bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurosurgery
Authors: Pereira Erlick A. C. , Hyam Jonathan A. , Green Alexander L.
Published: August 2018

Neurosurgery encompasses brain, spine, and peripheral nerve disorders that may benefit from operative management. These include congenital neurological diseases, epilepsy, stroke, neurological infection, movement disorders, spinal cord disease, neurological tumours, and pituitary disorders. This chapter focuses on head injury and subarachnoid haemorrhage, two common neurosurgical disorders not detailed elsewhere in this book.
Drug-induced neurological disease
Authors: Ferner Robin , Cox Anthony
Published: August 2018

An adverse drug reaction is defined as ‘an appreciably harmful or unpleasant reaction, resulting from an intervention related to the use of a medicinal product; adverse effects usually predict hazard from future administration and warrant prevention, or specific treatment, or alteration of the dosage regimen, or withdrawal of the product’ (p. 1255, Edwards IR and Aronson JK. Adverse drug reactions: Definitions, diagnosis, and management. Lancet 2000; 356: 1255–9). Adverse drug reactions can cause or contribute to central and peripheral nervous system disorders, including traumatic, infective, neoplastic, demyelinating, and vascular diseases.
Functional and dissociative disorders in neurology
Authors: Stone Jon , Carson Alan
Published: August 2018

In this chapter, the focus is on patients who present with physical symptoms, such as weakness, or seizures, which can be positively identified as inconsistent with pathological diseases. These are called functional and dissociative neurological symptoms, although there are many other terms that could be used, such as conversion disorder, psychogenic symptoms, somatization, hysterical symptoms, medically unexplained symptoms, non-organic symptoms, and pseudoseizures, to name a few.
Normal skin function
Authors: Powell Jenny
Published: August 2018

In simplest terms, our skin is a layer that separates and protects us from the external environment. This assumes the skin is a passive covering to keep the insides safe and the outside out, and overlooks its enormous complexity. The skin is our largest organ and is constantly regenerating, but how efficiently it does so depends on a number of factors, some known, others unknown. It is an efficient mechanical barrier (designed for wear and repair), and a complex immunological membrane. It has a generous vascular, lymphatic, and nervous supply, all covering a considerable area. It has specialist structural and functional properties relating to specific areas, but also specialist cells within the layers of the skin. Most importantly, skin is the organ of display, an important part of social and sexual behaviour, immediately accessible to all, and often regarded as a barometer of the general state of health. Permanent scars inflicted on the skin may be a cause of great distress to the patient. Skin consists of a superficial layer, ‘the epidermis’ (concerned with producing protective keratin and a pigment called melanin), which adheres closely to the deeper layer, ‘the dermis’ (which provides the strength of the skin and houses the appendages), via the basement membrane. Loose connective tissue and fat underlie the dermis.
Approach to diagnosing skin disease
Authors: Powell Jenny
Published: August 2018

Making a diagnosis in dermatology may seem daunting when there are 6 000 or more possibilities, and the terminology seems so complex. This chapter suggests a systematic approach to picking up clues from symptoms and signs, and understanding how to describe skin disease; this approach, together with experience (obtained through seeing patients, asking more experienced colleagues, and reading) will help with pattern recognition and, sometimes, lead to the answer. The skin has such a wide range of structural and functional varieties that disorders of the skin are not only common but also very variable. However, it is important to be able to give a patient a diagnosis. This ‘working label’ means that the patient fits into a known group not only in their typical presentation but also as a guide for response to treatment, prognosis, and, sometimes, for explanation of etiology and whether genetic or infective factors are important; that is, it is helpful in explaining the disease to the patient. Despite the complexity of the skin, making a diagnosis in dermatology is no different from making a diagnosis in other areas; it is based on taking a history, examining the patient, and performing investigations, if indicated.
Investigation in skin disease
Authors: Powell Jenny
Published: August 2018

When taking a history and examining the patient do not provide all the information required, further investigation is possible. This may be to provide a diagnosis, to add to prognostic information, to help with treatment required, or to find an associated systemic disorder or underlying genetic disorder.
Skin infection and infestation
Authors: Soon Christine
Published: August 2018

An infection of the skin means a breach of the skin barrier has resulted in an organism gaining an opportunity to infect the area and causing inflammation, pain, erythema, and swelling. There can be associated systemic unwellness such as pyrexia, tachycardia, and hypotension. An infestation occurs when creatures inhabit the skin, lay eggs, and multiply. These creatures are usually dependent on their host for food and transmission to others. They typically cause intense pruritus in the affected areas.
Cutaneous vasculitis
Authors: Soon Christine
Published: August 2018

Vasculitis is inflammation of the blood vessels. It can affect large vessels, medium-sized vessels, or small vessels. Cutaneous vasculitis is inflammation of the blood vessels of the skin. This can include the capillaries, the venules, and the arterioles.
Acne
Authors: Esdaile Ben
Published: August 2018

