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1 23 Progress in Respiration Research Editor: H. Herzog O.P. Sharma Hypersensitivity Pneumonitis: A Clinical Approach Karger Hypersensitivity Pneumonitis: A Clinical Approach Progress in Respiration Research Vol. 23 Series Editor H. Herzog, Basel Karger Basel München Paris London NewYork New Delhi Bangkok Singapore Tokyo Sydney Hypersensitivity Pneumonitis: A Clinical Approach Om P. Shartna, Los Angeles, Calif. 43 figures and 27 tables, 1989 Karger Basel München Paris London NewYork New Delhi Bangkok Singapore Tokyo Sydney Progress in Respiration Research Library of Congress Cataloging-in-Publication Data Sharma, Om P. Hypersensitivity pneumonitis: a clinical approach. (Progress in respiration research; vol. 23) Downloaded by: /29/ :39:11 AM

2 Includes bibliographies. 1. Hypersensitivity pneumonitis. I. Title. II. Series. [DNLM: 1. Alveolitis, Extrinsic Allergic. W3 PR948 v. 23 / WF 652 S53lh] QP121.AlP7 vol. 23 [RC775.H94] sdc20 [616.2'44] ISBN Drug Dosage The author and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any change in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Copyright 1989 by S. Karger AG, P.O. Box, CH 4009 Basel (Switzerland) Printed by Konkordia Druck GmbH, Bühl/Baden (FRG) ISBN Contents Acknowledgements IX Preface X 1. History 1 2. What is Hypersensitivity Pneumonitis? 4 3. Who gets Hypersensitivity Pneumonitis? 6 Immunologic Reactivity of the Host: Atopic or Nonatopic 6 HLA Associations 7 Role of P1 Erythrocyte Antigen 7 Smoking 7 Nature of the Antigenic Material 8 Size of the Antigenic Material 8 Intensity of Exposure 8 Infection 8 Role of Air Pollution and Toxic Inhalants 9 4. Pulmonary Granulomas 11

3 What is a Granuloma? 11 Morphology of a Granuloma 11 Function of a Granuloma 12 Immunologic Events at the Site of Pulmonary Granuloma 12 Causes of Lung Granuloma 14 Differential Diagnosis Histopathology of Hypersensitivity Pneumonitis 23 Acute Stage 23 Subacute Stage 25 Chronic Stage 28 Differential Diagnosis 29 Electron Microscopic Features Immunopathogenesis 31 Immune Complex (Type III) 31 Type IV: Delayed Hypersensitivity 35 Alternative Complement (C3) Pathway Activation 36 Mechanism of Alveolitis and Granuloma Formation in Hypersensitivity Pneumonitis Clinical Features Radiologic Finding in Hypersensitivity Pneumonitis 43 Contents VI 9 Pulmonary Function Tests Role of Skin Tests Bronchoalveolar Lavage Role of Inhalation Challenge Serum Angiotensin Converting Enzyme Its Role in the Diagnosis of Pulmonary Granulomatous Disorders 59 Nature 59 Origin 59 SACE Measurements 60 Normal Range 60 Diagnostic Value 61 SACE and Sarcoidosis 61 SACE and Nonsarcoidosis Disorders 62 Disorders Confused with Sarcoidosis 62 Clinical Syndromes Not Confused with Sarcoidosis 63 Summary Differential Diagnosis 67 Diffuse Idiopathic Pulmonary Fibrosis (Cryptogenic Fibrosing Alveolitis) 67 Sarcoidosis 71

4 Treatment of Sarcoidosis 76 Course and Prognosis 78 Kveim Test in Sarcoidosis 78 Gallium Lung Scanning 78 Bronchoalveolar Lavage 79 Immunopathogenesis 79 Interstitial Lung Disease m Connective Tissue Disorders 81 Rheumatoid Pulmonary Fibrosis 83 Interstitial Lung Disease Due to Systemic Lupus Erythematosus 84 Progressive Systemic Sclerosis 86 Polymyositis-Dermatomyositis (PM-DM) 88 Pulmonary Fibrosis of Mixed Connective Tissue Disease 89 Pneumocystis carimi 90 Diagnostic Methods 93 Pulmonary Lymphangiomyomatosis 94 Eosinophilic Granuloma 96 Asbestosis 99 Berylliosis 101 Hard Metal Pneumoconiosis 103 Talc Pneumoconiosis (Talcosis) 105 Pulmonary Drug-Induced Granulomatous Disorders 106 Military Tuberculosis 109 Histoplasmosis 110 Amyloidosis 111 Lymphangitic Carcinomatosis 113 Pulmonary Vasculitis with Granulomatosis Diagnostic Caveats 116 Think of Hypersensitivity Pneumonitis 116 Contents VII Recognize the Temporal Relationship between the Appearance of Symptoms and Occupational or Environmental Exposure 116 Chest Roentgenograms Are Not Specific 116 Lung Function Tests Are Not Diagnostic of Hypersensitivity Pneumonitis 119 Routine Laboratory Tests are Unhelpful 119 Serum Precipitins 119 Skin Tests Are Inadequate and Unhelpful 120 Lung Biopsy 120 Bronchoalveolar Lavage 121 Inhalation Challenge Common and Uncommon Syndromes 122

