What is evans syndrome (ES)? 

It is a rare autoimmune disease. That means the body’s immune system attacks its own blood cells by mistake. Evans syndrome was first described by Dr Robert Evans in 1951.¹

It is characterised by the co-existence of autoimmune haemolytic anaemia (AIHA), when the immune system attacks red blood cells, and immune thrombocytopenia (ITP), when the immune system attacks platelets. A report shows that autoimmune neutropenia (low white blood cells) is a less common feature of Evans Syndrome. It happens in about 15% of adults and 20% of children, which is less frequent compared to other conditions like ITP (low platelets) and AIHA (low red blood cells).² Evans syndrome (ES) is mostly known as a paediatric disease, but it can also affect adults. The disease manifests differently in children and adults. In this article, we will share some information about the disease, symptoms, diagnosis, its clinical course in children and adults, as well as treatment.

Frequency of occurrence

Adults

A 2016 study from Denmark reported new cases in a year of 1.8 per one million person-years and an overall 21.3 cases per one million individuals. The average age at diagnosis is 52 years in adults, and the sex ratio is 3:2 in females to males, as it is typically for autoimmune diseases.² 

Children

In prepubertal children, new cases ranged from 0.7 to 1.2 cases per one million person-years. Male-to-female ratio in children is approximately 2:1. This contrasts with the typical pattern of autoimmune diseases, which generally occur more often in women.⁴

Classification

 Evans Syndrome (ES) is classified as :

•  Primary (or idiopathic), which means that the cause is unknown 
•  Secondary associated with other autoimmune disorders

Adults

Studies show that in 27–50% of cases, Evans syndrome (ES) occurs as a secondary condition, in adults with haematologic malignancies or systemic lupus erythematosus (SLE), Non-Hodgkin lymphoma (NHL),^2,3 chronic lymphocytic leukemia (CLL), viral infections (such as HIV, hepatitis C).⁶

Children

In children, Evans syndrome (ES) is linked with primary immunodeficiencies.³ It can appear as a secondary disease associated with immune dysregulation disorders, such as autoimmune lymphoproliferative syndrome (ALPS) and common variable immunodeficiency (CVID).^5,9

What causes evans syndrome?

Evans syndrome (ES) is an autoimmune disease in which the immune system destroys the body’s own blood cells, recognising them as foreign. Immune B cells produce antibodies that target and destroy specific types of blood cells, such as red blood cells, white blood cells and platelets. The attack often begins with one type of cell and gradually extends to others.

What are the symptoms of Evans Syndrome (ES)? 

The signs and symptoms of Evans syndrome (ES) are different among individuals. Mostly, they depend on the type of blood cell that is affected: red blood cells, platelets, and/or white blood cells. Many patients experience periods of remission, during which symptoms improve or temporarily disappear, often as a result of treatment.⁸

In case of low red blood cells - anaemia, symptoms that may appear are

• Unusual tiredness (fatigue)
• Pale complexion (pallor)
• Lightheadedness or dizziness
• Shortness of breath (dyspnea)
• Rapid heartbeat (tachycardia)
• Unusual heartbeat or heart palpitations

In case of low platelets - thrombocytopenia, symptoms that may appear are

• Tiny red spots of bleeding under the skin (petechiae)
• Unexplained bruises (ecchymosis)
• Heavily bleeding gums or nosebleeds
• Heavy menstrual bleeding
• Blood in your poop or in your pee

In case of low neutrophils - neutropenia symptoms that may appear are

• Fever
• Mouth sores (ulcers)
• Frequent colds, flus and stomach bugs
• Recurring ear infections
• Persistent fungal infections
• Urinary tract infections (UTIs)

Diagnosis 

There is no standard procedure for the diagnosis of Evans Syndrome. It depends on the severity of the symptoms and other autoimmune diseases and cancers. Prior to confirmation of the diagnosis, doctors should exclude the possibility of other autoimmune diseases and cancers.⁶