Acne vulgaris is a common, chronic inflammatory disorder of the pilosebaceous unit (the hair follicle and accompanying sebaceous gland). It can be classified as mild, moderate, or severe. Mild acne is characterized by comedones (non-inflammatory lesions: ‘blackheads’ and ‘whiteheads’) being the predominant lesions. Papules and pustules may also be present but are few in number. Moderate acne is defined by more inflammatory lesions such as papules and pustules, with comedones also usually present. Severe acne is defined as widespread inflammatory lesions, nodules, cysts, and scarring. Moderate acne that has not settled within 6 months of treatment, or acne that is causing serious psychological effects, is also categorized as severe.
Psoriasis
Authors: Esdaile Ben
Published: August 2018

Psoriasis is a common, chronic inflammatory skin disease that is associated with joint disease in approximately 25% of patients. The most common variant of psoriasis is chronic plaque psoriasis (psoriasis vulgaris), which has the hallmark of well-demarcated erythematous plaques covered by silvery scale. There are a number of other variants of psoriasis, including guttate, inverse, palmoplantar, flexural, pustular, and erythrodermic.
Eczema
Authors: Esdaile Ben
Published: August 2018

Eczema is a descriptive term for a set of symptoms and signs which usually involve itchy inflammation of the skin, and is subcategorized into many different forms. Atopic eczema (atopic dermatitis) is the most common chronic inflammatory disease amongst children. Other types of eczema include seborrhoeic eczema, discoid eczema, asteatotic eczema, contact allergic eczema, contact irritant eczema, pompholyx eczema, venous eczema, juvenile plantar dermatosis, and lichen simplex. This chapter covers atopic eczema, which is referred to as ‘atopic’ due to its association with other atopic disorders such as asthma and allergic rhinitis.
Urticaria
Authors: Wakelin Sarah
Published: August 2018

Urticaria is an inflammatory complaint characterized by short-lived skin swellings termed ‘wheals’ or ‘hives’. It can be divided into acute urticaria, where the disease has an abrupt onset, and chronic urticaria, where wheals have occurred on a regular basis for over 6 weeks. Physical urticaria is a subgroup of chronic urticaria where an underlying external/physical trigger can be identified, while contact urticaria arises from contact with a chemical substance on the skin or mucous membranes. Angiooedema represents a similar process affecting the deeper dermal tissue and has a predilection for the skin around the eyes and mouth. It may occur in association with urticaria or as an isolated complaint.
Hair disorders
Authors: Berker David de
Published: August 2018

This chapter discusses inflammatory scalp diseases and hair shedding (telogen effluvium and pattern hair loss). Inflammatory diseases of the scalp can affect all epidermal surfaces or focus upon the follicle, with relative sparing of the interfollicular skin. Eczema and psoriasis are examples of the former; other diseases, such as lichen planopilaris or discoid lupus erythematosus, are examples of the latter. Some follicular diseases, such as the family of diseases based on alopecia areata (alopecia areata (small areas of hair loss), alopecia totalis (whole scalp), and alopecia universalis (whole body)), cause barely visible follicular inflammation which results in hair loss but no scarring. Some patients present with hair shedding or change of hair pattern as their primary complaint, with no scalp disease; this is telogen effluvium. Others present with an altered pattern of scalp hair without conspicuous shedding; this is pattern hair loss.
Nail disorders
Authors: Berker David de
Published: August 2018

Nail diseases present as alteration of the nail plate, alteration of the periungual tissues, or as a combination of the two. Most commonly, external agents, such as fungus or trauma, affect the nail alone, whereas all inflammatory and neoplastic processes affect the surrounding tissues as a primary process giving rise to secondary nail plate alteration.
Mucosal disease
Authors: Taghipour Kathy
Published: August 2018

This chapter discusses the following mucous membrane disorders: pemphigus vulgaris, lichen planus, and Stevens–Johnson syndrome. Pemphigus vulgaris is an autoimmune disease that affects the skin and the mucosal membranes with blisters and erosions. Lichen planus is a cell-mediated immunological mucocutaneous disease; oral lichen planus may present with erosions, white streaks, or plaques in the oral cavity. Stevens–Johnson syndrome is an emergency dermatological condition in which an immunological hypersensitivity causes erosions and inflammation of mucosal membranes and the skin. As well as providing definitions of these diseases, this chapter discusses their etiology, typical symptoms, uncommon symptoms, demographics, natural history, complications, diagnostic approach, other diagnoses that should be considered, prognosis, and treatment.
Genital disease
Authors: Cooper Susan , McPherson Tess
Published: August 2018

The term ‘genital disease’ refers to a spectrum of diseases. Certain systemic diseases preferentially affect mucous membranes. Local factors including warmth, occlusion, irritants, and friction are important and contribute to skin disease in this region and increase the risk of certain infections. Skin conditions may be difficult to diagnose, as they may have atypical appearances. Therefore, the diagnosis of disease in the anogenital region may be complex. This chapter will focus on the most common diseases seen in the dermatology clinic: lichen sclerosus, lichen planus, eczema, genital pain syndromes, and pre-malignant and malignant disease. Other less common dermatological conditions seen in this area will be briefly covered.
Polymorphic light eruption and actinic prurigo
Authors: McGregor Jane
Published: August 2018

This chapter discusses polymorphic light eruption, actinic prurigo, sunburn, and sunburn-related disorders. It explores definitions of the diseases, etiologies, typical symptoms, uncommon symptoms, demographics, natural histories, complications, diagnostic approaches, other diagnoses that should be considered, prognoses, and treatments.
Disorders of pigmentation
Authors: Gawkrodger David J.
Published: August 2018

