Eosinophilic pneumonia

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohammed Abdelwahed M.D[2]

Eosinophilic pneumonia (EP) is a disease in which a certain type of white blood cell called an eosinophil accumulates in the lung. These cells cause disruption of the normal air spaces (alveoli) where oxygen is extracted from the atmosphere. Several different kinds of eosinophilic pneumonia exist and can occur in any age group. The most common symptoms include cough, fever, difficulty breathing, and sweating at night. EP is diagnosed by a combination of characteristic symptoms, findings on a physical examination by a health provider, and the results of blood tests and x-rays. Prognosis is excellent once most EP is recognized and treatment with corticosteroids is begun.

In 1944, Hamman described a group of four otherwise healthy patients who developed progressive lung disease, known as Hamman-Rich syndrome. In 1989, acute eosinophilic pneumonia was first described by Badesch and colleagues. In 1969, Carrington was the first to describe chronic eosinophilic pneumonia and known as Carrington syndrome.

Eosinophilic lung diseases may be classified according to the cause into pneumonia of unknown cause such as idiopathic chronic eosinophilic pneumonia and idiopathic acute eosinophilic pneumonia, pneumonias of known cause such as allergic bronchopulmonary aspergillosis, eosinophilic pneumonias of parasitic origin, and eosinophilic airways diseases such as hypereosinophilic asthma and idiopathic hypereosinophilic constrictive bronchiolitis.

Eosinophils migrate to inflammatory sites in tissues in response to chemokines like CCL11, CCL24, CCL5,, and certain leukotrienes like leukotriene B4. When eosinophils are activated, they release eosinophilic granules. Following activation, eosinophils effector functions include production of reactive oxygen products such as superoxide and peroxide produced by eosinophil peroxidase, growth factors such as TGF beta and cytokines such as IL-1, IL-2, and TNF alpha.

Causes of eosinophilic lung diseases are acute eosinophilic pneumonia, chronic eosinophilic pneumonia, tropical pulmonary eosinophilia, eosinophilic granulomatosis with polyangitis, allergic bronchopulmonary aspergillosis, and medications such as nonsteroidal anti-inflammatory drugs, anticonvulsants, antidepressants, angiotensin converting enzyme inhibitors, and beta blockers.

Acute eosinophilic pneumonia may be differentiated from other causes of pulmonary eosinophilia such as acute eosinophilic pneumonia, the transpulmonary passage of helminth larvae (Löffler syndrome), tropical pulmonary eosinophilia, eosinophilic granulomatosis with polyangiitis, allergic bronchopulmonary aspergillosis, and drugs and toxins.

The prevalence of idiopathic chronic eosinophilic pneumonia (ICEP) remains unknown. The incidence of chronic eosinophilic pneumonia in an Icelandic registry was 0.23 cases/100,000 population per year between 1990 and 2004. ICEP has been reported to contribute to 0 to 2500 per 100,000 of cases included in different registries of interstitial lung diseases. There is no racial predilection for ICEP. Women are more commonly affected by ICEP than men. ICEP typically affects patients in their 30s or 40s.

Risk factors for eosinophilic pneumonia vary according to the type; acute pneumonia is related to the recent initiation of tobacco smoking. One third to one-half of the chronic pneumonia patients have a history of asthma.

There is no specific screening for eosinophilic pneumonia.

If left untreated, patients with eosinophilic pneumonia may progress to develop dyspnea, pleural effusion, and respiratory failure. Common complications of eosinophilic pneumonia include respiratory failure, relapse, and adverse effects of steroids. Prognosis is generally excellent, and only a couple of lethal cases have been reported.

Diagnostic criteria of idiopathic chronic eosinophilic pneumonia include diffuse pulmonary alveolar consolidation, eosinophilia at bronchoalveolar lavage, respiratory symptoms present for at least 2 to 4 weeks, and absence of other known causes of eosinophilic lung disease. Idiopathic acute eosinophilic pneumonia criteria are acute onset with febrile respiratory manifestations, bilateral diffuse infiltrates on imaging, lung eosinophilia, with 25% eosinophils at bronchoalveolar lavage, and absence of determined cause of acute eosinophilic pneumonia.

