Eosinophilia

What is eosinophilia?

The main functions of eosinophils include involvement in defence against parasites, allergic responses, tissue inflammation and immunity. Eosinophilia is a peripheral eosinophil count greater than the upper limit of normal range, usually around 0.50 x 10⁹/L. In many cases the cause is clear - eg, atopic disease. However, the differential diagnosis includes many serious diseases, including malignancy.

Based on the counts, eosinophilia can subdivide into different categories: mild (0.50-1.5 x10⁹, moderate (1.5-5.0 x10⁹), and severe (> 5.0 x10⁹).¹

How common is eosinophilia? (Epidemiology)

• In the UK, eosinophilia is most often due to allergic conditions.

• Worldwide, helminth infections are the most common cause of eosinophilia.²

Symptoms of eosinophilia (presentation)¹

There are heterogeneous manifestations of the disease with severity varying from mild to end-organ damage. Skin, pulmonary, and gastrointestinal organ systems are commonly involved. Constitutional symptoms like low-grade fevers, night sweats, fatigue, weight loss can occur in multiple conditions.

Comprehensive history taking and thorough physical examination are extremely important, and sometimes enough, for diagnosis.

• Travel history to assess whether a patient has travelled to an area that is endemic for certain infections, including helminthic infections.

• Medication and diet history to evaluate for allergic reactions associated with eosinophilia.

• History of symptoms associated with possible underlying causes (see 'Causes', below).

• A complete physical examination is required because diseases associated with eosinophilia can involve any part of the body.

Causes of eosinophilia (aetiology)³

• Allergy diseases: asthma, urticaria, eczema, allergic rhinitis, angioneurotic oedema.

• Drug hypersensitivity. Drugs which more commonly cause eosinophilia include anticonvulsants, allopurinol, sulfonamides and certain antibiotics. When eosinophilia is accompanied by a rash and systemic symptoms, this is called the DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms).⁴

• Connective tissue diseases:
  

  • Eosinophilic granulomatosis with polyangitis (formerly known as) Churg-Strauss syndrome. Vasculitis causing multisystem disease, but particularly of the lungs. It is associated with asthma, lung infiltrates and eosinophilia.⁵

  • Rheumatoid arthritis.

  • Eosinophilic fasciitis. A rare condition characterised by eosinophilia with inflammation and thickening of the skin and fascia.⁶

  • Polyarteritis nodosa.

  • Eosinophilia myalgia syndrome. A rare condition associated with myalgia and eosinophilia.

• Infections: in particular, parasitic infections including ascariasis, schistosomiasis, trichinellosis, visceral larva migrans, strongyloidiasis, echinococcosis, coccidioidomycosis.

• Hypereosinophilic syndromes (HES) is characterized by: >1.5 x 10⁹ eosinophils on 2 examinations >1 month apart; the percentage of eosinophils in the bone marrow (BM) section must exceed 20% of all nucleated cells; the pathologist's assessment that the tissue infiltration by eosinophils is extensive and/or marked deposition of eosinophil granule proteins is found; evidence of organ or tissue damage attributable to tissue hypereosinophilia (HE); exclusion of other disorders or conditions as major reasons for organ damage.⁷

• Neoplasia:
  

  • Lymphoma (eg, Hodgkin's lymphoma, non-Hodgkin's lymphoma).

  • Leukaemia: chronic myeloid leukaemia, adult T-cell leukaemia/lymphoma (ATLL), eosinophilic leukaemia (very rare).

  • Gastric cancer or lung cancer (ie paraneoplastic eosinophilia).

• Endocrine: adrenal insufficiency - eg, Addison's disease.

• Skin disease - pemphigus, dermatitis herpetiformis, erythema multiforme.

• Löffler's syndrome (accumulation of eosinophils in the lungs, due to parasitic infection).⁸

• Löffler's endocarditis (restrictive cardiomyopathy with eosinophilia).⁹

• Irradiation.

• Post-splenectomy.

• Cholesterol emboli.

Diagnosing eosinophilia (investigations)³

Investigation is guided by the history, examination, and clinical picture and may include:

• FBC, including differential white cell count.

• Renal function tests, LFTs.

• Urine tests: all patients with blood eosinophilia and haematuria and who have been in Africa should have their urine examined for the eggs of Schistosoma haematobium. Cystoscopy may be required to confirm the diagnosis.

• Lumbar puncture: CSF eosinophilia due to worm infections (eg, Angiostrongylus cantonensis), drug reactions, and coccidioidomycosis meningitis.

• CT scans of the lungs, abdomen, pelvis, and brain evaluate for focal defects due to diverse causes of eosinophilia - eg,:
  

  • Worm infections of the liver (eg, Fasciola hepatica) can cause focal hepatic lesions.

  • Coccidioidomycosis can cause focal lesions in the lung, which are visible on CXR or CT scan.

  • Hodgkin's lymphoma or non-Hodgkin's lymphoma can cause lymphadenopathy in the abdomen, which can be seen on a CT scan.

• Echocardiogram to assess for thrombi (eg, mural, endocardial) due to hypereosinophilic syndrome.

• Bone marrow biopsy may be required.

Outlook for eosinophilia (prognosis)¹

Prognosis can vary from mild disease to fatal outcome, depending on multiple factors like the cause of the eosinophilia, the presence of organ damage, the subtype of eosinophilia, and the timeliness of appropriate medical treatment. Eosinophils can produce proinflammatory cytokines and contain proteolytic enzymes that can damage the host cell wall, so tissue damage can occur if eosinophilia is not treated appropriately.