Pulmonary Eosinophilia

Eosinophilic Pulmonary Diseases : 

Eosinophilic Pulmonary Diseases By Chest Department Ain Shams University

Eosinophil – our friend and foe : 

Two-lobed, polymorphonuclear leukocyte 12 to 15 um diameter Created by IL-3, Il-5 and GM-CSF Three granule types, largest made up of MBP (major basic protein), kills Parasites, tumor cells, respiratory epithelium Hypodense and normodense varieties Circulates <18 hours Chemotaxis complement, histamine, ECF-A, PAF, leukotrienes, lymphokines, tumor factos, IL-5 100-400x more in tissues than in blood Eosinophil – our friend and foe

Eosinophils: What’s Normal : 

Blood EOS (#) = 50-250 per microliter Bronchoscopy (BAL) EOS Percentage (%) rather than absolute number Normal volunteers = < 1% ARDS usually none Increased (= >5%) five percent of the time Mostly PCP, drug-related, idiopathic Eosinophils: What’s Normal

Classification : 

Reeder and Goodrich, 1952 Pulmonary Infiltrates & Eosinophilia (PIE) Croften et al, 1952 Simple pulmonary eosinophilia (Loffler’s) Prolonged pulmonary eosinophilia Tropical eosinophilia Pulmonary eosinophilia with asthma Polyarteritis nodosa (PAN) Liebow and Carrington, 1969 Added Chronic eosinophilic pneumonia (CEP) McCarthy and Pepys, 1973 Either ABPA or “cryptogenic” Schatz et al, 1981 Back to “PIE” Classification

Classification : 

Airway Lung parenchyma – known systemic illness Lung parenchyma – idiopathic Classification

Airway disorders : 

Airway disorders Asthma Allergic Bronchopulmonary Aspergillosis Bronchocentric granulomatosis

Lung parenchymaknown systemic illness : 

Lung parenchymaknown systemic illness Hypereosinophilic syndrome Vasculitis (Churg-Strauss) Hodgkin’s disease Drug reactions Lung cancer

Lung parenchymaidiopathic : 

Lung parenchymaidiopathic Simple eosinophilic pneumonia (SEP, Loffler’s pneumonia) Chronic eosinophilic pneumonia (CEP) Acute eosinophilic pneumonia (AEP)

Asthma : 

Asthma Peripheral eosinophilia often noted “intrinsic” and “extrinsic” Proportional to airflow obstruction Eosinophil MBP results in airway shedding, may contribute to “creola bodies”

ABPA : 

ABPA Asthmatics (6%), Cystic fibrosis (10%) Aspergillus fumigatus Others= Candida albicans, Heliminthosporium, Curvularia lunata Proximal obstruction and bronchiectasis

ABPA : 

ABPA Difficult asthma Blood eosinophilia Elevated IgE Total and specific Aspergillus skin prick Aspergillus precipitins Radiographic infiltrates Aspergillus in sputum Brown mucous plugs Arthus (Type III) skin reaction Radiographic clues “gloved-finger” “ring shadows” “tram-tracking”

ABPA Staging : 

ABPA Staging I Acute II Remission III Exacerbation IV Steroid-dependent V Fibrotic

ABPA treatment : 

ABPA treatment Oral corticosteroids Hi-dose for 1-4 weeks Change to QOD over next three months Slow taper over following three months Itraconazole* Surveillance CXR Q4 x 6, Q6 x 2, Q12 months IgE Q1 month

Bronchocentric granulomatosis : 

Bronchocentric granulomatosis Liebow 1973 Clinical and radiographic pattern variable Surgical biopsy required Inflammation, esosinophilia, Charcot-Leyden crystals NO extrabronchial granulomas Diagnosis of exclusion TB, fungal infection Wegener’s or Rheumatoid lung disease Aspiration

Bronchocentric granulomatosis : 

Bronchocentric granulomatosis 1/3 of patients Asthma, eosinophilia, fungal hyphae on bx, aspergillus in sputum “tissue-destructive” ABPA 2/3 of patients Neutrophils without asthma or fungi evident Corticosteroids can be effective

Idiopathic Hypereosinophilic Syndrome (HES) : 

Idiopathic Hypereosinophilic Syndrome (HES) “eosinophilic leukemia” Rare, often fatal EOS >1500/microliter for six months 7:1 male predominance Usually age 30s (oldest reported = 70) Blood EOS 30-70% Bronchoscopy (BAL) EOS up to 73%

Churg-Strauss Syndrome : 

Churg-Strauss Syndrome Churg and Strauss - 1951 “Allergic angiitis and granulomatosis” Three phases Prodromal allergic rhinitis, asthma (years) Dramatic peripheral eosinophilia (months, yrs) Tissue infiltration like Loffler’s or CEP Systemic vasculitis

Churg-Strauss Syndrome : 