Skin colour is due to a mixture of the pigments melanin, oxyhaemoglobin (in blood), and carotene (in the stratum corneum and subcutaneous fat). Pigmentary diseases are common and particularly distressing to those with darker skin. Disorders of pigmentation often involve melanocytes. Vitiligo is the commonest disease of reduced pigmentation, and melasma is the commonest of hyperpigmentation.
Skin markers of internal medicine
Authors: Archer Charles M. G. , Archer Clive B.
Published: August 2018

Some of the most interesting aspects of dermatology are seen when internal medicine and dermatology overlap. Skin lesions may be part of a systemic disease, as occurs in sarcoidosis or SLE, or may be a manifestation or ‘marker’ of an underlying disease or process, as in acanthosis nigricans. Here, we will focus on the diagnosis and treatment of selected skin markers of internal medicine.
Drug-induced skin disease
Authors: Sivaramakrishnan Muthu
Published: August 2018

Drug-induced skin disease is one of the commonest dermatological presentations in both hospitalized and ambulatory patients. It affects 2%–3% of hospitalized patients, and it is estimated that 1 in 1000 hospitalized patients has a serious cutaneous drug reaction. The clinical presentation can mimic any skin disease and should be considered in the differential diagnosis of any acute-onset symmetrical skin eruption. It is important to make a correct diagnosis, as removal of the offending drug results in clinical resolution in most instances.
Psychocutaneous medicine
Authors: Bewley Anthony
Published: August 2018

The links between the mind and the skin have long been recognized. The skin has been described as the mirror of the mind, and so it is not surprising that the interface between dermatology and psychiatry (‘psychocutaneous medicine’ or ‘psychodermatology’) is emerging as a specific subspeciality of dermatology. Psychodermatological conditions can be classified as either primarily psychiatric disorders which manifest via skin disease, for example delusional infestation, or primarily dermatological disorders, for example psoriasis, which may be caused by, or associated with profound psychiatric morbidity (e.g. anxiety, depression).
Normal function of the musculoskeletal system
Authors: Shaffu Shireen , Taylor James
Published: August 2018

The musculoskeletal system consists of specialized connective tissue whose primary function is to allow locomotion. The tissues of the musculoskeletal system are bones, muscles, tendons, and ligaments. In particular, the bony skeleton also has the task of protecting vital internal organs, contains the bone marrow, and is an intrinsic part of the metabolic pathways involved in calcium homeostasis. Motion is allowed by specialized articulating structures, the joints.
Diagnosis in suspected rheumatological disease
Authors: Jeffery Rachel
Published: August 2018

Musculoskeletal symptoms may be the sole presenting complaint of a rheumatological disease or may be a minor part of a presenting symptom complex. Determining whether or not these symptoms reflect serious pathology requiring specialist management relies on careful history taking and a thorough examination. The majority of rheumatic conditions are chronic, and a holistic approach to patient management is required to establish how the illness affects the physical and psychological functioning of the patient, and to explore how symptoms may be managed. In assessing the patient with musculoskeletal symptoms, the following questions must be considered. First, are the symptoms due to an inflammatory process or a non-inflammatory process? Second, do the symptoms reflect a primary rheumatological disease or are they secondary to another pathology (e.g. infection or malignancy)? Third, are the symptoms a complication of the disease or a complication of treatment? Fourth, is there evidence of non-articular disease, which may be relevant to diagnosis or management? This chapter focuses on how elements of the history and examination can help answer these questions.
Osteoarthritis
Authors: Doherty Michael
Published: August 2018

Osteoarthritis (OA) is a disorder of synovial joints and is characterized by the combination of focal hyaline cartilage loss and accompanying subchondral bone remodelling and marginal new bone formation (osteophyte). It has genetic, constitutional, and environmental risk factors and presents a spectrum of clinical phenotypes and outcomes. OA commonly affects just one region (e.g. knee OA, hip OA). However, multiple hand interphalangeal joint OA, usually accompanied by posterolateral firm swellings (nodes), is a marker for a tendency towards polyarticular ‘generalized nodal OA’.
Rheumatoid arthritis
Authors: Raza Karim , Cardy Caroline , Justice Elizabeth
Published: August 2018

Rheumatoid arthritis is a chronic systemic inflammatory disorder. It is characterized by inflammation of the synovium with consequent cartilage and bone destruction. Extra-articular manifestations frequently occur.
Seronegative spondyloarthropathy
Authors: Gaston Hill
Published: August 2018

Spondyloarthropathies consist of several rheumatic conditions, initially grouped together on the basis of shared clinical features, later reinforced by their strong association with HLA-B27. The distinctive features are axial involvement, including sacroiliac joints, and enthesitis—inflammation at ligament and tendon insertions—together with certain extra-articular manifestations. The presentation of a patient with combinations of inflammatory spinal pain, peripheral synovitis and/or enthesitis, and typical extra-articular manifestations, often with a family history, is characteristic.
Infection of joints and bones
Authors: Bloch Benjamin
Published: August 2018

