Evans Syndrome Research Articles

Familial autoimmunity and risk of developing immune thrombocytopenia and Evans syndrome.

Immune thrombocytopenia (ITP) and Evans syndrome (ES) are manifestations of immune dysregulation. Genetic variants in immune-related genes have been identified in patients with ITP and especially ES. We aimed to explore familial autoimmunity in patients with ITP and ES to understand possible contributions to chronicity. We assessed family history in two ways: via patient report for ITP and ES and by population-based analysis using the Utah Population Database (UPDB) for ITP. A total of 266 patients with ITP and 21 patients with ES were identified via chart review, and 252 of the 266 patients with ITP were also identified in the UPDB. Chart review showed familial autoimmunity in 29/182 (15.9%) and 25/84 (29.8%) of patients with newly diagnosed+persistent (nd+p) ITP and chronic ITP (cITP), respectively, (p=.009). The UPDB analysis revealed that autoimmunity in relatives of patients with nd+pITP was higher than in relatives of controls (odds ratio [OR]: 1.69 [1.19-2.41], p=.004), but was not significantly increased in relatives of patients with cITP (OR 1.10 [0.63-1.92], p=.734). Incomplete family history in medical records likely contributed to the observed discrepancy. The findings suggest that familial autoimmunity may have a stronger association with the development of ITP rather than its duration. Twelve (57.1%) patients with ES reported autoimmunity in their relatives. UPDB analysis was omitted due to the small number of patients with ES. The use of population databases offers a unique opportunity to assess familial health and may provide clues about contributors to immune dysregulation features within families.

Association of paediatric autoimmune cytopenia and inflammatory bowel disease suggests a common genetic origin.

The association of autoimmune cytopenia (AIC) and inflammatory bowel disease (IBD) has been reported in small series, but the incidence of and risk factors for IBD in children with AIC are not known. One thousand six hundred nine children with chronic immune thrombocytopenic purpura, autoimmune haemolytic anaemia or Evans syndrome from the prospective OBS'CEREVANCE cohort are included in this study. Overall, 15 children were diagnosed with IBD, including 14 who developed IBD after AIC diagnosis (median delay: 21 months). The only risk factor for IBD development is age at AIC over 10 years. Out of 10 children genetically tested, germline variants associated with autoimmune disorders were identified in three (CTLA4: two, DOCK11: one). In children and adolescents monitored for AIC or past history of AIC, especially children over 10 years, gastro-intestinal (GI) symptoms (recurrent abdominal pains, GI bleeding, chronic diarrhoea, weight loss) should suggest IBD and deserve specific work-up and genetic studies. Identification of a causal germline variant will allow targeted therapy.

Differential diagnosis of Guillain-Barré syndrome: steroid-responsive radiculopathy in Evans syndrome

Guillain-Barré syndrome is the most common acute inflammatory demyelinating peripheral nerve condition. Occasionally, other autoimmune conditions can mimic Guillain-Barré syndrome but may require different diagnostic workup and treatment. We report here two patients with Evans syndrome, a rare hematological autoimmune condition who developed a subacute inflammatory radiculopathy. Similarities and distinguishing clinical and diagnostic features are discussed.

Chinese expert consensus on the diagnosis and treatment of Evans syndrome (2024)

Evans syndrome (ES) is a rare autoimmune disorder characterized by the presence of at least two autoimmune cytopenias (AIC), including immune thrombocytopenia (ITP), autoimmune hemolytic anemia (AIHA), and autoimmune neutropenia (AIN). Secondary ES accounts for 21%-50% of cases. ES is characterized by recurrent relapses, serious complications such as thrombosis and infection, and high mortality. The management of ES is highly heterogeneous, necessitating treatment for AIC, the primary disease, as well as associated complications. However, there remains a lack of prospective evidence, randomized clinical trials for ES. To standardize the diagnosis and management of ES in China effectively, this consensus was developed by the Red Blood Cell Diseases (Anemia) Group under the Chinese Society of Hematology within the Chinese Medical Association. It aims to provide valuable guidance for diagnosing and managing ES in clinical practice based on international consensus and comprehensive review of both domestic and international literature.