5 Farmer's Lung 122 Clinical Features 123 Radiographic Features 123 Histopathology 123 Laboratory 123 Lung Function Tests 124 Immunologic Studies 124 Bronchoalveolar Lavage 125 Inhalational Challenge 125 Lung Biopsy 125 Diagnosis 125 Treatment 126 Case Case History 131 Pidgeon Breeder's Lung (Bird Fancier's Lung) 133 Clinical Features 134 Histological Features 135 Chest Roentgenographic Features 135 Serological Tests 135 Skin Tests 136 Lung Function Tests 136 Treatment 136 Prognosis 136 Case Report Case Report Case Report Case Report Summer-Type Hypersensitivity Pneumonitis 145 Bagassosis 150 Detergent Worker's Lung 152 Byssinosis 153 Humidifier Lung 154 Fuel-Chip-Induced Hypersensitivity Pneumonitis 156 Silicone-Induced Hypersensitivity Pneumonitis 157 Mushroom Worker's Lung 162 Spaetlese Lung 163 Contents VIII Cheese Worker's Disease 164 Cheese Washer's Disease 164 Wood Dust Disease 166 Maple Bark Stripper's Lung 167

6 Suberosis 168 Vineyard Sprayer's Lung 170 New Guinea Lung 170 Sisal Worker's Lungs 171 Coffee Worker's Lung 171 Pituitary Snuff Taker's Lung 172 Sporobolomyces-Induced Hypersensitivity Pneumonitis 172 Furrier's Lung 173 Maltworker's Lung 173 Paprika Splitter's Lung 174 Grain Weevil Disease 175 Feather-Picker's Disease 175 Smallpox Handler's Lung 175 Potato Riddler's Lung 176 Alginate Pulmonary Hypersensitivity 176 Subject Index 179 Acknowledgements Many individuals have helped directly or indirectly in the preparation of this monograph. I am indebted to my colleagues at the Los Angeles County University of Southern California Medical Center, Los Angeles, and the physicians in hospitals and clinical practices throughout the country who have referred patients with hypersensitivity pneumonitis to me. Special thanks are due to Drs. Thomas Boylen, Kevin Lake, Crawford Judge, Michael Koss, Adrian Williams and James Tuchschmidt. Dr. Takateru Izumi (Chest Research Institute, Kyoto, Japan), and Dr. Teruo Tachibana (Osaka, Japan) were particularly kind. Illustrations for the chapter on suberosis were provided by late Dr. Thomé Villar of Lisbon, Portugal. Most of the illustrations and the photographic material are the excellent work of Andy Gero and his staff of the Medical Photography Unit of the LAC-USC Medical Center. I am most indebted to Ms. Linda Goggins, my secretary, for her help in typing the manuscript. Finally, my deep appreciation and gratitude to Maggie, my wife, without whose help this monograph would never have seen the light of day. Preface Although the disease entity, hypersensitivity pneumonitis, in one form or another, has been with us for the last three decades, only recently has it begun to attract attention from practitioners of various medical disciplines. This relatively obscure, poorly understood, yet universally observed clinical

7 syndrome is now vigorously pursued by clinicians, pulmonologists, epidemiologists, pathologists, radiologists, physiologists and immunologists. Their concerted efforts have provided, and continue to add, valuable information to the treasure trove of granulomatous lung disease. Hypersensitivity Pneumonitis: A Clinical Approach is a summary of the ever-growing field with an appropriate balance of clinical medicine, immunological advances and laboratory information. The book will serve as a practical introductory guide to physicians in training in internal medicine, pulmonology, allergy and immunology, and pathology. Busy clinicians who need quick access to essentials of hypersensitivity pneumonitis will find this easily readable and well-illustrated manual a handy companion.