Onset of chronic type is more than 2-4 weeks and acute one is less than 1 month. A history of atopy is found in 60 percent. Symptoms of idiopathic eosinophilic pneumonia include dyspnea, fever, cough, wheezing, sputum, myalgias.

Physical examination may reveal fever or sometimes low body temperature, an increased respiratory rate, low blood pressure, a fast heart rate, or a low oxygen saturation, which is the amount of oxygen in the blood as indicated by either pulse oximetry or blood gas analysis. Patients who have difficulty breathing, who are confused, or who have cyanosis (blue-tinged skin) require immediate attention. Auscultation findings include lack of normal breath sounds, the presence of crackling sounds (rales), or increased loudness of whispered speech (whispered pectoriloquy) with areas of the lung that are stiff and full of fluid, called consolidation. Vital signs are useful in determining the severity of illness and have predictive values. However, a high degree of suspicion should be kept in elderly as the presentation could be subtle in them.

No laboratory studies are specific for acute or chronic eosinophilic pneumoina. The usual laboratory tests include complete blood count, pulmonary function tests, liver function tests, renal function tests, and tests to exclude other causes of pulmonary eosinophilia.

The chest x-ray of eosinophilic pneumonia may show reticular or ground glass opacities. The distribution of opacities is localized to the lung periphery in acute pneumonia and diffuse in chronic one.

Characteristic CT findings of CEP include ground-glass attenuation, consolidation, nodules, septal thickening, pleural effusions, and thickening of bronchovascular bundles.

Thoracic US can be used to follow-up patients with acute eosinophilic pneumonia. The US shows that all patients exhibited multiple diffuse bilateral B-lines and lung sliding which was consistent with the alveolar-interstitial syndrome. B-line numbers fell during the course of treatment. The US is a useful modality for evaluating the treatment response in patients with acute eosinophilic pneumonia.

In acute eosinophilic pneumonia (AEP), Pulmonary function tests show reduced forced vital capacity and total lung capacity with a normal forced expiratory volume in one second; diffusing capacity for carbon monoxide (DLCO) is commonly reduced. Bronchoalveolar lavage (BAL) is performed in the majority of patients to exclude infection, hemorrhage, or malignancy. The BAL is performed using a sequential installation and recovery of 50 to 60 mL. The median BAL cellularity was 350,000/mm3. BAL eosinophilia was present in all cases with a median of 38%. Lung biopsy is rarely necessary to make a diagnosis of AEP in immunocompetent patients with a compatible history and prominent BAL eosinophilia in the absence of infection or another known precipitant.

Medical treatment of eosinophilic pneumonia include supportive care with supplemental oxygen, empiric antibiotics until culture results are available, and systemic glucocorticoid therapy, systemic glucocorticoids for almost all patients except those with clear evidence of an improving course. Prednisone is the preferred drug of choice. The dose of 40 to 60 mg daily is reasonable. Glucocorticoid tapering over 7 to 14 days may be acceptable for patients who present with initial eosinophilia. If a patient fails to respond to glucocorticoids, an alternative diagnosis should be used such as subcutaneous interferon, high-dose intravenous immunoglobulins, plasma exchange. Relapse can be treated with a dose of 20 mg per day of prednisone.

Surgery is not indicated for eosinophilic pneumonia.

Relapses occur in more than half the patients while decreasing or after stopping corticosteroids. Relapses typically can be treated with a dose of 20 mg per day of prednisone.

There are no established measures for the secondary prevention of eosinophilic pneumonia.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Mohammed Abdelwahed M.D[2]

In 1944, Hamman described a group of four otherwise healthy patients who developed progressive lung disease, known as Hamman-Rich syndrome. In 1989, Acute eosinophilic pneumonia was first described by Badesch and colleagues. In 1969, Carrington was the first to describe chronic eosinophilic pneumonia and known as Carrington syndrome.

