Eosinophilia

At a Glance

Eosinophilia is defined as an absolute eosinophil count greater than 2SD above the mean for the population being tested. Typically, this represents an absolute peripheral blood eosinophil count greater than 500 cells/microliter (µL).

Peripheral blood eosinophilia may be further categorized as mild (500-1,500 eosinophils/µL), moderate (1,500-5,000 eosinophils/µL), or severe (>5,000 eosinophils/µL). This categorization is important, as organ damage (e.g., heart, kidneys, lungs) is associated with peripheral eosinophil counts greater than 1,500/µL and higher counts typically require aggressive therapy.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

Although the causes of peripheral blood eosinophilia are numerous, the vast majority of cases are due to production of interleukin-5 (IL-5) by T helper type 2 (TH2) lymphocytes secondary to allergic conditions (e.g., asthma, rhinitis), parasitic infections (especially helminths), and drug reactions (e.g., cephalosporins, allopurinol, synthetic penicillins). In cases of mild to moderate eosinophilia, the initial evaluation should be directed at identifying these common causes of secondary eosinophilia.

In a patient without an obvious cause for eosinophilia (e.g., allergic symptoms), it is probably most appropriate to simply repeat a complete blood count (CBC) on a new sample to confirm that eosinophilia is truly present. Although uncommon, sample mislabeling or laboratory error may result in an erroneous eosinophilia that may simply disappear on repeat testing.

If eosinophilia is present on repeat testing, it is appropriate to thoroughly review the remainder of the CBC for other abnormalities and ask the laboratory to review a well made peripheral smear for red cell, white cell, and platelet morphology. The presence of atypical eosinophils, blasts, immature granulocytes, dysplastic red cells, leukocytes or platelets, lymphocytosis, and/or atypical lymphocytes suggests the presence of either a clonal marrow or lymphoproliferative disorder as the cause of eosinophilia.

If there is no direct evidence of a neoplastic process, a thorough patient history and physical examination is the next step in the evaluation of eosinophilia. Specifically, a complete travel and dietary history (some parasitic infections may remain asymptomatic for years), complete medication history (including herbal remedies), and evaluation for malignancy risk factors are required. Physical examination should look for evidence of atopic conditions (e.g., eczema, rhinitis); evidence of a neoplastic process; and signs of heart, lung, and kidney damage.

The laboratory evaluation of a patient with eosinophilia should identify both common, treatable causes of eosinophilia, as well as evaluate the patient for evidence of organ damage.

Initial laboratory assessment in patients with mild or moderate eosinophilia should include:

Evaluation for parasitic infection: stool ova and parasites (O&P) examination x3, urinalysis and urine sediment examination (Schistosomiasis), and total serum immunoglobulin E (IgE) levels

Evaluation for allergic conditions: nasal and/or sputum smears for eosinophils, total and specific IgE levels (In patients with asthma, cystic fibrosis or bronchiectasis specific testing for antibodies to Aspergillus sp. should be considered to rule out allergic pulmonary aspergillosis.)

Evidence of organ damage, assessed with serum chemistries (alanine aminotransferase [ALT], total bilirubin, blood urea nitrogen [BUN}/creatinine, electrolytes) and a cardiac troponin level

Testing for antibodies to human immunodeficiency virus (HIV)

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

Numerous drugs have been associated with eosinophilia. In some cases, peripheral eosinophilia may be the only manifestation of a drug reaction; however, evidence of other organ damage may provide clues as to the potential offending agent(s).

Generalized rash and eosinophilia may be seen with almost any medication, although antibiotics are the most frequent cause. Interstitial nephritis may be seen with allopurinol, gold compounds, and antibiotics. Pulmonary infiltrates may be associated with nitrofurantoin, minocycline, naproxen, penicillin, phenylbutazone, or sulfonamides. Pleuropulmonary symptoms may be encountered in patients taking dantrolene, bleomycin, and methotrexate. Hepatitis has been associated with phenothiazines, penicillins, tolbutamide, allopurinol, methotrexate, and fluoroquinolones. Vasculitis has been associated with allopurinol and phenytoin. Rhinitis, nasal polyps, and asthma are associated with aspirin. The drug rash with eosinophilia and systemic symptoms (DRESS) syndrome has been associated with carbamazepine, allopurinol, and antibiotics.

