Skip to main content

Health condition

Hypereosinophilic syndrome, from FIP1L1-PDGFRA testing to imatinib and mepolizumab.

A rare but treatable group of disorders where persistent eosinophilia damages heart, skin, nerves and gut. Getting the type right transforms the treatment.

Jump to treatment
A radiographer guides a patient onto the bed of an advanced 3 Tesla MRI scanner in a London imaging suite

Why trust this guide

  • 01

    Editorial team

    Written by our editorial team from the UK sources listed on each page.

  • 02

    Sourced from guidance

    Checked against BSH, ERS and peer-reviewed haematology sources you can see at the end.

  • 03

    Current for 2026

    Reflects modern UK practice including FIP1L1-PDGFRA testing, imatinib and mepolizumab for HES.

Key facts

HES at a glance.

The essentials, in plain English - what HES is, the WHO types, and how it is treated in specialist-commissioned UK haematology today.

  • What it is

    Persistent eosinophilia above 1.5 x 10^9/L for more than six months, with end-organ damage attributable to eosinophils.

  • Types

    Primary (clonal, e.g. FIP1L1-PDGFRA), secondary (reactive - parasites, allergy, malignancy), idiopathic, lymphocytic and episodic.

  • Why it matters

    Eosinophils release granule proteins that can scar the heart, injure nerves, damage gut and skin, and drive clots.

  • Key molecular test

    FIP1L1-PDGFRA fusion identifies patients who respond dramatically to imatinib - and must not be missed.

  • Newer option

    Mepolizumab (Nucala), an anti-IL-5 antibody, is NICE-approved for HES since 2020 and reduces steroid burden.

  • Where care sits

    Diagnosis and long-term management are specialist-commissioned haematology - often with cardiology and immunology input.

Why this guide matters

The right classification changes the treatment.

HES is rare, but it is not one disease - and the three points below shape everything else on this page.

  • Find the fusion first

    FIP1L1-PDGFRA is the single most consequential test in HES - patients respond to imatinib within weeks and often reach molecular remission.

  • Steroids remain a mainstay

    For reactive, idiopathic and lymphocytic-variant HES, prednisolone still buys time and controls disease - with a plan for tapering.

  • Biologics have changed the ceiling

    Mepolizumab is NICE-approved for HES and reduces flares and steroid burden - a step change for patients living with the condition.

How the diagnosis is made

From raised eosinophils to a treatable subtype.

The steps a UK haematology team will normally follow, in order - so you know what to expect and why each investigation matters.

  1. 01

    Assessing

    History and exposures

    Travel, occupation, drug history (DRESS), atopy, asthma, weight loss and symptoms of end-organ damage - cardiac, neurological, skin, gut.

  2. 02

    Assessing

    Examination for end-organ signs

    Skin (rash, urticaria, angioedema), heart (murmurs, failure), neurology, splenomegaly and lymphadenopathy.

  3. 03

    Assessing

    Baseline bloods

    FBC to confirm sustained eosinophilia, LDH, tryptase (mastocytosis overlap), IgE and vitamin B12 - raised B12 is a clue to FIP1L1-PDGFRA.

  4. 04

    Confirming

    Rule out reactive causes

    Parasitic serology and stool studies (strongyloides), HIV, autoimmune screen, endocrine and Addison workup - specialist microbiology.

  5. 05

    Confirming

    Molecular and clonality testing

    FIP1L1-PDGFRA by FISH and PCR, PDGFRB, FGFR1, JAK2, karyotype and T-cell receptor gene rearrangement - specialist-commissioned haematology.

  6. 06

    Preparing

    End-organ imaging and biopsy

    Echo, cardiac MRI for endomyocardial fibrosis and Loeffler endocarditis; bone marrow biopsy; skin, gut or tissue biopsy where selective - specialist.

  7. 07

    Preparing

    Specialist MDT decision

    Haematology-led MDT with cardiology, dermatology and immunology sets treatment - specialist-commissioned pathway.

Typical timeline: weeks to a molecular diagnosis and MDT plan in a specialist-commissioned centre.

Symptoms

What HES actually looks like.

Eosinophils can damage almost any organ. The pattern of symptoms often points to the subtype and steers the workup.