• At the turn of the 20th century, it was recognized that some patients died with bilateral lung disease that was unusual these days.

• In 1944, Hamman described a group of four otherwise healthy patients who developed progressive lung disease, and died of respiratory failure within 1 to 3 months of presentation. This disorder became known as Hamman-Rich syndrome.^[1]
• In 1989, Acute eosinophilic pneumonia was first described by Badesch and colleagues and later individualized by Allen and colleagues.^[2]

• In 1969, Carrington was the first to describe chronic eosinophilic pneumonia and known as Carrington syndrome.^[3]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohammed Abdelwahed M.D[2]

Eosinophilic lung diseases may be classified according to the cause into pneumonias of unknown cause such as idiopathic chronic eosinophilic pneumonia and idiopathic acute eosinophilic pneumonia, pneumonias of known cause such as allergic bronchopulmonary aspergillosis and eosinophilic pneumonias of parasitic origin, and eosinophilic airways diseases such as hypereosinophilic asthma and idiopathic hypereosinophilic constrictive bronchiolitis.

The eosinophilic lung diseases can be classified according to the cause into:^[1][2][3]

• Solitary idiopathic eosinophilic pneumonia
• Idiopathic chronic eosinophilic pneumonia
• Idiopathic acute eosinophilic pneumonia
• Eosinophilic pneumonia in systemic syndrome
• Eosinophilic granulomatosis with polyangiitis
• Idiopathic hypereosinophilic syndrome

• Allergic bronchopulmonary aspergillosis and related syndrome
• Eosinophilic pneumonias of parasitic origin
• Eosinophilic pneumonias of other infectious cause
• Drug-induced eosinophilic pneumonia

• Eosinophilic asthma
• Hypereosinophilic asthma
• Idiopathic hypereosinophilic constrictive bronchiolitis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Priyamvada Singh, M.D. [2]

Eosinophils migrate to inflammatory sites in tissues in response to chemokines like CCL11, CCL24, CCL5,, and certain leukotrienes like leukotriene B4. When eosinophils are activated, they release eosinophilic granules. Following activation, eosinophils effector functions include production of reactive oxygen products such as superoxide and peroxide produced by eosinophil peroxidase, growth factors such as TGF beta and cytokines such as IL-1, IL-2, and TNF alpha.

• Eosinophils differentiate from myeloid precursor cells. IL-5 controls the development of eosinophils in the bone marrow.
• Prior to their exit from the bone marrow, eosinophils produce many secondary granule proteins.
• Eosinophils migrate to inflammatory sites in tissues in response to chemokines like CCL11, CCL24, CCL5, and certain leukotrienes like leukotriene B4.
• When eosinophils are activated, they release eosinophilic granules.
• Following activation, eosinophils effector functions include production of reactive oxygen products such as superoxide and peroxide produced by eosinophil peroxidase, growth factors such as TGF beta and cytokines such as IL-1, IL-2, and TNF alpha.
• These products cause direct cytotoxicity, upregulation of chemoattraction, expression of adhesion molecules, regulation of vascular permeability, and contraction of smooth muscle cells.
• Eosinophils interact with basophils, endothelial cells, macrophages, platelets, fibroblasts, and mast cells through cell membrane signaling molecules and receptors including Toll-like receptors and receptors for cytokines, immunoglobulins, and complement.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Mohammed Abdelwahed M.D[2]

Causes of eosinophilic lung diseases are acute eosinophilic pneumonia, chrnoic eosinophilic pneumonia, tropical pulmonary eosinophilia, eosinophilic granulomatosis with polyangitis, allergic bronchopulmonary aspergillosis, and medications such as nonsteroidal anti-inflammatory drugs, Anticonvulsants, Antidepressants, Angiotensin converting enzyme inhibitors, and Beta blockers.

