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Eosinophilic lung disease 

Eosinophilic lung disease
Chapter:
Eosinophilic lung disease
Author(s):

Stephen Chapman

, Grace Robinson

, John Stradling

, Sophie West

, and John Wrightson

DOI:
10.1093/med/9780198703860.003.0025
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date: 27 October 2021

Eosinophilic lung disease

Definition

Pulmonary eosinophilias are disorders classically associated with CXR infiltrates and a raised blood eosinophil count, although eosinophilic infiltration of the lung can occur without blood eosinophilia. Eosinophilia is found on lung biopsy or BAL.

  • Eosinophils are phagocytes that are produced in bone marrow and circulate for up to 10h before localizing in tissues

  • Their blood levels are usually tightly regulated

  • In health, they accumulate in the GI tract mucosa, but they may be attracted to other tissues by chemoattractant mechanisms, including mast cell activation and complement activation

  • Eosinophils can survive in the tissues for weeks if appropriate cytokines are present

  • Normal eosinophil counts are below 0.4 × 109/L (1–3% of peripheral WCC)

  • Counts of 0.4 × 109/L upwards can be seen in pulmonary eosinophilia

  • Persisting high eosinophil levels (‘hypereosinophilia’) cause tissue damage, due to their pro-inflammatory effects, whatever the cause

  • Eosinophils accumulate in allergic or hypersensitivity disease, parasitic infections, and cancer

  • Steroids and severe sepsis both decrease eosinophil levels

  • Asthma can cause a raised eosinophil count, especially if there is associated eczema, but an absolute eosinophil count of >1 × 109/L is very unusual and raises the possibility of an alternative diagnosis such as Churg–Strauss syndrome (now known as eosinophilic granulomatosis with polyangiitis, EGPA)

  • Blood eosinophilia can occur in a variety of conditions. 1° eosinophilia occurs in haematological malignancies; 2° eosinophilia is a response to a stimulus, such as a parasite or allergy, and third, idiopathic eosinophilia, with no identifiable cause, is also known as the hypereosinophilic syndrome

  • Possible causes of CXR infiltrates ± blood eosinophilia are shown in Table 25.1.

Table 25.1 Causes of CXR infiltrates ± blood eosinophilia

Condition

Characteristic points

Asthma with ABPA

Known asthma, with worsening symptoms, over weeks to months. Associated systemic symptoms. Raised blood eosinophil count, positive Aspergillus skin test, raised IgE, raised Aspergillus precipitins

Simple pulmonary eosinophilia (Löffler’s syndrome)

Foreign travel. Symptoms for days to weeks. Cough, malaise, anorexia, rhinitis, night sweats, fever, dyspnoea, wheeze. Sputum contains eosinophils and larvae. Low-level blood eosinophilia. Occurs due to an allergic response to the passage of larvae through the lungs

Tropical pulmonary eosinophilia

Foreign travel. Symptoms for weeks to months, with remissions and relapses. Cough, wheeze, sputum, dyspnoea, chest pain, fever, weight loss, fatigue. Sputum contains eosinophils. Raised blood eosinophil count, high IgE. Occurs in response to filaria in blood and lymphatics

Chronic eosinophilic pneumonia

Symptoms for weeks to months, with associated systemic symptoms. Cough, sputum, haemoptysis, dyspnoea, recent-onset asthma, fever, weight loss, night sweats. Sputum eosinophilia, but blood levels can be normal

Acute eosinophilic pneumonia

Short duration of symptoms, <5 days. Fever, cough, dyspnoea, and myalgia. Unwell, hypoxic. High BAL eosinophil count, no blood eosinophilia

Hypereosinophilic syndrome

Symptoms for weeks to months. Associated systemic symptoms and other organ involvement. Fever, weight loss, cough, night sweats, pruritus. High blood eosinophil count

Churg–Strauss syndrome/EGPA

Rhinitis, past history of asthma. Other organ involvement. Associated systemic symptoms. Longer duration of symptoms, weeks to months. Blood eosinophilia and eosinophilic tissue infiltration

Drug-induced pulmonary eosinophilia

Recent new drug. Possible associated skin reaction. Symptoms within hours to days. Spectrum of illness, from mild to severely unwell, with cough, dyspnoea, fever, and hypoxia. Eosinophilic tissue infiltration, but blood eosinophilia not universal

Causes of eosinophilic lung disease 1

Asthma and ABPA

(See Eosinophilic lung disease pp. [link][link].)

