JANET CUSHNAGHAN AND JACKIE McDOWELL
Learning objectives
After reading this chapter you should be able to:
• Discuss the anatomy and physiology of the musculoskeletal system in health and illness.
• Describe the process of inflammation and the immune response.
• Develop an understanding of the rheumatic diseases where drug therapy is required.
• Discuss the effects of rheumatic disease on physical, psychological and social well-being.
The primary objective of this book is to provide the nurse with the knowledge and subsequent understanding of the role drug therapy plays in the management of rheumatological conditions. It is essential therefore that nurses must have a good knowledge and understanding of rheumatological conditions themselves.
Rheumatology is the branch of medicine dealing with disorders of the joints, muscles, tendons and ligaments. Arthritis and the rheumatic diseases in general constitute the major cause of chronic disability in the United Kingdom. It is estimated that musculoskeletal diseases account for one third of the physical disability experienced in the community in the United Kingdom and have an economic cost that exceeds that of heart disease and cancer.
The terms arthritis and rheumatism or rheumatic disease encompass a host of conditions causing much pain and suffering to those affected. The burden of these diseases is felt not only by the sufferer and their family, but also by the community, in terms of the cost of healthcare and the loss of working days. Because of the diversity of rheumatic conditions it is helpful to classify them into groups. This may be undertaken in different ways incorporating:
• clinical and laboratory features;
• disease mechanisms - for example, autoimmunity;
• anatomic structures involved;
• genetic factors;
• involved organ systems and specific abnormalities or deficiencies.
Table 1.1 Classification of rheumatic diseases.
Inflammatory arthritis
Rheumatoid arthritis
Juvenile arthritis
Polymyalgia rheumatica
associated with spondylitis
Ankylosing spondylitis
Reiter’s syndrome
Psoriatic arthritis
associated with infectious agents
Septic arthritis
Reactive arthritis
associated with crystals
Gout
Pseudogout
Non inflammatory
Osteoarthritis
Fibromyalgia
Connective tissue disorders
Systemic lupus erythematosus
Scleroderma
Polymyositis
__________
Classification is hampered by the absence of firm aetiological evidence for most diseases but for this chapter we intend to use a simplified classification, which will correspond to the philosophy of drug therapy which is the main purpose of this text. Table 1.1 classifies the rheumatic diseases according to the presence or absence of inflammation and further subclassifies inflammatory arthritis according to associations that may be present.
Symptoms of rheumatic disease can be determined by a clinical history taking and thorough physical examination. Laboratory and radiographic investigations can aid diagnosis and eliminate certain features but nothing can replace the clinician’s clinical skills and pattern recognition. Patients with a rheumatological condition often experience symptoms of pain, swelling, stiffness and loss of function. These symptoms give rise to impairments, which in turn may produce handicap or disability, depending on the interaction of environmental, resource and psychological factors.
One of the primary objectives of the clinical history is to ascertain a greater understanding of the pain:
• Is it inflammatory?
• What is the origin of its presentation?
• What are the aggravating factors?
• What is its temporal pattern?
• Are there any constitutional symptoms suggesting a systemic illness, such as fever or weight loss?
PAIN
Arthralgia implies pain originating from or around a joint, but not necessarily from within the joint itself. Periarticular structures may be responsible for the pain or it may be referred from somewhere away from the joint. Pain originating from joint structures should be improved by resting the joint and aggravated by stretching the joint or weight bearing.
STIFFNESS
Stiffness after prolonged immobility suggests inflammatory joint disease or synovitis. Stiffness alone is a non-specific symptom and can be present in other diseases such as Parkinsonism. It is also present in older individuals. Clinically significant stiffness lasts more than 30 minutes, and in inflammatory disease the duration of stiffness is proportional to the severity of inflammation.
SWELLING
Swelling may be due to synovitis, cellulitis or oedema and it is important to distinguish between them. Joint swelling may be due to soft tissue swelling or synovitis or it may be due to bony swelling indicating osteoarthritis (OA).
JOINT INVOLVEMENT
The pattern of joint involvement, including its symmetry, is helpful in making a diagnosis, although it should be noted that there is considerable overlap between the major causes of inflammatory polyarthritis.
FUNCTION
Loss of function is an important consequence to the patient and should be assessed in work, leisure and home activities. Functional ability depends on need, motivation and environmental factors. The assessment of function will be discussed later in this chapter.
Epidemiology is the study of the incidence, distribution and determinants of disease in populations in order to identify causes and ultimately lead to prevention (Table 1.2). In studying the epidemiology of rheumatic disease it is important that diagnostic criteria are used to ensure standardization of disease definition and allow comparisons between populations. Criteria that are designed for research purposes or for entry into clinical trials may not be suitable for routine clinical practice. The prevalence estimates for selected rheumatological disorders are shown in Table 1.3.
Mortality from musculoskeletal disorders is low. The major impact in the population is in terms of morbidity and disability. OA is the most common type of arthritis and its frequency increases with age. Back complaints represent a quarter to a third of all musculoskeletal morbidity.
Table 1.2 Epidemiological definitions.
|
Incidence |
The number of new cases of disease per unit time (for example, cases per annum) |
|
Prevalence |
Total number of cases of the disease at a given time point in a defined population |
|
Morbidity |
Number of cases with a defined outcome of the disease |
|
Mortality |
Number of cases dying from the disease per unit time (for example, deaths per annum) |
Table 1.3 Prevalence estimates for selected rheumatological disorders.
Before learning about the pathology of rheumatic diseases it is important to have an understanding of the anatomy and physiology of the musculoskeletal system in health. The musculoskeletal system serves several purposes:
• it provides stable support;
• it facilitates movement
• it protects vital organs
• it allows for growth and renewal over the lifetime of the individual (Simkin, 1994).
Components of the musculoskeletal system are muscle, bone, tendons, ligaments, cartilage and synovial tissue. All musculoskeletal tissues are supplied by the circulation and guided and protected by their innervation.
MUSCLE
Skeletal or striated muscle provides the energy or driving force for musculoskeletal activity. Chemical energy derived from foodstuffs is ultimately converted to the mechanical energy required to do work. Individual striated fibres are bundled in perimysial tissue that transmits the force of muscle contraction through tendons to attachments on bone. Each fibre can only work in the direction of its long axis and it is only the variety of arrangements within muscles and the cooperation between muscles that allow the full range of possible human activities.
BONE
No muscle contraction would be effective unless it could produce directed motion through a skeletal lever. Each effective motion comes about as muscles act on bones to move the limbs, head or torso. In some cases the mechanical advantage of the muscles is poor and they exert substantial transarticular compressive forces in order to generate the desired movement. The bones of the skeleton have evolved to withstand and distribute these forces. Bone is characterized by the deposition of hydroxyapatite crystals in a well organized, collagenous matrix. There are two types of mature bone: compact and trabecular.
Compact bone is predominant and found in the shafts of long bones. The shafts of long bones contain little or no internal osseous structure, but have a marrow cavity filled with fat and loose interstitial tissue. The bone is covered by a sensitive periosteum that is capable of new bone formation.
Trabecular bone refers to the cross-braced architecture found beneath articular surfaces and in the vertebral bodies. All trabeculae undergo remodelling through ongoing processes of osteoclastic resorption and osteoblastic formation of bone.
CARTILAGE
The contact surfaces of bones are covered by a cushion of cartilage. For the most part this is hyaline articular cartilage, which is principally comprised of water. Its structure is of proteoglycan aggregates restrained within a framework of type II collagen fibres. These aggregates are made up of keratan sulfate and chondroitin sulfate. Cartilage is remarkably firm and resilient. It undergoes continuous turnover, the principal players in this being the chondrocytes that are individually active but are relatively sparse in numbers so the overall metabolic activity of cartilage is relatively low. Normal hyaline cartilage lacks blood vessels and nerves and relies on adjacent structures for nutrition, namely the synovial microvessels.
The synovial fluid is the vehicle carrying nutrients to the chondrocytes and returning waste products to the blood stream. The absence of nerves in articular cartilage means that damage to this structure alone cannot be painful but in conjunction with the involvement of adjacent soft tissues or subjacent bone it will cause pain. A second type of cartilage is fibrocartilage, found at sites subject to shearing forces or under tensile stress. Examples include the moon-shaped cartilages called menisci over each tibial plateau and the principal load-bearing region in the roof of the acetabulum. This type of cartilage is more notable for its fibrous component (mainly type I collagen) than for its proteoglycan composition.
SYNOVIUM
This is a living lining and covers all intra-articular surfaces other than the articulating areas of cartilage. It is a thin structure, in health, with a normal depth of 25-35µm. It is comprised of a well-organized matrix of numerous microfibrils and abundant proteoglycan aggregates. Within this matrix lie the synovial cells. The structure has protective and synthetic capabilities.
LIGAMENTS AND TENDONS
Ligaments are strong bundles of parallel type I collagen fibres that serve as ‘check-reins’ to prevent inappropriate movements. Each hinge joint, for example, is bordered by collateral ligaments to limit movements to flexion and extension. Every ligament runs from bone to bone. Tendons act as active drivers of joint motion as opposed to passive restrainers (ligaments). Tendons and ligaments insert into bone at anatomic sites known as entheses.
TENDON SHEATHS AND BURSAE
Tendons connect muscle bodies to, sometimes distant, insertion sites, and therefore often run through sheaths to avoid adherence to other structures. Similarly, points of potential friction, such as those between ligaments, bony prominences and overlying skin are often protected by lubricating bursae. These flimsy structures are flattened sacks lined by a tissue that is histologically indistinguishable from synovium. They contain a fluid that appears synovial. It is no surprise therefore that tendon sheaths and bursae are the targets of the same inflammatory diseases that affect synovial joints.
SYNOVIAL JOINTS
These are the commonest type of articulation in the body. They are actively driven by muscles and tendons, stabilized by ligaments, cushioned by hyaline cartilage and are both nourished and lubricated by synovial tissue. A film of synovial fluid lubricates the bearing surfaces and the adjacent interfaces of synovium on cartilage and synovium on synovium.
PHYSIOLOGY
Physiology is the study of how living things work. The principal function of almost all joints is movement. Microscopic examination of synovium and cartilage shows them to be composed of metabolically active cells. This implies that they have the same nutritional requirements as other tissues, produce similar waste products and respond to hormonal and other metabolic stimuli in ways analogous to other tissues. Joints age as do other tissues, with subsequent effects on function. Aspects of physiology include circulation, lymphatics, pressure, diffusion, temperature and innervation. Changes in one ‘system’ can have clinically important effects on another and all are uniquely modified by physical movement.
CIRCULATION
Joints require a blood supply to ensure the health of the cartilage, which lacks blood vessels of its own. The nearest available blood vessels are the capillaries of the synovium. Transport of nutrients is dependent on diffusion. The synovium and synovial space have a major role in facilitating metabolic exchange and in maintaining a normal joint space environment. Large blood vessels of the limbs pass the articular regions, and feeder vessels enter and leave the joint capsule at positions that protect them from mechanical embarrassment during movement.
LYMPHATICS
There is a typical lymphatic system in the synovium but not in the cartilage. Synovial lymphatics carry excess fluid, high molecular weight solutes and protein, tiny particulates and some cells out of the joint. This transfer is powered by normal movement of the joint.
INTRA-ARTICULAR PRESSURE
Normal intra-articular pressure in a resting joint is subatmospheric. In conditions where there is an abnormal volume of fluid in the joint the pressure will rise nonlinearly. The resulting pressure volume curve defines the compliance of the joint space and its surrounding connective tissue.
MOTION
Motion is the function of diarthrodial joints, but motion itself affects the physiology and health of the joint. If a joint is immobilized cartilage thins and loses its mechanical properties. The application and release of weight-bearing forces play a part in joint lubrication and in the diffusion of substances in and out of cartilage. Joint movement is also required to maintain health by:
• Maintaining normal strength and coordination of muscles
• Preserving bone mass
• Maintaining desired weight
• Preserving normal range of joint motion
• Increasing blood flow to the synovial tissues
• Permitting the lymphatic system to clear the joint of particulates and excess fluid.
