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. Early echocardiogram in all patients with eosinophils above 1.5 × 10⁹/L is therefore an important cardiac surveillance requirement — 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. 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 200 mcg/kg OD × 2 doses (available on a named patient basis in the UK — Mectizan) treats Strongyloides effectively before immunosuppression. 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 expensive investigations — an automated FBC with differential may misclassify band neutrophils, immature myeloid cells, or artefactually stained lymphocytes as eosinophils. 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. The IgE total level provides useful clinical context: markedly elevated total IgE (>150 IU/ml) supports atopic or parasitic cause; normal IgE with significant eosinophilia suggests 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 typically appears 1–4 weeks after starting the causative drug, and resolves within 3 weeks of stopping it. If eosinophilia persists beyond 3–4 weeks 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 — any patient starting allopurinol who develops eosinophilia within 3 months should have the drug stopped and the eosinophil count rechecked. If DRESS is suspected (eosinophilia + fever + skin rash + liver dysfunction) — hospital admission immediately.

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, ivermectin treatment should be completed before initiating immunosuppression. This is a straightforward, life-saving protocol that GPs initiating immunosuppressive therapy should know. The UK OHID (formerly PHE) provides specialist advice on tropical parasite treatment for GPs unfamiliar with these agents.

Mepolizumab (anti-IL-5 monoclonal antibody) is approved by NICE for refractory EGPA as of 2021 — 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 exquisitely sensitive to imatinib at lower doses than used for CML (100 mg OD vs 400 mg OD). Complete remission is achieved in >95% of PDGFRA-positive HES patients with imatinib alone.

The HLA-B*5801 screening before allopurinol is a pharmacogenomic test that is not yet universal in UK practice but has strong evidence — the HLA-B*5801 allele is present in approximately 7–8% of Han Chinese and 6–8% of Thai patients, and carriers have an approximately 100× higher risk of severe allopurinol-induced DRESS/SJS/TEN. CPNDS (Canadian Pharmacogenomics Network for Drug Safety) and the Taiwan FDA recommend screening all patients of South/East Asian ancestry before allopurinol initiation. UK practice currently does not universally mandate this, but NICE CG56 (Gout) acknowledges the risk. In a UK primary care context, GPs initiating allopurinol in patients of Han Chinese, Thai, Korean, or related East/Southeast Asian ancestry should consider HLA-B*5801 testing or discuss the risk with the patient. Similarly, HLA-B*1502 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 despite serological treatment at 3 months should prompt retreatment and/or Tropical Medicine review.