Hypereosinophilic syndrome (HES) cardiac involvement (Löffler endocarditis) is the most feared complication of sustained hypereosinophilia — eosinophils degranulate and release toxic proteins (major basic protein, eosinophil cationic protein) that directly damage cardiac myocytes, endocardium, and heart valves. The pathological sequence is: acute necrotic phase (eosinophil infiltration + granule release → myocyte death) → thrombotic phase (mural thrombus formation on damaged endocardium) → fibrotic phase (endomyocardial fibrosis → restrictive cardiomyopathy). Each phase can cause sudden death or permanent cardiac impairment. Cardiac assessment (ECG, troponin, echocardiography) is therefore needed when eosinophilia is significant or persistent, or there are cardiac symptoms — catching endomyocardial involvement in the early phase before fibrosis develops is critical. EGPA (formerly Churg-Strauss syndrome) is a fascinating disease with a characteristic three-phase presentation that GPs should recognise: Phase 1 — allergic phase (asthma + allergic rhinitis — can precede vasculitis by years); Phase 2 — eosinophilic phase (blood and tissue eosinophilia, eosinophilic pneumonia, gastroenteritis); Phase 3 — vasculitic phase (mononeuritis multiplex, skin purpura, pericarditis, renal involvement). The triad of asthma + peripheral eosinophilia + mononeuritis multiplex is EGPA until proved otherwise.

The helminth infection-eosinophilia connection is critically important in primary care because UK GPs increasingly see patients from countries where tissue-invasive helminths are endemic, and because immunosuppressive treatment in a patient with undiagnosed strongyloidiasis can cause life-threatening disseminated disease. The key principle: any patient from a tropical/subtropical region (South Asia, sub-Saharan Africa, South America, Southeast Asia, Southern Europe — Strongyloides is present in some Southern European areas) who requires systemic corticosteroids or immunosuppressive therapy should be screened for Strongyloides serology first, based on exposure geography and clinical risk (UKHSA: Strongyloides can persist for decades). Corticosteroids reduce eosinophil-mediated killing of Strongyloides larvae and allow unchecked autoinfection → hyperinfection syndrome → gram-negative bacteraemia from larvae carrying gut bacteria through the intestinal wall → potentially fatal sepsis. Ivermectin (commonly 200 micrograms/kg, regimen per current tropical medicine/local protocol) is used for uncomplicated infection; patients who are immunosuppressed or need urgent immunosuppression should be discussed urgently with infectious diseases/tropical medicine rather than relying on a simple two-dose regimen. This screening principle should be part of the standard pre-immunosuppression workup for patients from endemic regions.

The blood film is mandatory for any unexpected or significant eosinophilia before proceeding to further investigations — an unexpected result should be confirmed with a repeat FBC and blood film. The blood film allows manual examination of eosinophil morphology, confirmation of the count, identification of blast cells (leukaemia), hypersegmented eosinophils (HES), and reactive changes. Before arranging tropical parasitology serology or ANCA testing, confirming that the eosinophilia is real on film is a key quality step. Total IgE is not required for every patient; where atopy, allergic disease or a lymphocytic variant is suspected, a markedly elevated total IgE supports an atopic or parasitic cause, while a normal IgE with significant eosinophilia suggests a non-allergic cause (EGPA, HES, malignancy, drug reaction). Specific IgE to common aeroallergens (grass pollen, HDM, cat) can confirm atopic aetiology.

The drug eosinophilia timeline is practically important — drug-induced eosinophilia usually follows the start of the causative drug and settles after stopping it. If eosinophilia persists on recheck after drug cessation, an alternative or additional cause should be sought. Allopurinol is one of the most common causes of drug-induced eosinophilia in primary care (given its widespread use for gout), and can also cause the more severe DRESS syndrome — a patient starting allopurinol who develops eosinophilia should be checked for rash, fever, facial oedema, lymphadenopathy, hepatitis, renal injury and respiratory symptoms; stop the drug if clinically safe and recheck the count. Eosinophilia alone is not always a reason to stop a necessary drug — seek specialist advice when the drug is essential or the diagnosis is uncertain. If DRESS is suspected (eosinophilia + fever + skin rash + organ involvement) — same-day hospital assessment.