Elective splenectomy for hematological diseases: a vanishing indication.

Splenectomy has been used as a diagnostic and therapeutic tool in the management of hematological diseases for many years. However, the emergence of new medical therapies has modified guidelines for many hematological diseases for which splenectomy was previously considered. We aimed to evaluate the evidence of a decrease in the hematological indications for splenectomy and the reasons and justifications for this change. We conducted a single-center, retrospective analysis of patients who underwent laparoscopic splenectomy for hematological disease between January 2010 and December 2023. Patients were classified into four groups: 1 autoimmune and hemolytic diseases (HAD), (2) lymphomas, (3) myeloproliferative diseases (MPN), and (4) other splenic diseases. We recorded the annual incidence of splenectomy and the ratio of new medical cases, demographic and clinical data and surgical outcomes. During the study period, 98 patients were referred for splenectomy. There was a significant progressive decrease in this surgical indication, particularly regarding HAD (p < 0.001). The indication for splenectomy for immune thrombocytopenic purpura (ITP) declined to zero despite an increase in the number of patients diagnosed with this disorder (p < 0.001). The pattern of decrease in AHAI and Evans syndrome was similar to that in ITP. The group of splenectomies due to lymphoma persisted consistently during the study period, as did the indication for splenectomy in the context of lymphoma treatment. Splenectomy due to massive splenomegaly secondary to MPN was indicated only in one patient. Splenectomies due to other causes were similarly distributed over the years. Our findings confirm a significant decrease in the indication for elective surgery for hematological diseases, mainly regarding autoimmune disease. The surgical community and surgical departments should be aware of this situation yet maintain the skills to adopt this technique both safely and efficiently.

Fisher – Evans syndrome: rare cause of cytopenias in children

Interested in the problem of cytopenic conditions in children is associated with a various causes of them. The spectrum of differential diagnostic search is very wide: hemoblastoses, myelodysplastic and paraneoplastic syndromes, aplastic anemia. It is necessary for assessment of the main cause of cytopenia to pay attention on the patient’ common status (his complaints, anamnestic data — features of the start of the disease, previous diseases, concomitant somatic pathology, constant medication). Also on the complex and features of the clinical manifestations, the functional state of organs and systems, and in particular the liver, hematological changes in peripheral blood and bone the brain. The combination of immune thrombocytopenic purpura with autoimmune hemolytic anemia are named Fisher — Evans syndrome (FES). The article presents a clinical case of the combination Fisher — Evans syndrome and preceding B-lymphoma in a preschool child, and also reflects the main etiopathogenetic mechanisms of development this pathology. Fisher — Evans syndrome (SFE) is a rare autoimmune disease characterized by the immune thrombocytopenia (ITP) and Coombs–positive autoimmune hemolytic anemia (AIGA), which can develop simultaneously or sequentially, and in some cases are combined with immune neutropenia. The primary and secondary variants of Fisher — Evans syndrome are described. The secondary is the background of the following pathology: Epstein — Barr viral, cytomegalovirus, immunodeficiency virus, hepatitis C, parvovirus, varicella zoster virus, mycoplasma infection, tuberculosis), immunodeficiency and lymphoproliferative conditions, rheumatoid, autoimmune and malignant diseases such as systemic lupus erythematosus (SLE), antiphospholipid syndrome (AFLS), Sjogren’s syndrome, immunoglobulin A deficiency (IgA), autoimmune lymphoproliferative syndrome (ALPS), general variable immune deficiency (OVIN), lymphogranulomatosis (LGM), chronic lymphoblastic leukemia (CLL), autoimmune thyroiditis, autoimmune hepatitis, Takayasu arteritis, systemic sclerosis. The difficulties of searching causes are and indicated this diagnosis of exclusion. The question remains: is B-lymphoma the cause or accomplice of SFE in a child?

Spectrum of renal disease in scleroderma other than scleroderma renal crisis: A review of the literature.