  • Skin - rash and itch

    Urticaria, angioedema and pruritic eczema-like rash are among the commonest presentations of HES.

  • Cardiac involvement

    Endomyocardial fibrosis, Loeffler endocarditis, mural thrombus, arrhythmia and heart failure - see /conditions/endomyocardial-fibrosis/.

  • Neurological features

    Encephalopathy, stroke from cardiac thrombus, peripheral neuropathy and cognitive slowing.

  • Gastrointestinal

    Eosinophilic enteropathy and overlap with eosinophilic oesophagitis - see /conditions/eosinophilic-esophagitis-eoe/.

  • Pulmonary

    Eosinophilic pneumonia, cough, wheeze and infiltrates - often with underlying asthma - see /conditions/asthma/.

  • Thromboembolism

    Arterial and venous clots, often intracardiac - a leading cause of morbidity in untreated disease.

  • Splenomegaly and systemic

    Fatigue, night sweats, weight loss and an enlarged spleen suggest a clonal or myeloproliferative variant.

  • Red flag - cardiac symptoms

    Chest pain, breathlessness or new arrhythmia with eosinophilia is a specialist emergency - urgent echo and MDT.

Treatment

How HES is treated in the UK.

Treat the underlying cause first. For clonal disease, imatinib is transformative. For reactive and idiopathic HES, steroids and biologics carry the load.

  • Treat the underlying cause

    Parasites, offending drugs, allergy and malignancy are addressed first - reactive eosinophilia often resolves once the trigger is removed.

  • Imatinib for PDGFRA-positive

    A dramatic, often complete response - see /treatments/imatinib-hes-clinic/. First-line where the fusion is present, specialist-commissioned.

  • Prednisolone

    Corticosteroids remain the mainstay for reactive, idiopathic and lymphocytic-variant HES - specialist-led with a steroid-sparing plan.

  • Mepolizumab (anti-IL-5)

    NICE-approved for HES since 2020 - see /treatments/mepolizumab-clinic/. Reduces flares and steroid dependence.

  • Benralizumab and other biologics

    Emerging anti-IL-5-receptor options where mepolizumab is not tolerated or effective - specialist-commissioned.

  • Hydroxycarbamide and interferon-alpha

    Cytoreductive options for myeloproliferative HES variants and steroid-refractory disease - specialist supervision.

  • Cytotoxics and targeted immunotherapy

    Cyclophosphamide, mycophenolate, alemtuzumab and rituximab in refractory or lymphocytic-variant disease - specialist only.

  • Stem cell transplant and anticoagulation

    Allogeneic transplant for chronic, refractory disease; anticoagulation for cardiac or thromboembolic involvement - specialist-commissioned.

What this guide is based on

The sources behind every claim on this page.

UK national guidance, specialist haematology guidelines and peer-reviewed sources, current at the time of last review.

Key references

Guidelines and standards we relied on.

A quiet reminder

This guide is for information, not medical advice.

Your haematologist knows your bloods and history and can tell you which parts of this guide apply to you. If in doubt, get seen.

  • British Society for Haematology (BSH). Guidelines on the investigation and management of eosinophilia.

  • NICE TA (2020). Mepolizumab for treating hypereosinophilic syndrome.

  • European Respiratory Society / ERS statement on eosinophilic lung disease.

  • World Health Organization (WHO) classification of haematolymphoid tumours - eosinophilic disorders.

Red flags

When HES needs urgent attention.

Some situations should not wait. These are the ones where a specialist opinion is needed - quickly.

  • New cardiac symptoms

    Chest pain, breathlessness, syncope or arrhythmia with eosinophilia can indicate Loeffler endocarditis or endomyocardial fibrosis - urgent specialist review.

  • Neurological deterioration

    New focal deficit, confusion or seizure raises the possibility of embolic stroke from cardiac thrombus - emergency assessment.

  • Very high eosinophil counts

    Counts persistently above 5 x 10^9/L carry a high risk of end-organ damage even without symptoms - specialist-commissioned haematology.

  • FIP1L1-PDGFRA suspected

    Male patient, raised B12 and tryptase, splenomegaly - do not delay molecular testing; imatinib response is dramatic.

  • DRESS or severe drug reaction

    Fever, rash, lymphadenopathy and eosinophilia after a new drug - stop the drug and seek specialist immunology or dermatology urgently.

