SARAH RYAN AND MARGARET ANN VOYCE
After reading this chapter you should be able to:
• Describe the philosophy that underpins rheumatology nursing.
• Explain the role of the nurse in preparing the patient to commence a DMARD.
• Demonstrate an understanding of the safety monitoring required in the surveillance of DMARDs.
• Discuss the role of community provision for patients with musculoskeletal conditions.
• Explain the drug management of a person with osteoporosis.
Patients with inflammatory arthritis such as RA can experience a range of physical, psychological, social and/or sexual problems. The role of the nurse is to support, guide, educate and empower the patient and their family so that problems can be identified and care that has meaning and relevance for the patient implemented. This has to be a shared process between the patient and the nurse, as conditions such as RA are not curable and the patient must be committed to a long-term treatment plan. Patients with active disease activity (determined by haematological and biochemical markers, X-ray results and clinical findings) will require a combination of drug therapy to reduce symptoms such as pain and stiffness and also to suppress disease activity, minimizing the potential harm that prolonged inflammation can cause. Analgesia and non-steroidal anti-inflammatory drugs can provide symptoms relief and the DMARDs (see Table 3.1) can suppress disease activity. The nurse requires in-depth knowledge regarding the condition and treatment options and will need to employ the skills of educator to provide the patient with sufficient information to contribute to shared decision making prior to the commencement of drug therapy.
Therapeutic nursing has been defined by Powell (1991) as that practice where the nurse has made a difference to the patient’s or client’s health state and where he or she is aware of how and why this positive difference has occurred. Levine (1973) distinguishes between nursing which is supportive in nature and seeks to prevent further deterioration and that which is therapeutic, promoting adaptation and contributing to the restoration of well-being. The introduction of drug therapy in conjunction with other treatment interventions — for example, exercise — can be seen as fulfilling both a supportive and a therapeutic role, preventing deterioration and leading to an improvement in symptoms, enabling the patient to participate more fully in meaningful life activities.
Table 3.1 Disease-modifying anti-rheumatic drugs.
• Gold injections
Caring is the most important value of rheumatology nursing. Although often referred to as a basic requirement there is nothing basic about high quality nursing care, which requires a combination of knowledge, understanding and expertise. Caring involves both an action element in identifying and meeting the needs of the patient and an emotional element, which involves having regard for people as individuals and being concerned about what happens to them (Malin and Teasdale, 1991). It would appear that in many situations the action element remains the dominant feature of nursing practice with interactions with patients governed by their physical care needs, resulting in the neglect of the emotional needs of the patient (Henderson, 1994). Yet we know that from the patient’s perspective it is how the individual nurse relates to the patient, the emotional style, that determines whether a patient perceives a care episode as satisfactory or not (Smith, 1992). For care to be effective and holistic in nature the nurse must incorporate both the action and emotional element into care delivery. The adoption of this approach is as important in the instigation of drug therapy as in all treatment interventions, as the patient will have to be satisfied on an emotional level as to the value of drug therapy for compliance to occur.
THE NURSE-PATIENT RELATIONSHIP
The most important element in rheumatology nursing is the relationship that exists between the patient and the nurse. Such a relationship requires both time and knowledge for the nurse to begin to empower the patient so that an informed decision regarding care management can be reached. The relationship needs to be founded on participation. There is the assumption that by involving the patient in their own care they will ultimately obtain the status of participant but it may well be that the patient is participating from the nurse’s frame of reference, rather than from their own view point. Asking the patients to write down their expectations regarding drug therapy may provide the starting point from which the partnership can commence.
The factors needed for a therapeutic relationship include:
• Genuine participation.
It is important to encourage the patient to participate in as many treatment decisions as possible. When a patient chooses a course of action such as commencing sulfasalazine they are more likely to adhere even if the beneficial effects take some time to emerge, which in the case of this particular drug could be anything from two to four months. Informing the patient about different drug options and enabling the patient to choose from them should heighten his or her sense of control.
• The exploration of lay beliefs.
Until the nurse has spent time exploring the patient’s own beliefs about the purpose and outcome of drug therapy it will not be possible to arrive at shared treatment objectives.
• The establishment of realistic goals.
Trying to reach unrealistic goals will only demoralize and adversely affect selfesteem. If the patient is not informed that DMARDs take many months before benefit can be assessed they could become disillusioned with the treatment if symptoms did not improve after the first few weeks and discontinue the regime.
• The provision of information specific to the individual’s situation.
It is not helpful to be given generalized information and told what percentage of patients respond well to a given treatment. The individual requires information that is relevant to their own particular situation.
• The involvement of significant others.
It is important that family members are included and assist in care planning so that care options decided can be endorsed and implemented within the patient- supportive framework and within their own social setting.
• Maintaining contact.
It is important that the patient has access to a knowledgeable practitioner who is familiar with their care, at any time when there is a perceived change in disease activity or self-management. This can be maintained through a telephone helpline system, which provides the patient with a designated point of contact and helps to reduce anxiety and provide support.
Telephone advice lines have become an integral part of rheumatology care and are traditionally run by clinical nurse specialists or other heath professionals in extended roles (Thwaites, 2004). This service provides patients with the means of contacting professionals directly involved in their care management, for advice regarding symptoms management and concerns relating to drug therapy. The telephone advice line also provides direct access for other members of the team involved in the patient’s medical and nursing care to seek advice. For example, a general practitioner may ring to question whether gold injections should be discontinued due to the slight presence of haematuria on a urinalysis dipstick test. The immediate advice by the nurse to continue will prevent treatment being stopped unnecessarily. It will also enable a consistency to care management to develop between members of primary and secondary healthcare. This will reinforce communication links and promote a greater appreciation of the different roles of these two groups.
A philosophy of practice is required to enable nurses within rheumatology to work as a united team with identified shared goals for patient management. A philosophy consists of a system of beliefs from which core practice evolves. The establishment of a philosophy has to include debate and discussion from all members of the nursing team. It is a statement of purpose and will require commitment from all concerned for it to be integrated into practice. If a shared approach to care is not adopted then disunity and fragmentation of care will occur. A rheumatology nursing philosophy of care can be divided into four main areas which are interlinked and complementary to each other. These include:
• Beliefs relating to the environment.
• Beliefs relating to the individual patient.
• Beliefs relating to nursing.
Health is achieved when the patient is able to function on a physical, psychological and social level. This is not a reinstatement of complete well-being in all these spheres of life; rather that the patient perceives that they are able to make a useful contribution to all areas of activity. Health requires adaptations and the development of coping strategies to minimize the symptoms of arthritis. Health does not mean the removal of all symptoms; this would be an unrealistic outcome and an unfair burden to place on patients. Health and illness are not static entries and vary depending on:
• disease activity;
• coping strategies;
• available resources;
RA is characterized by flares and remissions of disease activity and the patients may find themselves alternating between health and illness or functioning well on a physical level but not on a psychological level. The patient will need to know how to access a knowledgeable nurse when they experience a stage in their condition that presents different or recurring problems, so that the situation can be reassessed collectively and necessary modifications to the treatment programme made.