Systemic sclerosis (SSc) is a multi-system rheumatic disease characterized by vascular and fibrotic manifestations that can affect practically every organ. Scleroderma renal crisis (SRC) is the most common renal manifestation of SSc. However, with the use of angiotensin-converting enzyme inhibitors (ACEi), the morbidity and mortality associated with SRC has significantly reduced. Renal manifestations in SSc other than SRC have been generally under-recognized and can be left untreated, which can lead to grave consequences in this patient population. In this article, we will describe the spectrum of renal disease in SSc besides SRC. A literature search was conducted on PubMed and Cochrane from inception to December 2022 using medical subject headings (MeSH) terms for "scleroderma", "systemic sclerosis" combined with "renal injury", and "renal dysfunction". We included case reports, case series, observational studies, and literature reviews. The initial search revealed 393 articles. After the exclusion of duplicates and non-relevant articles, data was included from 30 articles and 45 patients. The mean age was 55.2 years, 9 males (20%) and 36 females (80%). The most reported renal manifestations included: ANCA-associated vasculitis (n=22), penicillamine-induced renal injury (n=8), oxalate nephropathy (n=5), Goodpasture syndrome (n=4), nephrotic range proteinuria (n=2), renal artery stenosis (n=2), membranous glomerulonephritis (n=1), and Evans syndrome (n=1). The spectrum of kidney involvement in SSc can range from asymptomatic reduction of the glomerular filtration rate to life-threatening scleroderma renal crisis. Therefore, it is essential that physicians closely monitor renal function in these patients for any emerging renal dysfunction.

Navigating the conundrum of co-existing autoantibodies and alloantibodies in a case of Evans syndrome.

Navigating the conundrum of co-existing autoantibodies and alloantibodies in a case of Evans syndrome.

Haploinsufficiency in PTPN2 leads to early-onset systemic autoimmunity from Evans syndrome to lupus.

An exome sequencing strategy employed to identify pathogenic variants in patients with pediatric-onset systemic lupus or Evans syndrome resulted in the discovery of six novel monoallelic mutations in PTPN2. PTPN2 is a phosphatase that acts as an essential negative regulator of the JAK/STAT pathways. All mutations led to a loss of PTPN2 regulatory function as evidenced by in vitro assays and by hyperproliferation of patients' T cells. Furthermore, patients exhibited high serum levels of inflammatory cytokines, mimicking the profile observed in individuals with gain-of-function mutations in STAT factors. Flow cytometry analysis of patients' blood cells revealed typical alterations associated with autoimmunity and all patients presented with autoantibodies. These findings further supported the notion that a loss of function in negative regulators of cytokine pathways can lead to a broad spectrum of autoimmune manifestations and that PTPN2 along with SOCS1 haploinsufficiency constitute a new group of monogenic autoimmune diseases that can benefit from targeted therapy.

The Successful Management of Stroke in Evans Syndrome by Anticoagulation with Warfarin, Intravenous Immunoglobulin (IVIG), and High-Dose Corticosteroid.

Evans syndrome is a rare autoimmune disorder characterised by the coexistence of autoimmune haemolytic anaemia and immune thrombocytopenia, which potentially increase venous and arterial thrombotic risk.Managing strokes in Evans syndrome remains challenging due to its rarity and lack of definitive guidelines, necessitating individualised treatment approaches.Future prospective studies are warranted to determine the optimal patient population that needs secondary prevention with anticoagulants following a stroke in the context of Evans syndrome.

Evans syndrome: Disease awareness and clinical management in a nation-wide ITP-NET survey.