INNERVATION
There are no nerves in articular hyaline cartilage. Most of the synovium is insensitive but there are small and isolated areas that are painful when stimulated mechanically. Small diameter nerve fibres are present within the confines of the capsule. The capsule, intra-articular fat pads, ligaments, periosteum, muscles and adjacent bone have abundant innervation. The major function of joint innervation appears to be proprioception - the perception of joint position, and the direction and velocity of movement.
TEMPERATURE
The normal intra-articular temperature of peripheral joints is far less than 37°C. Temperature is largely a function of blood flow. Joint movement increases joint temperature.
The inflammatory arthritides are characterized by inflammation and damage to the joints and their surrounding structures, mediated by the immune system. It is believed that trigger factors (for example, infection) initiate a pathological process in a susceptible individual because of genetic factors. Only a small proportion of susceptible individuals develop disease. Understanding the aetiology of rheumatic diseases requires knowledge of immunopathogenetic mechanisms, determinants of susceptibility and the nature of putative trigger factors.
IMMUNOPATHOGENETIC MECHANISMS
There are four types of immune mechanisms:
• Type I Allergic
Allergic reactions are mediated by IgE and provoke vasomotor and bron- chospastic changes leading to asthma, urticaria or anaphylaxis.
• Type II Cytotoxic
Cytotoxic reactions involve cellular injury mediated by antibodies (IgG or IgM) and the activation of the complement system.
• Type III Immune complex
Immune complexes from the circulation deposit in the tissue where they cause activation of the complement system and the generation of proinflammatory mediators.
• Type IV Cell-mediated
Injury may be mediated by T cells rather than antibodies. T cells may cause tissue injury by direct killing of cells or the elaboration of cytokines which disturb cell growth or function.
Rheumatic diseases are usually the result of type II-IV reactions, although more than one mechanism may operate concomitantly in patients.
In the initiation of the immune response T cells recognize antigen via receptors (T cell receptors). After activation by antigen, T cells can proliferate to serve as helper cells for B-cell antibody production or the generation of cytotoxic T cells. In addition, activated T cells can produce cytokines leading to functional changes, such as synovial cell proliferation in rheumatoid arthritis (Figure 1.1).
Figure 1.1 The inflammatory cascade.
SUSCEPTIBILITY
Several factors may influence disease susceptibility (Table 1.4).
• Hormones of the neuroendocrine system can modulate immune responses, an action exploited in the use of corticosteroids as anti-inflammatory and immunosuppressive agents.
• Many rheumatic diseases show an unequal representation of the sexes, with women displaying a generally higher prevalence of inflammatory disease as well as a more serious outcome (Pisetsky, 1994).
• Environmental factors may affect levels of immune cell function and together with inherited factors promote disease pathogenesis.
Table 1.4 Factors influencing disease susceptibility.
|
Genetic |
Environment |
|
MHC |
Stress |
|
T-cell receptor |
Diet |
|
Immunoglobulins |
Drugs |
|
Complement system components Cytokines Stress responses Gender |
Infection |
• Emotional and physical stress can perturb neuroendocrine function resulting in changes in immune cell function. Rheumatic diseases have long been considered to have a psychosomatic component, indicative of the belief that psychological factors influence disease onset or course (Levine, Goetzl and Basbaum, 1987).
• Diet may have a role in influencing disease susceptibility; in the extreme, malnutrition and serious vitamin or mineral deficiency can impair immune function. The strong influence of environmental factors on disease susceptibility can be observed by comparing disease prevalence in populations that have migrated (Solomon, Robin and Valkenburg, 1975).
• Socioeconomic group and educational level also influence the susceptibility or severity of rheumatic disease, although both are likely markers for other health- related factors which include diet, hygiene, occupation, lifestyle, exposure to infection, use of tobacco and alcohol and access to medical care.
SYNOVITIS
The synovium is the soft connective tissue lining the enclosed spaces of synovial joints, tendon sheaths and bursae. These spaces all contain a small amount of fluid rich in hyaluronic acid (synovial fluid). The functions of the synovium are:
• maintenance of an intact nonadherent tissue surface;
• control of volume and composition of synovial fluid;
• lubrication of cartilage and nutrition of chondrocytes within joints.
Inflammatory arthritides are characterized by synovitis, that is inflammation of the synovium. Acute inflammation begins when an extravascular inflammatory stimulus provokes capillary dilatation, the accumulation of plasma and fluid, and recruits circulating effector cells to the site (Figure 1.1).
There is emerging evidence that the ultimate outcome of the inflammatory response with resulting injury can be ascribed to a complex network involving products of both neutrophils and macrophages (Varani, Mulligan and Ward, 1994).
Inflamed synovium appears dramatically increased in size because of oedema, multiple redundant folds and villae. It takes on a red hue because of a dramatic increase in blood vessels. If the condition becomes chronic, synovial lining hyperplasia becomes prominent. The sublining of the synovium also undergoes dramatic alterations in the degree and content of the cellular infiltrate. The most prominent change is an exuberant infiltration with mononuclear cells, including T cells, B cells, macrophages and plasma cells. Multinucleate giant cells can be seen in granuloma-like lesions in the synovium.
RHEUMATOID ARTHRITIS
Rheumatoid arthritis (RA) is the commonest form of chronic inflammatory joint disease and a common cause of disability. The consensus view, backed up by clinical evidence, is that RA should be treated as early as possible to improve long-term outcome (Maddison and Huey, 2006).
RA is two to three times more common in women compared to men. The current annual incidence is reported as 36/100 000 in women and 14/100 000 in men (Symmons, 2005). The prevalence is 0.8% of the adult population. Symmons (2005) reports that the incidence, prevalence and mortality of RA have fallen in women in the last 50 years. Excess mortality is predominantly due to cardiovascular disease (Symmons, 2005). Sex differences decrease with age as the prevalence of RA appears to increase with age; by the age of 69 years the sex distribution is equal (Dieppe et al., 1985). The peak age of onset varies but is common in the fourth and fifth decades of life. RA imposes a substantial economic burden on both patients and society. This is usually quantified in terms of both direct costs such as treatment and hospitalization and indirect costs resulting from loss of resources due to productivity loss (Cooper, 2000).
RA is a chronic, systemic, inflammatory, autoimmune disease of unknown aetiology. It is hypothesized that viruses, bacterial infection or psychological trauma may be initiating factors. There is a threefold increased risk for first degree relatives of those with RA developing the disease themselves. This risk is approximately sixfold higher in those possessing ‘at risk’ human leucocyte antigen-DRB1 genotypes (MacGregor and Spector, 2004). Up to 70% of people with rheumatoid arthritis test positive for human leucocyte factor (HLA) DR4 antigen (Le Gallez, 1995). The detection of anticyclic citrullinated peptide (anti-CCP) antibodies in patients has recently been shown to have great specificity for RA (Maddison and Huey, 2006). Anti-CCP antibodies appear early in RA and can predate the clinical onset of disease by years (Rantapaa-Dahlqvist et al., 2003).
Ryan (1997) explains that ‘inflammation is usually a self-limiting process - the response of the body to an offending antigen. But for reasons not fully understood, in conditions such as RA the inflammatory response becomes a continual process and can lead to destruction of much of the surrounding tissue’.
Ryan (1997) goes on to to describe ‘whereas the complexes created by the immune system are usually ingested by the reticuloendothelial system, and deactivated once their mission is completed, in RA this does not happen. Instead, the joint lining or synovial lining proliferates, which results in pannus formation. Cartilage, and tissues supporting the joints, are destroyed by enzymes released as a consequence of the inflammatory response. Bone is then also destroyed by the increasing synovial membrane. As the joint space constricts, articular surfaces are reduced and joint movement is restricted.’
It has been suggested that sex hormones may also have a role in the cause of RA (Maini and Feldman, 1993). Whilst their role is not entirely clear, the evidence points to the predominance of RA in females and the increased onset of the disease during the reproductive years and at the menopause (Le Gallez, 1995). Hormones have an important influence in women with RA. In approximately 70% of women the manifestations of RA subside during pregnancy and recur in the early postpartum period (Nicholas and Panayi, 1988).
Areas Affected by RA
RA is characterized by symmetrical small joint polyarthritis involving the hands and feet, particularly the metacarpophalangeal (MCP) and the proximal interphalangeal (PIP) joints in the hands and the metatarsophalangeal (MTP) joints in the feet. RA causes inflammation of the synovium, which lines both the joints and tendon sheaths of the body. In RA as the disease progresses other joints may also be affected, for example the wrists, elbows, shoulders, cervical spine, ribs, jaw (temporomandibular joints), knees and ankles (Figure 1.2 ).
The course of the disease is variable with exacerbations and remissions over a period of time, and in the majority of patients progressive joint erosions and deformity occurs. Around 30% of people will recover completely within a few years while 5% will deteriorate until they have a significant disability (Ryan, 1997).
The 1987 American Rheumatism Association Revised Criteria for the classification of RA (Table 1.5) currently presents the best definition of the disease in the form of a clinical description (Arnett et al., 1988). However, these criteria were not designed for the diagnosis of early RA and are fairly insensitive in patients with disease duration of less than 12 months (Huizinga et al., 2002).
In practice, therefore, recognition of early RA is usually based on a combination of clinical features and appropriate investigations as well as on the exclusion of other disorders that may mimic RA (Pipitone and Choy, 2003).
Figure 1.2 Joints affected by rheumatoid arthritis.
Rheumatoid Factor
About 70-80% of patients with RA have circulating rheumatoid factor (an IgM/IgG complex of two immunoglobulins) in the blood (Bird, Le Gallez and Hill, 1985; Ferrari, Cash and Maddison, 1996). These patients are classified as sero-positive; those without a circulating rheumatoid factor are classified as sero-negative.
Table 1.5 1987 American Rheumatism Association Revised Criteria for the classification of RA.
Morning stiffness of at least one hour* * *
Arthritis in at least three joint areas* with swelling or fluid*
Arthritis of hand joints (at least one area swollen in a wrist, MCP, or PIP joint)*
Symmetric joint swelling and involvement*
Subcutaneous nodules
Radiographic changes typical of RA
Positive rheumatoid factor
__________
Notes
* Specified criteria that must be present for at least six weeks
*Right or left proximal interphalangeal (PIP), metacarpophalangeal (MCP), wrist, elbow, knee, ankle and metatarsophalangeal (MTP) joint
However, it is important to remember that in 5-15% of healthy subjects rheumatoid factor can be detected. Many patients who test positive for rheumatoid factor (RF) do not have RA. Other diseases commonly associated with rheumatoid factor are:
• Sjogren’s syndrome
• systemic lupus erythematosus
• systemic sclerosis
• subacute bacterial endocarditis
• sarcoidosis
• chronic liver disease
• polymyositis
• acute viral infections
• parasitic infections
• tuberculosis
• syphilis (Ferrari, Cash and Maddison, 1996).
Rheumatoid factor can be identified using the sheep cell agglutination test (SCAT), in which serum from a patient containing rheumatoid factor, heavy with immunoglobulin complexes, causes the agglutination of sheep red blood cells that have been previously coated with immunoglobulin (IgG). This test is performed at serial dilutions of the patient’s serum. If a large amount of rheumatoid factor is present, flocculation of the sheep cells is likely to be observed with dilutions of the patient’s serum as great as 1 in 256. By contrast, if only a small amount of rheumatoid factor is present flocculation will only occur with undiluted serum, perhaps 1 in 8 or 1 in 16 (Bird, Le Gallez and Hill, 1985). A positive SCAT titre of 1 in 80 is normally recognized as significant.
Pain and Stiffness
Widespread symmetrical joint pain and swelling affecting the small peripheral joints are the commonest presenting symptoms. The immediate result of inflammation of the synovial membrane, known as synovitis, is a painful, stiff, hot and swollen joint. During a ‘flare’ or acute attack of the disease many joints may be involved at the same time. Pain is often the first reported physical symptom, and may vary in intensity and duration from one day to the next. The patient reports early morning stiffness (EMS) of variable duration and tenderness in the affected joints, which because they are swollen and painful are difficult to move, limiting the range of movement of the joints affected. EMS can last from a few minutes to several hours with the duration of EMS being a guide to the level of disease activity. Muscle weakness and spasm are common in the early stages and can be followed by marked muscular atrophy.
