Hypereosinophilic syndrome (NORD)
Hyper eosinophilic syndrome or HES is a group of disorders that are characterized by elevated levels of eosinophils in the blood called eosinophilia, as well as accumulation of eosinophils in at least one organ in association with tissue damage and dysfunction.
In HES, large numbers of eosinophils, a type of white blood cells, accumulate and become activated, releasing excess amounts of their cellular constituents, most notably their granules, which instead of being helpful, are toxic to a variety of tissues, resulting in organ dysfunction.
There are 3 main types of HES categorized based on the underlying cause primary or neoplastic, secondary or reactive, and familial or hereditary.
Primary or neoplastic HES is caused by de novo genetic changes or variants, which means that a new DNA sequence change is typically responsible.
The DNA change is not inherited but occurs later in life, called a de novo variant. The result is myeloid cell expansion or expansion of an abnormal clone of T cells, a type of immune cell that stimulates production of eosinophils.
The myeloid expansion is often referred to as hematological or neoplastic HES, whereas the T cell expansion is referred to as clonal lymphoid HES.
Secondary HES, also known as reactive HES, is the most common and is caused by a response to a secondary stimulus such as an infection, like from a parasite or an underlying inflammatory process, drugs such as anti-seizure medications, or some cancers.
Hereditary or familial type HES is characterized by a history of eosinophilia in several family members and is caused by inherited gene changes.
This form of HES is often more benign. Individuals with HES may have no symptoms, mild symptoms, or severe symptoms like heart failure or stroke.
Symptoms may come on gradually or all of a sudden. Symptoms may be general, such as fatigue, fever, muscle pain, and night sweats.
Or specific to the affected organ like the skin, lungs, gastrointestinal tract, heart, and nervous system. The skin is the most commonly affected organ, and AGS can cause itching, rash, or hives.
When the lungs are involved, individuals may experience shortness of breath, coughing, and wheezing. Gastrointestinal symptoms include weight loss, difficulty swallowing, abdominal pain, vomiting, diarrhea, and jaundice, or yellowing of the skin.
Heart symptoms include cough, shortness of breath, chest pain, palpitations, or heart failure. Nervous system involvement can cause numbness or tingling in the hands or feet, muscle and joint pain, confusion, memory loss, and even strokes.
HES is diagnosed when the eosinophil count is persistently elevated, greater than 1500 cells per microliter of blood, there is evidence of organ or tissue damage, and other diagnoses have been eliminated.
Specific testing typically involves extensive blood work, genetic testing, and other tests dependent upon symptoms. For example, if an individual with eosinophilia has gastrointestinal symptoms, a CT scan of the abdomen or endoscopy and biopsy is often performed.
In those with heart involvement, an electrocardiogram, chest X-ray, echocardiogram, or ultrasound of the heart may be done.
After HES is diagnosed, additional evaluations may be necessary to determine the type of HES. A family history of eosinophilia supports hereditary HES.
A history of taking drugs such as anti-seizure medications or positive testing for a parasitic infection may point to secondary HES.
Hematologic and bone marrow genetic testing can detect de novo and inherited gene changes supporting primary or neoplastic HES.
Treatment varies based on the type and severity of HES. Individuals with secondary HES due to parasitic infection can be treated with anti-parasitic medications, whereas those with secondary HES due to medication use are treated by stopping the offending drug.
Some people, especially those with hereditary HES who do not have any or many symptoms, may not need treatment, but should be carefully monitored for worsening organ involvement.
In those that are treated, the goal is to lower eosinophil levels, stop progression of organ damage, and reduce symptoms.
The only approved treatments for HES are imatinib and mepolizumab. Initial treatment is often with imatinib, an oral tyrosine kinase inhibitor, but this is limited to adult patients with known genetic mutations that cause primary or neoplastic HES that is specifically susceptible to this drug.
Mepolizumab is a biological agent that blocks the eosinophil growth factor interleukin 5 and thereby lowers eosinophils and their activation status.
Mepolizumab is typically used after glucocorticoids, an anti-inflammatory medication that reduces the body's immune response and normally lowers eosinophils.
Glucocorticoids can be given orally or intravenously based on symptom severity and may be taken for several months or lifelong.
Hydroxyurea can be used in individuals who are not eligible for imatinib or who do not improve with glucocorticoids alone.
Like imatinib, hydroxyurea can be used by itself or with glucocorticoids. Interferon alpha may be used to block T cells from releasing interleukin 5, reducing eosinophilic granular release and symptoms in those with T cell anomalies.
While many patients are responsive to glucocorticoids, mepolizumab and hydroxyurea can be used as steroid sparing agents.
All right, as a quick recap, HES is a group of disorders that are characterized by eosinophilia, organ damage, and dysfunction.
There are 3 main types of HES categorized based on the underlying cause. Symptoms are based on the affected organ.
Treatment varies based on the type and severity of HES and includes imatinib, glucocorticoids, hydroxyurea, and mepolizumab.
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