Evans syndrome (ES) is rare and mostly treated on a "case-by-case" basis and no guidelines are available. With the aim of assessing disease awareness and current management of adult ES, a structured survey was administered to 64 clinicians from 50 Italian participating centers. Clinicians had to be involved in the management of autoimmune cytopenias and were enrolled into the ITP-NET initiative. The survey included domains on epidemiology, diagnosis, and therapy of ES and was designed to capture current practice and suggested work-up and management. Thirty clinicians who had followed a median of 5 patients (1-45)/15 years responded. The combination of AIHA plus ITP was more common than the ITP/AIHA with neutropenia (p < .001) and 25% of patients had an associated condition, including lymphoproliferative syndromes, autoimmune diseases, or primary immunodeficiencies. The agreement of clinicians for each diagnostic test is depicted (i.e., 100% for blood count and DAT; only 40% for anti-platelets and anti-neutrophils; 77% for bone marrow evaluation). Most clinicians reported that ES requires a specific approach compared to isolated autoimmune cytopenias, due to either a more complex pathogenesis and a higher risk of relapse and thrombotic and infectious complications. The heterogeneity of treatment choices among different physicians suggests the need for broader harmonization.

Evans Syndrome: A Case Study with Substantial Comparison of Literature Review

Evans Syndrome: A Case Study with Substantial Comparison of Literature Review

Evans syndrome and systemic lupus erythematosus (SLE): a case report

Evans syndrome and systemic lupus erythematosus (SLE): a case report

Evan’s syndrome, primary or secondary? Navigating the diagnostic puzzle

Evans syndrome (ES) is a rare autoimmune disorder characterized by the simultaneous or sequential occurrence of autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP). Distinguishing between primary and secondary forms is crucial for management. This report presents a 69-year-old male with bleeding gums, anemia, and thrombocytopenia, who was diagnosed with ES following an extensive workup. Multiple potential triggers, including recent vaccinations, antibiotic use, past tuberculosis, and skin malignancies, were identified, highlighting the multifactorial nature of ES. The patient was treated with glucocorticoids, intravenous immunoglobulin (IVIG), Rituximab, and Romiplostim resulting in improved hematologic parameters. This case underscores the diagnostic challenges and importance of individualized therapeutic approaches in managing ES. Understanding the potential triggers and underlying immune dysregulation is pivotal for accurate diagnosis and effective treatment.

Double Trouble: A Case of Secondary Evans Syndrome from Systemic Lupus Erythematosus with May-Thurner Syndrome

Double Trouble: A Case of Secondary Evans Syndrome from Systemic Lupus Erythematosus with May-Thurner Syndrome

Sirolimus is effective and safe in childhood relapsed-refractory autoimmune cytopenias: A multicentre study.

Autoimmune cytopenias are a heterogeneous group of disorders characterized by immune-mediated destruction of haematopoietic cell lines. Effective and well-tolerated treatment options for relapsed-refractory immune cytopenias are limited. In this study, the aim was to evaluate the efficacy and safety of sirolimus in this disease group within the paediatric age group. The study enrolled patients in the paediatric age group who used sirolimus with a diagnosis of immune cytopenia between December 2010 and December 2020, followed at six centres in Turkey. Of the 17 patients, five (29.4%) were treated for autoimmune haemolytic anaemia (AIHA), six (35.2%) for immune thrombocytopenic purpura (ITP) and six (35.2%) for Evans syndrome (ES). The mean response time was 2.7 months (range, 0-9 months). Complete response (CR) and partial response (PR) were obtained in 13 of 17 patients (76.4%) and nonresponse (NR) in four patients (23.5%). Among the 13 patients who achieved CR, three of them were NR in the follow-up and two of them had remission with low-dose steroid and sirolimus. Thus, overall response rate (ORR) was achieved in 12 of 17 patients (70.5%). In conclusion, sirolimus may be an effective and safe option in paediatric patients with relapsed-refractory immune cytopenia.

Unveiling Complexity: A Case Study of Evans Syndrome Secondary to Atypical Pneumonia

Abstract Evans syndrome (ES) is a combined presentation of immune thrombocytopenia along with autoimmune hemolytic anemia with a positive direct antihuman globulin test. Approximately half of the cases of ES may be secondary to diverse causes, including infections, systemic autoimmune, transplantation, and lymphoproliferative syndromes. We discuss a 53-year-old male who came with complaints of low-grade fever, breathlessness, and cough and was found to have low hemoglobin levels and reduced platelet count. His Coomb’s test was positive, and his chest X-ray suggested pneumonia. The serum nucleic acid amplification test was positive for mycoplasma. A diagnosis of atypical pneumonia with ES was confirmed.

