Intended for healthcare professionals

Practice Rational Testing

Investigation of an incidental finding of eosinophilia

BMJ 2011; 342 doi: https://doi.org/10.1136/bmj.d2670 (Published 18 May 2011) Cite this as: BMJ 2011;342:d2670
  1. Hannah Sims, haematology specialist registrar,
  2. Wendy N Erber, consultant haematologist
  1. 1Haematology Department, Addenbrooke’s Hospital, Cambridge CB2 0QQ, UK
  1. Correspondence to: Professor Wendy N Erber, Pathology and Laboratory Medicine, M504, University of Western Australia, 35 Stirling Highway, Nedlands WA 6009, Australia werber{at}meddent.uwa.edu.au

The causes of eosinophilia fall into three categories (reactive disorders, clonal disorders of the bone marrow, and hypereosinophilic syndrome). This article outlines the appropriate use of investigations to establish the cause of eosinophilia

Learning points

  • When eosinophilia is found, ensure that a blood film has been reviewed. This can give insight into the underlying aetiology

  • If the eosinophil morphology is normal or the blood film appearances favour a reactive (secondary) cause the patient should be reviewed to establish the likely aetiology

  • Persistence of eosinophilia >1.5×109/L for three months or a rising eosinophil count without an obvious cause warrants referral to a haematologist

A 57 year old man presented to his general practitioner with symptoms of a persistent dry cough and general fatigue. He had no notable medical history; he was a non-smoker and was not taking any regular medication. Clinical examination was unremarkable. A full blood count showed haemoglobin 141 g/L (normal range 130-180 g/L), mean cell volume 92 fL (80-100 fL), platelets 178×109/L (150-400×109/L), and leucocytes 9×109/L (4-13×109/L). The leucocyte differential showed neutrophils 4.3×109/L (2-8×109/L), lymphocytes 3×109/L (1-4×109/L), monocytes 0.5×109/L (0.2-0.8×109/L), and eosinophils 8.2×109/L (0.1-0.6×109/L). The blood film confirmed the presence of the eosinophilia and the eosinophil morphology appeared normal. Red cells, other leucocytes, and platelets were also morphologically normal. On the basis of the blood appearances the reporting haematologist favoured a reactive cause for the eosinophilia (such as infection, allergy, and hypersensitivity disorders; vasculitis; and autoimmune disorders). The haematologist recommended a repeat blood count to establish whether the eosinophilia was persistent, and investigations to determine the aetiology.

What is the next investigation?

Eosinophilia is a common abnormality present in 1-1.5% of blood counts in the United Kingdom (personal observation (WNE)). The causes of eosinophilia can be grouped into three categories: reactive (non-clonal or secondary) disorders; clonal (primary) disorders of the bone marrow; and hypereosinophilic syndrome.

  • Reactive (non-clonal or secondary) disorders—The most common disorders associated with an eosinophilia are infection (especially parasitic—schistosomiasis, hookworm, giardia, filaria, strongyloides), drugs (such as sulfonamides, penicillins, carbamazepine), allergy, and hypersensitivity disorders (such as asthma, acute urticaria, and atopic dermatitis); these account for >95% of cases. Less common reactive causes are Churg-Strauss syndrome, connective tissue and autoimmune diseases, and other infections (such as bacterial, fungal).

  • Clonal (primary) disorders of the bone marrow—These disorders are rare and include chronic myeloid leukaemia and chronic eosinophilic leukaemia. Eosinophilia may also be present in Hodgkin lymphoma and T cell lymphoma.

  • Hypereosinophilic syndrome—This is extremely rare, accounting for <1% of cases of eosinophilia.1

The underlying cause of the eosinophilia may be evident from the:

  • Clinical history (such as atopy, medication history)

  • Extent of the eosinophilia (for example, when it is caused by atopy, the eosinophil count is rarely >2×109/L, whereas an eosinophilia of >10×109/L is rare in reactive conditions other than parasitic infections and drug reactions). Reactive eosinophilias may be transient and resolve within 24 hours of appropriate treatment, as in acute asthma

  • Eosinophil morphology: in a reactive eosinophilia the morphology is generally normal (figure) and may be accompanied by a neutrophilia. In the rare primary or clonal disorders, the eosinophils may have morphological abnormalities (such as variation in cell size and distribution and number of cytoplasmic granules). There may be accompanying red cell abnormalities (such as macrocytosis), circulating myeloid precursors, blast cells, or thrombocytosis.