Beliefs Relating to the Environment
A patient needs to be involved in the planning of all aspects of care to feel committed and able to implement the agreed treatment programme based on the individual’s perceived needs (Tones, 1991) and this applies equally to drug therapy. Neglect of individual concerns can lead to non-adherence with treatment. Nurses need to identify any existing internal and external barriers. A patient may not be able to open their medication container due to reduced manual dexterity or be afraid to continue with treatment due to adverse peer pressure. If the orientation of the consultation between the nurse and the patient does not encourage shared discussion, the patient may not feel part of the treatment regime and discontinue their medications if they are not immediately effective.
Beliefs Relating to the Individual Patient
The individual’s lay beliefs must be explored before any treatment plan is decided so that the care programme that emerges has both relevance and meaning of the individual concerned. Lay beliefs are usually consistent over time and pertinent to the individual concerned (Donovan, 1991). If a patient has in their lay belief system the thought that drug treatment such as gold has only the potential for damaging side effects to occur and not the potential for improvement they may reject this as a treatment option. The patient will require explanation on the disease process before they can understand the role of drug therapy. If they do not understand that their pain, stiffness and fatigue is related to disease activity they may not perceive drug treatment as a useful adjunct to other therapy.
The individual has a right to be an active not a passive recipient of care so informed decisions can be made and the management of the condition viewed as a shared commitment between the patient and the health professional. Patients may not feel equipped to adapt to this role at first but as the nurse begins to share knowledge with the patient and a therapeutic relationship develops the patient may feel more able to contribute to care decisions.
Beliefs Relating to Nursing
The nurse will be a knowledgeable practitioner using evidence-based practice to underpin holistic care management.
Once the clinical decision has been made to commence a patient on DMARD therapy, the patient will require to spend time with a knowledgeable practitioner so that the following aspects can be discussed:
• The purpose of the medication.
• The dosage and time of administration.
• Potential side effects.
• Monitoring regime.
• The patient’s expectations of treatment.
• The course to take if a problem arises.
Tones (1991) defines empowerment as the process whereby an individual or community of individuals acquire power - that is, the capacity to control other people and resources. By explaining about the particular drug therapy and the rationale for its introduction the patient will begin to determine its acceptability from their particular view point.
Klein (1974) describes five categories of patient involvement:
• Information. This is the process whereby the health professional gives the information to the patient and the patient passively receives it. This will not be useful for commencing patients on drug therapy as the patient will be the individual responsible for the administration of the medication and to adhere with the proposed regime must be committed to the type of treatment being advocated. Patient-physician communication may be the single most important variable affecting adherence (Bradley, 1989). For communication to be successful the nurse must present information clearly whilst the patient needs to seek clarification and ensure that their concerns are addressed (Newman et al., 1996).
Factors that influence effective practitioner-patient communication include: (Newman et al., 1996)
1) The nature of the explanation concerning the diagnosis, and the course and purpose of treatment. When rheumatologists were recorded as having made a clear statement about the purpose of the drug treatment 79% of patients adhered with their therapy compared to only 33% of patients when the explanation offered was not clear (Daltroy, 1993).
2) An overuse of medicaljargon, which excludes the patient from shared discussion.
3) A shared agreement of the goals for treatment are essential. Arluke (1980) found that some patients with RA stopped their medication at the first sign of improvement as they held the belief that drug efficacy would reduce over time.
4) The need to obtain the patient’s concerns regarding drug treatment. Several studies have shown that practitioners misperceive patients’ needs regarding the amount, content and preferred method forproviding information (e.g. drug information sheets) on arthritis and its treatments (Potts, Mazzuca and Brandt, 1986).
• Consultation. The health professional may consult the patient and may use the information gained. This will not lead to a shared approach towards treatment management as the practitioner may not have obtained the patient’s beliefs, values and expectations, which are all potent factors affecting adherence, not only because of their direct relationship to health behaviour but also because they are subject to misinterpretation unless clarification is sought and will ultimately influence how satisfied the patient is with the consultation.
• Negotiation. Here equality exists and both parties contribute to the decision making and negotiate the treatment. The nurse would begin by ascertaining the patient’s concerns regarding treatment and identify potential compliance difficulties and jointly plan how to overcome them (Daltroy, 1993).
• Participation. A patient’s values are taken into account and underpin the decision process. A patient may prefer not to commence methotrexate if they drink alcohol regularly and will be more likely to comply with an alternative drug where they do not have to abstain from alcohol.
• Veto-participation. The patient holds the right not to comply with treatment. Liang (1989) describes non-compliance as the ultimate experience of independence. If this occurs it should do so only after full negotiation has occurred and not as a result of ignorance or non-disclosure. The nurse would seek to ascertain the reason why the patient was declining drug therapy. It may be due to a lack of knowledge or apprehensions that have not been discussed. If patients decline therapy they must be given the opportunity to reaccess the service at any time to reassess their condition and other treatment options.
The mode of action of DMARDs has been discussed in depth in Chapter 2. Patients often commence DMARDs at a time when their arthritis is in an illness phase
with evidence of increased disease activity. This will often cause the patient to experience an increase in symptomatology inducing pain, stiffness, fatigue, low mood and systemic manifestations such as anaemia. The majority of DMARDs take many months before their ability to affect the disease process can be assessed. Patients respond at different times but will require education, support and guidance at the commencement of treatment and on an ongoing basis. The nurse will need, in conjunction with the patient, to plan interventions to enable the patient to cope with increased symptomatology. This may include a combination of exercise, relaxation, pacing activities, review of analgesia or an inpatient stay.
The objective of ongoing education and care provision are to enable the patients to participate effectively in their own management, develop coping skills, make informed choices about their treatment and weigh up the consequences of their action or inaction.
In a comprehensive review of patient education studies, Lorig et al. (1987) demonstrated positive improvement in patient knowledge, self-care beliefs, medication adjustment and compliance; as well as psychosocial characteristics such as anxiety, depression, self-esteem, locus of control and health status.
After the patient has received a full explanation regarding the drug treatment proposed and been given the opportunity to discuss concerns and expressed a commitment to the therapy there may be safety preparation that needs to occur prior to commencement of the named drug - for example, if a patient is to commence methotrexate a chest X-ray will need to be obtained.
Patients receiving DMARDs require regular safety monitoring of therapy and assessment of disease activity. This is usually carried out within the holistic framework of a nurse led follow up clinic. The full functions of such a clinic can be seen in Table 3.2.
Running drug monitor clinics is a major component of the nurse specialist role (Phelan et al., 1992; Ryan and Hill, 2004) Nurse-led clinics allow partnership, intimacy and reciprocity to evolve between the nurse and the patient and provide the medium for an ongoing therapeutic partnership to develop in which the nurse will be assessing all care needs and identifying problems that may require a referral to other members of the healthcare team such as the chiropodist. The clinic will also provide the forum for education and the development of coping strategies. The nurse’s role evolves from supportive to therapeutic, instead of concentrating exclusively on preventing deteriorating. The nurse will incorporate essential nursing functions (see Table 3.3) to promote adaptation to the condition for the patient and their families.
