Evans Syndrome Symptoms, Diagnosis and Treatment

Evans Syndrome is a combination of two or more immune hematological disorders where your immune system attacks your white blood cells, red blood cells and/or platelets. These include immune thrombocytopenia (ITP), autoimmune hemolytic anemia (AIHA), and/or autoimmune neutropenia (AIN). These diagnoses might occur at the same time but can also occur in the same patient at two different times. For example, if you are diagnosed with ITP and then two years later are diagnosed with AIHA, you would have Evans Syndrome.

Symptoms

In most circumstances, you have already been diagnosed with one of the individual disorders: ITP, AIHA, or AIN. Evans Syndrome presents like any one of the individual disorders. 

Symptoms include:

Low platelet counts (thrombocytopenia):

• Increased bruising
• Increased bleeding: blood blisters in the mouth, nosebleeds, gum bleeding, blood in urine or stool
• Tiny red dots on the skin called petechiae

Anemia:

• Fatigue or tiredness
• Shortness of breath
• Elevated heart rate (tachycardia)
• Yellowing of the skin (jaundice) or eyes (scleral icterus)
• Dark urine (tea or coca-cola colored)

Low neutrophil count (neutropenia):

• Fever
• Infections of skin or mouth
• Often there are no symptoms

Why Evans Syndrome Causes Blood Counts to Be Low

Evans Syndrome is an autoimmune disease. For some unknown reason, your immune system incorrectly identifies your red blood cells, platelets, and/or neutrophils as "foreign" and destroys them.

It is not entirely understood why some people only have one blood cell affected, as in ITP, AIHA, or AIN, versus more than one in Evans Syndrome. 

Diagnosis

As most people with Evans Syndrome already carry one of the diagnoses, the presentation of another one equals Evans Syndrome. For example, if you have been diagnosed with ITP and develop anemia, your physician will need to determine the cause of your anemia. If your anemia is found to be due to AIHA, you will be diagnosed with Evans Syndrome. 

Because these disorders affect your blood counts, a complete blood count (CBC), is the first step in the work up. Your physician is looking evidence of anemia (low hemoglobin), thrombocytopenia (low platelet count) or neutropenia (low neutrophil count, a type of white blood cell). Your blood will be examined under a microscope to try to identify the cause. 

ITP and AIN are diagnoses of exclusion meaning there is no one specific diagnostic test. Your physician must rule out other causes first. AIHA is confirmed by multiple tests, most specifically a test called DAT (direct antiglobulin test). The DAT looks for evidence that the immune system is attacking the red blood cells.

Treatment

There is a long list of possible treatments. Treatments are directed at the specific blood cell affected and whether you have any symptoms (active bleeding, shortness of breath, elevated heart rate, infection): 

• Steroids: Medications like prednisone have been used for years in various autoimmune disorders. They are the first line treatment for AIHA and are also used in ITP. Unfortunately, if you have Evans Syndrome, you may require steroids for long periods of time which may result in other issues like high blood pressure (hypertension) and elevated blood sugars (diabetes). For this reason, your physician may look for alternative therapies.
• Intravenous Immunoglobulin (IVIG): IVIG is a first-line treatment for ITP. Essentially, the IVIG distracts your immune system temporarily so that the platelets are not destroyed as rapidly. IVIG is not as effective in AIHA or AIN. 
• Splenectomy: The spleen is the main location of the destruction of the red blood cells, platelets, and neutrophils in Evans Syndrome. In some patients, surgical removal of the spleen might improve blood counts, but this may be only temporary.
• Rituximab: Rituximab is a medication called a monoclonal antibody. It reduces your B-lymphocytes (a white blood cell that makes antibodies), which can improve your blood counts.
• G-CSF (filgrastim): G-CSF is s a medication used to stimulate the bone marrow to make more neutrophils. It is sometimes used to increase the neutrophil count in AIN, particularly if you have an infection.
• Immunosuppressive Medications: These medications inhibit the immune system. These would include medications like mycophenolate mofitel (MMF), azathioprine (​Imuran), tacrolimus (Prograf). ​

Although patients may respond to individual treatments with improvement in blood counts, this response if often temporary requiring additional treatments.