Infection can arise at any time within the bone or soft tissues, and sepsis should always be a consideration in the assessment of an acutely swollen, painful joint. An acute infection is an orthopaedic emergency, and prompt assessment should always be sought. Infection can affect either joints (septic arthritis) or bones (osteomyelitis). Septic arthritis can affect either a native joint or a prosthetic one, and the presentation can be acute or chronic. Similarly, osteomyelitis can present acutely or chronically, and can be due to haematogenous spread (particularly affecting the long-bone metaphyses in children, and the vertebral bodies in adults), direct inoculation via trauma or surgery, or communication from a contiguous infection site.
Vasculitis
Authors: Luqmani Raashid
Published: August 2018

The vasculitides are a heterogeneous group of disorders that can range from mild inflammation of blood vessels in the skin, to organ- and life-threatening diseases. The term ‘vasculitis’ is a pathological description of blood vessel wall inflammation which leads to ischaemia and infarction of the target organs. Definitions and classifications of the primary vasculitides are mainly based on the predominant calibre of the blood vessels involved but incorporate clinical, pathological, and laboratory features. The secondary vasculitides usually occur in the context of other connective tissue diseases and are not discussed further in this section. Goodpasture’s disease is not usually included in the primary vasculitides, but has compatible clinical features of pulmonary capillaritis and glomerulonephritis.
Osteomalacia
Authors: Javaid Kassim
Published: August 2018

Osteomalacia is a disorder of bone mineralization and is due to a lack of vitamin D. Vitamin D is a prohormone formed by the action of UV radiation on the vitamin’s precursor (7-dehydrocholesterol) in the skin. It undergoes two hydroxylation steps to become an active hormone. The commonest cause of osteomalacia is vitamin D deficiency due to a lack of UVB skin exposure. Other causes include malabsorption (coeliac disease and pancreatic insufficiency), obesity, and chronic kidney disease. The typical symptoms of osteomalacia are non-specific bone pain, proximal myopathy, fatigue, and polyarthralgia. This chapter addresses the causes, diagnosis, and management of osteomalacia.
Paget’s disease of bone
Authors: Javaid Kassim
Published: August 2018

Paget’s disease of bone is an uncommon bone disorder with increased bone resorption and disorganized bone formation of woven bone. Its cause is unclear; there is a clear genetic component but additional environmental factors are important, given the reduction in severity and prevalence in the UK. Paget’s disease is usually asymptomatic and detected by an unexplained raised alkaline phosphatase on routine biochemistry. Symptoms include focal bone pain, including headache. Other symptoms include bone deformity and complications such as fracture and nerve conduction. Paget’s disease can sometimes present with immobilization-associated hypercalcaemia or high-output cardiac failure, and rarely can transform to an osteosarcoma. This chapter addresses the clinical features, diagnosis, and management of Paget’s disease of bone.
Osteoporosis and fragility fracture
Authors: Javaid Kassim
Published: August 2018

Osteoporosis is defined as a systemic bone disease with reduction in both bone density and microarchitectural integrity, resulting in an increase in fragility fracture risk. It is a multifactorial disease which, through effects on bone formation and resorption, reduces the peak bone mass achieved during early adulthood and increases the rate of bone loss in later adulthood. Osteoporosis is clinically silent until a fragility fracture occurs. There are 3 million patients with osteoporosis in the UK, with over 200 000 fractures per year and 80 000 hip fractures. This chapter addresses the causes, clinical features, diagnosis, and management of osteoporosis.
Genetic bone and joint disease
Authors: Price Susan
Published: August 2018

Genetic conditions affecting the skeleton and supporting structures are individually rare and heterogeneous. This chapter presents an approach to assessing patients with suspected skeletal dysplasia, osteogenesis imperfecta, Marfan syndrome, and Ehlers–Danlos syndrome. Skeletal dysplasias are caused by abnormalities of bone growth and modelling; the commonest non-lethal type is achondroplasia, with an incidence of 1/10 000 to 1/30 000. The typical presentation of osteogenesis imperfecta is with multiple fractures, sometimes prenatally. There may be associated short stature, bone deformity, dentogenesis imperfecta, blue sclera, and hearing loss. Most patients with osteogenesis imperfecta have mutations in COL1A1 or COL1A2. Marfan syndrome is a connective tissue disease with a pattern of symptoms related to the presence of fibrillin in tissues. Typically, affected individuals are of tall, thin stature, with long fingers and toes (arachnodactyly), a pectus deformity, and scoliosis. Between 66% and 91% of individuals with Marfan syndrome have a mutation in fibrillin-1 (FBN1; locus: 15q21). All forms of Ehlers–Danlos syndrome present with variable thinning and fragility of skin, leading to easy bruising and poor scar formation. There is skin and joint laxity. In severe forms, blood vessels and internal organs are affected.
Normal blood function
Authors: Bunch Chris
Published: August 2018

This chapter reviews normal blood function and disorders of haemopoiesis. Blood consists of cells of three main types, suspended in plasma. The cellular component comprises about 40%–50% of the total volume and consists of red cells (erythrocytes), white cells (leucocytes), and platelets. Blood cells are formed from progenitor cells in the bone marrow by haemopoiesis, a process of proliferation and differentiation. Failure of haemopoiesis usually results from damage to proliferating marrow cells by cytotoxic drugs or radiation, haemopoietic malignancy, or a combination of the two.
Diagnosis and investigation in haematology
Authors: Bunch Chris
Published: August 2018