Extra-Articular Manifestations
It is important to remember that the disease will have an impact on the patient as a whole by affecting their overall physical condition, psychological well-being and social life. The onset of RA is usually insidious and affects the patient’s body as a whole; commonly seen symptoms are general fatigue, fever, depression, weight loss and weakness. Patients may describe extreme mental and physical tiredness that is not relieved by sleep (this is caused by the inflammatory component of RA). Weight loss often occurs early in the disease, but with good disease control weight should be regained and remain stable thereafter. A normochromic or mildly hypochromic anaemia is often found in active RA. The cause seems to be a combination of poor iron intake and absorption, depression of bone marrow function, poor iron utilization and mild haemolysis (Le Gallez, 1995). Iron deficiency anaemia may also be present. People with RA can have any type (or combination) of anaemia; but of those with anaemia, 77% will have anaemia of chronic disorders, and about 23% will have iron deficiency anaemia (Wilson et al., 2004). Tenosynovitis and bursitis commonly accompany the disease.
Many extra-articular features of RA can occur as listed in Table 1.6. The presence of rheumatoid nodules is often associated with a positive rheumatoid factor. They appear principally on extensor surfaces or areas subjected to pressure, including the elbows, finger joints, ischial and sacral prominences, occipital scalp and Achilles tendon. They are not usually painful. Care should be taken to avoid trauma so that nodules do not become ulcerated acting as a possible source of infection. They are composed mainly of fibrinoid material (degenerative tissue cells) and granulation tissue (Judd, 1997). Subcutaneous nodules may regress during treatment with disease-modifying anti-rheumatic drugs (DMARDs), usually as RA improves (Matteson, Cohen and Conn, 1994). Methotrexate treatment may result in an increase in nodules, particularly over finger tendons, despite improvement in the overall disease activity (Segal et al., 1988). In general, higher concentrations of rheumatoid factor, together with the presence of nodules and radiological evidence of erosions, are associated with a poorer prognosis.
Table 1.6 Extra-articular manifestations of RA.
|
Skin |
Palmar erythema Subcutaneous nodules Vasculitis Ulceration |
|
Lung |
Pleurisy, pleural effusions Pneumonitis Lung nodules Bronchiolitis obliterans Fibrosis |
|
Heart |
Pericarditis, pericardial effusions Valvular disease Myocarditis |
|
Neuromuscular |
Nerve entrapment Cervical cord compression Muscle wasting Mononeuritis multiplex Diffuse peripheral neuropathy |
|
Mouth |
Sicca symptoms |
|
Eye |
Episcleritis Scleritis, scleromalacia perforans Melting cornea syndrome |
|
Haematologic |
Normocytic, normochromic anaemia Felty’s syndrome Amyloidosis Thrombocytosis |
|
Miscellaneous |
Sjogren’s syndrome Pulmonary infections, septic arthritis Osteoporosis Tenosynovitis Bursitis Reactive lymphadenopathy Splenomegaly |
Progression
If RA is allowed to continue uncontrolled, inflammation will eventually lead to erosion of the joint, including damage to the tendons and ligaments surrounding the joint. As the disease progresses this damage will cause the joint to become
unstable, with corresponding deviation resulting in deformity (Le Gallez, 1995). Such deformities may include:
• radial deviation at the wrist;
• ulnar deviation at the MCP joints;
• palmar subluxation of proximal phalanges;
• swan-neck deformity (hyperextension of PIP with flexion of DIP);
• boutonniere deformity (flexion of PIP, extension of DIP);
• hyperextension of first IP joint with flexion of first MCP (causing loss of thumb mobility and pinch);
• metatarsal prolapse;
• arch collapse;
• hallux valgus;
• atlantoaxial subluxation (Ferrari, Cash and Maddison, 1996).
Judd (1997) describes how instability and irritation of the joint may cause muscle contraction with resulting flexion or extension deformity or subluxation of the joint. Fibrous scar tissue and adhesions develop between the opposing joint surfaces, leading to fibrous ankylosis of the joint. The exposed, roughened ends of bone tissue may eventually proliferate bone cells into the joint cavity, resulting in calcification and bony ankylosis.
Erosions
Erosions can occur in any of the joints involved in RA; they may take many months or even years to develop. Initially, the erosions develop marginally, at the point where the synovium joins the bone, as this is the seat of inflammation (Le Gallez, 1995). Erosions normally occur in the MTP heads of the feet before they are seen in the MCP joints of the hands.
Several conditions that commonly occur with RA adversely affect outcomes and may lead to disability and death. The most important co-morbidities are cardiovascular disease, infection, malignancy, gastrointestinal (GI) disease and osteoporosis. RA is associated with a marked increase in morbidity and mortality and all patients with RA should be screened annually for cardiovascular risk factors (Symmons and Bruce, 2006).
A number of guidelines and standards of care are available to guide practice, and assist and support clinicians in the provision of high quality care and management of RA patients (ARMA, 2004; BSR, 2004; NICE, 2002; SIGN, 2000).
At the present time there is no cure for RA. The management goals include:
• control of the inflammatory process;
• relief of symptoms;
• prevention of joint deformity;
• empowerment of the patient by assisting them to adjust to this chronic condition.
Drug treatment remains one of the major interventions in the relief of symptoms and the prevention of progress. Until the cause of RA becomes known it cannot be precisely defined. Gordon and Hastings (1994) state: ‘it may be one disease with more than one cause or more than one disease with a single cause.’
JUVENILE IDIOPATHIC ARTHRITIS
Inflammatory joint disease is common not only in adults but in children also. Juvenile idiopathic arthritis (JIA) is the new term unifying the existing classifications for inflammatory arthritis in children — encompassing juvenile chronic arthritis and juvenile rheumatoid arthritis (Petty et al., 1998).
Juvenile idiopathic arthritis (previously known as juvenile chronic arthritis), and known as juvenile rheumatoid arthritis in the United States, is the most common rheumatic disease of childhood and is often an important cause of disability and blindness (White, 1994). In the United Kingdom the prevalence of JIA is approximately 10 per 100 000 of population (Symmons et al., 1996). The term is used to describe arthritis affecting one or more joints, which occurs in someone under 16 and lasts for more than three months when other forms of arthritis and connective tissue disorders have been excluded (Leach, 1997). It is not a single disease but rather a heterogeneous group of diseases. In patients with a diagnosis of JIA regular assessment by an ophthalmologist and rheumatologist is generally recommended (Ferrari, Cash and Maddison, 1996).
Juvenile arthritis was first described by George Frederick Still, a children’s specialist, in 1896. The term ‘Still’s disease’ was used for many years in relation to childhood arthritis. The term ‘Still’s’ tends to be used today only to describe the rash associated with systemic onset arthritis (Leach, 1997).
In very young children who cannot express their pain the first signs may be limping, guarding of joints or even an outright refusal to move (Leach, 1997).
The goals of therapy in juvenile arthritis are pain relief and preservation of joint function, so as to maintain normal growth and psychosocial development (Cassidy, 1994).
The International League of Associations for Rheumatology (ILAR) (Foeld- vari and Bidde, 2000) unified the classification of JIA, with clinical criteria as follows:
• age at onset <16;
• minimum duration of arthritis six weeks.
Subtypes:
• Systemic arthritis: arthritis with/preceded by daily fever for at least two weeks and one/more of evanescent non-fixed erythrematous rash, generalized lymphadenopathy, hepato/splenomegaly and serositis.
• Oligoarthritis: arthritis of one to four joints during the first six months. persistent: affects no more than four joints throughout the disease course; extended: affects more than four joints after the first six months.
• Polyarthritis (rheumatoid factor-negative): affects five or more joints in the first six months of the disease. Tests for rheumatoid factor are negative.
• Polyarthritis (rheumatoid factor-positive): affects five or more joints in the first six months of disease. Tests for rheumatoid factor are positive on two occasions at least two months apart.
• Enthesitis-related arthritis: arthritis and enthesitis, or arthritis or enthesitis with at least two of: sacroiliac tenderness and/or inflammatory spinal pain; HLA B27- positive; family history in a first or second degree relative of medically confirmed HLA B27-associated disease.
• Psoriatic arthritis: arthritis and psoriasis, or arthritis and at least two of dactylitis, nail abnormalities, family history of psoriasis in at least one first degree relative.
• Other: arthritis of unknown cause persisting for at least six weeks that either does not fulfil criteria for any categories or fulfils criteria for more than one category.
Further details about the subtypes are as follows:
Oligoarticular onset (55-75%) arthritis affects fewer than five joints. The knee and ankle are the most commonly affected joints, but the small joints of the hand or the elbow can also be involved (Ansell, 1977). The majority present before the age of five years, approximately twice as many girls are affected than boys (Leach, 1997). Antinuclear antibodies (ANAs) are present in 40-75% of children and are associated with chronic anterior uveitis. Routine eye examination is essential (White, 1994). These children are usually RF-negative (Ferrari, Cash and Maddison, 1996). A subset of children, usually male, are HLA-B27-positive and often develop spondylitis (Leach, 1997).
Polyarticular onset (15-25%): arthritis affects more than five joints. Onset is usually gradual, affecting knees, ankles, wrists, elbows. The smaller joints of the hands and feet may be affected. Most cases are RF-negative, those cases that are RF-positive are similar to adult onset RA and may be titled juvenile-onset adult RA (Leach, 1997). This type is often ANA-positive.
In systemic arthritis (Still’s disease, 10-20%) presentation is with systemic features, which may precede the arthritis. These may include:
• remitting fever (more than 39°C);
• adenopathy;
• hepatosplenomegaly;
• pericarditis;
• leucocytosis;
• anaemia (Leach, 1997).
There may be a rash, which coincides with the peaks of fever. The arthritis usually involves multiple joints. Negative RF and ANA are typical (Ferrari, Cash and Maddison, 1996).
Children with arthritis require a multidisciplinary team approach (Hackett et al., 1996). The primary aim is the preservation of joint function and vision. The importance of JIA lies not in its frequency, but in the potential severity of its effects on children, and the misconceptions that surround its treatment (Southwood, 1993). Southwood states that despite their limitations, children with JIA should be able to continue their education in the mainstream schooling system, approximately one third of children will still have uncontrolled arthritis or physical disabilities into adulthood.
POLYMYALGIA RHEUMATICA
Polymyalgia rheumatica (PMR) is a syndrome of older patients characterized by pain and stiffness in the neck, shoulders and pelvic girdle persisting for at least one month (Healey, 1993). It is rare before the age of 50 and becomes more common with increasing age; the cause is unknown. Morning stiffness is very prominent. There are often systemic symptoms such as anorexia, malaise, depression, fever and weight loss. Occasionally there may be synovitis of the large joints. About 10-20% of patients go on to develop temporal (giant cell) arteritis (Bird, Le Gallez and Hill, 1985; Ferrari, Cash and Maddison, 1996). Presentations of temporal arteritis can include scalp pain, pain on chewing, loss of vision in one eye or even stroke (Edwards, 1991).
Diagnosis
There is no diagnostic test for PMR; the diagnosis is based on the clinical presentation. On physical examination there is little to be found other than tenderness and limited motion in the shoulders. Muscle strength is normal. X-rays are unrevealing. The erythrocyte sedimentation rate (ESR) may be very elevated and is an aid to the diagnosis. Other acute phase reactants such as C-reactive protein (CRP) and fibrinogen are also increased. RF and ANAs are not present (Healey, 1993).
The pain of PMR responds dramatically to steroids; patients should expect to be on therapy for at least a year (Ferrari, Cash and Maddison, 1996). The disease is usually self-limiting with a mean duration of two years; during this time patients may need to be on a maintenance dose of prednisolone. In those patients who develop symptoms of temporal arteritis the dose of prednisolone would be increased (Bird, Le Gallez and Hill, 1985).
• The clinical picture of PMR may drift towards RA.
• Here the synovitis is usually more prominent, the arthritis eventually erosive, and the response to low-dose steroids used for PMR usually insufficient (Ferrari, Cash and Maddison, 1996).
INFLAMMATORY ARTHRITIS ASSOCIATED WITH SPONDYLITIS
The sero-negative spondyloarthropathies are characterized by:
• absence of rheumatoid factor;
• a high frequency of HLA-B27 antigen positivity;
• iritis;
• spine and sacroiliac disease;
• a variable extent of peripheral arthritis.