Table 3.2 Functions of a nurse-led clinic (Hill, 1992).
• Assessing the progress of the disease
• Monitoring the progress of the disease
• Monitoring drug response
• Initiating and interpreting clinical and laboratory data
• Acting as educator
• Expert source of referral to other members of the multidisciplinary team
Table 3.3 Key nursing functions (Wilson Barnett, 1984).
• Understanding illness and treatment from the patient’s viewpoint
• Providing continuous psychological care during illness and critical events
• Helping people cope with illness or potential health problems
• Providing comfort
• Coordinating treatment and other events affecting the patient
For care to be meaningful within an individual context nurses must understand the impact of illness from the patient’s view point (Ryan, 1996). The nurse must work actively with the patient to establish realistic achievable goals which incorporate the patient’s lay beliefs.
The Operational Workings of a Drug Monitoring Clinic
Patients receiving DMARDs and cytotoxic agents require regular blood tests and in certain cases urinalysis and blood pressure monitoring. The British Society of Rheumatology and the British Health Professionals in Rheumatology have produced guidelines for clinicians and these are available from either society. Kay and Puller (1992) found marked variations amongst respondents in monitoring schedules and in the interpretation of results.
At each visit the patient is seen by the same rheumatology nurse to allow the continuation of the therapeutic relationship. The nurse will:
• Assess safety in administration - for example, ensuring that methotrexate is taken on a weekly basis.
• Monitor and observe for any drug reactions that have occurred - for example, gastrointestinal, skin, urinary abnormalities and chest manifestations.
• Take blood to ascertain any bone marrow suppression leading to a reduction in red blood cells, white blood cells and platelet count; elevation in liver function tests, creatinine levels and urea and electrolytes where indicated. Hill’s (1994) research demonstrated that the nurse practitioner is able to identify and instigate appropriate action from blood results.
• Provide the patient with time to discuss any perceived problems or concerns - for example, is it safe to have vaccinations? Is it normal to experience increased stiffness after the administration of intramuscular gold?
• Assess for evidence of increased disease activity - for example, synovitis. This may necessitate a different treatment intervention - for example, the administration of intra-articular injections. About 12% of nurse specialists within rheumatology are engaged in the provision of intra-articular injections (Phelan et al., 1992) and this number is rapidly increasing as nurses seek to develop their practice around patient need and provide a more comprehensive programme of care expansion and is in accordance with principles established in the scope of professional practice (UKCC, 1992). This framework encourages and supports nurses to develop practice which has been shown to directly benefit patient care, as long as it does not fragment existing care or involve inappropriate delegation of duties. It would be inappropriate, indeed unsafe practice, to develop one’s role without first obtaining the necessary theoretical knowledge and practical expertise necessary to ensure understanding and safe practice. Benner (1984) states that an expert nurse requires a combination of academic achievement, recognized clinical expertise and practical experience.
• Access other care needs within a holistic framework (see Figure 3.1) and refer where appropriate to other members of the multidisciplinary team.
• Provide the patient with the telephone helpline - providing a designated point of contact with a knowledgeable practitioner should any problems or concerns arise before the next appointment.
The Staffordshire Rheumatology Centre uses a computerized drug monitor program. Kay (1989) states that more use could be made of computer technology in drug monitoring. All relevant information about the patient is recorded. This includes demographic data, blood and urine results, medications taken and reasons for discontinuation where appropriate. The computer is programmed to alert the operator to any results that fall outside the normal parameters such as three consecutive falls in platelets. It is also an invaluable communication tool as any member of the nursing and medical team can place a message on the patient’s computerized record that will be acknowledged by the nurse conducting the clinic. This may include requests for additional investigations to be made while the patient is in clinic so that they do not have the inconvenience of being recalled. Other units use a metrology graph which includes a visual analogue pain scale, early morning stiffness, articular index, grip strength and the recording of drug regimes. A list of past medication and the reasons for discontinuation is kept on the reverse of the graph. Joint injections, intramuscular steroid injections, infusions, admissions, trauma and even domestic stress are recorded on the chart because they all have a bearing on disease activity. This method of documentation enables the course of the disease to be followed easily (Thompson, Morgan and Fletcher, 1992).
THE USE OF PROTOCOLS
Figure 3.1 The rheumatology nurse forum problem model.
The establishment of protocols to guide decision making, ensure continuity of care and safety in practice requires collaboration and commitment from all healthprofessionals involved in the monitoring and assessment of drug therapy. They provide an educational tool for nurses by ensuring that practice is research-based, and act as a dynamic structure updated when new evidence becomes available. The protocols may cover:
• Urinary abnormalities.
• Gastrointestinal side effects.
• Skin manifestations.
• Chest symptoms.
• Alteration of drug dosages.
Included below are the protocols used for the daily drug monitor clinic at the Staffordshire Rheumatology Centre. This provides an example of the framework we have adopted enabling these protocols to be a fluid and dynamic tool supporting nurses in the decision making process.
DRUG MONITOR CLINIC PROTOCOLS
Reactions can occur in many sites. The nurse needs to:
• Be aware of what to look for.
• Know how to respond.
1. Skin manifestations. Changes in skin integrity can be related to:
(a) The disease process - that is, vasculitis and leg ulcers.
(b) The drugs used for therapy - that is, gold injections.
(c) Difficulties faced in maintenance of skin integrity.
- May occur with any medication but is most commonly seen in those patients having gold therapy.
- Can vary from minor eczematous lesions to severe widespread problem.
If a patient presents with a rash:
- Ask if they have recently changed their detergent. Consider sun burn, insect bites.
If the rash is isolated to an odd patch, advise E45 cream. Review in a month’s time.
If it is a severe, persistent or generalized rash, this may require a dermatology opinion - arrange referral.
If the itching is:
- troublesome - continue with treatment. Advise use of E45 cream or antihistamines. If the scalp is itchy, scaly or dry, advise a coal tar-based solution - for example, Baltar.
- unbearable - that is, cannot sleep with it - stop the medication and refer to the doctor’s clinic.
2. Urinary manifestations
Urinary abnormalities may be due to:
(a) The disease itself - amyloid.
(b) Gold or D-penicillamine and are less likely with sulfasalazine and methotrexate.
(c) Asymptomatic urinary tract infections, which are common in RA patients.
(d) The ultra-sensitivity of lab stick testing.
- A trace or one + in isolation ignore.
- ++ repeat dipstick testing, if ++ still present then send midstream specimen of urine (MSSU) (patient and GP will be contacted if infection is present).
- If patient is symptomatic send MSSU.
- If MSSU reveals no infection but ++ persists arrange 24-hour urine collection.
