Hypereosinophilia

How is eosinophilia treated when its cause has been identified?

If a classical cause of eosinophilia is found, it must be treated. For example, a parasitic infection will be treated with antiparasitic medication (often a very simple, well-tolerated, short course taken by mouth), a drug allergy will be treated by stopping the medication, and lung cancer will be treated with surgery, chemotherapy and/or radiotherapy.
If the treatment is effective, the eosinophilia will disappear. A short course of cortisone may sometimes be added to lower the eosinophil count more rapidly, if the doctor considers that the eosinophils are causing concerning tissue damage.

Treatment of rarer chronic inflammatory diseases is often based on cortisone and/or other immunosuppressive medicines (which reduce the immune response).
Chronic eosinophilic leukaemia responds poorly to cortisone. However, in almost all cases, it responds extremely well to low doses of imatinib mesylate (Glivec). This is a highly specific treatment that directly targets the cellular defect responsible for the proliferation of eosinophils. This low-dose treatment is taken by mouth, is effective within a few days and is very well tolerated.
Treatment of the other haematological diseases differs for each one and is beyond the scope of this summary.

When hypereosinophilia remains unexplained despite an extensive work-up, it must nevertheless be treated to limit and prevent the damage it causes and, where possible, reverse it. The blood eosinophil count and clinical manifestations are used to determine whether the patient is responding to treatment.
At the start of treatment, and for as long as the situation is not under control, medical check-ups are frequent in order to monitor several elements: the response to treatment, any treatment-related toxicity, and the progression of complications or the emergence of new complications of hypereosinophilia that may require additional symptomatic treatment (for example, heart failure requires medicines specifically intended to support cardiac function, in addition to treatment aimed at reducing the eosinophil count).
Once the situation is under control, visits can gradually be scheduled less frequently.

Treatment is started with corticosteroids (Medrol, or prednisolone capsules prepared by the pharmacist), which are effective in the majority of cases and act rapidly, within a few hours or days.
Corticosteroids have numerous mechanisms of action; in particular, they accelerate eosinophil death and reduce the production of growth factors, including interleukin-5, by T lymphocytes.
The side effects of corticosteroids are numerous and often well known to the general public: facial swelling, reduced muscle mass, the appearance of stretch marks and thinning of the skin, high blood pressure, diabetes, cataracts, glaucoma, gastric ulcer, bone demineralisation (osteoporosis), and increased susceptibility to certain infections, to mention the most common ones.

1. In the event of a response to corticosteroids

If there is a good response to corticosteroids, the dose will be gradually reduced to the lowest dose that ensures disease control. This so-called “maintenance” dose will then be continued for at least several months.
If corticosteroids are effective but the maintenance dose is high and/or causes significant side effects, second-line treatments will be used (known as “corticosteroid-sparing treatments”, as they make it possible to reduce the dose of corticosteroids needed to control the disease).

The most commonly used agent is hydroxyurea (Hydrea), as it is easy to take (tablets taken by mouth) and prescribe (available on prescription from all pharmacies), and is free of charge in Belgium. This medicine, used to treat haematological diseases such as chronic myeloid leukaemia or essential thrombocythaemia (an abnormally high platelet count), works by reducing the production of blood cells in the bone marrow, including eosinophils.
The main side effects are haematological toxicity, with an excessive decrease in white blood cells, red blood cells and/or platelets. Patients may also experience digestive intolerance, with abdominal discomfort, loss of appetite, nausea, diarrhoea and/or mouth ulcers.

Interferon-alpha is also used to treat idiopathic hypereosinophilic syndrome. This treatment acts on eosinophils and T lymphocytes by “modulating” their functions. For example, it reduces the production of interleukin-5 by T lymphocytes without reducing immune defences. It belongs to a family of molecules that we naturally produce to fight certain viral infections, such as influenza.
This agent is rarely prescribed in Belgium to treat hypereosinophilic syndrome because it is not reimbursed for this indication and costs several hundred euros per month. In addition, it is administered by subcutaneous injection several times a week, and the side effects are often poorly tolerated. Among these, a flu-like syndrome (with fever, chills, muscle pain and headaches) is the one most likely to lead to discontinuation of treatment.

Some immunosuppressive medicines are sometimes tried to reduce the corticosteroid dose, but they are rarely effective and have numerous side effects: ciclosporin (Neoral), azathioprine (Imuran), cyclophosphamide (Endoxan).

Mepolizumab (Nucala) is an agent that specifically targets interleukin-5 (it binds to this growth factor and neutralises its effects). It has recently been approved as a treatment for severe eosinophilic asthma that is not controlled by standard treatments. It proved to be an effective corticosteroid-sparing treatment for hypereosinophilic syndrome when administered intravenously once a month as part of a clinical study. However, it is not yet available to treat this disease because it has not been approved for this indication by the regulatory agencies (in particular, the Food and Drug
Administration, or FDA, in North America; and the European Medicines Agency, or EMA, in Europe). It is currently available to treat hypereosinophilic syndrome only במסגרת a compassionate-use programme based on an individual case assessment, for patients with disease considered very severe (potentially life-threatening), for whom the conventional treatments mentioned above are ineffective and/or poorly tolerated.
A new clinical study assessing the efficacy of subcutaneous mepolizumab administration in patients with hypereosinophilic syndrome is currently being prepared.

2. In the absence of a response to corticosteroids

If the eosinophil count and symptoms do not respond, or respond only very partially, to corticosteroids, selecting an effective treatment may require several trials and changes of medicines over a period of several months, during which eosinophils may continue to cause damage. Close medical follow-up is essential during this period.

The corticosteroid-sparing agents mentioned in the previous section may sometimes be effective, possibly in combination (for example, hydroxyurea and interferon-alpha).

Rarely, some of these patients have an acquired genetic mutation that remains undetected (it is invisible using the techniques currently available to us) and that justifies a short trial (one month) of imatinib mesylate (Glivec). The recommended dose is higher than that used for chronic eosinophilic leukaemia and is therefore more often associated with side effects, including swelling of the legs and eyelids, fatigue, and
bone marrow toxicity.

Mepolizumab has never been tested in corticosteroid-resistant patients as part of a clinical study. However, it is available במסגרת the compassionate-use programme mentioned above, with patient eligibility determined individually after assessment of the medical file.

Very rarely, a patient may not respond to any of the treatments mentioned above, while persistent hypereosinophilia continues to cause significant damage (to the heart, brain or blood vessels, for example) that threatens survival. The possibility of a stem cell transplant (formerly called a bone marrow transplant) from a healthy donor (either a close family member, where possible, or an unrelated donor) must then be discussed. This procedure consists of administering high-dose chemotherapy in the hope of killing all the abnormal cells in the bone marrow that are
responsible for the hypereosinophilia. One consequence (unintended but unavoidable) of this treatment is that the other bone marrow cells needed to produce red blood cells, healthy white blood cells required to protect us against infections, and platelets will also be destroyed. It is then necessary to provide the patient with healthy cells (collected from a healthy donor), which will repopulate the bone marrow and enable it to produce
new red blood cells, white blood cells and platelets. This procedure exposes the patient to the risk of numerous serious complications during the period before the donor cells have colonised the bone marrow, and will therefore be reserved for the most severe cases.