Conditions included in this classification are:
• ankylosing spondylitis;
• psoriatic arthritis;
• reactive arthritis (including Reiter’s syndrome);
• bowel associated arthritis (Ferrari, Cash and Maddison, 1996).
ANKYLOSING SPONDYLITIS
Ankylosing spondylitis (AS) is a chronic disorder characterized by inflammation and ensuing ankylosis of the sacroiliac joints and spinal articulations (Judd, 1997). Spondylitis implies inflammation of the spine and is usually used to mean a diffuse inflammation of ligamentous insertions. AS is more frequently seen in males than females, although an increasing number of females who do develop the disease are now recognized (Bird, Le Gallez and Hill, 1985; Judd, 1997).
Symptoms
AS is characterized by stiffness in the back; common sites are the thoracolumbar junction and low cervical region particularly in the early morning or after a period of inactivity. The onset is usually insidious. Stiffness is initially due to inflammation, which can lead to fibrous and eventually bony ankylosis. Spondylitis is associated with sacroiliitis in nearly all cases. Patients with AS generally find their pain improves with exercise and is worst when at rest.
An enthesopathy is responsible for many of the features of AS. It involves inflammation, fibrosis and ossification (reactive bone formation) at the enthesis (site of insertion of ligaments, tendons and joint capsules to the bone) (Ferrari, Cash and Maddison, 1996).
In the early stages of AS attention may be diverted from the back by complaints of aching or sharp pains in the heels, pelvis, buttocks, hips and shoulders. The back may remain silent until years after disease onset. A peripheral arthritis involving usually large joints may occur and the arthritis may precede or follow spine disease by years.
Assessment
Examination of the spine may reveal restriction of movement. Objective assessments and spinal measurements may be undertaken to confirm and monitor this by performing a Schober’s test (this assessment has been shown to correlate well with radiological movement of the lumbar spine), tragus to wall test, lateral flexion measurements and chest expansion measurements (Bird, Le Gallez and Hill, 1985; Ferrari, Cash and Maddison, 1996). More recently developed assessments are now in common use, especially when deciding whether patients are eligible for antitumour necrosis factor (anti-TNF) therapy or not. These are divided into scales for metrology, disease activity, functional ability and global score. The metrology index incorporates measurements of cervical rotation, lumbar side flexion, lumbar flexion, tragus to wall distance and intermalleolar distance (BASMI Jenkinson et al., 1994, BASDAI Garrett et al., 1994, BASFI Calin et al., 1994 and BAS-G Jones et al., 1996).
Iritis occurs in 20-40% of cases and has little correlation with spine disease. Uveitis (inflammation of the iris, ciliary body and choroid of the eye) responds well to local steroid therapy. Prompt recognition and treatment is important; an ophthalmological opinion is therefore worthwhile (Bird, Le Gallez and Hill, 1985; Ferrari, Cash and Maddison, 1996; Judd, 1997).
Other complications that may occur for patients with AS include:
• lung fibrosis;
• aortitis with aortic valve regurgitation;
• psoriasis;
• inflammatory bowel disease.
Management
Treatment consists of anti-inflammatory medication for pain relief and exercises to maintain mobility. Management has been revolutionized by the introduction of intensive exercise programmes, with close involvement from a physiotherapist, the importance of which cannot be overemphasized.
Some AS patients may require disease-modifying treatments such as sulfasalazine or methotrexate as used in rheumatoid arthritis.
Anti-TNF therapy has been shown to be effective in AS (Van den Bosch et al., 2002; Brandt et al., 2003; Braun et al., 2002). There are guidelines for its use that are similar to those for rheumatoid arthritis. That is they define the requirements for starting a patient on therapy and suggest criteria for assessing response to therapy and whether or not to continue it (Braun et al., 2003).
REITER’S SYNDROME
Reiter’s syndrome is a type of reactive arthritis in which certain classic extra- articular features are present. These are typically not seen in the other sero-negative spondylarthropathies. There are two variants of Reiter’s syndrome. One is venere- ally acquired, the initial event being a urethritis, which is caused by Chlamydia. The other is acquired from food poisoning and starts with diarrhoea, the episode following infection with Shigella flexneri, Salmonella species, Yersinia species or Campylobacter species (Bird, Le Gallez and Hill, 1985; Ferrari, Cash and Maddison, 1996). Commonly the infectious process subsides before the onset of the arthritis. Approximately 50% of patients with Reiter’s syndrome will be HLA-B27 antigenpositive (Bird, Le Gallez and Hill, 1985).
Symptoms
The classic triad of Reiter’s syndrome refers to the presence of arthritis, urethritis and conjunctivitis, and is observed in 33% of patients (Cush and Lipsky, 1993), although the majority of cases do not have all three features (Ferrari, Cash and Maddison, 1996). The diagnosis of these individuals may be identified on the basis of an acute, additive, lower extremity oligoarthritis accompanied by one or more of the following extra-articular features: diarrhoea, urethritis, cervicitis, ocular inflammation, low back pain, enthesitis, keratoderma blennorrhagica or other mucocutaneous lesions (Cush and Lipsky, 1993).
The arthropathy of Reiter’s syndrome is typically an acute, asymmetric, additive and ascending inflammatory oligoarthritis. At onset involvement of the first metatarsophalangeals, ankles, knees and toes is most common (Cush and Lipsky, 1993). This is a disease of young people, males being more commonly affected than females. Involvement of the digits is sometimes accompanied by the presence of dactylitis; inflammatory swelling of a whole digit, resulting in the so-called ‘sausage digit’.
Management
The aims of management of Reiter’s syndrome are:
• to maintain function
• to achieve optimum joint protection
• pain relief
• suppression of inflammation
• when appropriate, eradicate infection.
For the majority of patients the initial episode of arthritis is of between two and three months’ duration, but may last up to a year. About 20-50% of patients demonstrate a chronic course of peripheral arthritis with the potential for progressive spondylitic changes (Cush and Lipsky, 1993).
PSORIATIC ARTHRITIS
Psoriatic arthritis (PsA) is an inflammatory erosive arthritis associated with psoriasis, a negative rheumatoid factor and the absence of rheumatoid nodules. Dactylitis, iritis, unilateral oedema and enthesopathy (particularly around the heel) may occur. The skin manifestations may precede or follow the arthritis by many years; when arthritis antedates the skin lesions the definitive diagnosis cannot be made and only becomes apparent with time. A family history of psoriasis should be sought. Familial aggregation suggests there is a genetic susceptibility to PsA. There is poor correlation between the severity of skin lesions and the arthritis. The sex ratio in PsA is close to unity.
Psoriasis is a papulosquamous, coarse scaling lesion. It may be localized (scalp, chest, periumbilicus, perianal, and extensor limb surfaces), and may have accompanying pustular lesions, diffuse erythroderma and generalized exfoliative dermatitis (Ferrari, Cash and Maddison, 1996).
Five clinical patterns of PsA have been recognized:
Group 1
Predominant involvement of the distal interphalangeal joints (DIP), almost always associated with psoriatic nail changes (nail pitting, onycholysis, subungual hyperkeratosis and transverse ridges - the presence of 20 pits in total suggests PsA, more than 60 being diagnostic).
Group 2
Arthritis mutilans. This is rare. Dissolution of the bones produces shortening of the digits with redundant folds of skin, the so called main-en-lorgnette deformity (opera-glass hands).
Group 3
Symmetric polyarthritis. This is similar to RA, but with a higher frequency of DIP involvement, association with psoriasis, persistent sero-negativity, associated sacroiliitis, and distinctive radiographic changes.
Group 4
Oligoarthritis. This affects large joints such as knee or hip, together with one or two DIP, PIP, MCP and MTP joints, and a dactylitic or ‘sausage’ digit or toe.
Group 5
Axial involvement. Both sacroiliitis and spondylitis can be associated with PsA. Spine symptoms are seldom the presenting complaint (Bennet, 1993; Helliwell and Wright, 1994).
Patients with PsA have to bear the burden of two chronic and currently incurable diseases and have a dual disability in terms of employment since certain industries have self-imposed limitations on patients with any form of skin disease (Helliwell and Wright, 1994). These patients require a multidisciplinary approach to give support in the emotional adjustment to the presence of arthritis and skin rash.
Methotrexate can be useful in the treatment of PsA as it is particularly effective in managing the skin disease as well. The use of systemic corticosteroids is avoided where possible as tapering can cause an exacerbation of the skin disease. Antitumour necrosis factor therapy has been shown to be effective for treating both the joints and the skin (Antoni et al., 2005; Brandt and Braun, 2006; Kavanaugh et al., 2006; Mease et al., 2005).
SEPTIC ARTHRITIS
Definition
Septic arthritis is defined as joint inflammation caused by the presence of live intraarticular micro-organisms and must be distinguished from reactive arthritis in which synovitis is triggered by a primary infection at a site distant from the joint (Hughes, 1996). Hughes states that septic arthritis arises as a result of infection with bacteria, viruses, fungi and, more rarely, other obscure micro-organisms such as protozoa.
Septic arthritis is uncommon but early diagnosis is vital to ensure that effective antimicrobial treatment may commence as delay may cause joint destruction.
Presentation
Characteristically septic arthritis has a monoarticular presentation. Typical onset would be acute, with an infected joint that is warm, painful and effused. Erythema - superficial redness of the skin - may be present. The affected joint will have a restricted range of movement. The patient may have a fever with chills from haematogenous bacterial entry into the joint.
Atypical onset also occurs, where infection may not be obvious in joints previously damaged by prior disease that are chronically painful and swollen. Patients undergoing treatment with immunosuppressive or corticosteroid therapy are more vulnerable and may show less evidence of inflammation than other patients (Schmid, 1993). Prosthetic joints are more susceptible to infection; in these joints pain that is dull, is present at night, and is described as deep and gnawing could indicate infection (Ross, 1990). The appearance of sinuses or fistula and tissue necrosis surrounding prosthetic joints also suggests joint infection (Hughes, 1996).
Atypical onset may be seen in children; for example, when sepsis of the hip is present it will be held immobile in flexion and abduction with little pain or swelling apparent.
Other conditions can mimic septic arthritis and should be excluded:
• crystal arthritis (gout, pseudogout);
• acute inflammatory arthritis or palindromic arthritis;
• post-traumatic arthritis;
• extra-articular inflammation (e.g. olecranon bursitis);
• haemarthrosis (an effusion of blood into a joint);
• rheumatic fever;
• oligoarticular syndromes associated with the spondylarthropathies or juvenile RA.
Routes of Infection
Hughes (1996) describes the five main routes by which infection of the joint in septic arthritis can occur:
• Haematogenous spread, for example, following septicaemia from wound infection, abscesses, mouth sepsis following dental procedures, recent respiratory or urogenital infection.
• Direct trauma, for example, penetrating trauma with a sharp object or during a traumatic injury.
• Diagnostic and therapeutic procedures to a joint, for example, joint aspira- tion/injection/surgical procedure for example, joint replacement.
• Osteomyelitis.
• Inflamed extra-articular structures, for example, inflamed bursae or tendon sheaths.
Micro-Organisms Responsible for Arthritis
Almost any micro-organism can cause infectious arthritis and the aetiology will vary according to the age of the patient and other concomitant diseases present, the route of spread of infection and the distribution of joints affected. The main micro-organisms causing bacterial septic arthritis are:
• Gram-positive cocci: Staphylococcus aureus (the most common cause in all ages and clinical situations), Streptococcus pyogenes, Streptococcus pneumoniae, viridans-group streptococci.
• Gram-negative cocci: Haemophilus influenzae, Neisseria gonorrhea and meningitidis.
• Gram-negative bacilli: Escherichia coli, Salmonella species, Pseudomonas, Coliforms, Bacteroides fragilis, Brucella species, Fusiform bacteria.
• Acid-fast bacilli: Mycobacterium tuberculosis, atypical mycobacteria.
• Spirochaetes: Leptospira icterohaemorrhagica (Hughes, 1996; Schmid, 1993).
Investigation and Diagnosis
The history obtained should include evidence of prior or current infection elsewhere in the body; exposure to recent antibiotic treatment could mask ongoing joint infection.
Where sepsis is suspected in a joint, aspiration carried out under aseptic technique is essential so that fluid analysis can be undertaken and the diagnosis confirmed. The presence of crystals should be excluded. A high neutrophil and total white cell count in the synovial fluid raises the probability of infection. Blood cultures should be taken. Swabs should be taken, if appropriate after examination, from the ears and throat especially of children. If gonococcal infection is a possibility in adults, genital, throat and anal swabs are required.