- When sending off an MSSU please record on the form whether or not the patient is taking antibiotics.
- If +++ protein stop treatment and collect 24-hour urine, unless the patient is known to have proteinuria.
- Confirm that the patient is not menstruating.
- A trace or one + in isolation ignore.
- If ++ or +++ MSSU - continue treatment.
- If the patient has observed blood loss, inform doctor.
- If nitrate positive with protein or blood, send MSSU.
- Nitrate in isolation ignore.
- If known diabetic, advise, refer back to diabetic monitoring.
- If not known to be diabetic arrange random blood sugar (if over 11 mmol = diagnostic of diabetes, and will require fasting blood sugar. Fasting blood sugar of over 8 = diagnostic of diabetes.
If the patient presents with a sore mouth:
(a) If dentures are worn ensure these are fitted correctly.
(b) For minor ulcers (i.e. one or two in isolation) continue treatment and suggest: Bonjela, Bioral Gel (apply after meals and bedtime), Bioplex mouth rinse.
(c) For major mouth ulcers - that is, acute severe crop, more than two ulcers: The patient may require Difflan mouth wash and Corlan lozenges or Adcortyl in Orabase. Inform GP.
4. Gastrointestinal tract
(a) Anorexia, dyspepsia and nausea can occur with any drug.
(b) Sulfasalazine - if nausea and/or vomiting occurs. Reduce back to the dose that was not causing this problem and increase as per protocol on fortnightly not weekly basis. If a rash occurs desensitization may be appropriate for early onset (first 14 days/rash - require 2/52 monitor and increase as per protocol).
(c) Leflunomide - if loose stools are experienced patients should be encouraged to remain on the medication and treat the bowel problem.
(d) Penicillamine - taste alteration can occur for up to 12-16 weeks. Support and reassure the patient. May require advice on nutritional supplementation.
(e) Methotrexate - if nausea/vomiting occurs split the dosage over the day, or two days. If nausea/vomiting continues to persist, patient will require domperidone (10 mg three times a day).
(f) Remember gastrointestinal intolerance could be due to NSAIDs - advise over-the-counter antacids and, if it persists, to see doctor.
(a) Common with sulfasalazine, can occur with leflunomide.
(b) If severe stop drug. Reintroduce after one month at two-weekly intervals.
6. Active joint involvement
(a) Joint stiffness - may follow administration of gold.
7. Chest symptoms
Breathlessness with or without a cough in a patient on gold, leflunomide or methotrexate. Inform doctor.
Can occur whilst taking cytotoxic drugs - that is, cyclophosphamide or methotrexate. If troublesome or severe inform doctor.
If the patient notices weakness, double vision, swelling or speech difficulties this raises the possibility of drug-induced myositis (inflammation of muscle) or myasthenia gravis (disorder of the neuromuscular junction) - inform doctor.
• Septic joint - if patient has a pyrexia and a hot red joint think of sepsis and inform doctor.
• Neck instability - sudden onset of weakness in hands and legs. Recent onset of bladder and/or bowel incontinence - inform doctor.
• Early herpes zoster - if patient on immunosuppressants they may need anti-viral therapy. Stop cytotoxic medication temporarily until herpes zoster has cleared.
Patients who require blood pressure recording.
1. Patients receiving ciclosporin or leflunomide or present with significant protein- urea or haematuria - if the diastolic is greater than 95 Hg discuss with the doctor
Having such a framework enables the nurse to take immediate action when faced with side effects. Ryan (1997) states that during the first year of using such protocols over 800 patients were reviewed in the clinic with only 2% requiring medical referral. Before the instigation of the protocols 16% of patients were referred annually for a medical consultation primarily as a result of limitations being placed on nurse decision making skills.
The protocols can also ensure continuity of care when the patient moves back in to the community setting.
The most frequently requested laboratory test is the full blood count (Higgins, 1996). This test examines three groups of cells with different functions: platelets, red cells (erythrocytes) and white cells (leucocytes). Around 2-2.5 mls of venous blood is required in a tube containing an anticoagulant.
Red Blood Cells
RBCs are biconcave disks. Their main function is to transport haemoglobin around the body and supply oxygen to the tissues. The average number of RBCs per cubic millimetre of blood is about 5 million. The number of RBCs available in the circulation is regulated so that there is an adequate source to provide oxygenation of the tissues without stopping blood flow. The RBC has a very flexible structure which allows it to alter shape as it passes through the capillaries without damage. Altitude and the degree of exercise undertaken can affect the number of circulating RBCs.
RBCs derive from a cell known as the haemocytoblast and are produced in the bone marrow.
Vitamin B12 (Cyanocobalamin)
Vitamin B12 is a nutrient that is required for all cells of the body. An absence or reduced supply of vitamin B12 will severely hinder the rate of RBC production, the problem often being the failure to absorb vitamin B12 from the gastrointestinal tract, as occurs in pernicious anaemia. Gastric secretion contains a substance called the intrinsic factor which combines with vitamin B12 in food, so preparing it for absorption by the gut; but in pernicious anaemia the gastric muscosa does not secrete the intrinsic factor and therefore absorption cannot occur.
In the normal process vitamin B12 is stored in large quantities in the liver after being absorbed from the gastric system. The total amount of vitamin B12 required every day to assist in RBC production is less than 1 microgram and the store in the liver is a thousand times that amount.
Folic acid is part of the vitamin B complex and deficiency can also hinder the production of RBCs.
The typical anaemia of RA is a normocytic normochromic anaemia; the haemoglobin being around 10-12 g/dl. There appears to be a correlation between disease activity and the severity of anaemia. Some disease modifying anti-rheumatic drugs (e.g. gold) may induce anaemia by attacking erythyroid progenitor cells but in other situations studies show that these therapies may normalize erythropiesis (Pincus et al., 1990).
The cause of anaemia in RA is multifactorial. Iron utilization is impaired as indicted by reduced serum iron and transferritin concentration. As with other forms of chronic inflammation there is an increased synthesis of ferritin and haemosiderin, abnormal retention of iron from FBCs by the reticulo-endothelial system and an increase of lactoferritin, which contributes to the binding and lowering of serum iron (Matteson, Cohen and Conn, 1994).
Anaemia means a deficiency of RBCs with haematocritis sometimes as low as 10%. The anaemia of RA can be complicated by:
• blood loss - NSAIDs can cause intestinal blood loss;
• poor nutrition;
• intercurrent infections;
• autoimmune haemolytic anaemia;
• bone marrow suppression secondary to drug treatment - for example, gold.
A macrocytic macrochromic anaemia may be due to vitamin B12 or folate deficiency, alcohol intake or the mechanisms of sulfasalazine or methotrexate (Hernadez et al., 1975).
When stained and viewed under the microscope it is possible to identify five types of leucocyte. A full blood count measures both their total number and counts the number of each of the five types. This is the differential count. The normal range of values and differential results can be seen in Table 3.4.