This chapter addresses the interpretation of the full blood count, blood film, bone marrow examination, and related tests in the diagnosis of haematological disorders. Examination of a stained blood film, which should always be requested if a blood count abnormality cannot readily be explained by the clinical context, may give clues to the cause of the abnormality or prove diagnostic. Examination of the bone marrow is essential to the proper evaluation and diagnosis of many haematological disorders. The simplest form of marrow examination involves needle aspiration of marrow cells from the posterior iliac crest; smears are made and stained in the same way as a blood film. Bone marrow can also be biopsied for histological examination, at the same time as marrow aspiration.
Haemolytic anaemia
Authors: Bunch Chris
Published: August 2018

Haemolytic anaemias occur when the rate of red-cell breakdown is increased and exceeds the marrow’s capacity to generate new cells. Increased red-cell destruction, or haemolysis, may reflect a broad range of disorders. Some involve intrinsic defects in the red cell itself; in others, the red cells are normal but are subjected to external factors which lead to premature destruction. Many of the intrinsic defects are due to inherited disorders affecting the red-cell membrane, its enzymes, or haemoglobin. The marrow can normally compensate for moderate haemolysis by increasing red-cell production up to tenfold. Only when haemolysis is severe and the red-cell lifespan is reduced to less than about 15 days, or the marrow is unable to compensate, will anaemia occur. This chapter addresses the diagnosis, investigation, and management of haemolytic anaemias, including hereditary spherocytosis, paroxysmal nocturnal haemoglobinuria, glucose-6-phosphate dehydrogenase deficiency, haemoglobinopathies, and mechanical and immune haemolytic anaemias.
Normal platelet function
Authors: Curry Nicola , Alikhan Raza
Published: August 2018

The platelet is a small (2–4 µm in diameter), discoid, anucleate cell that circulates in the blood. In health, it plays a vital role in haemostasis, and in disease it contributes to disorders of bleeding and thrombosis. Platelets are produced from the surface of megakaryocytes in the bone marrow, under tight homeostatic control regulated by the cytokine thrombopoietin. Platelets have a lifespan of approximately 7–10 days, and usually circulate in the blood stream in a quiescent state. Intact, undamaged vessel walls help to maintain platelets in this inactive state by releasing nitric oxide, which acts both to dilate the vessel wall and to inhibit platelet adhesion, activation, and aggregation. After trauma to the blood vessel wall, platelets are activated and, acting in concert with the endothelium and coagulation factors, form a stable clot. This chapter addresses platelet structure and function, and the response of platelets to vessel injury.
Platelet disorders
Authors: Curry Nicola , Alikhan Raza
Published: August 2018

The term ‘platelet disorder’ covers a very large and heterogeneous group of diseases that have a multitude of causes. Platelet disorders are either inherited or acquired and are due to an abnormality of platelet number (quantitative disorder), an abnormality of platelet function (qualitative disorder), or a combination of both. This chapter addresses the causes, diagnosis, and management of platelet disorders.
Normal haemostatic function
Authors: Alikhan Raza
Published: August 2018

Humans have evolved an intricate system that maintains blood in a fluid state. This relies on an intact vascular endothelium modulating vascular tone and forming a barrier between blood components and reactive subendothelial components. It also involves the production of inhibitors of both blood coagulation and platelet aggregation. In addition, haemostatic systems are primed to convert blood from its fluid state to a solid state, to allow the formation of a haemostatic plug, following vessel injury, to stem the flow of blood from or within a blood vessel. This chapter reviews the physiology of haemostasis.
Bleeding disorders
Authors: Alikhan Raza
Published: August 2018

From the rabbinical writings in the second century AD, to the spread of haemophilia within the royal families of Europe, there have been reports of bleeding disorders throughout history. The most common inherited bleeding disorders are haemophilia and von Willebrand’s disease. There are also a number of rarer inherited bleeding disorders. This chapter reviews the clinical features, diagnosis, and management of haemophilia and von Willebrand’s disease.
Acute leukaemia
Authors: Collins Graham , Bunch Chris
Published: August 2018

Acute leukaemias are rapidly progressive, clonal haematopoietic stem cell disorders resulting in the accumulation of immature blood cell precursors (known as blasts) in the bone marrow. There are two main types, defined by the presence of myeloid lineage or lymphoid markers on the blast cells: acute myeloid leukaemia and acute lymphoblastic leukaemia. This chapter addresses the causes, diagnosis, and management of the acute leukaemias.
Myelodysplasia
Authors: Bunch Chris
Published: August 2018

The myelodysplastic syndromes (or myelodysplasias) comprise a spectrum of disorders characterized by dysplastic or ineffective haemopoiesis that leads to variable anaemia, neutropenia, and thrombocytopenia. There is often a degree of red-cell macrocytosis. The majority are clonal stem cell disorders in which the abnormal clone predominates and expands only slowly over a number of years. Myelodysplasias have a tendency to develop ultimately into acute leukaemia in some patients; for this reason, they are sometimes referred to as ‘preleukaemias’, even though two-thirds of patients will never develop this complication. This chapter addresses the causes, diagnosis, and management of myelodysplastic syndromes.
Lymphoma
Authors: Collins Graham , Bunch Chris
Published: August 2018