Treatment
Patients with a definitive diagnosis of septic arthritis should be admitted to hospital for intravenous antibiotics, even before an exact identification of the infecting micro-organism is made. When culture and sensitivity results are available treatment can be changed. The duration of intravenous antibiotics will vary and long-term oral antibiotics may be needed particularly for patients with prosthetic joints.
Non-steroidal anti-inflammatory drug (NSAID) therapy may not significantly affect septic arthritis. Corticosteroid injection is not recommended since it may significantly improve the symptoms of septic arthritis only to have joint destruction continue, and symptoms recur (Ferrari, Cash and Maddison, 1996).
Joint aspiration and surgical joint washout is sometimes performed. It may be necessary to surgically remove a prosthetic joint and all associated foreign material if a joint replacement is confirmed as being infected.
It is vital that, as soon as the patient’s pain and infection are improved, mobilization and the involvement of the physiotherapist is commenced to begin mobilizing the joint and to prevent joint contractures.
REACTIVE ARTHRITIS
Reactive arthritis refers to the occurrence of an acute, non-suppurative, sterile, sero-negative inflammatory arthropathy that is thought to occur after exposure to an infectious agent. The infectious agent is thought to initiate an immunologic response in the body, initiating a train of incompletely understood events, which result in the development of synovitis at a distant site, without viable micro-organisms travelling to the joint - that is, the infection is not active within the joints (Ferrari, Cash and Maddison, 1996; Keat, 1995). There is an association with the antigen HLA- B27 in patients with reactive arthritis. Reactive arthritis is the commonest form of inflammatory arthritis in young men (Keat, 1995).
Reiter’s syndrome, already discussed, is a common type of reactive arthritis in which certain classic extra-articular features are seen. Reactive arthritis is diagnosed in the absence of the classic findings of Reiter’s syndrome, the absence of psoriasis and a clear history of antecedent infection (Ferrari, Cash and Maddison, 1996).
The onset of reactive arthritis may be insidious or acute, with associated fatigue, fever or weight loss. In a substantial number of cases, an identifiable infectious event 1 -4 weeks beforehand precedes the onset of an asymmetric oligoarthritis involving the large joints. About 50% of patients present with synovitis and effusion in one or both knees (Keat, 1995). Other joints less commonly affected at onset are the metatarsophalangeals (MTPJs), ankle joints or symptoms resulting from extensor tendinitis or enthesopathy. The infectious process subsides before the onset of the arthritis. In some patients, an identifiable infectious trigger is not apparent. Extra- articular features may include inflammatory symptoms affecting the eye, mucosal surfaces and entheses. Although reactive arthritis is frequently self-limiting it does have the potential for chronicity and articular damage (Cush and Lipsky, 1993).
TRIGGERING FACTORS
Commonly associated and well documented with reactive arthritis are:
• gastrointestinal infections (salmonella, shigella, yersinia, campylobacter)
• genital tract infections (chlamydia).
Other infections less commonly reported are:
Bacterial:
• streptococcal (group A,G)
• Clostridium difficile
• propionibacterium acne
• staphylococcus aureus (toxic shock arthritis).
Spirochetal:
• borrelia burgdorferi (lyme disease).
Viral:
• human immunodeficiency virus (HIV)
• parvovirus.
Mycobacterial:
• mycoplasma pneumoniae.
Parasitic:
• cryptosporidium (Cush and Lipsky, 1993; Keat, 1995).
Information obtained during the history taking which may assist the clinician in reaching a diagnosis of reactive arthritis may be a recent viral or gastrointestinal infection, recent overseas travel (this may be associated with gastrointestinal infection) or a new sexual partner within three months of onset of the arthritis (associated with genital tract infection).
Management
Some patients whose disease is minor and short-lived may require no more than an accurate diagnosis and observation. However, the majority of patients will require treatment with a NSAID. Treatment of the original infection, where possible, with antibiotics is believed by some to be important (Ferrari, Cash and Maddison, 1996) but is of unproven efficacy (Hughes, 1996).
Local steroid injections are useful if only one or two joints are affected and joint infection has been excluded. Steroid injection may also relieve painful enthesopathies.
Associated Urethritis or Cervicitis
Antibiotic therapy with tetracycline may be given; treatment is advisable for both patient and sex partner, however this may not influence either the duration of the arthritis or the likelihood of recurrence (Keat, 1995).
Associated bacterial diarrhoea is usually managed without antibiotics.
Those patients with progressive disabling arthritis may require treatment with a disease-modifying anti-rheumatic drug (DMARD) such as methotrexate or azathioprine.
OSTEOARTHRITIS
OA is the commonest form of arthritis and accounts for a major amount of disability in the community (Felson, 2000). OA is primarily a disease of articular cartilage and subchondral bone. Focal loss of articular cartilage in part of a synovial joint is accompanied by a hypertrophic reaction in the subchondral bone and margin of the joint. There is a variable, patchy synovitis, and fibrotic thickening of the joint capsule (Figure 1.3). Radiographic changes include joint space narrowing, subchondral sclerosis and cyst formation, and marginal osteophytosis. It is an extremely common condition, which is age-related, the peak age of onset being between 50 and 60 years. Common sites which are affected include the knees, hips, distal interphalangeal and thumb base joints of the hands and facet joints of the spine. In all joint sites except for the hips it is commoner in women than men. There are marked racial differences in its prevalence and distribution. Clinical manifestations are use-related joint pain, stiffness of joints after a period of inactivity and loss of range of joint movement. Although age-related it is not simply an inevitable consequence of ageing but a dynamic reaction pattern of a joint responding to insult or injury. It can occur without any obvious predisposition, or it can result from a previous injury or disease of a joint (secondary OA); hence there is great heterogeneity in the spectrum of disease covered by this term (Table 1.7). There is a lack of correlation between radiographic, pathologic and clinical manifestations and therefore attempts at strict definition have failed. The exact aetiology and pathogenesis are unknown, but are thought to involve a complex interaction of intrinsic abnormalities in connective tissue integrity and extrinsic physical insults to joints. OA is currently viewed as a heterogeneous disease process rather than a disease entity.
Figure 1.3 An osteoarthritic knee joint. Reproduced by permission of The Arthritis Research Campaign.
Table 1.7 Classification of OA.
Classification by the joints involved
Monoarticular, oligoarticular or polyarticular (generalized)
Chief joint site and localization within the joint
Hip (superior pole, medial pole, concentric)
Knee (medial, lateral, patellofemoral compartments)
Hand (IP joints and/or thumb base)
Spine (facet joints or intervertebral disc disease)
Others
Classification into primary and secondary forms of OA
Primary = idiopathic
Secondary = a likely cause can be identified
Causes of secondary OA:
1. Metabolic
— for example, Ochronosis, Acromegaly, Haemachromatosis, Calcium crystal deposition
2. Anatomic
— for example, slipped femoral epiphysis, Epiphyseal dysplasias, Perthe’s disease, congenital dislocation of the hip, leg length inequality, hypermobility syndromes
3. Traumatic
— for example, major joint trauma, fracture through a joint, joint surgery (e.g. meniscectomy), chronic injury (occupational arthropathies)
4. Inflammatory
— for example, any inflammatory arthropathy, septic arthritis
Classification by the presence of specific features
Inflammatory OA
Erosive OA
Atrophic or destructive OA
OA with chondrocalcinosis
Others
_______
FIBROMYALGIA SYNDROME
This is a common but often overlooked condition. It occurs predominantly in women and is associated with marked disability and handicap.
Diagnosis
It presents with a variable symptom complex of widespread musculoskeletal pain (in all four quadrants), severe fatigue and multisystem ‘functional’ disturbance. Diagnosis is based on typical symptoms, the presence of multiple tender trigger sites (11 out of 18) and the exclusion of any inflammatory or endocrine disease. There is no specific treatment and the prognosis is often poor. Nevertheless, some patients may be helped by an explanation of the condition, limited tricyclic treatment, an increase in aerobic exercise and various coping strategies that shift the ‘control’ back to the patient. Medicine has a bias towards a pathological explanation of disease and fibromyalgia has often been considered an expression of psychological disturbance. The symptoms and disability, however, are real, not fabricated or imagined, and reflect ‘functional’ rather than ‘pathological’ abnormality. Figure 1.4 attempts to show a possible mechanism of induction and perpetuation of fibromyalgia syndrome. Fibromyalgia may be superimposed upon pre-existing painful conditions such as OA or cancer, although it is usually primary in nature. There is overlap in symptoms and impaired function between fibromyalgia, anxiety and depression, and fibromyalgia patients score highly on anxiety and depression questionnaires. Evidence for triggering viral infections in the vast majority of patients is lacking. Most patients are women, often in their forties and fifties; the condition is rare in children. Pain and fatigue are often associated with severe disability. Patients may not be able to cope with their jobs or household activities.
Figure 1.4 A possible mechanism of induction and perpetuation of fibromyalgia syndrome.
Symptoms
The pain is predominantly axial and diffuse but may affect any region and at times be felt ‘all over’. Characteristically the pain is not relieved by analgesics or NSAIDs. There is often a poor sleep pattern, with patients waking unrefreshed and feeling more tired in the morning than later in the day. It is important to take a full history and examination but clinical findings are usually unremarkable with no objective weakness, synovitis or neurological abnormality. The important and sometimes the only positive examination finding is the presence of multiple hyperalgesic tender sites (Figure 1.5). These sites are tender to pressure in the normal individual but in fibromyalgia patients similar pressure elicits marked tenderness and a wince/withdrawal response. Tender sites should be found axially, in upper and lower limbs and on both sides — i.e. widespread and symmetrical. In addition hyperalgesia should be absent at control sites such as the forehead, distal forearm and fibular head.
Figure 1.5 Common hyperalgesic tender sites. Reproduced by permission of The Arthritis Research Campaign.
Management
Aspects of management include:
• patient and family education about the condition;
• trial of tricyclics;
• cessation of other ineffective drugs;
• graded aerobic exercise regime;
• coping strategies - for example, yoga.
The prognosis is poor with less than 1 in 10 patients in a study in Nottingham losing their symptoms over a 5-year period. With suitable advice patients, although not ‘cured’, can learn to live better with their condition and more importantly avoid further unnecessary investigations and drug treatments (Doherty, 1993).
CONNECTIVE TISSUE DISEASE
The connective tissue diseases are a group of multisystem diseases frequently characterized by pathologic changes in blood vessels and connective tissues. These diseases often have overlapping clinical features and share immunologic abnormalities; these include:
• general systemic features (malaise, weight loss, fever);
• musculoskeletal involvement varying from inflammatory polyarthritis to generalized arthralgia and myalgia;
• immune aberration leading to immune-mediated inflammation as an underlying pathogenic mechanism (Kimberly and Urowitz, 1994).
SYSTEMIC LUPUS ERYTHEMATOSUS
SLE is an inflammatory, multisystem disease of unknown aetiology with diverse clinical and laboratory manifestations and a variable course and prognosis. Immunologic aberrations give rise to excessive autoantibody production, some of which cause cytotoxic damage, while others participate in immune complex formation resulting in immune inflammation.
Clinical manifestations may be constitutional or result from inflammation in various organ systems including skin and mucous membranes, joints, kidney, brain, serous membranes, lung, heart and occasionally gastrointestinal tract. Organ systems may be involved individually or in any combination. Involvement of vital organs (particularly kidneys and central nervous system) accounts for significant morbidity and mortality. Morbidity and mortality result from tissue damage due to the disease process or its therapy. SLE is recognized worldwide; its prevalence varies in different geographic areas. It is more prevalent in women, particularly in their reproductive years. In the United States it has been noted that SLE is three times more common among Blacks than Whites.
Symptoms
Clinical features of the disease include:
• General constitutional complaints (weight loss, fever, malaise, overwhelming fatigue);
• Skin manifestations (lupus-specific or lupus-nonspecific):
- Lupus-specific lesions:
(1) Acute (malar rash, generalized erythema, bullous LE).
(2) Subacute.
(3) Chronic lupus changes (localized discoid, generalized discoid, lupus profundus).
