Our immune system is our body’s sophisticated and powerful defense force, designed to identify and destroy foreign invaders like bacteria and viruses. In an autoimmune disease, this system becomes tragically misdirected, mistakenly attacking the body’s own healthy tissues. For individuals with Evans syndrome, this internal conflict is particularly complex and severe. Evans syndrome is a rare and serious autoimmune disorder where the immune system wages a “two-front war,” simultaneously or sequentially launching attacks on at least two different types of blood cells, usually red blood cells and platelets. This can lead to a dangerous combination of anemia and bleeding problems, requiring lifelong management by a specialist. Understanding this complex condition is the first step for patients and their families to navigate its unpredictable course.

Evans Syndrome is a rare autoimmune disorder in which the immune system mistakenly attacks the body’s own blood cells. It typically involves two or more autoimmune blood disorders, most commonly:

1. Autoimmune Hemolytic Anemia (AIHA): The immune system destroys red blood cells, the cells responsible for carrying oxygen throughout the body.
2. Immune Thrombocytopenia (ITP): The immune system destroys platelets, the tiny cell fragments essential for blood clotting.

In some individuals, the immune system may also target a type of white blood cell called the neutrophil, leading to a third condition called Autoimmune Neutropenia, which increases the risk of bacterial infections.

To grasp the complexity of this condition, it is helpful to use an analogy. Think of your immune system as an advanced security system with different targeting programs designed to eliminate specific threats. In a more common autoimmune disease like isolated ITP, a single targeting program malfunctions and instructs the system to attack your own platelets. In Evans syndrome, the security system itself is fundamentally dysregulated. Multiple targeting programs malfunction simultaneously or one after another, leading the security system to attack your red blood cells, your platelets, and sometimes your neutrophils. It is this multi-front, internal conflict that defines the syndrome and makes it so challenging to manage.

In my experience, Evans Syndrome can be frustrating for both patients and doctors. It often feels like treating one thing improves it briefly, only for another problem to flare up.

The exact cause of Evans Syndrome is still not fully understood, but it’s believed to be related to immune system dysregulation where the body can no longer distinguish between self and foreign cells. In a healthy body, the immune system produces antibodies to attach to foreign invaders, tagging them for destruction. In Evans syndrome, the immune system loses its ability to distinguish “self” from “non-self” and produces autoantibodies that mistakenly recognize specific proteins on the surface of its own blood cells as targets.

• In the AIHA component, autoantibodies coat the surface of red blood cells. As these “tagged” cells circulate through the body, they are recognized as abnormal and are prematurely destroyed by immune cells, primarily in the spleen and liver.
• In the ITP component, a different set of autoantibodies coats the surface of platelets, leading to their rapid destruction in the spleen.

The fundamental problem is deep immune dysregulation.  Patients often ask, “Did I do something to cause this?” and I reassure them that autoimmune conditions often appear unexpectedly and are not caused by anything they did.

Evans Syndrome can affect any age group, but it is most commonly diagnosed in children and young adults. You cannot “catch” Evans Syndrome, it’s not contagious, and it’s not caused by lifestyle choices. A person develops the condition when their immune system becomes severely dysregulated. This can happen spontaneously or in association with another disease. This distinction leads to two classifications.

Primary (or Idiopathic) Evans Syndrome In approximately 50% of cases, Evans syndrome occurs without any other identifiable underlying disease. The cause of the autoimmune attack is unknown, and it is considered a primary immune regulation disorder.

Secondary Evans Syndrome In the other half of cases, the development of Evans syndrome is associated with or triggered by another medical condition. The most common of these associated diseases include:

• Other Autoimmune Diseases: Evans syndrome can be a complication of another autoimmune disorder, most commonly Systemic Lupus Erythematosus (SLE). It can also be associated with Sjögren’s syndrome and antiphospholipid syndrome.
• Immunodeficiency Disorders: Certain primary immunodeficiency diseases, which are genetic conditions affecting the immune system, can lead to the development of Evans syndrome. These include Common Variable Immunodeficiency (CVID) and Autoimmune Lymphoproliferative Syndrome (ALPS), a rare genetic disorder of immune regulation.
• Cancers of the Lymphatic System: Certain blood cancers, particularly chronic lymphocytic leukemia (CLL) and some types of non-Hodgkin lymphoma, can be associated with secondary Evans syndrome.
• Following Infections: Rarely, the onset of the syndrome has been linked to a preceding viral infection.

Clinically, I always check for coexisting autoimmune diseases or lymphoproliferative conditions. Evans Syndrome is rarely just one thing.

The symptoms of Evans Syndrome vary depending on which blood cells are being targeted, the severity of the immune attack, and whether it is acute or chronic. Symptoms may come in waves or flare-ups.

The symptoms a person experiences depend on which cell line is being most actively destroyed at any given time.

Symptoms of Autoimmune Hemolytic Anemia (from low red blood cells):

• Profound fatigue, weakness, and lethargy that is out of proportion to daily activities.
• Shortness of breath, especially with physical exertion.
• Dizziness or lightheadedness.
• A rapid heartbeat or palpitations.
• Pale skin (pallor).
• Jaundice, which is a yellowing of the skin and the whites of the eyes, caused by a buildup of bilirubin from the breakdown of red blood cells.
• Dark, tea-colored or cola-colored urine, caused by hemoglobin being filtered into the urine.