Evans Syndrome Secondary to Celiac Disease - A Case Report

Evans Syndrome Secondary to Celiac Disease - A Case Report

Evan’s Syndrome Hemolytic Anemia with Thrombocytopenia in a Labrador Dog: A Case Report

A seven-year-old Labrador retriever intact male dog was presented to the Referral Veterinary Polyclinic, Indian Veterinary Research Institute, Izatanagar with a history of inappetance, melena, and petechial hemorrhages on the ventral abdomen and treated by a local veterinarian for a prolonged period of time. Clinical examination showed pale mucous membranes, peripheral lymphadenopathy, and mild hepatomegaly. A Complete blood count revealed anemia, leukopenia, and thrombocytopenia and serum biochemistry showed hypoalbuminemia and hypoproteinemia. The dog was suspected of having a haemoprotozoan infection, and a thin peripheral blood smear was submitted to the Division of Parasitology, Indian Veterinary Research Institute, Izatanagar, Bareilly, for examination. A blood smear was screened for haemoprotozoan examination using Giemsa’s stain, which showed positivity for Babesia vogeli. An abdominal ultrasound confirmed hepatic enlargement. The blood clotting profile reveals an increase in activated partial thromboplastin time and prothrombin time. The dog's blood sample tested negative for Babesia vogeli, B. gibsoni, E. canis, and H. canis by multiplex PCR; this could be because of prior initiation of antibiotics. A periheral blood smear showed elevated spherocytes count and saline agglutination test was positive. Based on history, clinical examinations, laboratory findings and cytological examinations the case was tentatively diagnosed as chronic case of tick fever with concomitant Evans syndrome. A blood transfusion was performed and around 300 ml of whole blood was infused. Treatment was initiated with triple antibiotic therapy and an immunosuppressive dose of steroids, but after 4 weeks, the dog succumbed to the condition. Further research is required to optimize treatment regimens for dogs with Evan's syndrome, as the prognosis is uncertain.

Daratumumab monotherapy in refractory warm autoimmune hemolytic anemia and cold agglutinin disease

AbstractAutoimmune hemolytic anemia (AIHA) is a rare autoantibody-mediated disease. For steroid and/or rituximab-refractory AIHA, there is no consensus on optimal treatment. Daratumumab, a monoclonal antibody targeting CD38, could be beneficial by suppression of CD38+ plasma cells and thus autoantibody secretion. In addition, because CD38 is also expressed by activated T cells, daratumumab may also act via immunomodulatory effects. We evaluated the efficacy and safety of daratumumab monotherapy in an international retrospective study including 19 adult patients with heavily pretreated refractory AIHA. In warm AIHA (wAIHA, n = 12), overall response was 50% with a median response duration of 5.5 months (range, 2-12), including ongoing response in 2 patients after 6 and 12 months. Of 6 nonresponders, 4 had Evans syndrome. In cold AIHA (cAIHA, n = 7) overall hemoglobin (Hb) response was 57%, with ongoing response in 3 of 7 patients. One additional patient with nonanemic cAIHA was treated for severe acrocyanosis and reached a clinical acrocyanosis response as well as a Hb increase. Of 6 patients with cAIHA with acrocyanosis, 4 had improved symptoms after daratumumab treatment. In 2 patients with wAIHA treated with daratumumab, in whom we prospectively collected blood samples, we found complete CD38+ T-cell depletion after daratumumab, as well as altered T-cell subset differentiation and a severely diminished capacity for cell activation and proliferation. Reappearance of CD38+ T cells coincided with disease relapse in 1 patient. In conclusion, our data show that daratumumab therapy may be a treatment option for refractory AIHA. The observed immunomodulatory effects that may contribute to the clinical response deserve further exploration.