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CPC Julye Carew, M.D. December 11, 2003 CASE REVIEW • • • • • 41 yo AA male No PMH, but allergic rhinitis 2 weeks of dyspnea and fever 3 ER visits-- ABX CT angio of chest-- neg for PE, but with bilateral lower lobe alveolar infiltrates • Progressive course with development of ARDS, hypoxic respiratory failure CASE REVIEW • MEDS: Zpack, antihistamine, Hydrocodone, nasal steroid • FH: NC • SH: No habits, construction with ceramics, fiberglass and flooring, no significant travel CASE REVIEW • ROS: • POSITIVE: fever, chills, cough with clear sputum, night sweats, fatigue • NEGATIVE: NO hemoptysis, CP, rash, meningismus, HA, N/V, GU or GI symptoms CASE REVIEW • • • • • PE: mild respiratory distress T 103.6, tachycardic, tachypneic HEENT and Neck-- negative PULM: Inspiratory rales in bases and dullness on left. • Remainder of exam-- negative • No mention of clubbing? CASE REVIEW • • • • • LABS: Renal function is normal TP 6.3, ALB 2.5 Mild transaminitis, total bilirubin 1.9 WBC mildly up, left shift and lymphopenia, mildly anemic • U/A minimal protein and no sediment CASE REVIEW • LABS cont: • Negative serologies for Legionella, Histo, Aspergillus, Blasto, Coccidio, Q-Fever, CMV, CVL cath tip, blood, sputum cultures negative • ABG: 7.42/40/61 on 100%, large A-a gradient ???, shunt • CXR: LL alveolar filling process, LLL air bronchograms HOSPITAL COURSE • Day 1: Started on broad-spectrum Abx and coverage for Legionella • Days 2-3: Fevers continue, Abx changed and Fluconazole added for thrush • Days 4-6: All cultures- negative. ARDS worsens, on PC. HP panel, IV steroids, becomes hypotensive HOSPITAL COURSE • Days 7-12: LFTs increase, drug effect? and fevers continue • Days 13-22: Multiple PTX, steroids continued, Legionella, Haanta, CMV-negative • Days 23-25: Worsening O2, bronch unrevealing, persistent hypotension and bradycardia, PEA. What’s Missing? • • • • • HIV??? Toxicology screen Echocardiogram BAL cell count Lung biopsy Approach • Alveolar filling process-- pus, blood, protein, fluid, cells (CA, immunologic) • ARDS • Subacute presentations of lung disease ARDS • Lung injury from some insult that causes inflammatory cascade • Three stages: Exudative (alveolar edema and hyaline membranes) Proliferative (fibrin ) >24 hr Fibrotic (collagen) >2 wks INTERSTITIAL LUNG DISEASES PRODUCING AN ALVEOLAR-FILLING PATTERN ON CHEST RADIOGRAPH Alveolar proteinosis (proteinaceous fluid) Alveolar cell carcinoma (malignant cells) Bronchioloalveolar metastases (malignant cells from pancreas, breast) Pulmonary lymphoma (malignant lymphocytes) Lymphocytic interstitial pneumonia (lymphoplasmacytic cells) Alveolar sarcoid (lymphocyte-macrophage alveolitis or confluent granuloma) Desquamative interstitial pneumonia (macrophages) Diffuse alveolar hemorrhage (red blood cells; hemosiderin-filled macrophages) Eosinophilic pneumonia (eosinophils, macrophages; lymphocytes) Alveolar microlithiasis (calcium-phosphate microliths) Bronchiolitis obliterans organizing pneumonia (collagen) Mineral oil aspiration (lipid-filled macrophages) Acute hypersensitivity pneumonia (lymphoplasmacytic cells) Infections • CAP: Pnemococcus, H. flu, Staph aureus, Mycoplasma, Legionella, Chlamydia-treated with multiple broad-spectrum Abx • Viral: Adenovirus, CMV, Haanta, HSV, influenza, RSV, Varicella-- negative titers for CMV, Haanta, wrong time course for flu, no pustules for varicella Infections • Fungal: Histo, Blasto, Coccidio, Aspergillus-- negative titers, Crypto usually in immunocompromised hosts • TB: possible, but probably too rapid • Parasites: Toxo, Strongyloides, Filaria, Trichinosis, Echinococcus (cysts), Shistosomiasis-- no peripheral eosinophilia • PCP?? Alveolar Hemorrhage • Caused by bleeding in the small pulmonary vessels, leading to syndrome known as Diffuse Alveolar Hemorrhage • “Pulmonary capillaritis” with PMN infiltration • Presentation: Cough, dyspnea and hemoptysis-- often delayed Alveolar Hemorrhage • Fever may be present if the patient has an underlying vasculitis (Goodpasture’s- antiGBM Ab, Wegener’s- cANCA) • Drop in hematocrit • BAL returns bloody fluid Alveolar Hemorrhage Etiologies of DAH Isolated pulmonary capillaritis Wegner’s Granulomatosis Microscopic Polyangiitis Connective Tissue Diseases-- SLE Behcet’s