Symptoms of Immune Thrombocytopenia (from low platelets):

• Easy or excessive bruising (purpura), often appearing without any known injury.
• Petechiae, which are pinpoint-sized, red or purple dots on the skin, usually most prominent on the lower legs. They look like a rash but are actually tiny bleeds under the skin.
• Frequent or prolonged nosebleeds.
• Gum bleeding, especially after brushing teeth.
• Unusually heavy menstrual periods in women.
• In cases of very low platelet counts, there is a risk of more serious internal bleeding.

If autoimmune neutropenia is also present, a person may experience recurrent fevers and frequent bacterial infections.

Patients often describe Evans Syndrome as a “rollercoaster” . One week they’re doing okay, and the next, they’re in the hospital for anemia or unexplained bleeding. That unpredictability is its hallmark.

Diagnosis is based on blood tests that show evidence of autoimmune destruction of blood cells and ruling out other causes like cancer, infections, or drug reactions.

1. Complete Blood Count (CBC): This is the initial blood test, which will confirm the low blood counts (cytopenias), showing anemia, thrombocytopenia, or neutropenia.
2. Tests for Autoimmune Hemolytic Anemia (AIHA):
   • Direct Antiglobulin Test (DAT or Direct Coombs Test): This is the key diagnostic test. It is a blood test that can detect the presence of antibodies and/or complement proteins attached to the surface of the patient’s red blood cells. A positive DAT confirms that the anemia is autoimmune in nature.
   • Other blood tests will show evidence of hemolysis, including a high reticulocyte count, high bilirubin, and high LDH levels.
3. Tests for Immune Thrombocytopenia (ITP): There is no single confirmatory test for ITP. It is largely a diagnosis of exclusion. When a patient has a confirmed diagnosis of AIHA and also has a low platelet count, and other causes have been ruled out, the ITP component of Evans syndrome is diagnosed.
4. Bone Marrow Aspiration and Biopsy: This procedure is often performed to examine the bone marrow. In Evans syndrome, the marrow is usually healthy and actively producing all the blood cells, but they are being destroyed in the bloodstream after they are released. This test is important for ruling out other causes of low blood counts, such as leukemia or aplastic anemia.
5. Screening for Secondary Causes: Once Evans syndrome is confirmed, doctors will perform further tests to look for an underlying condition, such as testing for the autoantibodies associated with lupus (ANA test) or screening for immunodeficiencies and lymphoproliferative disorders.

Clinically, we look for two or more low cell counts with immune markers pointing toward autoimmunity, that’s what defines Evans Syndrome.

There is no permanent cure for Evans Syndrome, but long-term management aims to suppress immune overactivity, support blood cell levels, and prevent complications. Treatment is complex and follows a tiered approach.

1. First-Line Therapy The initial treatment is focused on rapidly calming the immune system.

• Corticosteroids: High doses of steroids, like prednisone, are the standard first-line treatment. They are powerful immunosuppressants that can quickly reduce the destruction of red blood cells and platelets.
• Intravenous Immunoglobulin (IVIG): In cases of very severe bleeding from ITP or rapid hemolysis from AIHA, IVIG may be given. This infusion of donated antibodies can help to temporarily block the destruction of blood cells by the spleen.

2. Second-Line Therapies Unfortunately, many patients with Evans syndrome relapse as their steroid dose is tapered or do not respond adequately. In these cases, second-line therapies are needed.

• Rituximab: This is a monoclonal antibody medication that targets and destroys a type of immune cell called the B-cell. Since B-cells are responsible for producing the harmful autoantibodies, this treatment can be very effective at inducing a longer-lasting remission.
• Other Immunosuppressants: A variety of other immunosuppressive drugs may be used, often in combination, to keep the immune system in check. These include medications like mycophenolate mofetil (MMF), azathioprine, cyclosporine, and sirolimus.

3. Other Treatments and Supportive Care

• Splenectomy: The surgical removal of the spleen, a major site of blood cell destruction, may be considered for patients who do not respond to multiple medications. However, its effectiveness in Evans syndrome can be less predictable than in isolated ITP or AIHA, and it carries a lifelong risk of serious infections.
• Supportive Care: Blood transfusions, platelet transfusions, and prompt treatment of infections are critical.

I’ve seen some patients go years with stable counts after finding the right combination of immunosuppressants, others may need ongoing adjustments to avoid relapses.

Evans syndrome is a rare, chronic, and serious autoimmune disease that poses significant challenges for both patients and the doctors who treat them. It is characterized by an unpredictable, relapsing-remitting course where the body’s own immune system wages a war against its essential blood cells. While the journey of living with Evans syndrome can be difficult, filled with uncertainty and requiring long-term treatment with powerful medications, the outlook has improved with modern therapies. Patients often say they finally feel in control once they understand what’s happening in their body, and with the right support, Evans Syndrome becomes something they can live with, not fear.

1. National Organization for Rare Disorders (NORD). (2022). Evans Syndrome. Retrieved from https://rarediseases.org/rare-diseases/evans-syndrome/
2. National Institutes of Health, Genetic and Rare Diseases Information Center (GARD). (2021). Evans syndrome. Retrieved from https://rarediseases.info.nih.gov/diseases/6356/evans-syndrome
3. American Society of Hematology (ASH). (n.d.). Autoimmune Hemolytic Anemia. Retrieved from https://www.hematology.org/education/patients/anemia/autoimmune-hemolytic-anemia