The white blood cells (WBCs) are the mobile units of the body’s protective system. They are formed in the bone marrow and the lymph nodes prior to being transported in the blood to the different parts of the body where they are used. All WBCs have a limited life span and adequate numbers are maintained through marrow production.
WBCs play a central role in the process of inflammation. The purpose of the inflammatory response is a complex integration of cellular function and although each type of leucocyte has a different and well-defined function they operate in conjunction communicating via a range of chemical messengers called cytokines (Higgins, 1996). This concept is explained in greater detail in Chapter 1.
Table 3.4 White blood cells.
Leucocytosis (a raised WBC count) occasionally occurs in RA but it is not a typical feature. If marked it should raise suspicions of a superseded infection (either systemic or a septic arthritis), a post-infected arthritis or one of the varieties of polyarteritis.
Leucopaenia (a reduced WBC count) can occur in systemic lupus erythematosus and in Felty’s syndrome but the commonest cause is in the use of DMARDs.
From 40-75% of circulating WBCs are neutrophils, the first line of defence against bacterial invasions. They are present in large numbers at the place of invasion where they ingest and kill bacteria by a process of phagocytosis.
These are mobile WBCs that filter out of the blood and into the tissues, where they are referred to as macrophages. The key role is probably as an antigen-presenting cell. Lymphocytes cannot respond to naked antigen and it must first be processed by and presented on the surface of an antigen-presenting cell. Macrophages become attached to tissues and remain attached for months, even years. They are involved in the primary clearance of highly resistant bacteria such as mycobacteria.
Monocytes manufacture a range of cytokines that attract or activate other cells involved in the inflammatory response - for example, macrophages produce interleukin 1 which activates a type of lymphocytes to kill viruses (Oppenheim, Koacs and Matsushima, 1986).
These are seen only rarely in peripheral blood. They mature in the tissues, becoming mast cells. These cells liberate heparin into the blood to prevent blood coagulation and to assist in tissue repair. The mast cells also release histamine and small quantities of bradykinin and serotonin during inflammation.
These cells are natural phagocytes. They collect at the site of antigen antibody reaction in the tissues and ‘digest’ the combined antigen antibody complex after the immune process has performed its function. Eosinophils are involved in the pathogenesis of hypersensitivity (allergic) reactions. Their number is greatly increased in the circulating blood during allergic reactions.
Eosinophils accompanying RA is sometimes associated with extra-articular manifestations (Parrish, Franco and Schur, 1971). Although the pathogenesis is not known, immune complexes may be chemotaxis for eosinophils (e.g. attracted towards the source of the chemical).
Eosinophilia has also been associated with high titre of rheumatoid factor, elevation of serum gammaglobulins and diminished serum complement levels (Matteson, Cohen and Conn, 1994). Pulmonary complications may be associated with eosinophili (Crisp et al., 1982) or it may be associated with drug therapy such as gold.
From 20-40% of circulating WBCs are lymphocytes, which are the cells of the acquired immune system although a routine blood count cannot differentiate between them. There are two types - B lymphocytes and T lymphocytes. B lymphocytes produce antibodies and T lymphocytes are responsible for the elimination of viruses and other micro-organisms that infect the cell of the host and are not ‘visible’ for antibody attack (Higgins, 1996). Both types of lymphocyte function are independent and a normal immune response requires adequate numbers of both B and T lymphocytes.
Causes of Low White Cell Count
A low WBC count is significant because it reduces the body’s protection against infection. If the neutrophil count falls below 0.5 x 109 per litre patients are likely to become susceptible to frequently recurring bacterial infections. If levels drop further life is threatened by the risk of overwhelming infection.
Causes of leucopaenia include:
• Felty’s syndrome.
• Aplastic anaemia, which is a pancytopenia where reduced production of bone marrow stem cells results in reduced numbers of red cells, white cells and platelets. Aplastic anaemia can be inherited as can pancytopenia although most causes of the latter arise as side effects of cytotoxic drugs.
• Systemic lupus erythematosus.
• Side effect of DMARDs.
• Leukaemia is associated with reduced neutrophil count as bone marrow production of large numbers of abnormal immature white cells continues at the expense of normal white cell production.
• Acquired immune deficiency syndrome (AIDS).
• Hodgkin’s disease.
The bone marrow stops producing WBCs, leaving the body unprotected against bacteria and other agents that might invade the tissues. Within two days of production ceasing, ulcers appear in the mouth and colon and severe respiratory infection develops. Bacteria then rapidly invade the surrounding tissues and the blood; without treatment death usually occurs within a week.
The number of platelets in each cubic millimetre of blood is normally around 300 000. An increased amount of platelets (thrombocytosis) is a frequent finding in active RA and may well correlate with the number of joints involved, the amount of active synovitis and the presence of extra-articular features. The mechanism of thrombocytosis is uncertain; an increase in the intravascular coagulation with a compensatory increase in platelet production has been suggested (Matteson, Cohen and Conn, 1994). The thrombocytosis does not predispose to an increase in thrombotic events and is not correlated with bone marrow neoplastic changes. A reduced platelet count (thrombocytopenia) is rare in RA except when related to drug treatment or Felty’s syndrome.
Liver function abnormalities may reflect the anaemia, thrombocytosis and increased erythrocyte sedimentation rate of active inflammatory disease such as RA. Examination of liver histology at this time reveals only minimal non-specific change and some perioportal mononuclear cell infiltration (Matteson, Cohen and Conn, 1994).
Active RA may be associated with an increase in liver enzymes, especially serum glutamic oxaloacetic transaminase (SGOT) and alkaline phosphatase (Fernandes et al., 1979).
Total protein, total albumin and total globulin estimates are also taken. These reflect hepatic function (particularly albumin which is made in the liver) as well as absorption and inflammation. Apart from in lupoid hepatitis, which can mimic RA, bilirubin and SGOT are likely to be normal.
NSAIDs may induce liver enzyme abnormalities and it may be difficult to differentiate between drug effects and disease activity without discontinuation of NSAID therapy. NSAIDs seldom cause serious liver deterioration. Liver involvement may be present in up to 65% of patients with Felty’s syndrome (Thorne et al., 1982).
Calcium, phosphate and alkaline phosphatase are all measured. Calcium is bound to protein and this may need a correction factor if protein levels are abnormal as can occur in RA. A slightly raised calcium and raised alkaline phophatase level if of bony origin should alert the clinician to the possibility of osteomalacia. In Paget’s disease there is a markedly raised alkaline phosphatase of bony origin. X-ray confirmation of Paget’s disease should be sought since secondary cancer in bone can also cause a raised alkaline phosphatase.
Kidney involvement is usually sparse in RA although a low grade nephropathy, glomerulitis vasculitis and secondary amyloidosis have all been described (Matteson, Cohen and Conn, 1994). More commonly renal abnormalities result from agents used in the treatment of RA, notably gold, D-penicillamine, ciclosporin and the NSAIDs (Samuels et al., 1977). The renal involvement caused by nephrotoxic drugs is more likely to be seen first on routine urine testing.
