Chapter 34: Eosinophils and Their Diseases

• The normal absolute eosinophil count in adults is less than 0.5 × 10⁹ cells/L.

• The eosinophil count is higher in neonates.

• Eosinophils are primarily tissue dwelling, with 300 cells in the tissues for every blood eosinophil.

• The degree of eosinophilia is described as:

  — Mild (0.5 to 1.5 × 10⁹ eosinophils/L).

  — Moderate (1.5 to 5.0 × 10⁹ eosinophils/L).

  — Marked (>5.0 × 10⁹ eosinophils/L).

• The most common causes of eosinophilia include:

  — Worldwide: infections with helminthic parasites.

  — In industrialized countries: asthma and other allergic disorders (drug allergy, allergic rhinitis, atopic dermatitis).

  — Allergic diseases generally result in only mild eosinophilia.

  — The major causes of eosinophilia are listed in Table 34–1.

• Eosinophils appear to have a role in both ameliorating inflammatory responses and producing tissue damage.

• They may be important in wound healing and may act as accessory cells in T cell–mediated reactions.

• Because eosinophils can kill parasites, it has been hypothesized that their principal role is to counter parasitic infection.

• Eosinophils can cause airway damage in asthma and severe tissue damage in hypereosinophilic syndromes.

Asthma

• Inhaled antigen produces:

  — An early response, with fall in forced expiratory volume caused by release of mediators from mast cells.

  — A late response with influx of large numbers of eosinophils, activated T cells, and monocytes to the airways.

  — Correlation exists between the numbers of airway eosinophils and the severity of asthma.

  — Basic proteins secreted by eosinophils are toxic for airway epithelium and may be a better guide to the degree of inflammation than eosinophil numbers.

Parasitic Disease

• The mechanism of eosinophilia in parasitic disease is similar to allergic disease.

• The more pronounced eosinophilia in parasitic disease is presumably caused by the systemic nature of the disease compared with the more localized nature of allergic disease.

• Eosinophils can kill a number of opsonized parasite larvae but not adult worms.

• Table 34–2 describes the major parasitic causes of eosinophilia.

Idiopathic Hypereosinophilic Syndrome (Myeloid and Lymphoid Variants)

Definition

• The sporadic occurrence of striking eosinophilia (>1.5 × 10⁹/L) in the absence of a disease that is associated with reactive eosinophilia.

Myeloid Type

• Monoclonal eosinophilia, reflecting the expression of chronic eosinophilic leukemia. Marrow contains principally eosinophilic myelocytes and mature eosinophils, some with hypersegmented nuclei (>2 segments).

  — Onset with some or all of the following: anorexia, weight loss, fatigue, nausea, abdominal pain, diarrhea, nonproductive cough, pruritic rash, fever, night sweats, and venous thrombosis.

  — Skin signs: urticaria, papules, pruritus.

  — Cardiac involvement: endocardial fibrosis, restrictive cardiomyopathy, mitral or tricuspid valve incompetence, ventricular failure.

  — Neurologic findings: neuropathies.

  — Organ involvement as a consequence of the noxious effects of eosinophil granule contents is a feature of chronic eosinophilic leukemia.

  — Most patients have cardiac involvement, with congestive heart failure, new murmurs, conduction defects, and arrhythmias.

  — Hepatosplenomegaly, interstitial pulmonary infiltrates, and pleural effusions can occur.

  — Nervous system dysfunction may be profound, including confusion, delirium, dementia, and coma.

  — Anemia occurs in most patients.

  — Thrombocytopenia is seen occasionally.

  — All patients have leukocytosis with a striking eosinophilia, usually eosinophil counts greater than 1.5 × 10⁹/L, and counts of 50.0 × 10⁹/L or more are found in more than half the patients.

  — The eosinophilia may be progressive.

  — Cytogenetic abnormalities may be found in the leukemic eosinophilic cells in a proportion of patients. One of several translocations involving chromosome 5 may occur. Of particular importance is the occurrence of the FILIPI-PDGFR-α fusion gene since, if present, the patient will usually respond to tyrosine kinase inhibitor drugs, such as imatinib mesylate.

  — Elevated serum tryptase is common (suggesting unapparent mast cell involvement).

  — The disease is sometimes indolent, but more often progressive and fatal.

  — Signs and symptoms may remit and relapse, but organ damage is usually progressive.

