Oxford textbook of medicine

1873 Pages·2020·238.558 MB·English

by  John D. Firth (editor), Christopher P. Conlon (editor), Timothy M. Cox (editor)

Oxford Textbook of
Oxford
2
Medicine
Textbook
of
The Oxford Textbook of Medicine is the foremost international textbook of medicine. Unrivalled in its coverage
of the scientific aspects and clinical practice of internal medicine and its subspecialties, it is a fixture in the
offices and wards of physicians around the world, as well as being a key resource for medico-legal practitioners. M
More comprehensive, more authoritative, and more international than any other textbook, the Oxford Textbook
of Medicine focuses on offering perspective and practical guidance on the clinical management and prevention
of disease.
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Introductory sections focus on the patient experience, medical ethics, and clinical decision-making, outlining a
philosophy which has always characterized the Oxford Textbook of Medicine. It is humane, thought-provoking,
and aims to instil in readers an understanding of the role of medicine in society and the contribution it can d
make to the health of populations. In addition, it does not shy away from discussion of controversial aspects
of modern medicine.
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As always, there is detailed coverage of all areas of internal medicine by the world’s very best authors. The
Oxford Textbook of Medicine seeks to embody advances in understanding and practice that have arisen through
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scientific research. The integration of basic science and clinical practice is unparalleled, and throughout the
book the implications of research for medical practice are explained. The core clinical medicine sections offer
in-depth coverage of the traditional specialty areas. The Oxford Textbook of Medicine has unsurpassed detail on i
infectious diseases: the most comprehensive coverage to be found in any textbook of medicine. Other sections
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of note include stem cells and regenerative medicine; inequalities in health; medical aspects of pollution and
climate change; travel and expedition medicine; bioterrorism and forensic medicine; pain; medical disorders in
pregnancy; nutrition; psychiatry; and drug-related problems in general medical practice. The section on acute
medicine is designed to give immediate access to information when it is needed quickly. e
INTERNATIONAL EDITION
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of Medicine continues to meet the needs of its readers. Chapter essentials give accessible overviews of the
content and a new design ensures that the textbook is easy to read and navigate. The evidence base and Oxford Textbook of
references continue to be at the forefront of research.
Medicine
SIXTH
EDITION
VOLUME
2
SECTIONS 10-15

Firth SIXTH EDITION edited by
Conlon VOLUME 2 John D. Firth
Cox Christopher P. Conlon
1 Timothy M. Cox
ISBN 978-0-19-885345-9
2
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Oxford Textbook of
Medicine

Oxford Textbook of
Medicine
SIXTH EDITION
Volume 2: Sections 10–15
EDITED BY
John D. Firth
Christopher P. Conlon
Timothy M. Cox
1
3
Great Clarendon Street, Oxford, OX2 6DP,
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Foreword
Professor Sir John Bell, Regius Professor of Medicine, University of Oxford
In 1983, David Weatherall, John Ledingham, and David Warrell nomenclature of disease, all crucial roles for a textbook of medicine.
launched the first edition of the Oxford Textbook of Medicine. That We now are aware that many of the classic definitions of diseases
era of medicine looked entirely different from today but the need for such as diabetes or cancer were descriptions of phenotypic charac-
a scholarly repository of medical knowledge remains as important as teristics. Interrogation of these disorders at a molecular level has
ever. Medicine is now firmly in a digital age; sources of information demonstrated that these terms mask disease subtypes defined by
abound and are readily available and the field is moving so quickly molecular pathology where natural history and response to therapy
that it is harder than ever to provide up to date relevant informa- may differ. Combine this with the explosion of new diseases coming
tion for the profession. Despite this, the sixth edition of the Oxford from studies of rare disease and there is a challenge to conventional
Textbook of Medicine still provides the foundation of knowledge disease nomenclature. This molecular precision creates real oppor-
upon which good clinical practice is based. tunities for targeted highly effective therapies, but it also creates
Never before has there been such a rapid advance of medical know- challenges for the model of drug discovery when novel treatments
ledge and practice. Since the first edition of the Oxford Textbook of can only be used in increasingly small patient populations. These are
Medicine, medical practice has reduced cardiovascular mortality by major issues for medicine, health systems, but also textbooks such as
up to 70% in Western countries, there are now multiple new ther- this one where, historically, the stewardship of disease nomenclature
apies for diseases such as rheumatoid arthritis and multiple scler- has been maintained.