• The cause of acute eosinophilic pneumonia is unknown but an acute hypersensitivity reaction is suggested.^[1]

Chrnoic eosinophilic pneumonia (CEP)

• Chronic eosinophilic pneumonia is an characterized by an abnormal and marked accumulation of eosinophils in the interstitium and alveolar spaces of the lung.^[2]

• Three types of helminths, Ascaris, hookworms, and Strongyloides stercoralis, have larvae that reach the lungs, penetrate into alveoli, and ascend the airways then reach the gastrointestinal tract.
• Ascaris is the most common cause of Löffler syndrome worldwide.^[3][4]

• Tropical pulmonary eosinophilia is immune response to the lymphatic filariae and Wuchereria bancrofti.^[5]
• Pulmonary function tests may show a mixed restrictive and obstructive abnormality with a reduction in diffusion capacity.^[6]

• Eosinophilic granulomatosis with polyangiitis (Churg-Strauss) is a vasculitic disorder often characterized by sinusitis, asthma, and prominent peripheral blood eosinophilia.^[7]
• It is the sole form of vasculitis that is associated with both eosinophilia and frequent lung involvement.
• In addition to the lungs, the skin and the cardiovascular, gastrointestinal, renal, and neurologic systems may also be involved.

• Allergic bronchopulmonary aspergillosis is a complex hypersensitivity reaction that occurs when airways become colonized by Aspergillus.^[8]
• Immunologic responses elicited by Aspergillus fumigatus are responsible for this syndrome. It can lead to bronchiectasis, and fibrosis.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a drug-induced hypersensitivity reaction that includes skin eruption, eosinophilia, atypical lymphocytosis, lymphadenopathy, and kidney involvement. Drugs causing DRESS are:^[9]

• Nonsteroidal anti-inflammatory drugs
• Anticonvulsants
• Antidepressants
• Angiotensin converting enzyme inhibitors
• Beta blockers
• Hydrochlorothiazide
• Cocaine^[10]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Acute eosinophilic pneumonia may be differentiated from other causes of pulmonary eosinophilia such as acute eosinophilic pneumonia, the transpulmonary passage of helminth larvae (Löffler syndrome), tropical pulmonary eosinophilia, eosinophilic granulomatosis with polyangiitis, allergic bronchopulmonary aspergillosis, and drugs and toxins.

Acute eosinophilic pneumonia may be differentiated from other causes of pulmonary eosinophilia.

• The cause of acute eosinophilic pneumonia is unknown.
• Some investigators have suggested that AEP is an acute hypersensitivity reaction to an unidentified inhaled antigen in an otherwise healthy individual.

• Three types of helminths, Ascaris (A. lumbricoides, A. suum), hookworms (Ancylostoma duodenale, Necator americanus), and Strongyloides stercoralis, have larvae that reach the lungs, penetrate into alveoli, and ascend the airways then reach the gastrointestinal tract.
• Ascaris is the most common cause of Löffler syndrome worldwide.

• Tropical pulmonary eosinophilia is immune response to the bloodborne microfilarial stages of the lymphatic filariae and Wuchereria bancrofti.
• The typical symptoms are cough, breathlessness, wheezing, fatigue, and fever. Pulmonary function tests may show a mixed restrictive and obstructive abnormality with a reduction in diffusion capacity.

• Eosinophilic granulomatosis with polyangiitis (Churg-Strauss) is a vasculitic disorder often characterized by sinusitis, asthma, and prominent peripheral blood eosinophilia.
• It is the sole form of vasculitis that is associated with both eosinophilia and frequent lung involvement. In addition to the lungs, the skin and the cardiovascular, gastrointestinal, renal, and neurologic systems may also be involved.