(4) Photosensitivity (over 50% of patients).
(5) Alopecia (patchy or diffuse).
- Mucous membrane lesions (ulcers of the mouth or vagina or nasal septal erosions).
(1) musculoskeletal features (arthralgias and/or arthritis), often the presenting manifestation. The acute arthritis typically involves the small joints of the hands, wrists and knees. Most cases are symmetrical. Nodules are found in 10% of cases. Unlike RA the arthritis of SLE is typically not erosive or destructive of bone. However, clinical deforming arthritis does occur and may take a number of different forms; there may be mild synovial thickening about PIP joints or over tendon sheaths, ulnar deviation of the fingers and subluxations and contractures. Patients with SLE may complain of muscle pain and weakness. This may be due to arthritis, be drug- induced (corticosteroids, antimalarials) or due to true muscle inflammation (polymyositis).
• Renal disease (urinalysis and serum creatinine assessments must be made regularly). A renal biopsy may be needed to assess the lupus nephritis accurately.
• Neuropsychiatric manifestations (patients often present with a mixture of neurologic and psychiatric manifestations).
• Neurologic manifestations (seizures, headache, transverse myelitis, cranial or peripheral neuropathy).
• Psychiatric manifestations (psychosis, psychoneurosis and neurocognitive dysfunction).
• Serositis (pleurisy, pericarditis, peritonitis).
• Pulmonary involvement (lupus pleuritis, lupus pneumonitis, pulmonary haemorrhage, pulmonary embolism, pulmonary hypertension).
• Cardiac involvement (pericarditis, myocarditis, endocarditis, coronary artery disease).
• Gastrointestinal involvement (oesophageal disease, mesenteric vasculitis, inflammatory bowel disease, pancreatitis, liver disease).
• Haematologic abnormalities (anaemia, leucopenia or lymphopenia and thrombocytopenia). The most significant anaemia is the autoimmune haemolytic anaemia due to autoantibodies directed against red blood cell antigens. The lupus anticoagulant is the commonest haemostatic abnormality. The serology of lupus shows evidence for complement consumption by immune complexes. Antibodies seen in SLE include ANA, anti-smooth muscle, anti-Ro, anti-La and antibodies to double-stranded DNA (dsDNA).
There is a greater incidence of spontaneous abortion, prematurity and interuterine death, although SLE does not interfere with conception. Survival rates of SLE have improved over the last four decades from less than 50% at 5 years in 1955 to over 90% survival at 5 years in 1990. Reasons for this improvement include earlier diagnosis, better therapeutic modalities, improved antibiotics and antihypertensive drugs and the availability of renal dialysis and transplantation (Gladman and Urowitz, 1994).
SCLERODERMA (SYSTEMIC SCLEROSIS)
This is a generalized disorder of connective tissue affecting skin and internal organs. It is characterized by fibrotic arteriosclerosis of peripheral and visceral vasculature. Variable degrees of extracellular matrix accumulation occur (mainly collagen), both in skin and viscera. It is associated with specific autoantibodies, most notably anticentromere and Scl-70.
Clinical Features
• Raynaud’s phenomenon;
• tightening and thickening of skin (scleroderma);
• involvement of internal organs, including gastrointestinal tract, lungs, heart and kidneys, accounts for increased morbidity and mortality;
• risk of internal organ involvement strongly linked to extent and progression of skin thickening.
The first convincing description of scleroderma was of a 17-year-old woman in Naples in 1753 (Rodnan and Benedek, 1962). The relationship of scleroderma to Raynaud’s phenomenon was first described by Maurice Raynaud himself in 1865. In 1945 Goetz proposed the term progressive systemic sclerosis based on his detailed review of the visceral lesions (Goetz, 1945). The aetiology and pathogenesis remain unknown and no effective therapies for the basic disorder have been developed. Breakthroughs in treatment of specific clinical features have derived from agents developed for other purposes and include angiotensin-converting enzyme (ACE) inhibitors for the hypertension associated with renal involvement and histamine-2 (H2) receptor antagonists for chronic acid reflux.
Epidemiology
Studies based on hospital records and death registries suggest occurrence in between 4 and 12 individuals per million of population per year. It is likely that many cases of systemic sclerosis are unrecognized, particularly in limited disease. Onset is highest in the fourth and fifth decade of life and is three to four times more common in women than men (Medsger and Masi, 1971). Disease is not linked to race, season, geography, occupation or socioeconomic status. Environmental aetiologies are possible and include silica dust, silicone surgical implants and epoxy resins as implicated vectors. Familial occurrence is quite rare and convincing genetic associations are lacking.
Clinical Features
Systemic sclerosis is a remarkably heterogeneous disorder with diverse initial presentations and variable disease course. Periodic waxing and waning of symptoms is unusual (unlike RA or SLE).
Vascular Abnormalities
Raynaud’s Phenomenon
This is defined as episodic colour changes (pallor, cyanosis, erythema) occurring in response to environmental cold and/or emotional stress. Although most typically noted in the fingers, the circulation of the toes, ears, nose and tongue is also frequently affected. Subjects complain of symptoms of numbness and pain associated with the phases of pallor and cyanosis and of tingling and burning during the hyperaemic recovery phase. The impact on hand function in cold environments can be substantial. Raynaud’s phenomenon is the initial complaint in around three quarters of patients with systemic sclerosis. The potential importance of Raynaud’s phenomenon in systemic sclerosis cannot be understated. Taken alone it has considerable clinical impact; however, abnormalities similar to those of the peripheral circulation are widely distributed in the visceral vasculature as well and have major effects on morbidity and mortality. In systemic sclerosis structural narrowing of the digital arteries causes severe (>75%) attenuation of the arterial lumen. The principal lesion is one of intimal hyperplasia consisting of collagen. Lesser degrees of fibrosis are noted in the adventitia but the media (smooth muscle) is little affected. Normal peripheral vasoconstriction in response to cold superimposed on the narrowed vessel would cause occlusion of the lumen. Similarly, treatment of Raynaud’s phenomenon with smooth muscle relaxants is less likely to work in the presence of a fixed obstructive lesion. The hallmark of severity of Raynaud’s phenomenon in systemic sclerosis is the frequency of digital ischaemic injury. Around one third of patients experience at least one digital ulceration per year, and patients are at risk of catastrophic peripheral digital gangrene. Modern clinical studies suggest that the internal organs (heart, lungs) sustain Raynaud-like intermittent ischaemia during cold exposure.
Microvascular Abnormalities
There are characteristic architectural abnormalities of the microvasculature in systemic sclerosis, which are easily appreciated by widefield microscopy of the nailfold capillary bed (Maricq, 1981). These changes include enlargement and tortuosity of individual capillary loops interspersed with areas of capillary loop dropout. At later stages of clinical disease, punctate telangiectasias develop with typical locations including fingers, face, lips and oral mucosa.
Skin Involvement
The early tissue lesion features ingress of immigrant inflammatory cell populations. The net effect of this array of cells and signals is an accumulation of extracellular matrix including collagen glycosaminoglycan, fibronectin, adherence molecules and tissue water. The patient and clinician recognize the result as the tightened and thickened skin (scleroderma), which is the hallmark of disease.
Oedematous Change
An intrinsic feature of early systemic sclerosis is the painless swelling of the fingers and hands. Symptoms include early morning stiffness and arthralgia. Carpal tunnel syndrome is a frequent occurrence. Pitting oedema of the fingers and dorsum of the hand is present on examination.
Scleroderma
Scleroderma skin thickening begins on the fingers and hands in virtually all cases. The skin initially appears shiny and taut and may be erythematous. Pruritus is common and may be intense. Digital skin creases are obscured and hair growth is reduced. The skin of the face and neck is usually involved next. Facial scleroderma causes an immobile and pinched facies. The lips become thin and pursed. Local skin thickening limits the ability to fully open the mouth impairing effective dental hygiene. Skin thickening may stay limited to hands and face; in some patients there is rapid spread to the upper arms, shoulders, chest, back, abdomen and legs. Prominent localized areas of hyperpigmentation and hypopigmentation may develop.
Skin Thickening and Disease Classification
The diagnosis of systemic sclerosis is clinically obvious once skin thickening has developed. Accurate and early classification is the paramount clinical issue because the relative risk of accruing new internal organ involvement closely parallels the pace, progression and extent of skin involvement (Table 1.8).
Table 1.8 Classification of systemic sclerosis.1. Diffuse scleroderma — skin thickening present on the trunk in addition to the face, proximal and distal extremities.2. Limited scleroderma — skin thickening restricted to sites distal to the elbow and knee, but also involving the face and neck Synonym — CREST syndrome (calcinosis, Raynaud’s, esophageal dysmotility, sclerodactyly, telangiectasias).3. Sine scleroderma — no clinically apparent skin thickening but with characteristic internal organ changes, vascular and serologic features.4. In overlap — criteria fulfilling systemic sclerosis occurring concomitantly with criteria fulfilling diagnoses of SLE, RA or inflammatory muscle disease.5. Undifferentiated connective tissue disease — Raynaud’s phenomenon with clinical and/or laboratory features of systemic sclerosis.
________
Skin, Visceral Involvement and Disease Outcome
Skin involvement alone is symptomatic and by virtue of local tethering contributes to loss of motion, impaired hand function, cosmetic problems and lessened sense of well-being (McClosky, Patella and Seibold, 1990). The importance of skin involvement stems from its linkage with visceral changes.
Systemic Features
General Manifestations
Fever is uncommon; its presence should prompt a search for infection. Weight loss is universal even in the absence of gastrointestinal involvement. Profound fatigue occurs frequently and is often a limiting factor in daily activities. Both the unrelenting persistence of symptoms and concern over the cosmetic impact of the disease lead to frequent reactive depression. Systemic sclerosis is uncommon; many patients have not heard of the disease prior to their diagnosis.
Gastrointestinal Involvement
This is the third most common feature following Raynaud’s phenomenon and scleroderma. Incompetence of the lower oesophageal sphincter is suggested by symptoms of heartburn and associated bitter regurgitation. Impaired contractility of the smooth muscle of the oesophagus presents as dysphagia and odynophagia for solid foods. Complaints of a ‘sticking’ sensation are typical. Small intestine involvement is a major source of morbidity. Symptoms include intermittent bloating with abdominal cramps, intermittent or chronic diarrhoea and presentations of intestinal obstruction. Malabsorption can be shown by an increased quantitative faecal fat elimination. Bacterial overgrowth in areas of intestinal stasis is well documented.
Musculoskeletal Features
The majority of patients experience arthralgia and morning stiffness. Overt arthritis is uncommon; erosive arthropathy is demonstrable on radiograph in 20-30% of patients (Blocka et al., 1981). Inflammatory and fibrinous involvement of tendon sheaths may mimic arthritis. Muscle weakness occurs both from disuse atrophy and from a disease-related myopathy. Resorption of bone of the digital tufts occurs in long-standing disease. Subcutaneous calcinosis can occur; common locations include the fingers, preolecranon area, olecranon and prepatellar bursae. These areas become intermittently inflamed and a source of discomfort. Spontaneous extrusion through the skin is a frequent occurrence and a source of local infection.
Pulmonary Involvement
Pulmonary involvement is the leading cause of mortality and morbidity in later stages of systemic sclerosis. Any combination of vascular obliteration, fibrosis and inflammation may be present. Clinical presentations are insidious and include exertional dyspnoea, diminished exercise tolerance and nonproductive cough. Pulmonary function testing is the mainstay of clinical diagnosis and serial assessment.
Myocardial Involvement
Patchy fibrosis of the myocardium is present at autopsy in as many as 81% of patients with systemic sclerosis. Myocardial involvement is a principal determinant of survival. Many patients complain of diminished exercise tolerance, palpitations and dyspnoea and therefore separating myocardial from pulmonary involvement in clinical assessment is difficult.
Renal Involvement
The syndrome of ‘scleroderma renal crisis’ is due to the sudden onset of accelerated hypertension, rapidly progressive renal insufficiency, microangiopathic haemolysis and consumptive thrombocytopenia in the presence of hyperreninaemia.
Pregnancy
Menstrual irregularities and amenorrhoea occur in relation to the severity of illness. Difficulty with conception is frequent. Pregnancy is not associated with worsening of scleroderma.