osis, disorders where the descriptions of therapeutic options in the The therapeutic options available to practising clinicians have also
first edition were necessarily brief. Cancer is now increasingly man- advanced beyond all recognition since the first edition of the Oxford
aged with immune and targeted therapies. Whole new diseases have Textbook of Medicine. We have seen an era of biologic therapy which
appeared (Hepatitis C and HIV) and have been either controlled or has provided important new therapeutic alternatives for many hard-
conquered with drug therapy. The sequencing of the human genome to- treat diseases including cancer. We are now entering a new era
seemed an impossible dream in 1983 while today we have sequenced where modalities such as gene therapy and interfering RNA thera-
more than a million genomes and have had insights into rare disease peutics have demonstrated their utility in the clinic. Similarly, an
and cancer that were unimaginable then. Life expectancy has risen era of cell therapy has also begun which will provide important
by nine years for men and ten for women in the United Kingdom, new alternatives to some diseases. These new therapeutic alterna-
creating a demographic shift that will fundamentally change society tives and other opportunities for improving healthcare using med-
and medicine forever. The pace of change has been dramatic. ical technology or novel diagnostics such as sequencing also bring
The Oxford Textbook of Medicine gained a reputation by moving with them the challenge of how healthcare systems can continue to
medical practice forward from the Oslerian view of medicine ori- be affordable, either for individuals in private healthcare settings, or
ginally expounded in his text book the Principles and Practice of in state- funded, single- payer systems. In this context, it is remark-
Medicine into an era of more molecular and scientifically based able that the authors and editors of the Oxford Textbook of Medicine
understanding of disease. Constrained by the lack of tools for ex- have managed to sustain both its relevance and the accuracy of its
ploring the molecular basis of pathogenesis, Osler was limited in content.
how he could describe the world of disease, largely based on bed- The pace at which our understanding of disease, our therapeutic
side observations or those from the post- mortem room. The Oxford options, and our healthcare systems are likely to change makes it
Textbook of Medicine shifted this focus and aligned it with the nearly impossible for a textbook of medicine to be truly comprehen-
emerging field of molecular medicine which has begun to create a sive given the speed of change, the impact of new innovations and
new taxonomy of disease but also an approach to therapy which is the multiple additional sources of information available to practi-
based on pathogenesis. There has been a wave of new information, tioners. The Oxford Textbook of Medicine has provided remarkable
with new insights appearing weekly into the underlying molecular levels of detail in this rapidly changing world but, more importantly,
events associated with disease. Diseases characterized by phenotype the textbook continues to provide a source for readers to access
are now broken down into multiple subtypes and disease is being information on the fundamental features of disease. This founda-
individualized. This is rapidly leading to a very significant change tional knowledge remains crucial to our ability to understand, diag-
in our perception of pathogenesis as well as the classification and nose, and treat patients whether they are in the developing world or
vi Foreword
Western healthcare systems. Having a source of such information understanding of disease and has enabled progress in clinical medi-
across all major diseases accessible in a single source remains the cine to occur at a remarkable pace. By providing a textbook that
bedrock of both teaching and practising medicine. The foundations describes the foundations of our understanding of disease and its
provided by the Oxford Textbook of Medicine form a core of know- management, the editors have successfully given us an authoritative
ledge which practising clinicians will continue to need. text which practising clinicians will find invaluable to support their
The editors of this edition have been faithful to the vision of the day- to- day decisions. David Weatherall, one of the three original
original three editors. Science, in all its forms, is at the heart of our editors and who died in 2018, would be gratified by this new edition.
Preface
Changes in medicine responsibility, it is rare for doctors be able to stand back and perceive
genuine improvements. However, it is certainly true that today we
The Oxford Textbook of Medicine is published online and has been
have greater potential to prevent and treat disease and to maintain
regularly updated for many years, but the production of a new and
health than ever before. It is our hope that the Oxford Textbook of
very substantially updated edition provides a moment when it is nat-
Medicine will inform doctors about these changes and provide good
ural and proper to reflect on what has changed in medicine—a nd
guidance as to how they can be translated into clinical practice.
what has not— in recent years. In the context of burgeoning social
changes and inequality across the world, we have cause to weigh and Advances in biomedical sciences
consider exactly what modern medicine has to offer patients and
We seek to embody advances in understanding and practice that
their doctors. Here we reflect on aspects of Medicine that are chan-
have arisen through scientific research. In the ten years since
ging rapidly and set out a vision for this in the sixth edition of the
publication of the last edition of this book there has been spec-
Oxford Textbook of Medicine.
tacular progress in the application of science in medicine, espe-
cially the understanding of genomics and molecular cell biology.
