Normal volunteers < 2% Increased >5% Primary pulmonary eosinophilic syndromes >20-25% * Definition: Eosinophilic pneumonias are defined as a heterogeneous group of disorders characterized by varying degrees of pulmonary parenchymal or blood eosinophilia.
Also called pulmonary infiltrates with
eosinophilia(PIE)or eosinophilic pneumonia The precise role of eosinophils in the pathogenesis of the eosinophilic pneumonias is not clear However Initiation Perpetuation
Amplification of tissue inflammation
Injury
have been attributed to eosinophils
Diseases Associated with Pulmonary Infiltrates & Eosinophilia
Pulmonary Eosinophilic Syndromes of Known Cause
Pulmonary Eosinophilic Syndromes of Unknown
Cause
Other Lung Diseases Variably Associated with
Eosinophilia Pulmonary Eosinophilic Syndromes of Known Cause:
1. Loeffler’s syndrome Also called as Simple Pulmonary Eosinophila In 1932 Loffler first described it as a clinical syndrome characterized by Mild respiratory symptoms Peripheral blood eosinophilia Transient, migratory pulmonary infiltrates Immune hypersensitivity to Ascaris lumbricoides and other parasites Affects people of all ages Clinical features Low-grade fever Nonproductive cough Dyspnea (mild to severe) The pulmonary manifestations begin approximately 9 to 12 days following ingestion and occur during the migration of larvae through the lung. Respiratory manifestations are self limited, resolving in 1 to 2 wks Peripheral blood from patients reveals moderate to extreme eosinophilia. Expectorated sputum, if present, frequently contains eosinophils and Charcot–Leyden crystals Chest X ray shows Transient, migratory, nonsegmental interstitial & alveolar infiltrates(often peripheral or pleural based)
Pulmonary function evaluation typically reveals a
mild to moderate restrictive ventilatory defect Ascaris larvae may be identified in sputum or gastric aspirates during the pneumonic phase of disease. Stool examination for ova and parasites is typically negative until 8 weeks after the onset of the respiratory syndrome. Lung histology shows striking eosinophilic infiltration of interstitium and alveolar- capillary units Loeffler’s syndrome TREATMENT Since Loeffler’s syndrome may be induced by a variety of exposures, a search for an etiologic agent should be undertaken. Bronchodilators and rarely corticosteroids may be used for alleviation of Pulmonary symptoms, although these are usually self-limited. In cases due to Ascaris, treatment with oral mebendazole (100 mg twice a day for 3 days) should be given to prevent late GI manifestations of Ascaris infestation, which may include malnutrition, diarrhea, abdominal pain, and/or intestinal obstruction typically 8 weeks or more after onset of respiratory symptoms. Since stool specimens are negative for ova and parasites early in the illness, clinical follow-up over a 2- to 3-month period is Strongyloidiasis
Strongyloides is widely distributed in the
tropical and subtropical regions. Following initial transcutaneous infection, a Loeffler- like syndrome may occur as larvae migrate through the lungs. Chronic strongyloidiasis occurs as a result of autoinfection, whereby the noninfectious rhabditiform larvae transform within the GI tract into infectious filariform larvae, penetrate the colonic wall or perianal skin, and reinfect the host. Chronic strongyloidiasis may be associated with recurrent asthma-like symptoms that may worsen with the administration of corticosteroids. The hyperinfection syndrome results from accelerated autoinfection, and usually occurs in persons with defects in cell-mediated immunity (such as lymphoma, human immunodeficiency virus [HIV] or human-T lymphotropic virus type 1 [HTLV-1] infection, and with chronic corticosteroid use), as well as in persons with underlying GI disease, chronic lung disease,malnutrition, and use of H2 blockers or antacids. Respiratory manifestations include cough, dyspnea,chronic bronchitis, wheezing, hemoptysis, and patchy pulmonary infiltrates, in association with blood eosinophilia. Rarely, acute respiratory distress syndrome (ARDS) has been reported in patients with hyperinfection Diagnosis
The diagnosis of Strongyloides infection may
be established by identification of larvae in sputum, BAL fluid, bronchial brushings, or transbronchial biopsy specimens, pleural fluid or stool. Several stool samples are often required to identify the pathogen.Serologic testing, such as ELISA to detect IgG antibody to Strongyloides stercoralis can also be used to establish a diagnosis Thiabendazole (25 mg/kg twice a day for 2 days) or ivermectin (200 μg/kg given orally for 1–2 days) may be used for the treatment of uncomplicated or disseminated strongyloidias. ivermectin is generally better tolerated in terms of side effects 2. Drug and toxin induced eosinophilic pneumonia Several drugs have been implicated, many are commonly used Acetylsalicylic acid L-Tryptophan
