What is Evans Syndrome?
Evans syndrome is a disease where the body’s immune system mistakenly attacks its own cells, leading to a decrease in two or more types of blood cells. This usually includes conditions like autoimmune hemolytic anemia (AIHA) where the body destroys its own red blood cells, and immune thrombocytopenia (ITP) where the body destroys its own platelets, which are needed for blood clotting. In some cases (about 15%), it can also include immune neutropenia where the body attacks its neutrophils, a type of white blood cell.
In Evans Syndrome, the particular type of AIHA that occurs is called warm AIHA. This means that the body’s immune cells attach to red blood cells at body temperature, which is different from the other type of AIHA known as cold AIHA. As for ITP, it happens when the immune system targets a certain protein on the platelets.
Scientists have suggested that we should classify Evans syndrome as either primary, which means it occurs on its own, or secondary, which means it is linked to another disease. Secondary Evans syndrome can be linked to various diseases such as lupus, immune deficiency, non-Hodgkin’s lymphoma (a type of cancer), chronic lymphocytic leukemia (another type of cancer), viral infections like HIV or Hepatitis C, and following certain types of bone marrow transplants.
This distinction is vital because we’ve observed that the decrease in blood cells is generally more severe in Evans Syndrome compared to when AIHA or ITP occur on their own. Additionally, the treatment options change depending on whether the syndrome is primary or secondary.
What Causes Evans Syndrome?
The exact reason why this disease happens isn’t fully understood, that’s why it’s typically considered a condition with no known cause. It’s an autoimmune disease, meaning the body’s own immune system mistakenly attacks its own cells. The cells under attack in this case are red blood cells, platelets, and white blood cells, which are all key players for our body’s health.
In recent times, experts have suggested that the disease may be the result of the immune system not functioning properly or going into overdrive. In simple terms, it’s believed that this “misbehavior” of the immune system could be the driving force behind this condition.
Risk Factors and Frequency for Evans Syndrome
Evans syndrome is a rare condition, found in fewer than 5% of all patients who have either ITP or AIHA. The average age for diagnosis of Evans syndrome is 52 years old. This condition is more commonly found in women than men, with a 3:2 ratio. But it’s important to note that not only children are affected by Evans syndrome; adults can have it too. This is usually a random condition, with no known genes linked to it. In uncommon scenarios, it can be passed down through families, also known as “familial Evans syndrome”. There are reports of this condition occurring alongside other issues such as heart defects or inherited disorders like hereditary spastic paraplegia.
Signs and Symptoms of Evans Syndrome
Evans syndrome is a condition that affects various types of blood cells. Its signs and symptoms can change depending on which blood cells get affected. People with this disorder may experience tiredness, paleness, dizziness, shortness of breath, and restricted physical activity when anemia is part of the condition. Also, they may display pallor and jaundice, or yellowing of the skin or the whites of the eyes, and they might have an enlarged spleen. Those who have low platelet counts (ITP) might bruise easily or bleed even from small injuries. They may also have tiny red spots on their skin called petechiae, or larger patches of purpura due to bleeding under the skin. For those with low white blood cell counts (neutropenia), recurrent infections may occur.
In some instances, the low platelet count in Evans syndrome can lead to severe bleeding, which could be life-threatening. There have also been cases where anemia increased the risk of blood clot-related complications like heart attacks or strokes, particularly in people over 60 years old.
Testing for Evans Syndrome
If a blood test shows that you have anemia, and your doctor suspects you might have Evans syndrome, they will likely run some more tests. These tests can include checks for levels of lactate dehydrogenase, haptoglobin, bilirubin, and the count of reticulocytes (a type of immature red blood cell). These tests help the doctor see if your body is destroying its own red blood cells, a condition known as hemolysis. They may also perform what’s known as a direct antiglobulin test (DAT) and examine a sample of your blood under a microscope to look for spherocytes (round red blood cells), both of which can indicate warm autoimmune hemolytic anemia, a condition often associated with Evans syndrome.
