Page 598 - Clinical Immunology_ Principles and Practice ( PDFDrive )

576 ParT FIvE Allergic Diseases

Treatment of ABPA aims to suppress the inflammatory response the lungs. Expansion of Th2 cells and local and systemic release
to the fungus and to control bronchospasm with glucocorticoid of IL-4 and IL-5 are also frequently seen. The clonal expansion
therapy, the duration of which may be shortened by concomitant of Th2 cells in the absence of known antigen exposures, and the
use of oral antifungal agents, such as itraconazole. 15 association of idiopathic hypereosinophilic syndrome (IHES)
with a variety of chromosomal aberrations, strongly support
Acute Eosinophilic Pneumonia the concept that IHES is a myeloproliferative disorder involving
Acute eosinophilic pneumonia (AEP) is an acute, often debilitating Th2 cells, although aberrant secretion of IL-5 by both solid and
eosinophilic inflammatory syndrome that exclusively involves liquid tumors can produce very similar syndromes. Many organs
the lungs and is marked by pulmonary infiltrates, dyspnea can be affected, resulting in dysfunction or failure of the
progressing to frank respiratory failure, and fever. The diagnosis gastrointestinal (GI) tract, skeletal muscles (leading potentially
is dependent on eosinophils exceeding 25% of all inflammatory to respiratory failure), endomyocardial fibrosis, myocarditis, and
cells within the bronchoalveolar lavage (BAL) fluid. Increasing congestive heart failure. Pulmonary involvement manifests as
evidence suggests an association between AEP and respiratory obstructive airway disease, pulmonary edema, or pulmonary
fungal infections and recent-onset cigarette smoking. 16,17 AEP emboli caused by a hypercoagulable state. In addition to hype-
has also been reported following allogeneic hematopoietic stem reosinophilia, patients with IHES may have evidence of polyclonal
cell transplantation (HSCT) in the setting of graft-versus-host hypergammaglobulinemia. The diagnosis is based on the discovery
18
disease (GvHD). Prompt recognition of the disease and initiation of elevated peripheral blood eosinophilia in the setting of a
of treatment with glucocorticoids usually results in rapid radio- multisystem disorder, with evidence of aberrant Th2 responses
graphic and clinical improvement. or elevated IL-5 secretion and defined genetic mutations. The
most consistently effective therapy for IHES involves tyrosine
Intrinsic Eosinophilic Syndromes kinase inhibition, using agents such as imatinib mesylate. 20
Chronic Eosinophilic Pneumonia
This disorder presents similarly to AEP, but in a more chronic Churg-Strauss Syndrome
manner (greater than 6 weeks duration). Chronic eosinophilic Churg-Strauss syndrome (CSS), also termed eosinophilic granu-
pneumonia (CEP) can occur in isolation and/or in association lomatosis with polyangiitis (EGPA), is a necrotizing vasculitis of
with polyarteritis nodosa, rheumatoid arthritis, scleroderma, medium and small caliber vessels (Chapter 58), which is character-
ulcerative colitis, breast carcinoma, and histiocytic lymphoma. ized by airway obstruction and eosinophilia. The disease has an
Most patients have evidence of asthma and atopy. Like AEP, CEP autoimmune nature, given the presence of circulating anti-
can present with striking eosinophilic inflammation of the lung myeloperoxidase and antineutrophil cytoplasmic antibodies
(Fig. 41.4). Granulomas are occasionally seen on biopsy specimens, (p-ANCA) as seen in 60–70% of affected individuals. Because
suggesting that an antigen-driven, T cell–mediated process is CSS is seen in patients with a history of asthma and allergies
involved in the chronicity of the disease. Treatment, as for AEP, and the prominent pathological feature is necrotizing vascular
is based on steroid therapy, but unlike AEP, CEP frequently and tissue granulomas, the term “allergic granulomatosis and
relapses after discontinuation of treatment. 19 angiitis” is used synonymously. Inhaled or ingested antigens have
been proposed as causative agents in susceptible individuals.
Idiopathic Hypereosinophilic Syndrome Reports linking the syndrome with the LT inhibitors zafirlukast
This multisystem disease is characterized by the massive accumula- and montelukast in the setting of steroid withdrawal suggest
tion of eosinophils in many tissues and almost always involves that these agents may unmask preexisting CSS rather than directly
causing the disorder. Similar observations have been made with
omalizumab treatment. The vasculitis of CSS can affect the
sinuses, the central and peripheral nervous systems, the GI tract,
kidneys, and the heart. Treatment of CSS is based on the use of
systemic steroids, which leads to disease resolution in the majority
of patients. In severe steroid-resistant disease, cyclophosphamide
and other immunosuppressants may be required. 21
IMMUNOLOGICAL MECHANISMS OF ALLERGIC
AIRWAY DISEASE

All patients with major allergic airway disease syndromes include
patients who demonstrate evidence of allergic inflammation,
with elevated blood and airway eosinophilia, elevated serum
total and antigen-specific IgE levels, and positive skin prick tests.
However, not all patients demonstrate all markers of allergic
inflammation simultaneously, and some patients with apparent
allergic disease express none of these markers. Specialized testing
may also reveal predominant Th2 cytokine responses generated
FIG 41.4 Histology of Chronic Eosinophilic Pneumonia. Lung from peripheral blood mononuclear cells when stimulated with
biopsy specimen from a patient with chronic eosinophilic common allergens in vitro and the presence of Th2 cells, ILC2,
pneumonia demonstrates a confluent infiltrate with eosinophils eosinophils, and IgE-secreting B cells, and the secreted products
filling alveoli together with large, multinucleate macrophages. of these cells, within affected sinus and airway tissues. As well
Original magnification, ×200, hematoxylin and eosin stain. as the conventional causes of Th2-mediated airway inflammatory