Tests 

• Blood tests for checking the level of blood cells
• Test for infections like HIV and Hepatitis C
• Bone marrow 

Disease course in adults vs children

Evans syndrome (ES) is a rare and serious condition characterised by a challenging clinical course, with a high risk of relapse (return of the disease), frequent infections, blood clotting complications and in some cases, a life-threatening outcome.⁹

Adults

Adult-onset Evans syndrome (ES) is a rare, often severe, and potentially life-threatening condition. It is characterised by frequent relapses, prolonged or complex treatment regimen, and an increased risk of both infections and thrombosis (one or more blood clots form in the blood vessels). All of these factors can significantly impact patient survival.¹⁰

Children 

The paediatric clinical course of Evans syndrome (ES) is usually chronic and relapsing. It may present with autoimmune haemolytic anaemia and immune thrombocytopenia both at once, or occurring gradually and sometimes neutropenia. The onset can be acute or gradual, ranging from mild fatigue and bruising to severe anaemia or bleeding. Paediatric cases frequently experience relapses, with cytopenias alternating or recurring over time.^7,11

Possible complications 

Here are some possible complications that might appear:

• Severe Anaemia: Low red blood cells can cause tiredness, weakness, and even heart problems
• Bleeding Problems: Low platelets can make it easy to bruise or bleed, and in serious cases, bleeding in the brain can happen
• Infections: Some treatments weaken the immune system, making someone more susceptible to infections

Is there any cure for evans syndrome? 

As Evans syndrome (ES) is an autoimmune disease, there is no cure for the disease. The treatment depends on various factors such as: type of ES (primary or secondary) and the type of cells that are destroyed by the immune system, causing low levels of blood cells. Symptomatic treatment is applied, such as transfusion of blood cells,⁶ only in severe symptomatic patients due to the risk of worsening.¹¹

First-line therapy

Standard treatment for autoimmune diseases are immunosuppressants and intravenous immunoglobulin (IVIG). Immunosuppressants such as corticosteroids suppress the immune system. Intravenous immunoglobulins (IVIG) are human antibodies that enter directly into your bloodstream and stop the immune system from harming its own blood cells.⁶

Second-line therapy 

In case you are unresponsive to these treatments, rituximab, mofetil mycophenolate, cyclosporine, vincristine, azathioprine, sirolimus and thrombopoietin receptor agonists or splenectomy (surgery to remove spleen) are the second-line treatments your doctor may prescribe.^12,13

Stem cell transplant (HSCT)

Blood and marrow transplantation are the only treatments for the moment, with the potential cure for patients who suffer from Evans syndrome (ES) and do not respond to other treatments. However, because Evans syndrome (ES) is a rare disease with few reported cases, there is a lack of large, long-term studies.¹⁴

Summary

Evans syndrome (ES) is a very uncommon autoimmune disease in which immune cells are attacked by the body's immune system, causing different types of cytopenias. In children, Evans syndrome (ES) cause is almost unknown (idiopathic), but it can be secondary as well, associated with inherited immune disorders. While in adults, it is mostly secondary associated with other autoimmune diseases, systemic lupus erythematosus (SLE), haematological cancers, and viral infections. Based on the type of blood cells affected and the severity of the condition, when other autoimmune diseases coexist, the treatment of Evans syndrome (ES) can be personalised. Mostly used are corticosteroids and IVIG as first-line therapy, and in case of unresponsiveness to them, rituximab or splenectomy are recommended. Treatment management is similar for children and adults, but the outcome varies from many factors. Some people may be more responsive to treatment, and others less. Various people have different clinical courses of the disease. Symptoms can be mild to severe. For some, they seem to disappear (go into remission). And for others, they reappear later (relapse). When complications arise, it can be life-threatening. Mortality is high even though ES is rare. Early diagnosis and the right treatment are important in order to improve outcomes. Due to these reasons, people with ES need regular check-ups and blood tests. As a result, more studies and research are needed to have more accurate data and find new therapeutic ways for the disease.