Demand, capacity, magic solutions, and
These include: in diagnostics, non- invasive prenatal diagnosis of
the need for perspective
chromosome abnormalities and monogenic disease by sampling
Within all healthcare systems, in rich and poor nations alike, maternal plasma for cell- free fetal DNA, a technique which also
most physicians feel the inexorable rise in demand and are strug- holds promise for screening and monitoring of cancers; in meta-
gling to provide adequate ‘capacity’— the term commonly applied bolic disease, the introduction of molecular therapies that address
by healthcare managers charged with the impossible task of con- the defective chloride transport in cystic fibrosis; in oncology, in-
straining expenditure while serving political masters who, almost creased understanding of cancer immunity leading to the develop-
without exception, promise more and more and blame inefficiency ment of immunotherapies for cancers.
and ‘unwarranted variation’ for the failure to deliver. In response Our authors include the very best in their fields. The founding
to the difficulties, claims are made that some new technological editor and author in this edition, the late David Weatherall, was
advance, be it sequencing of patients’ genomes, healthcare apps, a recipient of the Lasker-K oshland Special Achievement Award
the application of artificial intelligence or ‘Quality Improvement’ in Medical Science. Two new authors have received the Nobel
methodology, will provide the solutions. In the Oxford Textbook of Prize recently— Professor Tu Youyou the 2015 prize for Medicine
Medicine, we do not shy away from these aspects and have several or Physiology, and Sir Greg Winter the 2018 prize for Chemistry.
new chapters that consider how rich and ‘resource-p oor’ countries Another new author, Professor Y.M. Dennis Lo, was one of two
might best invest their revenues on health. winners of China’s inaugural Future Science Prize in 2016.
It is often very hard for practising physicians, who care for patients Beyond scientific development, the introduction of new technolo-
as individuals, to maintain their bearings within the unfamiliar and gies into practice typically leads to a sequence of events including
depersonalized world of modern healthcare management. Many are initial ‘hype’ from many in the field, with extravagant claims of po-
left wondering whether those who organize health services ‘live on tential benefit. After an interval, these claims are followed by a more
this planet’, or ‘did any working doctor check out that latest directive realistic assessment of what the technology can— and cannot—
from above?’. When clinical outcomes that really matter are diffi- provide. Frequently, this familiar pattern is driven by powerful com-
cult to quantify, doctors find themselves and their services judged by mercial influences which can corrupt thinking in a manner that
spurious measures of ‘productivity’ in the process of healthcare ‘de- generates a climate in which those with views contrary to the big
livery’. Unrealistic and often clinically irrelevant targets might drive battalions are inevitably marginalized. In this edition of the Oxford
the thinking of the insurers, managers, and politicians, but who Textbook of Medicine we have strived to bring an authentic perspec-
can determine the human and clinical value of the care provided? tive and realism to recommendations for treatment. We sense, for in-
Timeliness of care is important and sometimes crucial for salutary stance, that the excitement generated by the sequencing of patients’
outcomes, but disaster strikes when clock- driven targets are blindly genomes continues to increase, but that this trajectory is flattening
pursued for all patients irrespective of clinical urgency and to the ex- and expectations becoming more realistic. For patients very likely
clusion of all else, including patients with greater clinical need. to have genetic disorders, diagnoses can be made for a proportion
In the morass created by financial constraints and zealous pol- that was unimaginable until recently, but for most patients with the
itical control of health services exercised by those without clinical degenerative and/ or polygenic diseases that are the greatest burden
viii Preface
to health, evidence of clinical benefit from genome sequencing re- One hundred and fifty years ago, Darwin’s 1859 masterpiece on
mains elusive. evolution was entitled ‘On the Origin of Species by Means of Natural
Beyond the progress in genomics and cell biology there has been Selection, or the Preservation of Favoured Races in the Struggle for
immense interest in bioinformatics and, especially with the enthu- Life’. The ‘less favoured’ undoubtedly have poorer health outcomes,
siasm of major biomedical charities such as The Wellcome Trust, due largely to the persistent social ill of inequality, in poor as well as
for ‘big data’, and the opportunities that these bring to the practice ostensibly rich countries. Continuing the tradition of previous edi-
of medicine. However, while there are plentiful examples of gen- tions, we have contributions that discuss the impact of social deter-
omics and cell biology having been translated productively from the minants of health, also thoughtful chapters on human disasters (by
bench to the bedside, with enormous benefit to patients, examples another Nobel laureate, Prof Amartya Sen), and the practical and
of transforming clinical impact from big data and bioinformatics critically important aspects of humanitarian medicine. In addition,
are sparse. But examples there are, such as in the analysis of out- the modern problems of pollution and climate change are exam-
breaks of the scourges Clostridium difficile and methicillin- resistant ined. We contend that all doctors would benefit from reading these
Staphylococcus aureus (MRSA). These discoveries give hope for the chapters.