Electrolytes (sodium, potassium, chloride and bicarbonate) together with urea and creatinine are usually measured. The chronic renal failure of connective tissue disorders may produce a raised potassium and a low bicarbonate level. The renal function in a normal population will deteriorate throughout adult life. Urea may be raised because of dehydration but creatinine is less likely to do so under those circumstances. Creatinine is the most sensitive simple estimation of renal damage and a raised level may indicate amyloidosis or chronic renal failure.
This may develop in patients with RA as a result of long-standing active inflammation and cause proteinuria. It is not specific to the kidneys and may affect other organs including the heart, liver, spleen, intestines and skin. The diagnosis of amyloidosis is confirmed by biopsy of the involved tissue. Unfortunately the presence of secondary amyloidosis in patients with RA heralds a poor outcome.
ASSESSMENT OF RHEUMATIC DISEASE ACTIVITY
This is a commonly requested immunological investigation. Rheumatoid factor (RF) is found in the blood of 75% of patients with RA of more than 12 months duration but in only 40-50% of those with early disease. Therefore the absence of RF does not preclude a diagnosis of RA; indeed the diagnosis of RA is not made on the presence of RF alone but includes a host of other factors. If the RF is absent and the patient has RA the arthritis is said to be sero-negative.
The RF, an IgM/IgG complex of two immunoglobulins, can also be found in other conditions including liver disease, sarcoidosis, subacute bacterial endocarditis and in 4% of healthy adults.
The RF is detected by one or more of the following tests:
• sheep cell agglutination (Rose Waaler) test;
• latex agglutination test.
The Rose Waaler test is given as a titre; below 1:32 is not significant, 1:64 is positive and values above 1:500 usually indicate severe rheumatoid disease.
The Anti-Nuclear Antibody
The ANA is regarded as an initial screening test for systemic lupus erythematosus but is not specific for this condition and if positive the clinician will proceed to request DNA binding from the same patient before confirming a diagnosis of lupus. ANA can occur in other connective tissue disorders such as systemic sclerosis and occasionally in low titre in RA. The ANA titre is important and titres of 1:200 or more in the presence of anti-DNA antibodies are likely to confirm the diagnosis of lupus.
Extractable Nuclear Antigen
The ENA is helpful for the diagnosis of mixed connective tissue disorder (Golding, 1981).
These can provide useful information when the ESR is raised for no obvious reason. In sero-positive RA serum IgM is usually though not always raised representing RF in the blood. Equally there may be a polycolonal increase of all immunoglobulins such as IgA, IgG and IgM.
IgA synthesized in mucous membranes may be raised in Sjogren’s syndrome.
Plasma Proteins and Electrophoresis
The alpha 2 globulin is an acute phase reactant which when elevated indicates tissue destruction in the early phases of rheumatic disease. In the later stages a raised gammaglobulin may indicate antibody formation and very high levels can occur in connective tissue diseases, sarcoidosis and myelomatosis (Golding, 1981).
Erythrocyte Sedimentation Rate
The erythrocyte sedimentation rate (ESR) is used as the standard test in many hospitals for evaluating disease activity in rheumatic disease. If inflammation is present in the body the ESR increases. This is due to the changes in the patient’s blood. A quantity (2 mls) of anticoagulated blood is sucked into a capillary tube and the speed with which red and white cells settle over a period of one hour is observed. Normal values vary with age and sex. ESR is of value in distinguishing inflammatory polyarthritis from the degenerative conditions.
ESR is elevated in RA, AS, acute gout, PMR, systemic connective tissue disorders, reactive and infective arthritis. A persistently raised ESR should alert the clinician to the possibility of myeloma (a malignant condition of the plasma cells). If suspected, urine should be collected to test for Bence Jones protein, a characteristic protein produced by the cell.
The ESR is not normally elevated in degenerative metabolic joint disease or in soft tissue rheumatism. The Westergren method of establishing the ESR is now universally used. ESRs of up to 20 mm/hr in males and 25 mm/hr in females are accepted as being within normal limits in rheumatological practice (Golding, 1981).
The plasma viscosity (PV) test mimics ESR evaluation but studies the movement of the plasma in the horizontal rather than the vertical plane. PV eliminates the variation caused by the anaemia of RA which can influence the ESR. High values are found in active RA.
C-reactive protein (CRP) is an acute inflammatory protein produced by the liver in response to infections, inflammation or acute injury. It rises in active RA falling back to normal levels once the disease has come under control. Changes in the CRP occur faster than in other biochemical assessments. Levels remain normal in systemic lupus erythematosus.
Other Acute Phase Reactants
Fibrinogen, hepatoglobin and caeruloplasmin all behave as acute phase reactants with high levels found in active disease and low values apparent as the conduction comes under control (Golding, 1981).
Urinalysis, the examination of urine, is a valuable tool for the diagnosis of and screening for several conditions. It also plays an important role in the surveillance of drug therapy especially in terms of toxicity. This will be discussed in further depth later on in the chapter. A patient who is asked to supply a specimen of urine for testing requires the following:
• An explanation of the reason for testing.
• Instruction in the method of collecting the specimen.
• The provision of suitable equipment, including a container for the specimen and washing facilities.
• An appropriate environment including wherever possible visual and auditory privacy and adequate time (Cook, 1996).
The appearance of the urine should be noted for colour and clarity. Colour changes may be due to endogenous pigments such as haemoglobin (red/brown colour), bilirubin (yellow) or intact red cells (smoky red). Exogenous pigments such as contamination with menstrual blood may also cause colour changes. The administration of sulfasalazine can cause orange discoloration.
Cloudiness is caused by suspended particles which will settle on standing to leave a deposit. Normal urine may contain some renal tubular cells and a few white and red blood cells; these will be prevalent in certain diseases contributing to a cloudy appearance (Cook, 1996).
Normal, freshly voided urine has very little odour but will develop an ammoniacal smell if left for any length of time. Infected urine has a characteristic fishy smell. The urine of patients with anorexia, or a ketoacidosis diabetic person will have a sweet smell. The administration of sulfasalazine and/or D-penicillamine can also cause a characteristic odour.
MEASUREMENT OF SPECIFIC GRAVITY
This can be measured using either reagent strips or a specially calibrated hydrometer. Specific gravity of the urine measures the ability of the kidneys to concentrate or dilute urine. A low specific gravity can occur if a patient has a high intake of fluid or it may indicate renal abnormalities or the presence of diabetes insipidious. A raised specific gravity may indicate dehydration.
Routine testing of urine may detect:
• Glucose. This is not usually found in urine. Its presence may be due to raised blood glucose levels or to reduced renal absorption. It can be associated with conditions such as diabetes mellitus, stress, Cushing’s syndrome and acute pancreatitis. Glycosuria occurring in the urine of a patient with rheumatic disease alerts the clinician to the possibility of corticosteroid-induced diabetes mellitus.
