Eosinophilia in a Healthy Man

Routine blood testing in a 43-year-old man reveals a white blood cell (WBC) count of 9800/µL with 8% eosinophils. A complete blood cell count performed 1 week later shows a WBC count of 9500/µL with 7% eosinophils. The patient feels well and denies any symptoms; specifically, he has no pruritus, fever, weakness, fatigue, GI symptoms, or cardiac symptoms.

HISTORY

His only medication is simvastatin, 20 mg/d, for hypercholesterolemia; he has started no new drugs within the past year. He has no history of sinusitis. His health has been excellent, and he is physically fit. He has no pets. Two months earlier, he went to Mexico to attend a wedding and traveled with his family about 50 miles from Mexico City. No one in his family experienced any symptoms or ill effects during or after this trip.

PHYSICAL EXAMINATION

Physical findings are unremarkable. No lymphadenopathy, hepato- splenomegaly, or skin lesions are noted.

LABORATORY AND IMAGING RESULTS

Results of other laboratory studies--including a serum chemistry panel and liver function tests--are normal. A chest radiograph is also normal.

CORRECT ANSWER: C

This patient has a true blood eosinophilia (absolute eosinophil count [AEC] greater than 650/µL). Eosinophils are unmistakable on a blood smear because of their bright orange-red staining, which gives them their name. These hematopoietic myeloid stem cell-derived cells contain a variety of proteins that are toxic to microbes and potentially toxic to normal human tissues as well.¹

When eosinophilia is detected, initiate an orderly investigation to ascertain the cause. In addition, regardless of the cause, the degree of risk associated with the eosinophilia and the need to treat must be determined. Both can be established based on the AEC, which is categorized as mild (between 600 and 1500/µL), moderate (between 1500 and 5000/µL), orsevere (greater than 5000/µL). Target organ damage can occur with severe eosinophilia, regardless of its cause.^1,2

Workup for eosinophilia. The first step in the investigation is to determine whether the eosinophilia is primary (clonal) or secondary (reactive). Secondary causes include infections, allergies, and drugs. The most common cause of eosinophilia worldwide is infection, specifically parasitic infections. Of these, helminthic infections, such as those caused by Toxocara canis and Trichinella, are most common. Helminthic infections are not rare in the United States; however, in this country, allergy and atopy are probably more common causes of eosinophilia. Drugs that can cause eo- sinophilia include anticonvulsants, sulfa-containing medications, tryptophan, and NSAIDs.

During the history taking at both clinic visits, this patient stated that he had used no new medications, either prescribed or over-the-counter, for at least the past year.

His recent travel to Mexico, however, is a strong clue--particularly because it included a 100-mile round-trip through the interior of the country. This fact, coupled with odds that favor any eosinophilia being acquired rather than primary, make the relatively simple screening test of stool examination for ova and parasites (choice C) the most appropriate next step.

Bone marrow examination with cytogenetics (choice D) is suggested in all patients in whom primary, or clonal, eosinophilia is suspected. Cytogenetics and genotype testing by polymerase chain reaction assays can reveal the different intrinsic marrow disorders that cause eosinophilia. These include a variety of acute leukemias and myeloproliferative disorders, such as chronic myelogenous leukemia (CML) and platelet-derived growth factor receptor a (PDGFRA)-rearranged eosinophilia disorder. Certain of these cytogenetic variants have great therapeutic significance (see below).

In this patient, however, the clinical findings do notyet mandate bone marrow testing. Enough evidence in the history suggests a more common, secondary cause, and the AEC is not yet high enough to preclude proceeding with an orderly workup.

Treatment. Specific therapies are used for certain specific forms of eosinophilia. In symptomatic idiopathic eosinophilia, interferon alfa (choice A) lowers the AEC very effectively. However, this therapy is usually reserved for patients in whom the easier (and generally effective) therapies of corticosteroids or hydroxyurea have not worked.³ Moreover, no eosinophil-lowering therapy is indicated unless the AEC is much higher than that seen here or eosinophil-related symptoms (eg, cough, diaphoresis, fatigue) are present.

Imatinib (choice B) is a tyrosine kinase inhibitor that is extremely effective as an inhibitor specifically of the oncoprotein tyrosine kinase made by the oncogene BCR-ABL in Philadelphia chromosome-positive CML.⁴ It has also been shown to inhibit other neoplastic tyrosine kinases, including several (eg, the PDGFR gene) seen in the clonal types of eosinophilia.

Outcome of this case. Several stool samples were negative for ova and parasites. However, at the patient's third follow-up visit, he brought a bottle of a vitamin and amino acid supplement he had purchased at his fitness center and had been taking recently. Because it was nonprescription and not purchased at a drugstore, he had not considered it a drug. A review of the supplement's ingredients revealed tryptophan. The pills were immediately stopped. By the third month after discontinuation, the patient's AEC was 100/µLand the remainder of the hemogram was entirely normal.

References:

REFERENCES:

1.

Tefferi A. Blood eosinophilia: a new paradigm in disease classification, diagnosis, and treatment

. Mayo Clin Proc.

2005;80:75-83.

2.

Huang MS, Hasserjian RP. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 19-2004. A 12-year-old boy with fatigue and eosinophilia.

N Engl J Med.

2004;350:2604-2612.

3.

Rothenberg ME. Eosinophilia.

N Engl J Med.

1998;338:1592-1600.

4.

Pardanani A, Reeder T, Porrata LF, et al. Imatinib therapy for hypereosinophilic syndrome and other eosinophilic disorders.

Blood.

2003;101:3391-3397.

FOR MORE INFORMATION:

• Bain BJ. Eosinophilia--idiopathic or not? N Engl J Med. 1999;341:1141-1143.