Page 1315 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 71 Eosinophilia, Eosinophil-Associated Diseases, Eosinophilic Leukemias, and the Hypereosinophilic Syndromes 1161

gold standard in diagnostic evaluation in patients with HE-related Neurologic Manifestations
cardiopathy.
Neurologic involvement is quite common in HES, affecting approxi-
mately 50% of all patients. In these cases, three different types of
Pulmonary Manifestations manifestations have been described. The first form of neurologic
involvement is caused by thromboemboli, which may originate from
Approximately 50% of HES patients have pulmonary involvement, intracardiac thrombi in the left ventricle but may also develop locally
with the most common symptom being a chronic and persistent in cerebral vessels. Some of these thromboembolic episodes may
(nonproductive) cough. In order to confirm pulmonary manifesta- occur before an overt cardiac manifestation has been documented.
tion in HES, a number of studies may be helpful, including pulmo- Patients with thrombotic complications may experience embolic
nary function tests, chest radiography and/or CT scan, and strokes or transient ischemic attacks that may be multiple and recur-
bronchoscopy with BAL studies and a tissue biopsy if necessary. The rent, and these episodes may occur even though the patient is ade-
physiologic basis of pulmonary involvement in HES remains quately anticoagulated. The second type of neurologic manifestation
unknown. As in the heart, several different eosinophil-derived (cyto- is primary diffuse CNS involvement. These patients may variably
toxic and stroma-targeting) mediators and cytokines may act together exhibit changes in behavior, confusion, ataxia, and loss of memory.
to induce tissue damage and tissue remodeling, as well as fibrosis and The third neurologic abnormality noted in HES is the development
thrombosis. Some of the pulmonary features may also reflect changes of peripheral neuropathy, which can occur in approximately 50% of
secondary to congestive heart failure. Although bronchospasm has HES patients exhibiting neurologic involvement. This includes sym-
been noted in some patients, full-blown asthma is rare in HES metric or asymmetric sensory polyneuropathies, including sensory
patients. Transudative pleural effusions are mostly seen in patients deficits, painful paresthesias, or mixed sensory and motor defects (see
with frank congestive heart failure. In contrast to chronic eosinophilic Table 71.7). These neuropathies may improve with corticosteroid
pneumonia, the pulmonary infiltrates seen in HES patients are either administration or other treatments, and may be stable or continue to
diffuse or focal, without any preference for particular regions of the progress despite therapy, or may improve or even resolve with time.
lung. Pulmonary infiltrates in HES often clear with prednisone treat- The histopathology of the involved nerves usually shows varying
ment, but not all patients are responders. Pulmonary fibrosis is rare, degrees of axonal loss, without evidence of vasculitis or direct or
but can develop in patients with endomyocardial fibrosis. The dif- peripheral eosinophil infiltration. Whether eosinophil-derived EDN
ferential diagnosis of HES R with pulmonary involvement includes and/or ECP, known to cause neurotoxicity in experimental animals,
drug allergy, CSS, chronic eosinophilic pneumonia, severe allergic are involved in the development of neuropathies in HES remains
bronchial asthma with eosinophilia, allergic bronchopulmonary unknown. Based on immunohistochemical studies, these proteins are
aspergillosis, and other eosinophilic lung infections. not detectable at the sites of ongoing neuropathology in HES patients.
All in all, the etiology of HES-related neuropathy remains poorly
defined. Differential diagnoses of HES-related neuropathies are
Cutaneous Manifestations manifold and include, among others, neurodegenerative disorders,
multiple sclerosis, and CNS infections.
The skin is frequently involved in HES, with cutaneous lesions
present in over 50% of all cases. In these patients, the cutaneous
lesions fall into three categories: (1) angioedematous and urticarial Gastrointestinal Manifestations
lesions; (2) erythematous, pruritic papules and nodules; and (3)
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mucosal ulcerations (see Table 71.7). Patients with angioedema and Compared to lung or skin, GI tract involvement is less common in
urticaria are more likely to have a benign disease that is responsive to patients with HES. Although any form of HES can present with GI
corticosteroids, without the development of cardiac or neurologic tract manifestation, GI tract symptoms are mostly recorded in
symptoms. A subgroup of patients with cyclical angioedema and patients with HES R or the idiopathic form of HES. In these patients,
eosinophilia are considered to have a syndrome (episodic angioedema a wide variety of symptoms and findings have been described, includ-
with eosinophilia = Gleich syndrome) that is distinct from classical ing abdominal pain, vomiting, diarrhea, or ulcerative disease, but also
HES. These patients have a disorder with recurrent attacks of angio- ascites or an overt colitis (see Table 71.7). These patients may also
edema and urticaria accompanied by fever and weight gain. In HES report bloody diarrhea and weight loss. Histologically, GI tract
patients with papular or nodular lesions, dermal biopsies usually show involvement with HES is characterized by an infiltration of the
mixed cellular infiltrates, including eosinophils, without signs of mucosa and submucosa with eosinophils. Immunohistochemical
vasculitis. Perivascular eosinophilic infiltrates are also found in these examination may reveal a huge infiltration with eosinophils as well
lesions. In a group of HES patients with skin involvement, the as extensive deposition of extracellular eosinophil proteins in the
erythematous pruritic eruptions and indurated papules and nodules gastric mucosa. In most patients with reactive HES, the GI tract
may respond to psoralen and ultraviolet light A. In other patients disease component responds to treatment with oral corticosteroids.
with HES-associated pruritus, the nodular lesions may respond to Differential diagnoses of GI tract involvement with HES include
dapsone and corticosteroids. Oral sodium cromoglycate (cromolyn localized (organ-restricted) inflammatory disorders, such as eosino-
sodium), administered before meals, has also been reported to be philic esophagitis, eosinophilic gastroenteritis, eosinophilic colitis,
efficacious, although neither dapsone nor cromolyn is able to reduce autoimmune diseases, chronic inflammatory bowel disease, GI infec-
eosinophil counts in the blood. Severe and sometimes incapacitating tions, GI tract lymphomas, and GI tract involvement in patients with
mucocutaneous ulcerations may be a prodrome to HES and indicate SM. Especially in patients with SM, the underlying disease is often
a subset of HES patients with a poor prognosis. These lesions can overlooked, since neoplastic mast cells are outnumbered by the
appear at multiple sites, including the mouth, nose, pharynx, penis, infiltrating eosinophils. In these cases, the use of mast cell-related
esophagus, stomach, and anus. The lesions can flare up independently immunohistochemical markers, such as tryptase, KIT (CD117), or
of other clinical manifestations of HES. Biopsies of the ulcerative CD25, may be helpful to diagnose an underlying SM.
lesions usually show mixed cellular infiltrates, without a predomi-
nance of eosinophils or any evidence of vasculitis or microthrombi.
These ulcers are usually resistant to treatment with corticosteroids, Hematologic Manifestations and BM Involvement
colchicine, and hydroxyurea (HU), but they usually respond to
interferon-α (IFN-α), with complete and durable remissions in most In HES patients suffering from an underlying myeloid neoplasm
patients. There are a number of differential diagnoses that have to be (HE N , HES N ), the BM is almost always involved. In these patients,
considered in HES patients with suspected skin involvement, includ- the BM is often hypercellular and shows a substantial increase
ing drug reactions, local infections, and atopic eczema. in eosinophil numbers. In addition, alterations in the BM