Amiodarone Methotrexate Bleomycin Minocycline Captopril Nitrofurantoin Carbamazepine Penicillamin Propylthiouracil Phenytoin Sulfasalazine Gold salts Drug and toxin induced eosinophilic pneumonia
Other causes are
Radiation therapy for breast cancer Iodinated contrast agents Heroin (inhaled) Have an acute or subacute onset and are not always related to either the cumulative dose of drug used or the duration of treatment. Respiratory symptoms vary widely in severity, from a mild Loeffler’s-like symptoms(dyspnea, cough & fever) to severe fulminant respiratory failure. Wheezing may be present, but obstructive physiology is not common on pulmonary function testing. A diagnosis of drug- or toxin-induced eosinophilic pneumonia is based upon a careful review of drug and other exposures (including nonprescription drugs, herbal preparations, street drugs, and environmental exposures). Other causes of eosinophilic lung disease should be excluded. A concomitant skin rash and pleural effusion can support the diagnosis of drug-induced eosinophilic pneumonia. The DRESS syndrome consists of acute eosinophilic pneumonia with drug rash and systemic manifestations. Although radiographic findings are not specific, interstitial or alveolar infiltrates are typically evident on chest radiograph and common high-resolution chest computed tomographic (HRCT) findings include bilateral consolidation and ground-glass opacities, both of which are frequently peripherally located. The prognosis is favorable in most cases. Elimination of exposure to the drug or other toxin - resolution of symptoms, eosinophilia, pulmonary infiltrates, and normalization of lung function within a month. Supplemental therapy with corticosteroids is not universally required, but it may hasten recovery in patients who are severely ill. 5. Idiopathic Acute Eosinophilic Pneumonia
Acute eosinophilic pneumonia (AEP) has been
recognized as a distinct clinical entity. More common in younger men, with a mean age of approximately 30 years. History of atopy is not essential. Occurs in recently commenced smokers and who have been involved in activities with unusual exposures(such as cave exploration, plant repotting, woodpile moving, and indoor renovations). It presents as an acute illness with fever, myalgias, cough, dyspnea, pleuritic chest pain with diffuse crackles & hypoxemia Symptoms may lasts upto 30 days with avg. of 3 days persons with a history of chronic myelogenous leukemia, hematopoietic stem cell transplantation or HIV infection Many cases have been reported in patients who have recently commenced smoking, used flavored tobacco products or had other changes in smoking habits. The disease may recur when former smokers resume smoking. Moderate Leucocytosis is typical but blood eosinophil count may be normal Serum IgE elevated and BAL fluid will contain eosinophils (25-50%). Pulmonary function tests reveal a restrictive ventilatory defect with a reduced DLCO. Radiological findings
Diffuse bilateral alveolar and
interstitial infiltrates on chest X ray
Diffuse parenchymal ground-glass
Opacity inerlobular septal thicken and/or consolidation and on CT Small to moderate bilateral pleural effusions are common. Fluid analysis typically reveals a high pH and marked eosinophilia. Light microscopic examination of lung tissue reveals prominent eosinophil infiltration in alveolar spaces, bronchial walls, and, to a lesser degree, the interstitium. The pathological pattern of diffuse alveolar damage with eosinophilic infiltrates should suggest the possibility of AEP. Role for Th2 lymphocytes and eosinophils in disease pathogenesis. It remains unknown, however, whether the eosinophils initiate the disease process or are a Idiopathic AEP is a diagnosis of exclusion & considered in patients with ALI or ARDS without a typical antecedent illness. The erythrocyte sedimentation rate (ESR) may be elevated as well. Serum levels of thymus and activation-regulated chemokine (TARC)/CCL17 (a ligand for CCR4 on Th2 lymphocytes) may be elevated and may help to distinguish AEP from other cause of acute lung injury(ALI). Striking eosinophilia (25%–55%)is present in BAL fluid Idiopathic AEP generally carries an excellent prognosis. Although fatalities have been reported, most patients demonstrate rapid dramatic responses to corticosteroid therapy. Methylprednisolone 60 to 125 mg 6 th hourly in respiratory failure. Abatement of fever and respiratory symptoms within 12 to 48 hours and complete resolution of infiltrates, pleural effusion, and pulmonary function impairment usually within 1 month Thereafter, oral prednisone 40 -60 mg per day for 2 -4weeks and tapered over weeks. 6.Chronic eosinophillic pneumonia
