemolytic anemia occur in 10-26% of patients with systemic lupus erythematosus(SLE). These hematological manifestations may be the sole presenting sign and can precede the appearance of diagnosable SLE in 5 to 23% of cases. The conventional treatment for SLE associated with these disorders includes corticosteroid therapy and splenectomy, but autoimmune thrombocytopenia or autoimmune hemolytic anemia may be refractory to both treatments. We experienced a case of a SLE patient complicated by severe autoimmune thrombocytopenia. Therapy with intravenous immunoglobulin and corticosteroids failed. She responded to danazol and remission of thrombocytopenia(platelet >100,000/mm3) was observed 7 days after starting danazol. Danazol therapy seems to be a useful and well tolerated treatment for refractory autoimmune thrombocytopenia associated with SLE.