OXFORD MEDICAL PUBLICATIONS Oxford Handbook of Clinical Diagnosis Published and forthcoming Oxford Handbooks Oxford Handbook for the Oxford Handbook of Genetics Foundation Programme 4e Oxford Handbook of Genitourinary Oxford Handbook of Acute Medicine, HIV and AIDS 2e Medicine 3e Oxford Handbook of Geriatric Oxford Handbook of Anaesthesia 3e Medicine 2e Oxford Handbook of Applied Dental Oxford Handbook of Infectious Sciences Diseases and Microbiology Oxford Handbook of Cardiology 2e Oxford Handbook of Key Clinical Oxford Handbook of Clinical and Evidence Laboratory Investigation 3e Oxford Handbook of Medical Oxford Handbook of Clinical Dermatology Dentistry 6e Oxford Handbook of Medical Imaging Oxford Handbook of Clinical Oxford Handbook of Medical Diagnosis 3e Sciences 2e Oxford Handbook of Clinical Oxford Handbook of Medical Examination and Practical Skills 2e Statistics Oxford Handbook of Clinical Oxford Handbook of Neonatology Haematology 3e Oxford Handbook of Nephrology Oxford Handbook of Clinical and Hypertension 2e Immunology and Allergy 3e Oxford Handbook of Neurology 2e Oxford Handbook of Clinical Oxford Handbook of Nutrition and Medicine – Mini Edition 8e Dietetics 2e Oxford Handbook of Clinical Oxford Handbook of Obstetrics and Medicine 9e Gynaecology 3e Oxford Handbook of Clinical Oxford Handbook of Occupational Pathology Health 2e Oxford Handbook of Clinical Oxford Handbook of Oncology 3e Pharmacy 2e Oxford Handbook of Ophthalmology 3e Oxford Handbook of Clinical Oxford Handbook of Oral and Rehabilitation 2e Maxillofacial Surgery Oxford Handbook of Clinical Oxford Handbook of Orthopaedics Specialties 9e and Trauma Oxford Handbook of Clinical Oxford Handbook of Paediatrics 2e Surgery 4e Oxford Handbook of Pain Oxford Handbook of Management Complementary Medicine Oxford Handbook of Palliative Care 2e Oxford Handbook of Critical Care 3e Oxford Handbook of Practical Drug Oxford Handbook of Dental Therapy 2e Patient Care Oxford Handbook of Pre-Hospital Oxford Handbook of Dialysis 3e Care Oxford Handbook of Emergency Oxford Handbook of Psychiatry 3e Medicine 4e Oxford Handbook of Public Health Oxford Handbook of Endocrinology Practice 3e and Diabetes 3e Oxford Handbook of Reproductive Oxford Handbook of ENT and Head Medicine & Family Planning 2e and Neck Surgery 2e Oxford Handbook of Respiratory Oxford Handbook of Epidemiology Medicine 3e for Clinicians Oxford Handbook of Rheumatology Oxford Handbook of Expedition and 3e Wilderness Medicine Oxford Handbook of Sport and Oxford Handbook of Forensic Exercise Medicine 2e Medicine Handbook of Surgical Consent Oxford Handbook of Oxford Handbook of Tropical Gastroenterology & Hepatology 2e Medicine 4e Oxford Handbook of General Oxford Handbook of Urology 3e Practice 4e Oxford Handbook of Clinical Diagnosis Third edition Huw Llewelyn Formerly Consultant Physician, Kings College Hospital, London. Honorary Departmental Fellow, Aberystwyth University, Ceredigion, UK Hock Aun Ang Honorary Senior Lecturer in Medicine, Penang Medical College, Senior Consultant Physician, Seberang Jaya Hospital, Penang, Malaysia Keir Lewis Associate Professor, College of Medicine, Swansea University. Chest Consultant Hywel Dda University Health Board, UK Anees Al-Abdullah General Practitioner, Meddygfa Minafon, Kidwelly, Carmarthenshire, UK 1 3 Great Clarendon Street, Oxford, OX2 6DP, United Kingdom Oxford University Press is a department of the University of Oxford. It furthers the University’s objective of excellence in research, scholarship, and education by publishing worldwide. Oxford is a registered trade mark of Oxford University Press in the UK and in certain other countries © Huw Llewelyn 204 The moral rights of the authors have been asserted First edition published 2006 Second edition published 2009 Impression:  All rights reserved. 