Pulmonary Eosinophilia

Prepared by Shahid Raja

Poulomi Jana
INTRODUCTION
Definition: Pulmonary eosinophilia (PE) is defined as
infiltration of eosinophils into the lung compartments
constituting airways, interstitium, and alveoli.Various
infections, drugs, parasites, autoimmune processes,
malignancies and obstructive lung diseases have been
associated with increased eosinophils in the lungs.

● Pulmonary eosinophilia category: 1.primary/idiopathic

2.secondary/extrinsic from external factors.

2
ETIOLOGY:
Intrinsic PE: It include a diverse group of autoimmune and idiopathic
syndromes ranging from blood dyscrasias to vasculitis. This group
includes acute eosinophilic pneumonia (AEP), chronic eosinophilic
pneumonia (CEP), idiopathic hypereosinophilic syndrome (IHES),
ChurgStrauss syndrome (CSS), and eosinophilic granuloma (EG; pulmonary
histiocytosis X or Langerhans cell granulomatosis).

Extrinsic PE: It is due inhaled or ingested extrinsic factors, including

medications and infectious agents (e.g. parasites, fungi, mycobacteria),
may trigger an eosinophilic immune response. medications, drugs (e.g.
cocaine), food (e.g. contaminated cooking oil), dietary supplements.

3
PATHOPHYSIOLOGY
Eosinophils are one of the main cells of
allergic inflammation. The basic
pathophysiology is an ovelap of 3 phases
1. Acute lymphocytic: infiltration.
2. Subacute granuloma formation.
3. Chronic fibrosis
Tissue pathology is largely related to the release of toxic
eosinophil products. These products include major basic protein,
eosinophil cationic protein, and eosinophil derived neurotoxin,
which damage the respiratory epithelium, induce ciliastasis, and
influence mucus production.
The release of platelet activating factor and leukotrienes
contributes to bronchospasm. Local tissue injury due to these
mediators causes respiratory tract damage and can lead to
respiratory failure. The distribution of EP depends on the
underlying etiology; it can be diffuse or focal.
✓ In EP due to Ascaris, the transmission is through the fecal-
oral route.
✓ In Strongyloidiasis, the entry is through the skin.

5
Extrinsic Eosinophilic Syndromes

• Loeffler syndrome: The pathogenesis unknown but presumably reflects a

hypersensitivity response to an ingested or inhaled antigen from food, medication,
or an infectious agent. Many of the original cases of Loeffler syndrome were
thought to be related to Ascaris infection.

• Parasitic infections: Migrating parasites traversing the lungs may cause

bronchospasm, dyspnea, and pulmonary infiltrates. Local elaboration of
chemokines and cytokines plays a role in T-cell recruitment and granuloma
formation. Persistent inflammation may lead to parenchymal necrosis and fibrosis.

• Schistosomiasis: The most common pulmonary complication is pulmonary

hypertension from chronic embolization of ova.

• TPE: These patients have marked immune responses to filariae,

6
Intrinsic Eosinophilic Syndromes

CEP: The pathogenesis is unknown. CEP may occur in isolation and/or in association with
polyarteritis nodosa, rheumatoid arthritis, scleroderma, ulcerative colitis, breast
carcinoma, and histiocytic lymphoma. Most patients have evidence of asthma and atopy.

IHES: Some patients display overproduction of proeosinophilic factors, including

interleukin (IL)–4 and IL-5, by clonally expanded differentiation clusters 3 and 4 (CD3+
and CD4+) and Th2-like lymphocytes. These patients also have evidence of polyclonal
hypergammaglobulinemia.

CSS: The pathogenesis is unknown. Inhaled or ingested antigens have been proposed as
causative agents in susceptible individuals.

EG: The cause is unknown, but the reactive histiocytic proliferation suggests a reactive
process, perhaps to an unknown antigen. Patients develop reticulonodular interstitial and
cystic disease.

7
MORTALITY
• With the exception of Loeffler syndrome and drug-induced disease, these
syndromes may be associated with significant morbidity. While most are responsive
to corticosteroids, recognition of infection and institution of an appropriate
therapy are important in preventing chronicity of symptoms and, in some cases,
respiratory failure.

• Patients with IHES may develop congestive heart failure, pulmonary emboli, and
multiorgan-system dysfunction. Now, 80% of patients are surviving at 5 years and
40% are surviving at 10-15 years.

• The mortality rate in cases of CSS has been decreasing, with approximately 75%
of patients surviving 5 years.

• No sexual predilection has been noted for extrinsic eosinophilic syndromes, with
the exception of TPE, which has been reported to have a male predominance at a
male-to-female ratio of 4:1. 8
CLINICAL FEATURES
1. In CEP and EG: Most have a cough, dyspnea, fever, and
chest discomfort. Wheezing may be reported. Patients may
develop symptoms related to the pneumothorax, bony lesions,
and diabetes insipidus.