Figure1

Blood film showing a reactive eosinophilia (E=eosinophil, N=neutrophil, L=lymphocyte)

A careful review of the blood film by the haematologist may therefore help in determining whether the eosinophilia is likely to be reactive or primary and guiding further investigations for the underlying aetiology.

To further establish the cause requires a more extensive history and clinical examination. Clinical history should inquire about recent foreign travel, medications (including non-prescription), rashes, and contact with animals; this should identify the more common reactive causes of eosinophilia.2 3 Clinical examination should specifically assess respiratory (such as for asthma, infection) function, cardiac function, and the skin. The box lists appropriate pathology investigations to further elucidate the cause.

Investigations for eosinophilia in primary care

  • A repeat blood count and blood film (within one to two weeks) to establish whether the eosinophilia is persistent

  • Inflammatory markers (erythrocyte sedimentation rate, C reactive protein, or both)

  • Immunoglobulins, including IgE

  • Autoantibodies: nuclear, extractable nuclear antigen, and DNA antibodies; rheumatoid factor; antineutrophil cytoplasmic antibodies

  • Chest radiography

  • If patient has a history of foreign travel, arrange:

    • -Hot stool specimen (for testing for ova, cysts, and parasites— three specimens on separate occasions are needed)

    • -Strongyloides serology

    • -Serology relevant to the specific area of travel

If no identifiable cause for the eosinophilia has been found or if the eosinophilia (>1.5×109/L) persists for three months or is rising without an obvious cause, the patient should be referred to a haematologist. Additional investigations by the haematologist will help in distinguishing between a reactive and primary clonal disorder of the bone marrow. Bone marrow aspiration and trephine biopsy will be done to assess the morphology, and this may lead to a specific diagnosis. Genetic tests may be performed on the marrow sample as specific genetic abnormalities occur in many of the malignancies (lymphoid and myeloid) associated with eosinophilia. For example, in chronic eosinophilic leukaemia there is a deletion of material on chromosome 4, resulting in a FIP1L1-PDGFRA fusion gene.4 These bone marrow tests may be supplemented by computed tomography for radiological evidence of a lymphoid malignancy.

The outcome

In our patient, the clinical history and primary investigations did not identify a reactive or secondary cause of the eosinophilia. The eosinophilia was persistent and rising without obvious cause so he was referred to a haematologist for further investigation. Bone marrow aspiration and trephine biopsy showed marked hyperplasia of eosinophil precursors and mature eosinophils, without an increase in blast cells. Genetic analysis identified the FIP1L1-PDGFRA fusion gene, and chronic eosinophilic leukaemia was diagnosed. He was started on imatinib, a tyrosine kinase inhibitor, with an excellent response. The blood eosinophil count and bone marrow morphology returned to normal and genetic monitoring at six months showed no evidence of the FIP1L1-PDGFRA fusion gene. He continues taking imatinib with regular blood counts and genetic monitoring under the care of the haematologist.

Chronic eosinophilic leukaemia is a rare malignancy that predominantly occurs in middle aged men and must be distinguished from the many (and more common) causes of reactive eosinophilia. Chronic eosinophilic leukaemia is a multisystem disorder characterised by a peripheral blood eosinophilia and tissue infiltration by the eosinophils. End organ damage, especially of the heart and lungs, occurs as a result of eosinophil degranulation and release of cytokines and humoral factors. The aim of treatment with imatinib is to protect the patient from long term complications associated with eosinophilia and from end organ damage, such as impaired respiratory function and cardiac failure.5 6

Notes

Cite this as: BMJ 2011;342:d2670

Footnotes

  • This series of occasional articles provides an update on the best use of key diagnostic tests in the initial investigation of common or important clinical presentations. The series advisers are Steve Atkin, professor, head of department of academic endocrinology, diabetes, and metabolism, Hull York Medical School; and Eric Kilpatrick, honorary professor, department of clinical biochemistry, Hull Royal Infirmary, Hull York Medical School. To suggest a topic for this series, please email us at practice{at}bmj.com.

  • Contributors: Both authors reviewed the literature and wrote the article. WNE is the guarantor.

  • Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Provenance and peer review: Commissioned; externally peer reviewed.

  • Patient consent not required (patient anonymised, dead, or hypothetical).

References

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