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958 Part VII: Neutrophils, Eosinophils, Basophils, and Mast Cells Chapter 62: Eosinophils and Related Disorders 959

chronic eosinophilic pneumonia. Some patients also appear to have a cell proliferation, mononuclear cell infiltrates around blood vessels
raised eosinophil count without any evidence of organ damage, a so- (vasculitis), and perineural inflammatory infiltrates were identified
called benign eosinophilia. histopathologically. Glucocorticoid therapy may have decreased
Treatment The rarity of HES means that there are few clinical tri- the pulmonary symptomatology. The disease was thought to be a
als and most agents are used on the basis of anecdotal experience, the response to an unlabeled food oil, aniline-denatured rapeseed oil,
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opinion of the HES community or experience with related diseases. marketed as pure olive oil.
However, the use of imatinib mesylate for some patients with the myelo-
proliferative variant and the potential use of anti–IL-5 for T cell-driven Reactive Hypereosinophilia and Neoplasms
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disease offers new promise to patients with HES. The mainstay of Eosinophilia is associated with a 2.4-fold increase of developing a hema-
treatment has been glucocorticoids, which in many cases, particularly tologic malignancy over 4 years of observation compared with subjects
those caused by something other than myeloproliferative disease, are with a normal eosinophil count. Exaggerated tissue and blood eosin-
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effective at controlling both the eosinophil count and the target organ ophilia has been reported in association with a variety of lymphoid and
damage, albeit at the risk of long-term side effects. In patients with a solid tumors particularly lymphoma of various types including Hodgkin
myeloproliferative neoplasm, the eosinophil count is not completely and non-Hodgkin lymphoma, cutaneous T-cell lymphoma, and mar-
controlled with glucocorticoids, although these drugs can still limit ginal zone lymphoma. In these cases, the eosinophilia is thought to be
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organ damage. In patients where glucocorticoids are not sufficiently the result of an increase in IL-5 and other cytokines or chemokines elab-
effective, hydroxyurea is a useful second-line agent. Other cytotoxic orated by the tumor cells. Unlike other types of reactive eosinophilia,
drugs, such as vincristine and cyclophosphamide, are less commonly the blood eosinophil count may not be suppressed by glucocorticoids.
used than in the past. Interferon-α has also been used with some suc- The eosinophilia may precede the clinical diagnosis of the tumor but
cess. As discussed above, imatinib mesylate has resulted in remission in usually occurs concomitantly. There is evidence that eosinophils slow
patients with the F/P mutation, usually at doses well below those used the rate of progression of solid tumors, presumably by being cytotoxic
in chronic myeloid leukemia and some patients remain in remission to tumor cells with the extent peritumoral eosinophils predicting recur-
when the treatment is stopped. In the absence of the F/P mutation rence of colon cancer although other studies have raised the possibility
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in patients with myeloproliferative features, a trial of imatinib is indi- of a tumor promoting role. 192,193
cated as occasionally F/P-negative patients have responded 180,181 and this
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form of CEL carries a poor prognosis. Response to imatinib at a dose of
400 mg a day should be rapid (within several weeks) and result in a return Eosinophilic Granulomatosis with Polyangiitis
of the eosinophil count to within the normal range if the cause of the eos- Clinical Features EGPA, formerly Churg-Strauss syndrome, is a rare
inophilia is an imatinib-responsive tyrosine kinase mutation. Resistance disorder of unknown etiology characterized by eosinophilic asthma,
to imatinib treatment has emerged in some cases as it does when used for chronic rhinosinusitis, and small vessel vasculitis. It is one of the three
chronic myeloid leukemia. In one patient who developed resistance an antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides
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alternative PDGFRα inhibitor was effective. Treatment with imatinib (AAV), alongside microscopic polyangiitis (MPA) and granulomatosis
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has caused acute left ventricular failure in some cases and cardiac tropo- with polyangiitis (GPA, formerly Wegener disease). Patients with EGPA
nin has been suggested to be useful in monitoring response. Another are ANCA positive in approximately 40 percent of cases and gener-
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novel approach to treatment has been the use of anti–IL-5 mAb. This ally this is of the perinuclear-ANCA antimyeloperoxidase type com-
approach has resulted in a dramatic response in some patients, even in pared to GPA which is generally proteinase-3 positive. ANCA titers
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the absence of raised serum IL-5 concentrations. 186,187 In a double-blind, do not appear to correlate well with disease activity. Patients who are
placebo-controlled trial of F/P-negative HES, patients requiring 20 mg ANCA-positive have a different profile of disease compared to those
or more of prednisolone, mepolizumab, a humanized mAb that binds who are ANCA-negative in that vasculitic features are more promi-
IL-5, allowed a reduction below 10 mg of oral prednisone in 84 percent of nent and renal disease more common, but there is less cardiac disease,
patients, compared to 43 percent given a placebo, without any increase although there is considerable overlap. 195,196 The vasculitic process leads
in the activity of the HES. to a multisystem presentation commonly affecting the respiratory sys-
Course and Prognosis The outlook for patients with HES was tem, heart, skin, and peripheral nerves, although it can cause damage to
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poor with a series in 1973 reporting a 3-year survival of only 12 per- any organ. A marked blood eosinophilia is a prominent feature as are
cent with cardiac failure accounting for much of the morbidity. In a lethargy, general malaise, and weight loss. Mononeuritis multiplex is a
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later report, the outlook had improved with a survival of 80 percent at particularly characteristic feature that sometimes leads to rapid onset
5 years. 188 of a peripheral neuropathy, which can be permanent, causing consid-
erable morbidity. Cardiac disease with valvular damage or endomyo-
Toxic Oil Syndrome carditis is one of the most serious complications. The epidemiology of
In 1981, more than 20,000 cases of a syndrome manifested by fever, EGPA is not precise, but the point prevalence of new cases is approx-
cough, dyspnea, leukocytosis, neutrophilia, and an eosinophil count imately 1:1,000,000 with an accumulated prevalence of approximately
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greater than 0.75 × 10 /L were reported in Spain. Occasionally, 1:50,000, with precise numbers depending on the diagnostic criteria
9
the eosinophil count rose above normal only after the onset of used. The condition generally presents in middle age and is very rare
the pulmonary symptoms. Eosinophil degranulation was seen in the in children. The adult onset in people with preexisting asthma has led
effected tissues. Pulmonary infiltrates were evident on x-rays of the to speculation that EGPA is the result of an inflammatory stimulus on
chest. Pleural effusion was common, and hypoxemia was frequent. the background of a respiratory eosinophilia leading to systemic eosin-
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There were 1500 deaths in the cohort. Approximately half of the ophilic activation. Consistent with this, case-control studies suggest
patients went on to a chronic course that mimicked the eosinophilia- a link with various environmental exposures, including farming, silica,
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myalgia syndrome, with myalgias, eosinophilia, peripheral neuritis, and solvents, but no single trigger has been identified. There is no
scleroderma-like skin lesions, hair loss, and a sicca syndrome. Most obvious gender, geographic, ethnic or socio-economic predilection.
patients improved from the acute or chronic symptoms and signs, but There are case reports of family clusters, but in most cases there is no
some residual nerve, muscle, or skin damage persisted. Endothelial evidence of an inherited cause. The syndrome is heterogeneous in its

Kaushansky_chapter 62_p0947-0964.indd 959 9/21/15 10:56 AM