• Allergic bronchopulmonary aspergillosis (ABPA) is a complex hypersensitivity reaction that occurs when airways become colonized by Aspergillus. 
• Repeated episodes of bronchial obstruction, inflammation, and mucoid impaction can lead to bronchiectasis, fibrosis, and respiratory compromise.
• Immunologic responses elicited by Aspergillus fumigatus are responsible for this syndrome.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a drug-induced hypersensitivity reaction that includes skin eruption, eosinophilia, atypical lymphocytosis, lymphadenopathy, and kidney involvement. Drugs causing DRESS are:

• Nonsteroidal anti-inflammatory drugs (NSAIDs)
• Anticonvulsants
• Antidepressants
• Angiotensin converting enzyme inhibitors
• Beta blockers
• Hydrochlorothiazide
• Sulfa-containing compounds

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

The prevalence of idiopathic chronic eosinophilic pneumonia (ICEP) remains unknown. The incidence of chronic eosinophilic pneumonia in an Icelandic registry was 0.23 cases/100,000 population per year between 1990 and 2004. ICEP has been reported to contribute to 0 to 2500 per 100,000 of cases included in different registries of interstitial lung diseases. There is no racial predilection to ICEP. Women are more commonly affected by ICEP than men. ICEP typically affects patients in their 30s or 40s.

• The prevalence of ICEP remains unknown.

• The incidence of chronic eosinophilic pneumonia in an Icelandic registry was 0.23 cases/100,000 population per year between 1990 and 2004. In registries of interstitial lung disease in Europe, chronic eosinophilic pneumonia accounted for 0 to 2500 per 100,000 of cases of interstitial lung disease.^[1]
• ICEP has been reported to contribute to 0 to 2500 per 100,000 of cases included in different registries of interstitial lung diseases.
• One third to one half of the ICEP patients have a history of asthma and less than 10% are active smokers.
• It has recently been reported that ICEP may be primed by radiation therapy for breast cancer.
• Two-thirds of patients are smokers, but there is usually no history of asthma.

• Patients of all age groups may develop ICEP but is extremely rare in childhood. CEP typically affects patients in their 30s or 40s.^[2]
• Young adults with a mean age of approximately 30 years.

• There is no racial predilection to ICEP.^[3]

• Women are more commonly affected by ICEP than men. The women to men ratio is approximately 2 to 1.^[3]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Mohammed Abdelwahed M.D[2]

Risk factors for eosinophilic pneumonia vary according to the type; acute pneumonia is related to the recent initiation of tobacco smoking. One third to one-half of the chronic pneumonia patients have a history of asthma.

• Risk factors of eosinophilic pneumonia are various respiratory exposures, especially a recent initiation of tobacco smoking.^[1]
• For acute type, two-thirds of patients are smokers, but there is usually no history of asthma.
• One third to one half of the chroinc pneumonia patients have a history of asthma.^[2]
• Idiopathic acute eosinophilic pneumonia occurs acutely in previously healthy young adults, with a mean age of approximately 30 years, and with male predominance.^[3]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohammed Abdelwahed M.D[2]

There is no specific screening for eosinophilic pneumonia.

There is no specific screening for eosinophilic pneumonia.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Priyamvada Singh, M.D. [2]

If left untreated, patients with eosinophilic pneumonia may progress to develop dyspnea, pleural effusion, and respiratory failure. Common complications of eosinophilic pneumonia include respiratory failure, relapse, and adverse effects of steroids. Prognosis is generally excellent, and only a couple of lethal cases have been reported.

If left untreated, patients with eosinophilic pneumonia may progress to develop dyspnea, pleural effusion, and respiratory failure.

• Chronic prednisone is associated with many side effects, including increased infections, weakened bones, stomach ulcers, and changes in appearance.^[3]
• Relapse: Relapses of ICEP are observed in up to 50% of patients. Relapses occur while tapering the dose of corticosteroids or after weaning.
• Respiratory failure: Only a couple of lethal cases have been reported.

• Some patients with ICEP require lifelong therapy.^[1]
• Response to corticosteroid treatment is dramatic and treatment always leads to complete resolution, pulmonary function tests return to normal after recovery from the illness.^[1]
• The pleural effusions may resolve more slowly than the pulmonary parenchymal opacities.^[2]
• Relapses of ICEP are observed in up to 50% of patients and is usually associated with resumption of cigarette smoking after initial cessation.
• These relapses occur while tapering the dose of corticosteroids or after weaning.^[3]

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