  — Cardiac failure may result from endomyocardial fibrosis.

  — Central nervous system dysfunction may lead to encephalopathy, polyneuropathy, or stroke.

  — Episodes of venous thrombosis may complicate the course.

  — In patients unresponsive to tyrosine kinase inhibitors, hydroxyurea and glucocorticoids may be of benefit in decreasing the eosinophil count and the risk of tissue injury.

  — Other therapies include etoposide, interferon-α, cladribine, and leukapheresis.

  — Surgical replacement of severely damaged heart valves has been successful.

  — Allogeneic hematopoietic stem cell transplantation has been used in some patients.

Lymphoid Type

• A less common cause of hypereosinophilia is a clonal T-lymphocyte disorder (lymphoma) with polyclonal eosinophilia resulting from lymphoma cell elaboration of eosinopoietic cytokines, especially interleukin-5.

  — In this lymphoid form of hypereosinophilia, eosinophil-induced tissue damage is not a feature of the disease, suggesting that the tissue damage is a feature of leukemic eosinophils.

  — The treatment is directed principally at the underlying lymphoma.

• Table 34–3 contains tests that may be helpful in evaluating patients with the hypereosinophilic syndrome.

Other Types

• The causes of the remaining cases of hypereosinophilia that are neither chronic eosinophilic leukemia nor related to lymphoma are still unclear.

Eosinophilia–Myalgia Syndrome

• First described in 1989, with more than 1500 cases reported and 30 deaths in the next 2 years.

• Caused by the ingestion of l-tryptophan, a nutritional supplement, containing a contaminant.

• Constant features are severe myalgia and eosinophil count greater than 1.0 × 10⁹/L.

• Common findings are arthralgias, cough, dyspnea, edema, hair loss, peripheral neuropathy, and scleroderma-like skin changes.

• Pathologic features mimic eosinophilic fasciitis (see below).

• Glucocorticoids improved symptoms and signs.

Toxic Oil Syndrome

• In 1981, in Spain, more than 20,000 people developed a syndrome of fever, cough, dyspnea, neutrophilia, and eosinophilia. More than 300 deaths occurred.

• Thought to be caused by ingestion of aniline-denatured rapeseed oil.

• Pulmonary infiltrates, pleural effusion, and hypoxemia were common findings.

• One-half the patients developed a chronic illness that mimicked the eosinophilia–myalgia syndrome (see above), with myalgias, eosinophilia, peripheral neuritis, scleroderma-like skin lesions, hair loss, and sicca syndrome.

• Glucocorticoids may have improved the pulmonary symptoms.

Reactive Hypereosinophilia and Neoplasms

• Marked eosinophilia has been reported in association with a variety of solid tumors and lymphomas (e.g., Hodgkin lymphoma), believed to be caused by IL-5 and other cytokines elaborated by tumor cells.

• Eosinophilia may precede the diagnosis but usually occurs concomitantly.

• Successful treatment of the malignancy may be associated with amelioration of eosinophilia.

Acute Eosinophilic Leukemia

• Rare forms of AML (see Chap. 46).

Eosinophilia, Angiitis, and Asthma

• Polyarteritis nodosa and allergic granulomatosis (Churg-Strauss angiitis) are associated with prominent eosinophilia.

• In patients with asthma and eosinophilia, the development of multiorgan signs (skin, nervous system, kidney, joints, lung, heart, gastrointestinal tract) should lead to consideration of this disorder.

Eosinophilic Fasciitis

• Characterized by stiffness, pain, and swelling of the arms, forearms, thighs, legs, hands, and feet in descending order of frequency.

• Malaise, fever, weakness, and weight loss also occur.

• Absolute eosinophil counts of greater than 1.0 × 10⁹/L are found in most patients.

• Biopsy is usually required for diagnosis and shows inflammation, edema, thickening, and fibrosis of the fascia and synovia.

• Aplastic anemia, cytopenias, pernicious anemia, and myelogenous leukemia have been associated.

• Excretion of eosinophils in the urine is seen most often in urinary tract infection or acute interstitial nephritis.

• Cerebrospinal fluid eosinophilia may occur with infection, shunts, allergic reactions involving the meninges, and Hodgkin lymphoma.

• The eosinophil count in hospitalized patients is less than 0.01 × 10⁹/L in only 0.1 percent of patients.

• Acute infections, glucocorticoids, and epinephrine all decrease the eosinophil count.