Lymphoma is a cancerous disorder characterized by a clonal proliferation of lymphocytes. There are two broad categories: Hodgkin’s lymphoma, and non-Hodgkin’s lymphoma, with Hodgkin’s lymphoma defined by the presence of Reed–Sternberg cells on histological examination of affected tissue. Within the non-Hodgkin’s lymphomas, there are the much more common B-cell lymphomas and the uncommon T-cell lymphomas. Within the B-cell non-Hodgkin lymphomas, there are clinically aggressive (high-grade) forms and much more indolent (low-grade) forms. This chapter addresses the causes, diagnosis, and management of Hodgkin’s lymphoma and non-Hodgkin’s lymphoma.
Multiple myeloma and related conditions
Authors: Collins Graham , Bunch Chris
Published: August 2018

Multiple myeloma is a cancerous disorder of the bone marrow and arises from a clonal proliferation of plasma cells, resulting in end-organ damage (e.g. renal failure, hypercalcaemia, bone disease, and bone marrow failure). When a plasma cell clone is only detected in one site (either bony or soft tissue), it is termed a plasmacytoma. Monoclonal gammopathy of uncertain significance is also a clonal proliferation of plasma cells but, by definition, does not result in end-organ damage. This chapter addresses the diagnosis and management of multiple myeloma.
Myeloproliferative disorders
Authors: Collins Graham , Bunch Chris
Published: August 2018

Myeloproliferative disorders (also called myeloproliferative neoplasms) can be defined as clonal haematopoietic disorders resulting in excess production of one or more blood cell lineage. The four main conditions are primary polycythaemia, which is characterized by excess red-cell production; essential thrombocythaemia, which is characterized by excess platelet production; chronic myeloid leukaemia, which is characterized by excess granulocyte production; and myelofibrosis, which is characterized by excess megakaryocyte proliferation, which results in a reactive fibroblast proliferation causing marrow fibrosis and failure. This chapter addresses the causes, diagnosis, and management of these myeloproliferative disorders.
Functions of the immune system
Authors: Bhole Malini
Published: August 2018

This chapter reviews the functions of the immune system, which has evolved to provide a defence mechanism against microbial challenges, and is divided into two main branches, innate and adaptive. In addition, there are physical and chemical barriers, including skin, mucous membrane, mucous secretions, saliva, and various enzymes, and these contribute to the first line of defence against pathogens. The innate immune system provides the initial quick response for rapid recognition and elimination of pathogens, as opposed to the adaptive immune system, which has evolved to provide a more definitive and finely tuned response. The common central feature of both of these systems is the ability to distinguish between self and non-self. The recognition of non-self or ‘foreign’ pathogens and the subsequent immune response is orchestrated by a whole range of cells and soluble (humoral) factors in both innate and adaptive immune systems.
Human immunodeficiency virus infection
Authors: Bhole Malini , Chaponda Mas , Beeching Nick
Published: August 2018

Since its discovery in the 1980s, infection with the human immunodeficiency virus (HIV) has rapidly spread across the world, especially to large parts of the African continent. By the end of 2013, an estimated 35 million people were living with HIV worldwide. In the UK, this figure was close to 108 000 (a prevalence of 2.8 per 1 000 population aged 15–59 years (1.9 per 1000 women and 3.7 per 1000 men)). Significant progress has been made in diagnosis, and current treatments are life-saving. However, there is still no cure and no vaccine. This chapter addresses the clinical features and management of HIV infection.
Complement deficiencies
Authors: Bhole Malini
Published: August 2018

The complement system comprises a group of heat-labile proteins which form part of the innate immune system. The main physiological functions of the complement system include defence against pyogenic bacterial infections, clearance of immune complexes and products of inflammatory damage, and acting as a bridge between the innate and adaptive immune system. The complement system is regulated by various complement inhibitors (regulatory proteins) that are present in both the classical pathway and the alternate pathway and which regulate and prevent spontaneous activation of the complement system, thereby preventing complement-mediated damage to tissues under normal circumstances. This chapter addresses the clinical features, diagnosis, and management of inherited and acquired deficiencies of complement proteins or inhibitors.
Hypersensitivity diseases
Authors: Bhole Malini
Published: August 2018

Hypersensitivity reactions are aberrant immune responses that are provoked by innocuous extrinsic or self-antigens, are mediated by B-cells or T-cells, and may result in tissue or organ damage. Coombs and Gell classified hypersensitivity reactions into four types, based on the different immune responses: type I, or immediate hypersensitivity; type II, or antibody-mediated (humoral) cytotoxicity; type III, or immune-complex disease; and type IV, or delayed hypersensitivity. This chapter reviews the clinical features, diagnosis, and management of hypersensitivity reactions.
Immunological support
Authors: Misbah Siraj
Published: August 2018

Until the 1980s, the use of immunoglobulin as a therapeutic agent was confined to replacement therapy in patients with primary or secondary antibody deficiency. Its role as an effective immunomodulator was discovered serendipitously, when IV immunoglobulin (IVIg) was shown to consistently increase the platelet count in a child with antibody deficiency and immune thrombocytopenic purpura. Since then, the use of high-dose IVIg as an immunomodulator has become established as an important therapeutic option in many immune-mediated diseases. This chapter reviews the therapeutic indications for immunoglobulin, and its potential adverse effects.
Immunosuppressive therapy and therapeutic monoclonal antibodies
Authors: Misbah Siraj
Published: August 2018

