Page 378 - Clinical Immunology_ Principles and Practice ( PDFDrive )

358 Part two Host Defense Mechanisms and Inflammation

abnormalities in the eosinophil lineage have been reported in a secondary eosinophil-mediated cardiac damage, for reasons that
few patients (see Fig. 24.4). are not known.
Another variant form of HES is a lymphoproliferative form
−
+
resulting from clonal expansions of lymphocytes, often CD4 CD3 Pulmonary Eosinophilias
29
Th2-like lymphocytes, which elaborate IL-5. These aberrant T Blood eosinophilia can infrequently accompany pleural fluid
cells can be sought by flow cytometry or T-cell receptor (TCR) eosinophilia, a nonspecific response seen with various disorders,
analysis. These patients, who may have elevated IgE levels, usually including trauma and repeated thoracenteses. In addition, several
do not develop eosinophilic endomyocardial disease but are at pulmonary parenchymal disorders can be associated with
risk for developing T-cell lymphomas. 29 eosinophilia (see Table 24.2). 32
In addition to these recognized variants, there are a substantial Helminth parasites are responsible for four forms of eosino-
number of patients with HES for whom the etiologies of the philic lung disease. 24,32 The first form, Loeffler syndrome, is marked
26
eosinophilia remain unknown. Some such patients develop no by blood eosinophilia, eosinophilic patchy pulmonary infiltrates
signs or symptoms of disease and can be monitored without that appear and resolve over weeks, and, at times, bronchospasm,
30
therapy. For those who require therapy, including those with and is typically caused by those helminth parasites (Ascaris
29
lymphoproliferative variants, glucocorticosteroids are the lumbricoides/Ascaris suum), and less commonly hookworm and
26
mainstay of treatment. With glucocorticoid therapy, partial or Strongyloides that migrate through the lungs early in their
24
complete remission of eosinophilia within 1 month has been developmental lifecycle. Stool examinations are not helpful, as
26
reported to occur in 85% of patients. Second-line agents include the pulmonary response is elicited by infecting larval forms
26
hydroxyurea and IFN-α. The neutralizing anti-IL-5 monoclonal months before productive egg-laying from later adult stages
antibody (mAb), mepolizumab, has beneficial and steroid-sparing begins in the intestines. Diagnosis is made on epidemiological
effects in those with FIP1L1-PDGFRA negative hypereosinophilic grounds. 24
31
syndromes, but it is approved by the US Food and Drug The second form of helminth-induced lung disease is the
Administration (FDA) for treating severe eosinophilic phenotype syndrome of tropical pulmonary eosinophilia, which develops
asthma but not yet approved for hypereosinophilic syndromes. in a minority of patients infected with lymphatic-dwelling filarial
23
Anti-CD52 mAb (alemtuzumab) and allogeneic hematopoietic species. This syndrome is characterized by marked blood
cell transplantation have been used for particularly severe and eosinophilia, a paroxysmal nonproductive cough, wheezing,
refractory HES. occasional weight loss, lymphadenopathy, and low-grade fevers.
In contrast to older reports, with earlier diagnosis and On chest X-rays, increased bronchovesicular markings, diffuse
therapy and with more varied and targeted therapeutic options, interstitial lesions 1–3 mm in diameter or mottled opacities,
morbidity and, particularly, mortality in HES syndromes have usually more prominent in lower lung fields, are common. Patients
been reduced. have markedly increased numbers of blood and alveolar eosino-
phils, and elevations in both total serum IgE and antifilarial
Eosinophilia With Tumors or Leukemias antibodies.
The F/P-positive and related chromosomal fusion gene mediated A third form of helminth-induced lung disease is caused by
27
myeloproliferative variants of HES are forms of CEL. Eosino- helminths that invade the pulmonary parenchyma, notably lung
philia is a characteristic of the M4Eo subtype of acute myeloid flukes that cause paragonimiasis.
leukemia, having the common M4 characteristic of chromosomal The fourth form of lung disease is caused by larger than usual
16 abnormalities. Other forms of eosinophilic leukemia, often numbers of helminth organisms that are carried hematogenously
with specific cytogenetic and molecular genetic abnormalities, into the lungs. Examples include schistosomiasis, trichinellosis,
27
have been recognized. Eosinophilia may accompany chronic and larva migrans.
myelogenous leukemia (often with basophilia) but is uncommon Bronchopulmonary aspergillosis constitutes another type of
with acute lymphoblastic leukemia. Eosinophilia may be observed eosinophil-associated pulmonary disease. Two forms of idiopathic
32
in some patients with lymphoma, including Hodgkin disease, eosinophilic pneumonia are recognized. In chronic eosinophilic
especially the nodular sclerosing form, T-cell lymphoblastic pneumonia, patients may exhibit peripheral pulmonary infiltrates
lymphoma, and adult T-cell leukemia/lymphoma. A small propor- that can extend across lobar fissures. Chronic eosinophilic
tion of patients with carcinomas, especially of mucin-producing pneumonia is of unknown etiology and is responsive to
epithelial cell origin, have associated blood and tissue eosinophilia. corticosteroids but is prone to relapse. An acute form of eosinophilic
Eosinophilia may accompany angioimmunoblastic lymphade- pneumonia, which manifests as fever, pulmonary infiltrates, and
nopathy, mycosis fungoides, Sézary syndrome, and lymphomatoid respiratory insufficiency, is diagnosable by finding eosinophils
papulosis. Eosinophilia occurs in about 20% of patients with in bronchoalveolar lavage (BAL) fluids or on lung biopsy. Acute
systemic mastocytosis and may be the presenting finding in the eosinophilic pneumonia, which often follows new exposures to
absence of cutaneous manifestations. cigarette or other smoke or dusts, responds to corticosteroid
treatment and does not relapse.
ORGAN SYSTEM INVOLVEMENT The major vasculitis associated with eosinophilia is eosinophilic
AND EOSINOPHILIA granulomatosis with polyangiitis (EGPA, formerly called Churg-
33
Strauss syndrome) (Chapter 58). Late-onset asthma, eosinophilia,
Eosinophilic syndromes limited to specific organs, such as and at times transient pulmonary infiltrates antedate the develop-
eosinophilic pneumonias or eosinophilic GI disorders (EGIDs; ment of systemic vasculitis in about half the cases. Pulmonary
Chapter 46), characteristically do not extend beyond their own involvement is seen in almost all patients, and pulmonary
target organ, and hence lack the multiplicity of organ involvement infiltrates occur in three-quarters of them. Nasal and sinus
often found with non–organ-specific hypereosinophilic syn- involvement is common. Corticosteroids, anti-IgE mAb, or
dromes. They also do not have the predilection to develop anticysteinyl leukotriene agent therapies for asthma may mask