Syndrome Idiopathic Pulmonary Hemosiderosis Goodpasture’s Syndrome Mitral Stenosis Pulmonary Venoocclusive Disease Alveolar Hemorrhage • No significant fall in hematocrit • No urine sediment to suggest a glomerulonephritis • No evidence of a CTD or vasculitis Pulmonary Alveolar Proteinosis • Insoluble, proteinaceous material, rich in phospholipids is deposited in alveoli • Very little inflammatory response, just hypoxemia • Degradation of Type II pneumocytes • BAL reveals PAS-positive fluid • Nocardia is common secondary infection PAP • “CXR looks much worse than the patient” • Patients can be severely hypoxic • Require serial BAL to remove proteinaceous material “whole lung lavage” • Most patients do quite well CHF • Multiple cardiac causes for pulmonary edema-- LVSF, valvular disease • No report of cardiomegaly, pleural effusions on CXR Malignancies • Bronchoalveolar cell carcinoma subtype of adenocarcinoma which fills alveoli viral etiology is postulated (retrovirus) role of tobacco is controversial • Primary Pulmonary Lymphoma occurs in immunocompromised hosts Bronchoalveolar Cell CA Drug Toxicities • Multiple drugs which cause acute lung injury and ARDS • Predominantly drugs of abuse, chemotherapeutics Drug Toxicity Heroin Naloxone Cocaine Barbiturates Salicylates Amiodarone Cyclosporine MTX Vinca Alkaloids Alkalating agents Retinoic Acid (AML) Tocolytic therapy HCTZ Paraquat (Insecticides) Nitrofurantoin Drug Toxicity • “No habits” • No exposure to chemotherapy • Overdose-- not acute Subacute Interstitial Diseases • Bronchiolitis Obliterans with Organizing Pneumonia • Hypersensitivity Pneumonitis • Acute Eosinophilic Pneumonia • Pneumoconioses • Sarcoidosis • Acute Interstitial Pneumonia BOOP • Clinicopathologic diagnosis characterized by “pneumonia-like” illness with proliferation of granulation tissue within small airways with chronic inflammation in the surrounding alveoli • Mean age at presentation is 58, M=F • Flu-like illness with cough, fever, malaise, fatigue and weight loss BOOP • • • • Subacute presentation <2 months duration Inspiratory crackles Finger clubbing is rare Labs are not helpful, with elevation of WBC and eosinophilia in about 50%, elevated ESR BOOP • CXR shows peripheral, bilateral, alveolar filling with normal lung volumes • CT reveals patchy air-space consolidation with bronchial wall thickening and dilatation • PFTs show restrictive defect, with significant hypoxemia. DLCO is often reduced BOOP BOOP • PATH: Intraluminal fibrotic buds (Masson bodies) in respiratory bronchioles and alveoli, foamy cells in alveolar spaces, Type II cell hyperplasia, and fibrinous exudates • Corticosteroid therapy results in complete resolution in >2/3 of patients and is rapid • Relapses can occur when steroids are withdrawn BOOP • Presentation is consistent • Steroid dose? • Most patients who develop a progressive fatal form of the disease have the diagnosis delayed or missed Hypersensitivity Pneumonitis • “Extrinsic allergic alveolitis” • Granulomatous, interstitial, bronchiolar, and alveolar-filling lung disease resulting from repeated inhalation of sensitization to a wide variety of organic aerosols and lowmolecular weight chemical antigens • Improvement or reversal if antigen exposure ceases, continued exposure leads to progressive fibrosis HP • List of specific agents is lengthy • Three major categories of antigens: Microbes Animal Proteins LMW Chemicals • Antigen is deposited in alveoli, triggering Tlymphocyte inflammation • Antigen is not digested and acts to fix complement and increase inflammatory response HP • Presbyterian has 3 HP Panels • “Extended” includes “farmer’s lung” and “bird fancier’s”: Aspergillus fumigatus and flavus, Aureobasidium Actinomyces, Microsporidium Pigeon feather antigen DOES not include any other animal or chemical Ag HP • Microbes • Animal: Avian antigens most common, also laboratory animal handlers (pelts, serum and excreta), miller’s lung (grain), silk producers (larval secretions and cocoons) and mollusk shell dust • Chemicals: Isocyanates in adhesive, foams and surface coatings and Ag in paints, plastics and resins HP • Development of disease is dependent upon the antigen, degree of exposure, host factors • Repeated antigen exposure • Immunologic sensitization of host to antigen • Immune-mediated