Evans syndrome is usually diagnosed only after other possible causes have been ruled out. So, your doctor may also need to check for other diseases that can cause similar symptoms, such as cold agglutinin disease, thrombotic thrombocytopenic purpura (a rare blood disorder), infectious diseases like HIV or Hepatitis C, other autoimmune conditions, and cancers.
There are no standard rules about which tests should be done in people with suspected Evans syndrome to search for an underlying disease. However, if you’re young and some common disorders such as Systemic Lupus Erythematosus (SLE) or Autoimmune Lymphoproliferative Syndrome (ALPS) are suspected, your doctor may do a minimal check for cancer. This could include a computed tomography (CT) scan of your chest and abdomen, which are ways to get detailed images of the inside of your body.
Treatment Options for Evans Syndrome
Managing Evans syndrome can be tricky since the condition often doesn’t respond well to treatments that typically work for isolated AIHA (autoimmune hemolytic anemia). The most suitable treatment for a patient will depend on their specific symptoms, the severity of their condition, and any other health problems they may have.
If the patient has a low blood count which is causing symptoms like fatigue (due to anemia) or excessive bleeding (due to a low platelet count known as thrombocytopenia), they might need supportive treatments such as blood transfusions.
In order to address the underlying problem, doctors usually recommend corticosteroids or intravenous immunoglobulin (IVIG) as the initial treatment. Corticosteroids are anti-inflammatory drugs that help to quieten the immune system, while IVIG is a therapy using donated blood antibodies to block the harmful effects of the antibodies causing Evans syndrome. It’s more often used in the presence of thrombocytopenia than with isolated AIHA.
Even though a majority of patients initially respond to corticosteroids, the effectiveness doesn’t last for everyone, and more than half of people experience a relapse. This means that other treatments often need to be considered.
Two such options are the drug rituximab or an operation called a splenectomy. Rituximab is often preferred, as it’s better received by the body, particularly when Evans syndrome occurs due to another underlying issue like cancer or lupus (SLE), or in those who have a high risk of infection that could make splenectomy risky. Using rituximab in combination with steroids has resulted in disease remission in as many as 76% of cases, according to one study. Splenectomy, the surgical removal of the spleen, is decreasing in frequency now because it has lower response rates, higher chances of relapse, and a risk of sepsis. Other medications such as Danazol have also been utilized as secondary treatments.
In cases where corticosteroids or rituximab aren’t effective, doctors might turn to immunosuppressant drugs. These medications work by damping down the immune system, which has become overactive in people with Evans Syndrome. Many different types of these drugs have been tried, but cyclosporin A and mycophenolate mofetil are often chosen because of their effectiveness in autoimmune conditions. Other used medications include cyclophosphamide, azathioprine, and sirolimus. The choice will depend on the patient’s specific circumstances and the severity of their disease.
In very rare cases, when all other treatments have failed, a hematopoietic stem cell transplant might be considered. This treatment involves receiving healthy stem cells to replace the diseased ones. Both autologous (using the patient’s own stem cells) and allogeneic (using donor stem cells) transplants have been performed in a small number of patients, with varying degrees of success.
What else can Evans Syndrome be?
There are several different medical conditions which could potentially cause certain symptoms, including:
- Autoimmune lymphoproliferative syndrome (ALPS)
- Thrombotic thrombocytopenic purpura (TTP)
- Systemic lupus erythematosus (SLE)
- Antiphospholipid syndrome (APLA)
- Sjogren syndrome
- Common variable immunodeficiency (CVID)
- IgA deficiency
- Lymphomas
- Chronic lymphocytic leukemia (CLL)
What to expect with Evans Syndrome
People with a condition called Evans syndrome usually need treatment. However, the effect of treatment can greatly vary, and there’s often a chance the symptoms could come back. Additionally, these individuals are at a higher risk of developing other, related health conditions, such as systemic lupus erythematosus (SLE) – an autoimmune disease where the body’s immune system mistakenly attacks healthy tissue.
Research focusing on patients with Evans syndrome showed that only 32% of patients were symptom-free without treatment over an extended period of roughly five years.