2. CSS: Patients often have antecedent rhinitis, sinusitis, and

nasal polyps, followed by the development of asthma symptoms.
Symptoms related to vasculitis occur years later and include
mononeuritis multiplex, abdominal pain, gastrointestinal
bleeding, symptoms of heart failure, arthralgias, myalgias,
urticaria, purpura, and nodular skin lesions.

9
3. Clonorchis sinensis infection:
Patients may relate a history of
ingestion of inadequately cooked or
pickled fish, abdominal pain, nausea,
vomiting, and/or diarrhea.
4. In Ascariasis: Mild pulmonary
symptoms are accompanied by
pruritic dermatitis.
5. In Strongyloidiasis abdominal pain
or distension, and/or diarrhea, with
or without immunocompromise.
Marked wheezing and/ or
respiratory distress may occur.
6. Loeffler syndrome occurs in
temperate and tropical climates.
Pulmonary symptoms are usually
coughing and wheezing with fever.
10
DIAGNOSIS :
It starts with history taking and physical examination. The
diagnosis is based on rule of exclusion.
Intrinsic eosinophilic syndromes, including AEP, CEP, and IHES,
become more likely in the differential diagnosis once extrinsic
etiologies have been excluded.

11
INVESTIGATION:
✓ Laboratory tests for complete blood count with differential,
and anti-nuclear cytoplasmic antibodies (ANCAs),
✓ serologic studies,
✓ stool for ova and parasites should be obtained.

The diagnosis of PE can be made in three different settings:

✓ Peripheral eosinophilia with lung opacities.
✓ Elevated BAL (Bronchoalveolar lavage )eosinophil count greater
than 25%.
✓ Lung tissue eosinophilia on biopsy.
Any one of the above findings can be used to diagnose PE. The
peripheral eosinophil count can be normal in PE.
12
✓ Bronchoscopy with BAL is a common diagnostic tool which identifies
the pulmonary eosinophilia with BAL fluid eosinophil greater than 25%.
Normally, eosinophils constitute less than 2% of the BAL cell count.

✓ Once a diagnosis of pulmonary eosinophilia is established, clues from

the history, physical and investigations should guide the clinician
towards further investigations and a diagnosis of the underlying
etiology.

✓ In patients with poorly controlled asthma, the work up would be

guided towards allergic bronchopulmonary aspergillosis (ABPA). Other
differentials to consider would be EGPA and CEP. Testing for ABPA
would include serum IgE levels, Aspergillus-specific antibodies,
Aspergillus skin testing, serum precipitins for Aspergillus and CT Chest
to assess for bronchiectasis.

13
✓ Chest radiography of intrinsic syndromes
✓ Chest CT scan
✓ ECG
✓ Pulmonary function testing
✓ Fiberoptic bronchoscopy with BAL
✓ Transthoracic needle aspiration/biopsy
✓ Transbronchial biopsy

14
TREATMENT:
A. Avoidance of the Causative agent
* Remove the patient from the environment or agent from the
environment.
* Pollen mask, personal dust respirators, air stream helmets and
ventilators helmets.
B. Glucocorticoid therapy
*Acute phase: Steroids may not be necessary
* Subacute phase: Prednisolone 1mg/kg/day for 7-14 days.
* Chronic phase: Steroids are of little or no value. Lowest dose for
maintenance, supportive treatment with oxygen.

15
C. Intrinsic syndromes

* Chronic eosinophilic pneumonia (CEP): CT scanning and

bronchoscopy are generally performed. If no infection is present, the
patient is treated with prednisone. Rapid clinical and radiologic
improvement must occurs within 24-72 hours.

* Hypereosinophilic syndrome (HES): Patients tend to respond

slowly, and only 50% respond to steroids. Patients may develop deep
venous thrombosis and pulmonary emboli. Then hydroxyurea,
interferon α, and imatinib can be administered.
✓ Additional
agents, including chlorambucil, vincristine, etoposide, cladribine,
cytarabine, methotrexate, cyclosporine, alemtuzumab, and
cyclophosphamide, have been used to treat steroid-unresponsive
16
patients
SURGICAL CARE :
1. Parasitic diseases: Echinococcal cystectomy or lung resection is the
preferred
treatment for this disease.
2. Malignancy: Lung
resection may be necessary if a solitary pulmonary nodule is
present or if malignancy is in the forefront diagnostically.
Mediastinoscopy may be necessary if lymphadenopathy,possibly representing
lymphoma, is significant.
3. Pneumothorax with obstructive lung disease: This may
require tube thoracostomy. If recurrent, such as with
eosinophilic granuloma (EG), pleurodesis may be required.

17
PROGNOSIS:
• Extrinsic diseases–
Medication-induced and Loeffler syndrome: Removal of the
offending agent usually results in a resolution of symptoms.–
Parasitic diseases: These are usually successfully treated but
may require a repeated course of therapy.

•Intrinsic diseases–
AEP: Patients often develop respiratory failure, but, with
treatment and supportive measures, they generally survive.–
CEP: Patients have a rapid response to therapy but may develop
relapse within 6 months. Some patients who initially present with
only pulmonary involvement actually have IHES.
18
THANK
YOU