damage to the lung • Exertional dyspnea, cough with sputum production, malaise, fever. Often misdiagnosed as infection, but patients improve b/c of removal from Ag HP • Chronic presentation leads to crackles on exam, clubbing and cor pulmonale • Unfortunately precipitating Ab tests are non-specific because of huge numbers of Ag MOST IMPORTANT IS HISTORY • CXR and CT reveal GG opacities and micronodules • BAL reveals lymphocyotosis with CD8 predominance HP HP • Symptoms usually respond to removal of antigen in acute cases • Chronic forms with repeat exposures have decline in lung function and fibrosis • ?? Role for steroids • This patient has no known exposure, and worsened despite “removal of Ag” Eosinophilic Pneumonias Acute Eosinophilic Pneumonia • thought to represent a hypersensitivity reaction to an inhaled Ag • Symptoms of fever, myalgias, hypoxemia (severe) for a few hours to days • WBCs elevated, eosinophilia in 1/3 • Diffuse infiltrates • BAL with eosinophils (>25%) Eosinophilic Pneumonias • May require mechanical ventilation • Respond to Solumedrol at high doses (60125 mg q 6 hours) • Must document an absence of infection • Do not develop relapses after steroids are tapered Eosinophilic Pneumonias Chronic Eosinophilic Pneumonia • Subacute presentation with cough, dyspnea, fever and night sweats • Mild hypoxemia • Diffuse, peripheral infiltrates “-- CHF” • Serum and BAL eosinophilia • Response to steroids, but relapses occur Eosinophilic Pneumonia Eosinophilic Pneumonias • • • • CXR is not consistent No response to steroids No eosinophilia Presentation too late for AEP and too short for CEP Sarcoid • Alveolar pattern which is coalescence of reticulonodular disease • Wrong time frame for presentation in our patient Sarcoid Occupational Exposures • Patient works with ceramics, fiberglass, and flooring • Literature to suggest no significant degree of lung fibrosis with fiberglass, but may be carcinogenic • Acute inhalational injury?? • HP Pneumocystis • PCP is the most common AIDS-defining illness • Ubiquitous fungus with transmission by inhalation • CD4<200 or chronic steroid therapy • CXR shows bilateral GG opacities with granularity, but any presentation is possible (not pleural effusions or LAD) PCP • Diagnosis is by BAL/sputum for silver stain or PCP-DFA • RX: Mild (PaO2 > 70, A-a gradient <35), Bactrim (TMP 15 mg/kg q 6 hours) PO • RX: Mod-severe (PaO2 < 70, A-a > 35) Bactrim IV plus Prednisone or Solumedrol • High mortality rate assoc. with resp. failure PCP • Presentation is consistent • Fever? • Nothing from the history to suggest HIV Acute Interstitial Pnemonia • Rare, fulminant lung injury that presents in days to weeks in a previously healthy patient • “Hamman-Rich Syndrome” • Mean age is 50 years • A prodromal illness lasting 7-14 days before presentation is common AIP • Symptoms include fever, cough and dyspnea • Routine labs are not helpful • Severe hypoxemia and respiratory failure • Diffuse, bilateral airspace disease on CXR • CT shows diffuse GG or air space consolidation AIP • Surgical lung biopsy is required to confirm DX of organizing diffuse alveolar damage • Mortality is greater than 60%, death within weeks- 3 months • Those who recover may have recurrence • Role for corticosteroids is not clear AIP • • • • • 13 biopsy-proven patients mean patient age was 54 years 12 required mechanical ventilation Mortality was 33% CXR revealed bilateral patchy densities that progressed to diffuse alveolar filling • Mean time from symptom onset to death was 26 days Vourlekis, et al. Medicine 2000. AIP • Outcome not related to steroid use Vourlekis, et al, Medicine 2000 REVIEW • 41 you AA male with 2 week h/o fever, dyspnea and malaise • He developed respiratory failure despite antibiotics, and failed to improve with broad antimicrobial coverage (all cultures negative) • ARDS requiring PC with development of PTX, eventual PEA and death Diagnosis • • • • • AIP BOOP if inadequate steroids Eosinophilic pneumonia PCP if HIV+ Influenza Pathologic Diagnosis • Extensive interstitial fibrosis on pathology with sheets of Staphylococcus in the background and consolidation. • Also diffuse Aspergillus seen with an approximately 13 cm Aspergillus abscess. • Final: Acute Interstitial Pneumonia – Precipitant ARDS with nosocomial pneumonia