  • Fever or worsening asthma symptoms may be caused by types I and II hypersensitivity reactions to airway colonization by Aspergillus fumigatus

  • Untreated, can cause central bronchiectasis

  • CXR shows fleeting shadows

  • Blood eosinophilia

  • Aspergillus skin prick test is positive, and serum Aspergillus IgG precipitins are positive. IgE levels are raised

  • Treatment is with steroids, and antifungal agents may be necessary.

Simple pulmonary eosinophilia (Löffler’s syndrome)

  • Caused by parasitic infection, usually Ascaris lumbricoides, but also Strongyloides and hookworm (e.g. Ancylostoma)

  • Occurs worldwide, especially in SE Asia, Africa, Central and South America

  • The eggs of the parasite are found in the soil and are ingested. After 10–14 days, larvae migrate from the intestine via lymph and blood to the liver and lung. From the lung, they pass up the bronchial tree to be swallowed, to develop into roundworms in the gut

  • The passage of larvae through the lung causes an allergic reaction. This may be asymptomatic but may cause cough, malaise, anorexia, rhinitis, night sweats, low-grade fever, occasional wheezing, and dyspnoea. The illness lasts around 2 weeks

  • CXR shows transient bilateral shadows that are discrete and perihilar. They disappear usually between 6 and 12 days but can take up to 1 month

  • Sputum also contains eosinophils and larvae

  • Blood eosinophilia at a low level

  • Stool examination reveals parasites, but only 2–3 months later when the adult worms are passed

  • Treatment is with an antihelminth agent, such as albendazole or mebendazole, for 3 days. Steroids may be necessary if the pulmonary manifestations are severe.

Tropical pulmonary eosinophilia

  • Hypersensitivity to migrating larvae of filarial worms Wucheria bancrofti, Brugia malayi, and Brugia timori, similar to Löffler’s syndrome

  • Occurs in the Indian subcontinent, SE Asia, and the South Pacific islands

  • Insidious onset of cough, wheeze, sputum, dyspnoea, and chest pain, with associated fever, weight loss, and fatigue. Symptoms last for weeks to months, with remissions and relapses

  • Examination reveals crepitations

  • CXR shows bilateral uniform mottling of the lung fields, especially in the middle and lower zones. There may be cavitation and pleural effusion

  • Sputum and BAL contain eosinophils

  • PFTs may be obstructive initially but can become restrictive in long-standing untreated cases

  • Histology shows eosinophilic bronchopneumonia and eosinophilic abscesses

  • Blood eosinophil count is raised. IgE is raised

  • Filarial complement test is positive

  • Treatment is with a filaricide diethylcarbamazine for 3 weeks. This rapidly improves symptoms.

Drug-induced pulmonary eosinophilia

  • Pulmonary shadowing develops within hours to days of starting the drug and resolves usually within 1 week of stopping it

  • It is due to an allergic reaction in the pulmonary vessel wall, caused by the drug, and occurs again on drug re-challenge

  • There may be an associated skin reaction

  • The drug should be avoided in the future and steroids given if necessary

  • Severity of illness varies from mild to severely unwell, with cough, dyspnoea, fever, hypoxia. May occur in those with concomitant asthma

  • Tissue eosinophilia, but may not have blood eosinophilia

  • Possible drugs include ampicillin, carbamazepine, chlorpropamide, cocaine (inhaled), daptomycin, inorganic chemicals such as nickel, methotrexate, minocycline, NSAIDs, nitrofurantoin, penicillin, phenytoin, sodium aminosalicylate, sulfonamides, tetracycline. There are case reports of others (Eosinophilic lung disease http://www.pneumotox.com).