• Bilirubin in the urine may be indicative of hepatic or biliary disease. It may also be present if the patient has been prescribed phenothiazides or chlorpromazine leading to a false positive result occurring.
• Ketones. These are not normal constituents of urine; they are the produces of the breakdown of fatty acids. Their presence may indicate starvation, excessive dieting or uncontrolled diabetes (Cook, 1996).
• Blood. Often found to be of no significance but should be investigated if persistent. It may be due to trauma, infection, tumour or stones. Haematuria is an early sign of polyarteritis and 50% of patients with lupus will have small amounts of blood and protein in their urine.
• Protein can indicate a range of conditions including renal disease, urinary tract infection, hypertension, pre-eclampsia or congestive heart failure. Transient positive tests are not always significant, and normal urine contains small amounts of albumin and globulin although not usually at a level that would be detected positively on a reagent strip. When testing for urinary protein a morning specimen of urine is recommended to ensure sufficient concentration (Cook, 1996). Proteinuria may be the first sign of a collagen disease such as polyarteritis. In rheumatoid disease it may indicate urinary infections, nephropathy due to gold or D-penicillamine or be secondary to amyloid diseases. If proteinuria persists a 24-hour urine specimen should be requested; more than 0.15 g protein/24 hours is abnormal. Over 1 g/24 hours is found when there is renal tubular damage and in nephrosis well over 5 g protein/24 hours can occur (Golding, 1981). The presence of albuminuria on routine testing often indicates a simple infection that will require treatment to prevent aggravation of a flare of RA but it may also indicate glomerular dysfunction in conditions such as lupus.
• Urobilinogen. This is normally found in urine but increased levels may indicate liver abnormalities or excessive destruction of red blood cells such as in haemolytic anaemia (Cook, 1996).
• Nitrate. This is not normally present in urine. It is produced when gram-negative bacteria such as Escherichia coli convert dietary nitrates (e.g. from the preservative in meat products and cheese and in smoked foods) to nitrites. As E. coli is responsible for 80% of urine infections (Talaro and Talaro, 1993), the presence of nitrites is strongly suggestive of urinary tract infection. The specimen for testing should have been in the bladder for at least four hours before voiding to allow sufficient time for the nitrate/nitrite conversion.
• Leucocytes. The presence of leucocytes in the urine is an indication of bladder or renal infection but follow-up testing such as urine culture is required. White blood cells should be sought in the urine when infections such as Reiter’s disease are suspected. Early morning specimens are more likely to contain tubercule bacilli than those taken later in the day if the condition is suspected.
The results of the urinalysis should be recorded in the patient’s records as soon as possible after testing. It is worth noting that a negative result on a particular date may acquire significance in retrospect so all results should be recorded in patient’s records at the time of testing (Cook, 1996).
Gold is used as long-term treatment for inflammatory joint disease (most commonly RA). Initially most patients are given a test dose of 10 mg intramuscularly (IM) and if no adverse effects are experienced progress to 50 mg IM weekly reducing to 50 mg fortnightly as the patient responds, normally around six months. With adequate control, frequency is reduced to monthly (around 12 months) and continued indefinitely until side effects occur. It may take three to six months for patients to respond to treatment with gold. There are vast variations in the implementation of gold therapy. Kay and Puller (1992) found that out of a survey of 100 rheumatologists 89% used a test dose of intramuscular gold but of those who gave a test dose 64% gave a single 10 mg dose, 9% gave 10 mg followed by 20 mg, 4.5% gave 5 mg followed by 10 mg and the remaining rheumatologists gave various slowly increasing incremental doses. Toxicity with injectable gold is common occurring in 30-40% of patients (Day, 1994).
Elderly, renal or hepatic impairment, urticaria, eczema or inflammatory bowel disease.
• Severe renal or hepatic impairment
• Blood disorders
• Systemic lupus erythematosus
• Significant pulmonary fibrosis
• Pregnancy and lactation.
Nephrotoxicity. It is the responsibility of the nurse administering the intramuscular injection of gold to test the urine prior to giving the injection. Minor transient proteinuria is common whilst on this therapy. A meta-analysis of clinical trials showed significant proteinuria in patients receiving gold (Day, 1994). A trace of proteinuria can be ignored but increasing proteinuria is an indication to stop gold. Treatment should be discontinued if 24-hour protein urinalysis exceeds over 1 g. Recovery is usual when gold is stopped.
Minor renal effects in the absence of proteinuria has been noted with the elevation of enzymes and tubular cell secretion, but this increased turnover of tubular cells has not been related to decreased tubular function later in life (Ganley, Paget and Reidenberg, 1989). Isolated microscopic haematuria is not usually attributed to gold (Leonard et al., 1987).
Dermatitis and oral reactions account for 60-80% of all reactions to injectable gold complexes (Champion, Graham and Zeigler, 1990). Oral mucosal lesions occur less often than rashes. Minor ulcers can be treated symptomatically. Check that ill-fitting dentures are not causing friction. Most rashes are usually erythematous and macular but rarely can exfoliate; 85% of rashes are severely pruritic.
Raised eosinophils may be the forerunner to a rash, and the rash may be associated with a metallic taste and organ toxicity such as proteinuria (Champion, Graham and Zeigler, 1990).
Minor rashes and/or pruritis can be treated symptomatically with aqueous cream or 0.5% hydrocortisone cream.
The nurse will also want to establish that the cause of the rash is related to drug therapy so that the treatment is not discontinued unnecessarily. The nurse will check that the patient has not recently changed their soap, washing powder or commenced new drug therapy. In some units close cooperation with the dermatologist can establish the cause of the rash and/or irritation and thus may provide valuable information in planning long-term care.
Gold should be withheld if there is a widespread pruritis, severe or rapidly progressive rash and/or mouths ulcers/stomatitis as these can be associated with exfoliative dermatitis.
Once moderate rashes and/or pruritis has settled it may be possible to reintroduce gold at a smaller dose.
It is important to consider whether a decrease in WBCs is due to the disease or related condition (e.g. Felty’s syndrome) or to the gold treatment. Careful attention needs to be paid to a rapid and/or progressive downward trend in neutrophils accompanied by a fall in platelets as this is often caused by bone marrow suppression as a direct result of gold treatment. (You can also get neutropenia related to gold without an accompanying fall of other blood cells). Increasing neutropenia will require increased surveillance, possible dosage reduction or cessation of gold.
This will occur in up to 50% of patients receiving gold at some stage of their treatment and although it does not generally correlate highly with toxicity it should not be dismissed as in some cases it may herald a toxic reaction to treatment (Elderman, Davis and Owen, 1983).
This occurs in 1-3% of patients receiving intramuscular gold. It is usually minor but can be serious (Day, 1994). It usually responds well to corticosteroids.
This is rare but has a high mortality rate, although the rate for survival is improving (Yan and Davies, 1990).