Immunologic Features
Systemic sclerosis occurs in overlap with other connective tissue disorders including SLE, polymyositis, RA and Sjogren’s syndrome. Antinuclear antibodies are present in the sera of over 90% of patients with systemic sclerosis.
INFLAMMATORY MUSCLE DISEASE (POLYMYOSITIS)
Definition
• A member of the connective tissue disease family (autoimmune disease associations, other immunologic features).
• Characterized by chronic inflammation of striated muscle (polymyositis) and sometimes the skin (dermatomyositis).
• Autoantibody associations define clinical subsets of the disease.
Signs and Symptoms
• Painless proximal muscle weakness with or without rash
• Elevation of serum muscle enzymes (creatine kinase)
• Other organ systems affected (joints, lungs, heart, gastrointestinal tract)
• Probable association with malignancy (elderly).
Epidemiology
Classification of these diseases is being refined as new insights into aetiology and pathogenesis emerge. These disorders are recognized as part of a single disease spectrum. Certain features are used to separate subsets:
• childhood versus adult onset
• polymyositis versus dermatomyositis
• presence or absence of other connective tissue diseases or malignancy.
In the future it is likely that disease subsets will be identified according to serum autoantibodies and/or other immunologic characteristics.
Incidence
The annual incidence of polymyositis/dermatomyositis ranges from 2-10 new cases per million persons at risk in various populations. Published rates are likely to be underestimates as not all possible sources of ascertainment are examined.
Inflammatory myopathy can occur at any age but the observed pattern of incidence includes childhood and adult peaks. The incidence sex ratio is 2.5:1 female to male. This ratio is 1:1 in childhood disease and associated malignancy but 10:1 when there is an associated connective tissue disease. Polymyositis/dermatomyositis has a 3-4:1 Black to White incidence ratio.
Environmental Factors
• No striking associations with environmental factors.
• Onset more frequent in winter and spring months (precipitation by viral and bacterial infections).
• D-penicillamine (drug-induced myositis).
Genetic Factors
At least in some families there seems to be a genetic predisposition. It is not uncommon to find close relatives suffer from other autoimmune diseases (Walker et al., 1982). The reported associations of certain HLA types with clinical subsets of disease are weak.
Presentations
• Insidious, progressive, painless proximal muscle weakness over three to six months.
• Acute onset muscle pain and weakness developing over several weeks (associated with fever and fatigue).
• Proximal myalgias only.
• Slowly evolving weakness over 5-10 years (inclusion body myositis).
Clinical Features
• Constitutional
Fatigue, fever and weight loss.
• Skeletal muscle
Patients complain of difficulty performing activities of daily living requiring normal muscle strength. Walking may become clumsy with a ‘waddling’ gait. Bulbar weakness results in hoarseness or dysphonia, difficulty in initiating swallowing with regurgitation of liquids and episodic coughing immediately after swallowing. Physical examination is necessary to confirm weakness of individual muscles or groups of muscles. The distribution of weakness is usually symmetric, affecting all proximal muscles. Distal muscles are only weak in 10-20% of cases. Ocular and facial muscles are rarely involved. Swelling of muscle is usual. Firmness to touch and incomplete passive stretching suggest fibrous replacement of muscle and contractures respectively.
• Skin
Dermatomyositis.
• Erythematous or violaceous
• Scaling
• Oedema
• Cuticular hypertrophy and haemorrhage, periungual erythema and telangiectasia
• Ulceration
Polymyositis/dermatomyositis.
• Panniculitis
• Cutaneous mucinosis
• Vitiligo
• Multifocal lipoatrophy.
Other Features
• Joints
Polyarthralgias and/or polyarthritis which are rheumatoid-like in distribution. Wrists, knees and small joints of the hands most frequently affected. Arthritis tends to occur early in the disease and is mild and transient.
• Calcinosis
Can be a late problem in polymyositis/dermatomyositis. Intracutaneous, subcutaneous and fascial sites are affected, as well as the connective tissue surrounding muscle bundles.
• Respiratory
Dyspnoea on exertion may be due to respiratory muscle (diaphragm, intercostal) weakness. It may be due to congestive heart failure or cardiac arrythmia from myocardial or conduction system involvement. Intrinsic causes of dyspnoea include interstitial alveolitis or fibrosis, aspiration pneumonia (from pharyngeal dysmotility), bacterial infection and methotrexate pulmonary toxicity (Dickey and Myers, 1984). Cough is frequent. There are three common presentations of lung disease:
(a) aggressive form of diffuse alveolitis (myositis often overlooked);
(b) slowly progressive lung disease (disability from myopathy may mask severity of lung disease);
(c) asymptomatic but with radiographic and/or physiologic manifestations of interstitial lung disease.
• Cardiac involvement
Common but seldom symptomatic until it is very advanced. The most frequent abnormality is a rhythm disturbance. Less common is congestive heart failure due to myocarditis or fibrous replacement of the myocardium.
• Gastrointestinal tract
Pharyngeal dysphagia can occur. Involvement of the smooth muscle of the intestinal tract is uncommon unless there is overlap with systemic sclerosis. Lower oesophageal dysphagia results in the sensation of food ‘sticking’ in the retrosternal area during the act of swallowing. A weak lower oesophageal sphincter leads to reflux of gastric acid causing heartburn. Chronic distal oesophagitis predisposes to stricture formation. Constipation is the most common symptom of colonic hypomotility.
• Peripheral vasculature
Raynaud’s phenomenon is a frequent accompanying complaint.
• Association with malignancy
The relationship between myositis and malignancy is controversial. Cancer in myositis patients is most frequently obvious rather than occult.
Investigations
• General
Low-grade anaemia is present in polymyositis (anaemia of chronic disease). ESR may be mildly elevated.
• Musculoskeletal
(a) Enzymes from injured skeletal muscle
Creatine kinase, aldolase, the transaminases (ALT and AST) and lactate dehydrogenase
(b) Electromyogram (EMG)
A sensitive but nonspecific method of evaluating inflammatory myopathy. Typical findings include irritability of myofibrils on needle insertion and at rest and short duration, low amplitude, complex potentials on contraction. The EMG is a useful method for following disease activity.
(c) Biopsy
Muscle biopsy should be performed in all cases to confirm the diagnosis of inflammatory myopathy. The presence of chronic inflammatory cells in the perivascular and interstitial areas surrounding myofibrils is pathognomonic. More common than inflammation are degeneration and necrosis of myofibrils, phagocytosis of necrotic cells and myofibril regeneration. In long-standing myositis, fibrous connective tissue replaces necrotic myofibres and separates bundles of myofibres.
• Lung
Reduced respiratory muscle strength is determined by measuring inspiratory pressures at the mouth. The chest radiograph in interstitial lung disease shows bilateral basilar thickening. Thin section computerized axial tomography reveals evidence of interstitial fibrosis. Ventilation-perfusion studies are abnormal and pulmonary function tests show a restrictive physiologic pattern with reduced forced vital capacity.
• Heart
The most common alterations are conduction defects and atrial and ventricular dysrhythmias, which are due to involvement of working myocardium and/or the conducting system.
• Intestine
Barium studies are used to demonstrate pharyngeal dysphagia, delayed gastric emptying and small bowel dilatation and hypomotility.
• Serum autoantibodies
In polymyositis/dermatomyositis, more than 80% of patients have autoantibodies to nuclear and/or cytoplasmic antigens (ANA, ANCA). About 50% of patients have myositis-specific antibodies. Myositis-specific antibodies may be important in the pathogenesis of the inflammatory myopathies (association with subsets, selective response against antigens, variation of antibody titre with disease activity).
Natural History
The majority of patients have multiple exacerbations and remissions or persistent disease activity. With each episode of myositis there is the potential for absolute loss of muscle mass.
Prognosis
Assessment of prognosis is difficult as the disease is relatively rare, a classification system based on meaningful pathophysiologic and serologic data has not been developed and objective criteria for improvement (or deterioration) are not standardized.
Survival
Since the availability of corticosteroids there has been improved survival, although there have been no double blind placebo-controlled studies. Currently the expected survival in incident cases of polymyositis/dermatomyositis is over 90% at five years after initial diagnosis. Factors associated with poor survival include:
• older age
• malignancy
• delayed initiation of corticosteroid therapy
• pharyngeal dysphagia with aspiration pneumonia
• myocardial involvement
• complications of corticosteroid/immunosuppressive drugs.
Disability
Each major exacerbation results in a reduction in muscle strength, but therapy almost never returns the patient to the preceding level of total body muscle mass or strength. Fortunately a minor amount of atrophy and weakness in one or more muscle groups most often does not translate into functional impairment.
Over 200 conditions affecting joints, bones, soft tissues and muscles are covered by the term arthritis, often referred to as ‘rheumatic disease’ or ‘musculoskeletal disease’ (Symmons and Bankhead, 1994). Arthritis is the biggest cause of physical disability in the United Kingdom (Martin, Meltzer and Elliot, 1988).
The two main types of arthritis in terms of diagnosis are:
• non-inflammatory — for example, OA
• inflammatory — for example, RA.
RA is characterized by progressive disability over time. Using the Stanford Health Assessment Questionnaire (HAQ) it has been clearly demonstrated that functional status deteriorates over time (Doyle, 1996). Research has shown that disability occurs early in the course of the disease (Wolfe and Cathey, 1991; Wolfe, Hawley and Cathey, 1991).
The impact and personal costs of rheumatological conditions on the individual and their family — in terms of pain, loss of physical movement, loss of independence, self-esteem, employment, education, disruption to relationships, reduced quality of family and social life — is incalculable (Ashcroft, 1997).
The current aim of medical care, in the absence of a cure, is a reduction in the impact of RA. Although some accept that there is a need to consider and take into account the impact of the disease on the individual’s social functioning (Long and Scott, 1994), health professionals tend to work within the medical model of disability and aim to establish ‘what works on whom, and why’ (Ashcroft, 1996). However, the impact of a chronic rheumatological condition on the quality of life for both individuals and their families should not be ignored. Carr (1996) states that quality of life measures are required to identify and assess the disabling consequences of RA and the effectiveness of medical attempts to prevent or postpone them.
The International Classification of Functioning, Disability and Health (WHO, 2001), known more commonly as ICF, has moved away from being a ‘consequences of disease classification’ (1980 version) to become a ‘components of health classification’ and provides a standard language and framework for the description of health and health-related states. The ICF is WHO’s framework for health and disability. In ICF disability and functioning are viewed as outcomes of interactions between health conditions (diseases, disorders and injuries) and contextual factors, among which are external environmental factors and internal personal factors that influence how disability is experienced by the individual. Measurement tools to assess impairment and disability are well established in the field of rheumatology; quality of life measurement tools to assess the consequences suffered by an individual as a result of a disease or handicap are not.
Carr (1996) tells us that ‘handicap is the social consequence of disease, is specific to individuals and depends not only on the severity of the disease, but also on his or her life role’. She goes on to say that ‘the degree to which an individual is handicapped depends on the perception of the importance of the role that can no longer be filled’. Discrepancies between the views of society (employers, healthcare professionals) and individuals with regard to handicaps can be considerable.
PERSONAL IMPACT OF ARTHRITIS
It must be remembered that RA affects the patient’s body as a whole, not just the articular system, and invariably has an impact on every aspect of the patient’s physical and psychosocial life (Gordon and Hastings, 1994).
The impact of a rheumatological condition can be felt even before a diagnosis has been made when, due to pain and stiffness in the joints, performing everyday activities of daily living such as washing, dressing and cooking are both painful and difficult.
From a patient’s perspective Ashcroft (1996) describes how ‘an early diagnosis brings with it a never ending stream of appointments with consultants, doctors, occupational therapists, physiotherapists, blood tests, X-rays, trips to the general practitioner (GP) and chemist etc. This, coupled with the extreme fatigue that accompanies RA, leads to your entire life being absorbed within the medical world.’ She goes on to describe how this ‘represents the insidious nature of RA, sucking you very quickly into an “illness mode” - the medical model of disability, and like most things held in by suction, it is very difficult, if not impossible to get back out’.
It is vital that health professionals ensure adequate information is given to every patient either newly diagnosed or who have established disease to enable them to understand what type of arthritis they have, its course and how it may progress and how they can learn to manage their condition themselves.
Diagnosis can bring about many emotions - denial, relief or disbelief to name but a few.