The term immunosuppressive therapy encompasses all forms of treatment that dampens function of the recipient’s immune system, with a view to controlling severe autoimmune, inflammatory, or allergic disease. The predominant targets of these agents are T-lymphocytes with multiple downstream effects, including containment of T-cell activation, inhibition of cytokine production, restriction of clonal expansion, and varying degrees of suppression of B-cell function. This chapter reviews the clinical use of monoclonal antibodies and other immunosuppressive agents, and their mechanisms of action.
Defences against infection
Authors: Lalvani Ajit , Pollock Katrina
Published: August 2018

The immune system is classified into a series of component parts, each specialized to defend the host against infection. Cells of the innate immune system are distributed throughout the body, in the tissues, and in the circulation, to defend against the first signs of danger, combining the acute inflammatory response with the ability to kill and remove invading pathogens. Monocytes, macrophages, and neutrophils phagocytose and kill exogenous and endogenous targets, using both oxygen-dependent and oxygen-independent mechanisms. The adaptive immune system creates a structurally specific and prolonged response, mediated by lymphocytes to clear infection and generate immunological memory. In this chapter, the functions of the innate and adaptive immune system are reviewed, together with the clinical features and investigation of acquired and inherited immune deficiencies.
Diagnosis in suspected infective disease: The history and examination
Authors: Lalvani Ajit , Pollock Katrina , Pareek Manish
Published: August 2018

The clinical presentation of infective disease results from the interaction between the causative organism and the host, modulated by the environment. Therefore, while the critical elements of the diagnostic process for an infective disease follow the same basic tenets as for any clinical assessment—in other words, history, examination, and supportive investigations—this should be tailored when assessing patients who are presenting with an infectious disease, so that appropriate antimicrobial and supportive therapy can be commenced. This chapter reviews the clinical assessment of the patient with suspected infective disease.
Treatment of infection
Authors: Bowler Ian , Scarborough Matthew
Published: August 2018

Infection can be regarded as a struggle between the host and the infecting organism, which may be a bacterium, a virus, a protozoan, or a fungus. The likelihood that an infection will occur will depend on the number of organisms, their virulence, and the quality of the host defences. ‘Treatment’ involves shifting the balance in favour of the host. In this chapter, the principles of treatment of infection are reviewed, with examples drawn from a range of clinical settings.
Viral infection
Authors: Cooke Graham
Published: August 2018

Viral infection includes any clinical illness caused by a pathogenic virus. Acute viral infections are amongst the most common illnesses of humans and range from minor upper respiratory tract infections to viral haemorrhagic fever. The principles in diagnosing acute viral infection are, first, recognize the syndrome, then identify key features that might suggest a specific diagnosis, and, finally, consider laboratory investigations to elucidate the specific causative agent. The host–pathogen response determines different outcomes for specific viral infections. After infection with some viruses (e.g. measles virus, rubella virus) protective immunity develops, there is no latency or chronic carriage, and reinfection is prevented. Another group of viruses, in the presence of inadequate immune response, can cause chronic infection (e.g. hepatitis B and C viruses). This chapter reviews the clinical features, diagnosis, and management of acute viral infections in immunocompetent individuals.
Bacterial infection
Authors: Bentley Tony
Published: August 2018

This chapter describes bacterial infections, including infections caused by staphylococci, streptococci, Neisseria spp., Haemophilus influenzae, bacterial enteric pathogens, and uropathogens.
Spirochaetal infection (non-syphilis)
Authors: Cottle Lucy , Beadsworth Mike
Published: August 2018

Spirochaetes are slender, helical, Gram-negative rods. The group includes Treponema, Leptospira, and Borrelia. This chapter focuses on leptospirosis and Lyme disease. Discussion of the non-venereal treponematoses and relapsing fevers is beyond the scope of this text; they are rarely encountered in the UK.
Syphilis
Authors: Wood Martyn , Bradley Marilyn
Published: August 2018

The term ‘syphilis’ describes the wide-ranging clinical manifestations of infection with the slowly dividing spirochete bacterium Treponema pallidum subsp. pallidum. T. pallidum infection is mainly sexually acquired; it is thought the bacterium enters through microabrasions in the skin or mucosa. Congenital infection via mother-to-child transmission is also recognized. The driving force of the clinical manifestations of all stages of syphilis is an underlying and often multisystem vasculitis. Acquired syphilis can be divided into early and late presentations. In early stage infection, the T. pallidum infection has been acquired within 2 years of the diagnosis. This early stage includes the symptomatic primary and secondary stages of infection, and the asymptomatic early latent stage. Late infection of over 2 years’ standing includes all the manifestations of tertiary syphilis and asymptomatic late latent infection. This chapter discusses syphilis, including its demographics, etiology, natural history, complications, diagnosis, prognosis, and treatment.
Rickettsial infection
Authors: Fletcher Tom , Beeching Nick
Published: August 2018