First described as a clinical entity by Carrington
and coworkers in 1969 Women > Men, usually Caucasians. 30 to 40 years of age 33-50% patients have history of atopy, allergic rhinitis, or nasal polyps,urticaria. Subacute presentation, with symptoms over several months symptoms
low-grade fevers wheeze drenching night sweats Moderate weight loss Cough (dry mucoid) May develop dyspnea and lead to ARDS Rarely ,patient may develop, arthralgias, skin rash, pericarditis or unexplained heart failure raising suspicion that there may be a continuum bw CEP and EGPA. Patients with CEP frequently manifest a moderate leukocytosis. The majority (66 to 95 percent) have peripheral blood eosinophilia, with eosinophils constituting more than 6 percent of their leukocyte differential. ( till 90% eosinophils have been documented) A moderate normochromic, normocytic anemia and thrombocytosis may be present. The ESR is typically elevated (greater than 20mm/hour), and IgE levels are elevated in up to one-half of cases. Analysis of BAL fluid reveals increased eosinophils, typically accounting for 40 percent or more of the white blood cell (WBC) differential. Blood and sputum cultures routinely fail to identify an infectious etiology in these patients. Carrington and colleagues described three radiographic features that are characteristic for CEP: (1) peripherally based, progressive dense infiltrates; (2) rapid resolution of infiltrates following corticosteroid treatment, with recurrences in identical locations; and (3) The appearance of infiltrates as the “photographic negative of pulmonary edema. Radiographic appearance of chronic eosinophilic pneumonia (CEP).
Variable computed tomography
appearance of infiltrates in two patients with chronic eosinophilic pneumonia.
Peripheral upper-lobe predominant infiltrates may have a ground-glass appearance (A) or
may appear as regions of dense
consolidation or nodular opacity (B). Radiological findings Infiltrates are bilateral, mid- to upper lung zones, and may mimic loculated pleural fluid. The areas of consolidation are patchy and dense and can have ill-defined margins. The characteristic “photographic negative of pulmonary edema” appearance (which occurs in less than 50 percent of cases) results if extensive infiltrates surround major portions of or the entire lung. Common CT scan findings include ground-glass opacities without clear consolidation. Mediastinal lymphadenopathy may be present. Pathogenesis
Th2 helper T cells likely have a role in disease
pathogenesis. Eosinophils play a primary pathogenetic role in the pulmonary tissue damage seen in this disorder. Increased numbers of eosinophils appear in the peripheral blood and bone marrow before the onset of clinical disease, and eosinophilia is the predominant abnormality in BAL fluid. These eosinophils appear to be activated, since they show evidence of degranulation on electron microscopy, eosinophil- derived granule proteins (EDGPs) have been identified microscopically within the pulmonary parenchyma and microvasculature. Treatment Corticosteroids are the mainstay of therapy for CEP. Even patients presenting with severe respiratory failure may respond well to steroid treatment. Dramatic clinical, radiographic, and physiological improvement occurs with steroid treatment. In most cases, treatment with steroids leads to defervescence within 6 hours, reduced dyspnea, cough, and blood eosinophilia within 24 to 48 hours, resolution of hypoxia in 2 to 3 days, radiographic improvementwithin 1 to 2weeks, complete resolution of symptoms within 2 to 3 weeks, and Normalization of the chest radiograph within 2 months. Prednisone 0.5 mg/kg/d (40–60 mg a day) continued until 2 weeks after resolution of symptoms and radiographic abnormalities, generally for 4 to 6 weeks. The dose of prednisone can then be tapered slowly by 0.25 mg/kg/d and then continued for the subsequent 8 weeks. Treatment is usually maintained for at least 3 months and optimally for 6 to 9 months; during this phase prednisone dosing can be decreased by 5 mg every 4 weeks. The prognosis of CEP is generally favorable. Patients may require 1 to 3 years of initial steroid treatment to control the disease,1 and up to 50% may require long-term maintenance treatment (2.5–10 mg prednisone a day) to remain disease-free. Clinical, hematologic, or radiographic evidence of relapses are common, occurring in 50% to 80% of cases when steroids are tapered or discontinued. Relapses should be managed by increasing the prednisone dose to ≥40 mg per day until 2 weeks after symptom control has been achieved, with gradual taper thereafter. The anti–IL-5 monoclonal antibody omalizumab has also been used successfully as a steroid-sparing agent in the treatment of CEP. THANK YO U