The Tropical Medicine/Infectious Diseases referral for suspected strongyloidiasis before immunosuppression is a GP-level decision — any patient from an endemic region (South Asia, sub-Saharan Africa, Southeast Asia) with eosinophilia who requires corticosteroids, rituximab, anti-TNF therapy, or other immunosuppression should be screened for Strongyloides BEFORE immunosuppression starts. If Strongyloides serology is positive, discuss with infectious diseases/tropical medicine and complete treatment per current protocol before initiating immunosuppression. Consider empiric treatment only when urgent immunosuppression cannot wait for testing, exposure risk is substantial, testing is unavailable or likely falsely negative, or on specialist advice — not routinely for every patient with a remote travel history. This is a straightforward, life-saving protocol that GPs initiating immunosuppressive therapy should know. Regional infectious diseases/tropical medicine units and the UKHSA Rare and Imported Pathogens Laboratory provide specialist advice on tropical parasite diagnosis and treatment for GPs unfamiliar with these agents.

Mepolizumab (anti-IL-5 monoclonal antibody) may be used by specialists for refractory EGPA, but it is not standard NHS treatment on the basis of NICE TA845 (that appraisal was terminated without a recommendation because no evidence submission was made) — it blocks IL-5, the primary cytokine driving eosinophil production and survival, and achieves significant reduction in relapse rates and steroid requirements in patients with EGPA not controlled by standard treatment. This is relevant for GPs managing patients with EGPA on long-term systemic steroids — awareness of mepolizumab as an available option means appropriate specialist referral (rheumatology or respiratory) for EGPA patients still on significant steroid doses. The imatinib-PDGFRA mechanism is a landmark discovery in precision oncology: the FIP1L1-PDGFRA fusion oncogene (which drives the myeloproliferative variant of HES) is a constitutively active tyrosine kinase that is highly sensitive to imatinib. Dose, monitoring and treatment duration are haematology-led.

HLA-B*58:01 carriage increases the risk of severe allopurinol-induced DRESS/SJS/TEN. The risk is particularly relevant in Han Chinese, Korean, Thai and some other south-east Asian populations, and may also be relevant in some individuals of African ancestry — do not imply that all people of South Asian ancestry require testing. UK practice does not universally mandate screening; follow current MHRA, CPIC and local allopurinol prescribing guidance. Similarly, HLA-B*15:02 testing before carbamazepine in patients of Han Chinese or Southeast Asian ancestry is recommended by the MHRA.

The pre-travel helminth education is a genuinely preventive intervention that GPs can provide at travel consultations — Strongyloides stercoralis, hookworm, and Toxocara are avoidable with straightforward behavioural measures. The percutaneous penetration route of Strongyloides (larvae in contaminated soil penetrate intact skin on bare feet or in contact with contaminated soil) means that the simplest prevention is wearing shoes or sandals when walking in soil in endemic areas. This message is not consistently communicated at travel consultations. GPs providing travel advice should include: always wear footwear outdoors in tropical/subtropical areas, wash all fruit and vegetables with clean water, and reattend for a post-travel check including stool examination and serology if any new symptoms (unexplained eosinophilia, abdominal symptoms, skin rash) within 3 months of return.

The 3-month serology persistence after Strongyloides treatment is an important patient communication point — Strongyloides IgG serology can remain positive for 6–12 months after successful treatment because the immunological memory persists. Using the eosinophil count (not the serology) as the primary treatment monitoring tool is more accurate: if eosinophilia resolves within 3 months of ivermectin treatment, treatment is likely successful regardless of serology. Persistent serology positivity without eosinophilia does not require retreatment. Persistent eosinophilia 3 months after treatment should prompt Tropical Medicine/infectious diseases review (retreatment per specialist advice) and reconsideration of other causes.