  • Suspected strongyloides

    Any traveller or patient from an endemic area should be screened before high-dose steroids - risk of hyperinfection.

  • Signs of malignancy

    B symptoms, lymphadenopathy or hepatosplenomegaly - see /conditions/hodgkin-and-non-hodgkin-lymphoma/. Specialist workup.

  • Pregnancy or planning pregnancy

    Imatinib, cytotoxics and biologics all need careful pre-conception counselling - specialist haematology and obstetric MDT.

  • EGPA features

    Asthma, sinus disease, mononeuritis - see /conditions/eosinophilic-granulomatosis-with-polyangiitis/. Different treatment pathway.

Living with it

A rare condition, with a treatable pathway.

Four things that make the biggest difference day to day - routine monitoring, cardiac vigilance, a steroid plan and specialist support.

A quiet reminder

Rhythm beats intensity, every time.

Regular bloods, echos when needed and a clear escalation plan do more than heroic one-off pushes that do not last.

  1. 01 Routine

    Keep monitoring simple

    Regular FBC and end-organ checks - most patients settle into a predictable rhythm of blood tests and reviews.

  2. 02 Vigilance

    Watch for cardiac symptoms

    Chest pain, breathlessness or new palpitations deserve prompt review - cardiac damage is the biggest long-term risk.

  3. 03 Steroids

    Plan the taper

    If steroids are needed, expect a slow taper with a steroid-sparing agent - not a life sentence at high dose.

  4. 04 Support

    Blood Cancer UK and specialist teams

    Rare-disease support and specialist-commissioned centres exist for HES - ask your team to link you in.

Frequently asked

Everything we get asked about HES.

Quick answers on subtypes, molecular testing, imatinib, mepolizumab and cardiac risk.

  • What is hypereosinophilic syndrome?

    HES is a group of disorders defined by persistent blood eosinophilia above 1.5 x 10^9/L for more than six months, together with end-organ damage caused by eosinophils. Types include primary (clonal - such as FIP1L1-PDGFRA), secondary (reactive - parasites, allergy, drug reactions like DRESS, malignancy, autoimmune, HIV, Addison), idiopathic HES, lymphocytic variant and episodic (Gleich) HES.

  • What organs can HES damage?

    The heart is the most feared target - endomyocardial fibrosis, Loeffler endocarditis, mural thrombus and arrhythmia. Skin (rash, urticaria, angioedema), nerves (encephalopathy, stroke, peripheral neuropathy), gut (eosinophilic enteropathy and eosinophilic oesophagitis), lungs (eosinophilic pneumonia), spleen and the clotting system can all be involved.

  • How is HES diagnosed?

    Diagnosis is specialist-led. A thorough history covers travel, drugs and atopy. Bloods include FBC, LDH, tryptase, IgE and vitamin B12. Molecular testing looks for FIP1L1-PDGFRA, PDGFRB, FGFR1, JAK2 and karyotype. T-cell receptor gene rearrangement helps identify lymphocytic-variant HES. Echo, cardiac MRI, bone marrow biopsy and selected tissue biopsies complete the workup.

  • Which patients respond to imatinib?

    Patients with the FIP1L1-PDGFRA fusion (and some other PDGFR fusions) respond dramatically to imatinib, often achieving molecular remission on modest doses. Identifying this subgroup is the single most important step in HES workup and is delivered through specialist-commissioned haematology - see /treatments/imatinib-hes-clinic/.

  • What is mepolizumab and who is it for?

    Mepolizumab (Nucala) is a monoclonal antibody against IL-5, the key cytokine driving eosinophil production and survival. It is NICE-approved for HES since 2020 and reduces flares, steroid dependence and end-organ damage in reactive, idiopathic and lymphocytic-variant disease - see /treatments/mepolizumab-clinic/.

  • Is HES a form of blood cancer?

    Some variants are clonal - driven by fusions like FIP1L1-PDGFRA, PDGFRB or FGFR1 rearrangements, or by JAK2 mutations - and behave as myeloproliferative neoplasms. Others are reactive to allergy, parasites or drugs, or are idiopathic. Careful classification decides treatment: cytoreduction and imatinib for clonal disease, steroids and biologics for reactive and idiopathic forms.

Related content

Keep reading.