Churg-Strauss Syndrome Upper airway Rhinitis, polyps, sinusitis Skin (70%) Nodules, purpura, urticaria Neurologic Mono.Multiplex (66%) CNS (27%) Gastrointestinal Abd pain (59%) Diarrhea (33%) Bleeding (18%) Cardiac CHF (47%) Pericarditis (32%) HTN (29%) Renal (49%)

Churg-Strauss Syndrome : 

Churg-Strauss Syndrome Pathologic diagnosis Renal histology non-specific, often no granulomas TBBX probably inadequate Open lung biopsy = “gold standard” Treatment = steroids x 1 yr, relapse rare Pulse steroids or cytotoxic agents for failure

Churg-Strauss Syndromedifferential diagnosis : 

Churg-Strauss Syndromedifferential diagnosis Wegener’s Nodules cavitate C-ANCA positive Histology different PAN Medium-sized vessels No lung involvement No eosinophilia CEP No granulomas Not “extra-pulmonary” Idiopathic hyper-eosinophilia syndrome No granulomas No vasculitis

Churg-Strauss Syndrome : 

Churg-Strauss Syndrome Associated with leukotriene antagonists Zafirlukast, montelukast Incidence = 1:20,000 Probably coincidental with steroid tapering of primary eosinophilic infiltrative disorder

Tropical Pulmonary Eosinophilia : 

Tropical Pulmonary Eosinophilia Ancylostoma sp.* Ascaris sp.* Brugia Malayi Clonorchis sinesis Dicrofilaria immitis Echinococcus sp. Opisthorchiasis sp. Paragonimus westermani Schistosoma sp. Strongyloides steratocolis* Toxocara sp.* Trichinella spiralis Wuchereria bancrofti * Can cause infection

Tropical Pulmonary Eosinophilia : 

Tropical Pulmonary Eosinophilia Ex: W. bancrofti GI symptoms predominate Lymphadenopathy common in children Blood EOS > 3000 Bronchoscopy (BAL) high EOS, IgE, IgG PFTS – usually restriction, 30% mixed

Drug reactions : 

Drug reactions Common cause of pulmonary infiltrates and blood or BAL eosinophilia Multiple medications: Nitrofurantoin, Sulfasalazine, Phenytoin, Bleomycin, Tetracycline Treatment with dicontinuation of drug and possibly corticosteroids

Drug reactions (Ex. 1) : 

Drug reactions (Ex. 1) Eosinophilic-myalgia syndrome (late 1980s) Contaminated L-tryptophan 50% of ingestions had myalgias, eosinophilia 50% of these had pulmonary involvement = cough, dyspnea, cxr infiltrates, effusions, muscle weakness IgE, CK normal, PFTs with restriction Histology with vasculitis, eosinophils

Drug reactions (Ex. 2) : 

Drug reactions (Ex. 2) “Toxic oil syndrome” (1981-1982) 20,000 cases – 300 deaths in Spain “olive oil” – rapeseed oil with oleoanilide Fever, respiratory/GI distress, rash, adenopathy CXR – interstitial/alveolar infiltrates, Kerley B’s Steroids helpful acutely, others progressed to pulmonary fibrosis of hypertension

Chronic Eosinophilic Pneumonia : 

Chronic Eosinophilic Pneumonia Christoforodis and Molnar 1960 (n=2) Carrington Peak incidence age - 50s Insidious onset – 7.7 months sxs pre dx Cough (90%), fever (87%), SOB (57%), weight loss (57%), asthma (50% - less than 5 yr duration) Peripheral EOS (>6%) = 88% BAL EOS usually >25% and may be 44%

CEP : 

CEP IgE elevated (66%) ESR, RF, immune complexes, thrombocytosis may be found Hypoxemia, PFTs with mild restriction Peripheral CXR infiltrates (63%) “photonegative of CHF” only 25%

CEP : 

CEP Unlike simple pulmonary eosinophilia (SPE, “Loffler’s pneumonia”) spontaneous resolution is rare (<10%) Steroids 40 mg/day – dramatic resolution Symptoms within 1-2 days CXR infiltrates within 10 days Relapse common in first 6 months

Acute Eosinophilic Pneumonia : 

Acute Eosinophilic Pneumonia First described 1989 Unknown cause ? Inhaled antigen hypersensitivity Similar to some cases in CML patients Similar to some postoperative events Unlike other ARDS (BAL = neutrophils) Must exclude infection (esp. fungus)

Acute Eosinophilic Pneumonia : 

Acute Eosinophilic Pneumonia Acute febrile illness < 5 days duration Hypoxemic respiratory failure Diffuse alveolar or mixed CXR infiltrates BAL EOS > 25% Absence of parasitic, fungal or other infections Prompt/complete response to steroids Failure to relapse after steroids

Miscellaneous thoughts (1) : 

Miscellaneous thoughts (1) Pleural fluid eosinophilia (PFE) Pneumothorax = most common Hemothorax (may take 1-2 weeks) Benign asbestos effusion Pulmonary embolism Parasites/ Fungus/ TB (rare) Drug induced Lymphoma/ Carcinoma (5-8%)

Thank You : 

Thank You