future as we learn which problems are tractable with this type of
approach and which are not. Patients and their expectations
Clinical skill There are continuing changes in patients’ expectations, particularly
those of articulate patients suffering from long- term conditions and
Until recently, it would have been, to paraphrase Thomas Jefferson,
residing in countries with a rich provision of healthcare. A paternal-
regarded as self- evident that the key requirements of a good phys-
istic medical approach is no longer acceptable, and several patients
ician are the ability and will to obtain an informative history, carry
have contributed greatly to the book by taking the opportunity to tell
out a thorough physical examination, formulate a relevant differ-
us how they think doctors should behave towards them and care for
ential diagnosis, instigate appropriate investigations, advise and
them. However, we are very aware that one size does not fit all, and
administer correct treatment, including best efforts to relieve symp-
that many patients want a doctor who will give them clear recom-
toms in all cases. These skills, and the commitment to use them,
mendations and not keep repeating a bewildering (to the patient)
are often forgotten when healthcare is described in the commercial
variety of options and ask them to choose. The mature and able
terms of demand and capacity.
physician will be alert and sensitive to those patients who want this
While advances in biomedical sciences have dramatically im-
and will provide them with clear advice, and we have endeavoured to
proved the outcome for some diseases, and Paul Erhlich’s century-
ensure that the Oxford Textbook of Medicine will assist.
old magische Kugel (magic bullet) has whetted our appetite for
wonder, it is prudent to recall Thomas Szasz: ‘Formerly, when reli-
Access to medical knowledge
gion was strong and science weak, men mistook magic for medicine;
now, when science is strong and religion weak, men mistake medi-
The ever- expanding world of the smartphone and tablet device gives
cine for magic’. The term ‘personalized’ medicine imputes remark-
patients, families, doctors, and other healthcare professionals ready
able and as yet unproven powers, excepting in a very few cases, to
access to more information about medicine than all but a very few
gene sequencing and molecular therapies, while the patient wants
would have thought possible a decade ago. This has many benefits
to be treated as a person. It is also alarming to us that some medical
but often leaves users of the internet thoroughly perplexed, and some
curricula increasingly focus on process, ‘behaviours’, and ‘communi-
desperate people vulnerable to online quackery. Those wanting de-
cation skills’, to the detriment of medical content or mature guidance
tails of particular studies will naturally refer to the original literature.
and attitudes to lifelong learning. There is a tendency to forget the
Those wanting in- depth reviews of particular subjects can refer to
very essence of being, and how to become, a physician in the time-
diverse resources: these are typically good at apprising the reader of
honoured understanding of the role.
plentiful options for investigation, diagnosis, or management, but
In the Oxford Textbook of Medicine we unashamedly emphasize
often leave them uncertain of what a clinically experienced expert
the primacy of history, examination, differential diagnosis, investi-
in the field would actually recommend. In the sections that form the
gation, and treatment. Without a firm grasp of these essentials the
bulk of the Oxford Textbook of Medicine, we have selected experts
doctor cannot provide good care for patients, and nor can anyone
with specific clinical experience and given them this task, and we
else. Furthermore, having a firm understanding of clinical context
contend that they have met the challenge.
and a well-i nformed clinical perspective is an essential prerequisite
for driving biomedical research into avenues that really matter.
Acknowledgements
The broader context of health and disease
The Oxford Textbook of Medicine is a large undertaking: this edition,
The world has become a smaller place. We are now in an era when the most substantial so far, comprises 647 chapters and covers 6654
many regard not having a smartphone as an index of deprivation. printed pages, and its production has required an extraordinary co-
An event that has happened on a different continent can, as a re- ordination of effort from many quarters. In darker moments the edi-
sult of social media, become known to millions of people within tors feared that the process would never end, but as we have read
hours— the term ‘viral’ has been rightfully translated from commu- and edited the chapters along the way, we have experienced the joy
nicable illness to global phenomenon. Narratives transmitted in this of learning a huge amount of medicine, often in fields far removed
way often concern disasters, wars, and disease, and they are typically from our own. For this we are very grateful to our contributors,
handled by the media in a sensationalized and superficial manner. including those whose submissions were delayed!
Preface ix
We wish to make particular acknowledgement of our friend and publishing process that at times seemed to be Byzantine in its com-
senior colleague, David Warrell, an editor from the first edition of plexity, as might perhaps be expected in an ancient university. We
this textbook, senior editor of the fourth and fifth editions, and au- also thank Anna Kirton, Jamie Oates, and Jess White at Oxford
thor in this edition. We and our readers, notably those seeking in- University Press for their considerable efforts on behalf of the book.
formation on tropical diseases and especially any who have been Finally, we record that the editors’ personal lives have remained
bitten by snakes, about which his knowledge is truly prodigious, calm, and we are very grateful to Helen, Jenny, and Sue for their in-
owe him a great debt. dulgence of our bizarre editorial pursuit.
We thank Helen Liepman, with whom we remain good friends: she
John D. Firth
has overseen and directed matters at Oxford University Press and
Christopher P. Conlon
coped in a steadfastly pleasant and professional way with expres-
Timothy M. Cox
sions of editorial frustration caused by our failure to understand a