Rickettsial infections are caused by a variety of obligate intracellular, Gram-negative bacteria from the genera Rickettsia, Orientia, Ehrlichia, and Anaplasma. Rickettsia is further subdivided into the spotted fever group and the typhus group. Bartonella and Coxiella burnetii bacteria are similar to rickettsiae and cause similar diseases. The range of recognized spotted fever group infections is rapidly expanding, complementing long-recognized examples such as Rocky Mountain spotted fever (Rickettsia rickettsii) in the US, and Australian tick typhus (Rickettsia australis), as well as those in southern Europe and Africa. Animals are the predominant reservoir of infection, and transmission to people is usually through ticks, mites, fleas, or lice, during blood-feeding or from scarification of faeces deposited on the skin. This chapter focuses on the two of the most relevant infections encountered in UK practice: African tick typhus, and Q fever.
Fungal infection
Authors: Todd Stacy , Beeching Nick
Published: August 2018

Fungi, comprising yeasts, moulds, and higher fungi, have a worldwide distribution and are uncommon causes of disease in healthy individuals. However, over the last 20 years, invasive fungal disease (IFD) has become an increasing cause of morbidity and mortality. This is probably due to the increasing numbers of patients with underlying host conditions, which predispose to opportunistic IFD (e.g. transplant and anti-tumour necrosis factor immunosuppression, HIV, or chronic lung disease), and to increased recognition of endemic IFD (e.g. histoplasmosis), which cause disease in both immunocompetent and immunocompromised hosts in selected geographic locations. Diagnosis of IFD remains a challenge. Symptoms are often non-specific, and a definite diagnosis requires invasive sampling with appropriate laboratory testing of these samples. Non-invasive tests are being developed, but their positive and negative predictive values still need validation. Diagnostic criteria (‘proven, probable, and possible’) established primarily for use in research and clinical trials can also prove useful in clinical environments. However, the most important step in identifying patients with IFD is to consider the diagnosis in those at risk. This chapter will focus on the commonest causes of IFD (Candida spp., Aspergillus spp., Cryptococcus spp., and histoplasmosis).
Protozoal infection: Gut organisms
Authors: Natarajan Pavithra , Beeching Nick
Published: August 2018

Protozoa are single-celled (unicellular) eukaryotic organisms. There are many protozoa causing parasitic infection in humans. This chapter will concentrate on the three that most commonly causes gastrointestinal disease worldwide and have the biggest impact in the UK: Giardia lamblia, Cryptosporidium spp., and Entamoeba histolytica. These three infections are of great significance worldwide, but are less common in Western settings. In the UK, they tend to be seen in more commonly in travellers returning from endemic countries, migrant populations, men who have sex with men, and the immunocompromised. The clinical features of all three infections vary from asymptomatic small- or large-bowel carriage with passage of cysts to infect others, to more serious manifestations.
Worm infection (including hydatid disease)
Authors: Thomas Sherine , Beeching Nick
Published: August 2018

The main clue to the diagnosis of all helminth infections is peripheral blood eosinophilia, the presence of which should always prompt taking a full travel history. Filarial infections are unusual in the UK. The most common imported filariasis is Loa loa infection from West Africa, characterized by transient ‘Calabar swellings’, particularly on the face, arms, and upper limbs.
Prion disease
Authors: Knight Richard
Published: August 2018

Prion diseases (also known as transmissible spongiform encephalopathies (TSEs)) affect animals and humans, although only the human diseases will be discussed in this chapter. Despite TSEs having somewhat disparate causes and effects, there are unifying features: TSEs are brain diseases with neurodegenerative pathology, which is typically associated with spongiform change, and, most characteristically, there is tissue deposition of an abnormal structural form of the prion protein. Some of the TSEs are naturally acquired infections and, while others are not, they are potentially transmissible in certain circumstances.
Sexually transmitted disease (gonorrhoea)
Authors: Wood Martyn , Bradley Marilyn
Published: August 2018

Gonorrhoea is the term used to describe the clinical manifestations of infection with the bacterium Neisseria gonorrhoeae. Neisseria gonorrhoeae is a Gram-negative diplococcus which usually infects the columnar epithelium of mucous membranes, including the lower male and female genital tracts, the rectum, the pharynx, and the conjunctivae. Transmission is by direct exposure of a mucous membrane to infected secretions, classically via sexual contact. Those who are most at risk of infection include younger age groups (15–29 years), inner-city residents, ethnic minority groups, and men who have sex with men. This chapter discusses the etiology, symptoms, demographics, natural history, complications, demographics, diagnosis, prognosis, and treatment of gonorrhoea.
Presentations in suspected cancer
Authors: Cutter David , Scott-Brown Martin
Published: August 2018

Malignant neoplastic disease includes a vast range of conditions that can originate from and can directly or indirectly affect virtually every organ system of the body. As a consequence of this, the presentation of malignancy can be similarly varied. While a diagnosis of malignancy may be clinically obvious in some cases, in others diagnosis and investigation may be delayed due to non-specific presentations and the attribution of symptoms to non-malignant conditions. Early diagnosis of cancer has an impact on the success of subsequent treatment and overall survival. It is therefore vital to maintain an appropriate level of clinical suspicion when deciding whether and how much to investigate patients with symptoms that could be secondary to an underlying malignancy.