The identification of the offending agent may be very difficult in a patient taking several medications. Withdrawal of any or all medications is not essential for the patient’s well being, reassessment, and cautious reinstitution of medications in a step-wise fashion may be required. Conversely, the presence of eosinophilia by itself is not an absolute contraindication to the continued use of a causitive medications if it is needed for the patient’s well being. However, the positive effects of the medication must be weighed against the potential for eosinophil induced organ damage, especially in patients with eosinophil counts at or above 1,500/µL. If medications must be continued in a patient who has developed eosinophilia, frequent reassessment for the level of eosinophilia and evidence of organ damage is mandatory.

Finally, ingestion of toxins, such as rape seed oil (toxic oil syndrome) or contaminated L-tryptophan (eosinophilia myalgia syndrome), may also produce eosinophilia.

What Lab Results Are Absolutely Confirmatory?

Absolute confirmation of eosinophilia is provided by repeat CBC with differential.

Confirmation of the common causes of eosinophilia is based on the identification of one of the following:

Parasites or their eggs in stool or urine samples confirms parasitic infection as a probable cause of eosinophilia.

Elevated total IgE and or specific IgE suggests an allergic response as the cause of eosinophilia. However, elevated total IgE levels may be seen in helminth infections and the Hyper-IgE syndrome.

Resolution of eosinophilia after discontinuation of 1 or more potentially causative medications strongly suggests a drug reaction as the cause.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

The sensitivity of detecting parasites by microscopic examination is relatively low, therefore, in patients with suggestive travel, lifestyle, or dietary history, negative stool and urine examinations for parasites does not rule our parasitic infection. Additional serologic tests (e.g. Enzyme Linked Immunosorbent Assay [ELISA]) for parasite antibodies or antigens should be considered based on the patient’s history. Note that, if corticosteroid treatment is being considered, it is important to rule out S. stercoralis infection by serologic testing before starting therapy because of the risk of disseminated hyperinfection. If steroid therapy must be instituted prior to obtaining the results of this testing, consideration should be given to coadministration of ivermectin.

If the initial and follow-up laboratory evaluations for common causes of eosinophilia are negative, especially if the eosinophil count is greater than 1,500/µL or there is evidence of organ damage, the patient should be referred for specialized testing to rule out less common causes of eosinophilia.

A. Consult to rule out unusual parasites (if suggested by travel history)

• Wuchereria bancrofti and Brugia malayi: tropical pulmonary eosinophilia: smears for blood obtained between 10PM and 2AM, serology or Ag testing (W. bancrofti)

• Onchocerca volvulus: skin snip culture, serology

• Paragonimus westermanii: sputum examination, skin testing

• Toxicara canis: enzyme-linked immunosorbent assay (ELISA)

B. Hematology-Oncology consult to rule out neoplastic or paraneoplastic eosinophilia

• Bone marrow aspiration and biopsy with cytogenetics, stains for mast cell tryptase to identify leukemia, myloproliferative disorders, myelodysplasia, systemic mastocysosis

• Peripheral blood fluorescent in situ hybridization (FISH) or Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) for FIP1L1-PDGFRA mutations to detect clonal eosinophilia and/or hypereosinophilic syndrome (HES)

• Flow cytometry of peripheral blood, marrow, or lymphoid tissue to identify B- or T-cell lympholiferative disorders

• T-cell receptor gene rearrangement studies to identify clonal T-cell disorders

• Imaging studies to identify occult solid tumors

C. Allergy/Rheumatology consult to rule out autoimmune disorders

• Systemic lupus: anti-nuclear antibody (ANA), double-stranded DNA (Ds-DNA)

• Rheumatoid arthritis: RA

• Dermatomyositis: anti-Ro, La, Sm, RNP

• Sjogrens syndrome: anti-Ro (SSA), anti-La (SSB)

D. Endocriology consult to rule out adrenal hypofunction

• Early morning cortisol and adrenocorticotropic (ACTH) levels

E. Genetic and/or Immunology consult to rule out immunodeficiency syndromes such as Omen’s syndrome and/or Hyper-IgE syndrome

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