It might be assumed that anxiety and depression would correlate with continuing disease activity, but it appears that socioeconomic factors may be greater determinants of depression than physical factors (Hawley and Wolfe, 1988; McFarlane and Brooks, 1988).
The impact of the diagnosis will affect not only the individual but family and friends also, and being diagnosed with arthritis at various age groups will have different implications (Ashcroft, 1997).
The Young Child
Children may become withdrawn, isolated and depressed if they are not able to join their friends in normal childhood school, playground and recreational activities. Schooling may be disrupted. Friction may develop with other siblings if they perceive more attention is given to the ‘disabled’ child by parents.
Teenagers
Although nearing independence they may require assistance due to physical limitations and may need help with personal care, which is difficult to come to terms with both for parent and child. The attainment of independence, physical maturity, social and sexual identity may all be delayed. Depression and anxiety may become problems. Parents can then become overprotective.
Young Adults
May no longer be able to pursue their chosen career ambition.
Middle Aged Adults
Can curtail a successful career or prompt an unwanted change of direction. A reduction of income may result. Taking time off work may be necessary and can affect relationships with workmates.
For any age group the impact on long-term relationships can be the greatest. Ashcroft (1997) explains ‘the spontaneity of a hug can cause excruciating pain and the reaction to being the cause of that pain is often guilt’. Tensions can easily develop within a relationship.
The fluctuating nature of arthritis can be a contributory factor to stress within the family and workplace as people find it difficult to understand the ability to do a thing one day and not the next.
FINANCIAL IMPACT OF ARTHRITIS
To the individual person and their family, living with arthritis can be expensive. Extra expenses incurred can include:
• additional heating and hot water;
• personal assistance and care;
• domestic help;
• household and garden maintenance;
• home adaptations;
• specialist equipment - lever taps, lever door handles, electric tin openers, bottle and jar openers, aids to assist with washing and dressing, aids to assist with preparing and cooking food;
• mobility - taxi or bus fares, car adaptations - power-assisted steering, automatic transmission, electric windows, central locking, hand brake adaption;
• prescription and non-prescription medicines.
IMPACT ON EDUCATION
Two important principles are at stake in the education of a child with arthritis (Southwood, 1993):
• The child should be made to feel as independent and normal as possible.
• Keeping the child in mainstream schooling is crucial.
The child with arthritis may have a decreased attention span, irritability, increased sleepiness and altered mood secondary to the disease itself or its treatment (Southwood, 1993).
It should be possible for children who need to spend time in hospital or at home to continue their education. Liaison between parents, school and hospital teachers and individual tutors is important to ensure a work plan is formulated. Minimal disruption is desirable to ensure career choices are not prejudiced at a later date.
Children with arthritis may have pain and stiffness in their hands, which may cause slowness and difficulty in writing. They should be allowed extra time to complete work and consideration for the use of a word processor, electric typewriter or tape recorder may be useful.
Mobility and movement in general may be a problem and extra time should be allocated, if necessary, for carrying books from one classroom to another.
It may not be possible to fully participate in physical education lessons but close liaison with a physiotherapist who can suggest appropriate exercises is useful. Swimming is excellent provided the pool is not too cold. Contact sports, which may cause direct injury to a joint, are not usually advisable; non-contact sports are preferred.
A patient’s educational background and occupation may affect management and outcome. Notwithstanding genetic and sex factors, patients with more years of education seem to develop less severe disease (Leigh and Fries, 1991).
Hilliquin and Menkes (1994) describe how relationships between education and outcome in RA are not well understood. They go on to explain how low formal education appears to be a marker identifying behavioural risk factors that may be associated with a poor outcome in RA. These factors include the patient’s sense of self-efficacy, problem-solving capacity, sense of personal responsibility and capacity to cope with life stress. Patients with less schooling may not know where to turn for help, may seek medical care less promptly and report to physicians later in the course of the disease. Compliance with treatments could also be reduced.
IMPACT ON EMPLOYMENT
Employment is known to be of benefit to health psychologically as it provides a source of identity, status and self-esteem (Gignac et al., 2004), giving purpose, structure and social contact to each day (Barrett, 1998).
The onset of arthritis, particularly inflammatory arthritis, may result in a change of a chosen career path. Some people who developed their arthritis at a young age may have difficulty gaining employment, whilst some people with arthritis may have to stop work altogether. For some the pain and fatigue associated with arthritis, which may be exacerbated by stress, affects the hours of work they can manage. Thus 40% of people with rheumatoid arthritis stop working within five years of being diagnosed with the condition (NICE, 2002).
Gordon and Hastings (1994) claim that people whose occupations are associated with less physical stress show a better functional outcome.
Mancuso et al. (2000) found individuals with RA made major adaptations to maintain employment and still perceived their employment to be at risk. Work changes made include use of holidays, sick days, reducing hours, reducing responsibilities, changing jobs or forgoing promotion (Gignac et al, 2004).
Individuals should be encouraged to discuss at an early stage with their employers modifications or adjustments that could reasonably be made to make it easier for them to carry out their work. Practical help and support is available to employers through the government’s Access to Work scheme. This scheme is administered by the employment service through local placing, assessment, and counselling teams (PACTs).
Being able to gain and retain employment is not easy at the best of times and for people with arthritis it can be more difficult. However, it is important to remember that everyone, regardless of whether they have arthritis or not, is an individual and will bring their own skills, strengths and weaknesses to their work.
THE ROLE OF SOCIAL SUPPORT
As has already been mentioned, coping with rheumatic disease involves facing a number of stresses and challenges. In addition to coming to terms with the meaning of the illness for one’s life, and the more emotive issues of disease progression and deformity, individuals must cope with pain, stiffness and activity restrictions on a daily basis. Many of these adaptive challenges require help from others. Thus, for patients with rheumatic disease an available and satisfying network of interpersonal relations is essential, on which they can count for both emotional support and more practical assistance during periods of pain and disability.
Rheumatic disease has an inevitable impact on the patient’s family. The emotional reactions of patients to their illness spill over into feelings of helplessness and distress among family members. The fluctuating nature of many of the rheumatic conditions means family members must learn when to give and when to withhold help, as providing too much support or providing it at the wrong time may produce negative outcomes (Revenson, 1990).
IMPACT ON FAMILY RELATIONSHIPS
Rheumatic disease can affect the family in many ways. Some patients report that their arthritis brings them closer as a family; some say it makes no difference and others feel it has a negative effect on family life.
The Spouse and the Marriage
There is conflicting evidence as to whether the divorce rate is higher in patients with rheumatic disease, whether illness precipitates divorce or whether the lower rate of remarriage is associated with disease course (Medsger and Robinson, 1972). There is no dispute that rheumatic disease causes stress for the healthy spouse and on the marriage. Stressors caused by the conditions create demands for increased emotional support and tangible assistance from the healthy partner. Responsibilities may move outside traditional gender roles (Staines, 1986). As well as the patient possibly feeling more anxious and depressed, the spouses of ill individuals often experience depression and anxiety, marriage communication difficulties and problems at work (Flor, Turk and Scholz, 1987).
Effects of Parent’s Disease on Children
In one study, adolescents with a parent who had arthritis had poorer self-esteem than the comparison group (no parental disorder) (Hirsch, Moos and Reischl, 1985). It has been suggested that for adolescents whose parents have arthritis, involvement of friends with their families presents more opportunities for friends to ‘see the disability’, and consequently evaluate the parent and, by extension, the adolescent negatively. Thus, the parent’s physical disability might have a negative impact on the adolescent’s ability to draw on friendships for support (Hirsch and Reischl, 1985).
Benefits of Social Support
Arthritis patients receiving more support from friends and family exhibit greater self-esteem (Fitzpatrick et al., 1988), psychological adjustment (Affleck et al., 1988) and life satisfaction (Burckhardt, 1985). They cope more effectively with the illness (Manne and Zautra, 1989) and show less depression (Fitzpatrick et al., 1988). Support from family members may also enhance compliance with treatment interventions (Radojevic, Nicassio and Weisman, 1992).
The Costs of Receiving Social Support
Receiving, using or requesting social support has its costs as well as its benefits (Revenson and Majerovitz, 1990). The costs of asking for or receiving help involve threats to self-esteem, loss of autonomy and decreased psychological well-being. In one study common types of unhelpful support were:
• minimizing illness severity;
• pessimistic comments;
• pity or overly solicitous attitudes (Affleck et al., 1988).
Support needs to change over time in response to changing treatment regime demands, disability, pain and symptomatology. What may be useful one day may be perceived as inappropriate the next.
Implications for Clinical Practice
Social support is amenable to change through psychosocial intervention. Goals for practitioners to work towards are:
• teaching patients how to develop and maintain family ties;
• teaching patients how to recognize and accept the help and emotional encouragement provided by family members;
• improving family members’ skills for determining the patients’ support needs, and offering help;
• facilitating positive appraisals of support.
The key is to promote open communication among family members including feedback, and not criticism, when the help that was offered was not the help that was desired (Revenson, 1990).
Spouses of chronically ill patients should be encouraged to build support networks outside the marriage, both within their existing social milieu and through more formal support groups of others facing similar stresses. These networks become critically important as the patient’s health declines and disability increases; however, network building should be encouraged in the early stages of the illness so that networks are in place later on, when the patient is more limited and social activities with the support network may be restricted.
DEPRESSION
The onset of symptoms and eventual diagnosis of a chronic disease typically cause emotional distress. Anxiety, depression, shock and anger can persist throughout the duration of the condition (Treharne et al., 2004) A significant minority of people, however, will develop less transient and more severe psychological distress that can result in additional disability and suffering. Depression is the most common psychological disturbance associated with medical illness and can significantly increase the disability associated with the medical condition (Wells et al., 1989). Depression in the medically ill frequently goes undetected and untreated; if this is so the depression can become progressively debilitating and interfere with the optimal treatment for the medical condition. The presence of depression in rheumatic disease is particularly problematic as it is often associated with somatic symptoms that overlap or resemble symptoms of arthritis. To further complicate the picture, depression can lead to the amplification of somatic symptoms of arthritis, causing physician and patient mistakenly to attribute worsening symptoms and disability to worsening of the medical condition. This in turn can result in unwarranted treatment changes and overmedication (Katon and Sullivan, 1990). Depression is a debilitating and often life-threatening disorder and rheumatologists must be on the alert for depressive co-morbidity among their patients and be prepared to provide appropriate treatment or referral. A diagnosis of major depression, according to DSM-III-R criteria, requires the occurrence of one or more major depressive episodes. A major depressive episode requires the presence of at least five of the following symptoms for at least two weeks:
• depressed mood;
• diminished interest and pleasure in activities;
• significant weight loss or gain;
• sleep disturbance;
• agitation or retardation;
• fatigue or loss of energy;
• feelings of worthlessness or guilt;
• poor concentration;
• recurrent thoughts of death or suicide.
One of the first two symptoms must be included in the five required to diagnose a depressive episode. Symptoms clearly due to a physical condition do not satisfy the diagnostic criteria - for example, fatigue. Most of the research efforts have focused on psychological sequelae in five rheumatological conditions (RA, juvenile RA, SLE, fibromyalgia and OA) (Baum, 1982). The majority of studies suggest that there is a greater prevalence of depressive symptoms and depressive disorders among clinical samples of people with rheumatological diseases than in the general population. Dickens and Creed (2001) found individuals with rheumatoid arthritis were twice as likely to experience depression as members of the general population. The level of disturbance, however, is comparable to that found among clinical samples of people with other chronic medical conditions. Rheumatological disease severity and status have, at most, a very weak direct relation to the presence of depressive disorders and level of depressive symptoms. Depressive disorders and symptoms among people with rheumatological diseases are influenced more by pain, socioeconomic factors and social and other psychological resources, such as social support, a sense of control, illness intrusiveness and coping than by disease severity itself. Depressive disorders and even depressive symptoms have devastating effects on social, family and vocational functioning; when added to a chronic medical condition such as arthritis functional declines are additive. Compared to the general population, the prevalence of depressive disorders and symptoms appears to be higher among people with rheumatological diseases. Rheumatologists therefore must be alert to depressive co-morbidity and must guard against mistakenly attributing the additive effects of these co-morbid conditions to worsening primary medical illness (DeVellis, 1993).
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