DISEASES ASSOCIATED WITH EOSINOPHILIA

Many diseases with allergic, infectious, hematologic, autoimmune, or idiopathic origins are associated
with moderate (AEC 1,500-5,000 cells/L) or severe (AEC >5,000 cells/L) eosinophilia in peripheral
blood. These disorders may range from mild and transient to chronic and life-threatening, and,
importantly, blood eosinophil numbers do not always reflect the extent of eosinophil involvement in
disease-affected tissues. Because prolonged eosinophilia is associated with end-organ damage,
especially involving the heart, patients with persistently elevated AECs should undergo a thorough
evaluation to search for an underlying cause.

Allergic Diseases

Patients with allergic asthma commonly have eosinophils in the blood, sputum, and/or lung tissue.
Hypersensitivity drug reactions can elicit eosinophilia, and when associated with organ dysfunction
(e.g., DRESS [drug rash with eosinophilia and systemic symptoms]), these reactions can be serious.
If a drug is suspected of triggering eosinophilia, biochemical evidence of organ dysfunction should be
sought and if found, the drug should be discontinued. Skin diseases have also been associated with
eosinophilia, including atopic dermatitis/eczema, pemphigus, urticaria, and toxic epidermal necrolysis.

Eosinophilic gastrointestinal diseases are important emerging allergic causes of eosinophilia in tissue
and, in some cases, peripheral blood. In these conditions, eosinophils are inappropriately recruited to
esophagus, stomach, and/or intestine, where they induce tissue inflammation and clinical symptoms
such as dysphagia, food aversion, abdominal pain, vomiting, and diarrhea. Treatment options include
allergen elimination diets and swallowed topical corticosteroids.

Infectious Diseases

Eosinophilia is often associated with invasive infection with multi-cellular helminthic parasites, which
are the most common cause in developing countries. The level of eosinophilia tends to parallel the
magnitude and extent of tissue invasion, especially by larvae such as visceral larva migrans. Eosinophilia
often does not occur in established parasitic infections that are well contained within tissues or are
solely intraluminal in the gastrointestinal tract, such as Giardia lamblia and Enterobius
vermicularisinfection. It is frequently necessary to examine the stool for ova and larvae at least 3 times.
Additionally, the diagnostic parasite stages of many of the helminthic parasites that cause eosinophilia
never appear in feces. Toxocara causes visceral larva migrans usually in toddlers with pica. Two fungal
diseases may be associated with eosinophilia: aspergillosis in the form of allergic bronchopulmonary
aspergillosis and coccidioidomycosis following primary infection, especially in conjunction with
erythema nodosum. HIV can also be associated with peripheral eosinophilia.

Hypereosinophilic Syndrome

The idiopathic hypereosinophilic syndrome is a heterogeneous group of disorders characterized by

sustained overproduction of eosinophils.

The 3 diagnostic criteria for this disorder are

(1) AEC >1,500 cells/L persisting for 6 mo or longer or at least on 2 occasions or with evidence of tissue
eosinophilia;

(2) absence of another diagnosis to explain the eosinophilia; and

(3) signs and symptoms of organ involvement.

The clinical signs and symptoms of hypereosinophilic syndrome can be heterogeneous because of the
diversity of potential organ (pulmonary, cutaneous, neurologic, serosal, gastrointestinal) involvement.
Loeffler endocarditis, one of the most serious and life-threatening complications, can cause heart failure
from endomyocardial thrombosis and fibrosis.

Eosinophilic leukemia, a clonal myeloproliferative variant, may be distinguished from idiopathic

hypereosinophilic syndrome by demonstrating a clonal interstitial deletion on chromosome 4q12 that
fuses the platelet-derived growth factor receptor-(PDGFRA) and FIP1-like-1 (FIP1L1) genes; this disorder
is treated with imatinib mesylate, which helps target the fusion oncoprotein. Therapy is aimed at
suppressing eosinophilia and is initiated with corticosteroids. Imatinib mesylate, a tyrosine kinase
inhibitor, may be effective in FIP1L1-PDGFRAnegative patients. Hydroxyurea may be beneficial in
patients unresponsive to corticosteroids. Specific anti-IL-5 monoclonal antibodies (mepolizumab) target
this cytokine, which has a central role in eosinophil differentiation, mobilization and activity. With
therapy, the eosinophil count declines and cortico-steroid doses may be reduced. For patients with
prominent organ involvement who fail to respond to therapy, the mortality is 75% after 3 yr.

Miscellaneous Diseases

Eosinophilia is observed in many patients with primary immunodeficiency syndromes, especially

hyperimmunoglobulin E syndrome, Wiskott-Aldrich syndrome, and Omenn syndrome. Eosinophilia is
also frequently present in the syndrome of thrombocytopenia with absent radii and in familial
reticuloendotheliosis with eosinophilia.

Eosinophilia can be found in patients with Hodgkin disease, as well as in acute lymphoid and myeloid
leukemia. Other considerations include gastrointestinal disorders such as ulcerative colitis, Crohns
disease during symptomatic phases, chronic hepatitis, Churg-Strauss vasculitis, and adrenal
insufficiency.