Causes of eosinophilic lung disease 2

Chronic eosinophilic pneumonia

  • Unknown cause

  • ♀:♂ = 2:1. Occurs in middle age, non-smokers

  • Insidious onset over weeks to months, with cough, sputum, possibly haemoptysis, dyspnoea, recent-onset asthma, weight loss, night sweats, and high fever. Differential diagnosis includes TB

  • Diagnosis is usually clinical and radiological but may need BAL or open lung biopsy

  • CXR shows peripheral dense opacities with ill-defined margins (photographic negative of pulmonary oedema)

  • CT shows peripheral airspace infiltrates

  • Sputum eosinophilia

  • BAL eosinophil count high

  • Blood eosinophilia may not occur. ESR is raised

  • Treatment is with steroids, such as prednisolone 30–40mg/day, and improvement is usually rapid, with the CXR clearing within 2–3 days and normal in 2 weeks. Decrease steroid dose once stable, but continue for 6 months

  • Relapses common when steroids stopped, and they may need further courses.

Acute eosinophilic pneumonia

Unknown cause, occurs in any age or sex. Presents with fever, dry cough, dyspnoea, and myalgia.

Diagnostic criteria:

  • Acute febrile illness of <7 days’ duration

  • Hypoxic respiratory failure

  • Interstitial or alveolar CXR infiltrates

  • BAL eosinophils >25%

  • No parasitic, fungal, or other infection

  • Prompt and complete response to steroids (oral prednisolone or IV methylprednisolone if respiratory failure)

  • Failure to relapse after stopping steroids.

May be unwell and hypoxic, requiring ventilatory support. No peripheral blood eosinophilia. High-dose steroids should be given until the respiratory failure resolves, and then the dose can be tapered over 2–4 weeks. It possibly represents an acute hypersensitivity reaction to an unidentified inhaled antigen; case series of recent-onset smoking in some.

Hypereosinophilic syndrome

  • Unknown cause. Rare

  • Most common in men aged 30–40

  • Present with fever, weight loss, night sweats, cough, and pruritus

  • Diagnosis based on:

    • Marked blood eosinophilia of >1.5 × 109/L for 6 months or more

    • Signs and symptoms of eosinophilic tissue infiltration on histology

    • No evidence of another cause of eosinophilia

  • Pulmonary involvement with interstitial infiltrates and pleural effusions on CXR. Cardiovascular involvement also occurs, with myocarditis, endocardial fibrosis, restrictive cardiomyopathy, valvular damage, and mural thrombus formation. These may cause considerable morbidity and mortality. Skin may be involved with urticaria and angio-oedema; CNS involved with encephalopathy, arterial and venous embolism, peripheral neuropathy, or mononeuritis multiplex; GI tract with gastritis, nausea, diarrhoea, alcohol intolerance, and hepato- or splenomegaly; joints with effusions and Raynaud’s. Kidney and muscles can also be infiltrated by eosinophils. Can be fatal

  • Blood eosinophil levels may be as high as 70%. IgE levels are high

  • Treatment is with high-dose steroids (e.g. 60mg prednisolone), which improves about 50% of cases. May need to use other immunosuppressants such as cyclophosphamide, hydroxycarbamide, azathioprine, or interferon-alfa. Treatment should be tapered, according to falling eosinophil counts and end-organ improvement.

Churg–Strauss syndrome/EGPA

(See Eosinophilic lung disease pp. [link][link].)

  • Severe asthma, blood eosinophilia, and pulmonary infiltrates occur as part of a small- and medium-vessel vasculitis

  • Also can affect GI tract, CNS, skin, and cardiovascular system

  • There may be eosinophilic tissue infiltration

  • ANCA usually, but not always, positive

  • Treatment with steroids and immunosuppression.