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Oxford disclaims any responsibility for the materials contained in any third party website referenced in this work. v Foreword to third edition Last year, I celebrated my 30th year as a doctor and my son began his training as a (graduate entry) medical student. I have come to enjoy the intergenera- tional ‘grand rounds’ in which one of us describes a case in the time-hon- oured format—starting with a structured history, going on to the clinical examination and adding diagnostic tests that progress from the simple and non-invasive to all the wonders and dreads of modern technology—while the other tries to guess the diagnosis from as few clues as possible. Given that most medical knowledge now lies in the category ‘forgotten by the mother and not yet encountered by the son’, this book is likely to become well thumbed by both of us as we play our diagnostic game. Much of this book reflects the fact that Huw Llewelyn is a mathematician and logician as well as a highly experienced physician. In many cases, diagno- sis can and should be a process of deduction that begins with a ‘diagnostic lead’ (a single symptom or sign, such as ‘right iliac fossa pain’, that gets you started), the cause of which can be progressively narrowed and refined by incorporating factors such as age and gender; the timing and speed of onset; the pattern of associated symptoms, signs and pre-existing conditions; and the results of investigations. Frontal headache in a teenager who was well until yesterday is likely to have a different cause from frontal headache that has been present for many months in a 65-year-old with hypertension and depression. Evidence can often be collected in the history and clini- cal examination that is ‘suggestive’ or ‘confirmatory’ (use these terms with care—they are defined in the book) of particular diagnostic possibilities. More rarely, certain tests or combinations of tests can effectively ‘rule in’ or ‘rule out’ certain diagnostic options. You probably knew all that already, so what will you learn from this book that goes beyond standard teaching on clinical diagnosis? For me, the added value was in the sophistication with which the principles of probability and decision science have been applied to the many and varied challenges of clinical practice. The book’s (mainly implicit) message is that if you take a logical and step-wise approach, using your experience, history-taking skills, and clinical acumen to select the best diagnostic leads and add granularity to your decision tree, you will often render costly and unpleasant diagnostic tests redundant. Less commonly, you will justify the expense and inconven- ience of such tests in selected patients. The skilled diagnostician is not the one who rattles off a long list of differ- ential diagnoses for every symptom, applies algorithms mechanically, ticks all the boxes on a blood request form or scans the head of every patient with blurred vision. Rather, the skilled diagnostician is the one who com- bines thoughtful history-taking, focused clinical examination, and judicious investigation so that each successive step contributes to an emerging picture of the problem and informs the selection of the next step. As the authors say (p.20), ‘It is important to understand that clinical diagnosis is not a static classification system based on diagnostic criteria or their probable presence. It is a dynamic process.’ vi FOREWORD TO THIRD EDITION The bulk of the book is a treasure-trove of diagnostic puzzles from red throat to wasting of the small muscles of the hands, from which I predict hours of fun for students and seasoned clinicians alike. There are also sec- tions on biochemical conundrums such as hyponatraemia, and radiologi- cal old chestnuts such as a round opacity on the chest X-ray. Reassuringly, theoretical sections such as ‘Grappling with Probabilities’ and ‘Bayes’ and other rules’ are relegated to a final chapter that can be safely omitted by those whose interests are more clinical than mathematical. Despite its emphasis on deductive logic, this book is by no means an uncritical offering to the gods of decision science. Llewelyn and his coau- thors are careful to point out (as Dave Sackett and colleagues did back in the 970s) that many diagnoses are made intuitively—for example via the pattern recognition that allows us to look at a patient and instantly think ‘Down’s syndrome’ or ‘chicken-pox’. They also remind us that mild symp- toms are often both non-specific and self-limiting (hence may need no more active management than advising the patient to return if not improving), and they warn us of the dangers of over-diagnosis and that increasingly com- mon problem in modern diagnostics, the ‘incidentaloma’. Like the birth of a third child, the publication of the third edition of a book is cause for much celebration: it tends to both reflect and build on significant success with earlier versions. Perhaps it is too early to encourage the authors of the Oxford Handbook of Clinical Diagnosis (3rd edition) to contemplate a companion volume to this magnum opus. But if they were open to such a suggestion, I would encourage them to team up with experts in public understanding of science and produce a version of the book aimed at patients and carers. After all, if your patients were reading the wisdom distilled in these pages, that would surely make for some interesting and productive conversations. Trisha Greenhalgh OBE Professor of Primary Health Care and Dean for Research Impact Barts and the London School of Medicine and Dentistry Queen Mary University of London 204 vii Preface This book helps doctors and students to arrive at a diagnosis, and to explain and to justify their reasoning, especially when seeing patients with new problems that lie outside their personal range of experience. This will hap- pen very frequently to students, frequently to house officers, but will still happen regularly to very experienced senior hospital doctors and general practitioners. The book adopts the approach used by experienced diagnosticians, by focusing on the finding with the shortest differential diagnosis (i.e. the best diagnostic lead). It describes the differential diagnoses of such findings that may be encountered by a reader in the history, examination and usual pre- liminary tests and how the diagnoses can be confirmed. It describes what tactics to adopt in order to find better leads, while not losing sight of the patient’s original concern. The probability and set theory of this process is explained in Chapter 3. The entries on each page of the book resemble a traditional past medi- cal history with multiple diagnoses. The reader scans down the page to see which of the diagnoses with its findings match the patient’s findings so far. The compatible findings can then be used as evidence for the diagnosis and treatment, to be shared with the patient and other members of the multidisciplinary team, such as nurses, pharmacists, physiotherapists, and other professionals allied to medicine. It can be used to create high-quality discharge or handover summaries. Patients or their carers may wish to share in the diagnostic and decision-making process. In order to do this, they need to know what prob- lems have been identified and the tests and treatments being proposed. They will need to know which of these diagnoses explain each problem and treatment. They may also need to know which findings are being used to confirm each diagnosis, and to choose its treatments and to mark the out- come. The book describes how this information can be provided in writing. The patient or carer will then be in a position to explain all this to another doctor, if necessary. In this third edition, there are sections on each page that show how the diagnosis may be finalized by the outcome of management. This replaces the section in the second edition that described the ‘initial management’ of the condition. The purpose of this is to show how the response of treatment, etc., affects the diagnostic process. Chest X-ray images have been added to illustrate the findings in Chapter 2. The appendix of the second edition has been replaced by Chapter 3 in this third edition and explains the basis of evidence-based differential diagnosis and diagnostic confirmation. Huw Llewelyn 204 viii Dedication For Angela. ix Contents Acknowledgements x Advisors xi Symbols and abbreviations xii  The diagnostic process  2 Interpreting the history and examination 25 3 General and endocrine symptoms and physical signs 6 4 Skin symptoms and physical signs 23 5 Cardiovascular symptoms and physical signs 73 6 Respiratory symptoms and physical signs 235 7 Gastrointestinal symptoms and physical signs 287 8 Urological and gynaecological symptoms and physical signs 399 9 Joint, limb, and back symptoms and physical signs 423 0 Psychiatric and neurological symptoms and physical signs 453  Laboratory test results 543 2 Chest X-rays 573 3 Making the diagnostic process evidence-based 65 Index 643