Inflammation Lung Reactions
Hypersensitivity pneumoconitis, distinguishable from rheumatoid lung by its acute or subacute onset, can occur and will necessitate cessation of gold. Obliterative bronchiolitis has been reported in patients with RA (Penny et al., 1982) but it remains unclear whether this is a result of gold therapy or the condition itself.
Pulmonary Involvement in Patients with RA
Pulmonary involvement in patients with RA is fairly common although the clinical features may be subtle (Matteson, Cohen and Conn, 1994). Pleurisy and pleural effusions may improve spontaneously or require treatment. The occurrence of persistent pleural effusions will lead to fibrosis.
Sero-positive RA patients may develop parenchymal pulmonary nodules which, although usually asymptomatic can cause pleural effusions.
Caplan’s syndrome (pneumoconiosis) is characterized by large multiple pulmonary nodules and is seen in individuals who have experienced prolonged exposure to coal dust.
Isolated pulmonary arteritis is a rare complication of RA and is frequently associated with interstitial fibrosis and nodulosis (Gardener et al., l957).
Neurotoxicity due to Gold
Neurotoxic reactions are uncommon but the following diverse reactions have been noted, including peripheral neuropathy, Guillan Barre syndrome, cranial nerve palsies and encephalopathy.
These are often referred to as ‘nitroid’ reactions and may occur within minutes of administration of the gold injection and necessitate that the patient remains in clinic for a period of time following the injection. Reactions are characterized by weakness, dizziness, nausea, sweating, facial flushing, erythema and hypotension.
Apart from the possibility of vasomotor reactions the patient may also experience transient polyarthralgia, myalgia, joint swelling, fatigue and malaise. It can be difficult at times to distinguish these effects from the symptoms of active inflammatory disease.
Incidence Rate of Side Effects
A meta-analysis of clinical trials (Clarke et al., 1989) found that 11% of all patients had to discontinue gold due to side effects experienced. The majority of side effects occur within the first 12 months of treatment and are not related to cumulative dose (Sambrook et al., 1982). Lockie and Smith (1988) published their experience with gold therapy in 1019 patients; the main reasons for discontinuation of gold was skin reactions (36%) and buccal irritation in 13% of patients.
Gold should be stopped if:
• Total white cell count is <3.5 x 109 L or neutrophils <2 x 109 L
• Platelets <150x109 L
• Eosinophilia >0.5 x 10/L
• Proteinuria > 1 g/24 hours
• There is a severe or progressive rash.
The majority of adverse reactions to gold resolve spontaneously within weeks to months following cessation of treatment.
AURANOFIN (RIDULA) THERAPY IN RA
Auranofin is used in the long-term treatment of RA. The usual dose is 3 mg twice daily. The absorption of gold from auranofin following a single dose is about 20-25% and there is less retention of gold in tissues than occurs with injectable gold. Nevertheless regular blood monitoring is required.
Elderly, renal or hepatic impairment (moderate) history of urticaria, eczema or inflammatory bowel disease.
• Severe renal or hepatic impairment.
• History of blood disorders.
• Significant pulmonary fibrosis and porphyria.
• Systemic lupus erthematosus.
• Pregnancy and lactation.
Rashes. Minor rashes can be treated symptomatically (aqueous cream, 0.5% hydrocortisone cream).
• Mouth ulcers
Minor ulcers can be treated with Bonjela, Difflam mouth wash or Adcortyl in orabase.
Diarrhoea is often the commonest side effect and may respond to the introduction of bulking agents such as bran or to a temporary reduction in dosage. Some patients experience nausea and vomiting and it is recommended that this therapy is taken with food.
The nurse must observe for any reductions in neutrophils and platelets.
Rarely colitis, peripheral neuritis, pulmonary fibrosis, hepatotoxicity with cholestatic jaundice and alopecia have all been reported.
Auranofin should be stopped if:
• Total white cell count is <3.5 x 109 L
• Platelets <150 x 109 L
• Proteinuria >1 g/24 hours
• Severe rashes or severe mouth ulcers occur.
D-penicillamine is used in the long-term treatment of rheumatoid arthritis and in scleroderma. Treatment is commenced at 125 mg or at 250 mg daily, increasing at four-week intervals by increments of 125 mg daily to 500 mg or 750 mg. The tablets are best taken as a single daily dose an hour before breakfast and not with iron tablets or milk as they interfere with drug absorption. Toxicity is common with this treatment with about 50% of patients with RA experiencing an adverse effect within the first six months of treatment at 600 mg daily resulting in 25% of patient discontinuing with this treatment. The incidence of toxicity increases as the dose increases (Kay, 1986).
Renal impairment, concomitant nephrotoxic dugs including gold treatment.
• Systemic lupus erythematosus
• Renal impairment
• Pregnancy and lactation.
• Antacids and iron: do not take within two hours as this reduces the absorption of D-penicillamine.
• Antipsychotic drugs: may increase agranulocytosis.
• Digoxin: Levels of digoxin can be reduced by concurrent use of D-penicillamine.
• Zinc supplements may reduce the absorption of D-penicillamine.
Urticarial, pruritic, macular and papular eruptions of apparent allergic origin account for the majority of skin reactions (Kay, 1986). Minor rashes can be treated symptomatically but severe rashes may necessitate stopping D-penicillamine and this will normally resolve the rash. Autoimmune bilious skin eruptions, typical of the pemphigus group, are the most worrying. Patients who have a penicillin allergy are at greater risk of experiencing a skin reaction. Oral ulcers and stomatitis may occur; if severe this will mean a discontinuation of therapy. Oral mucosal involvement is often present in pemphigus. There is a significant level of mortality amongst patients with D-penicillamine-induced pemphigus (Joyce, 1990).
A metallic taste and loss of taste may occur in the first eight weeks of treatment. It may take several months to recover. This can be a particularly distressing symptom for patients and advice may need to be given on food supplementation (Ryan, 1995). Taste disturbance may be a consequence of zinc chelation by the D-penicillamine but zinc therapy does not remove the complaint (Joyce, 1990).
Nausea and Anorexia
If these symptoms occur the patient may need to reduce the dose of D-penicillamine and then increase slowly when the symptoms settle. The use of anti-emetics should also be considered.
There can be a gradual or rapid haematological effects at any stage during treatment with D-penicillamine. Thromobocytopenia can be precipitated and serious.
Neutropenia due to D-penicillamine as opposed to RA itself is suggested by a rapid or progressive fall in neutrophils and is the commonest cause of death attributed to this treatment (Kay, 1979). Aplastic anaemia also has a high fatality rate.
Proteinuria is common. Increased urinary protein excretion can exceed 0.5 g/day in approximately 9% of patients taking this drug (Stein, Schroder and Dillion, 1986) . The presence of HLA B8 and DR 4 antigens coupled with the occurrence of previous proteinuria on gold therapy increases the risk of more severe proteinuria leading to nephrotic syndrome (Joyce, 1990).
The majority of patients experiencing severe proteinuria have membranous glomerulonephritis with minimal change neuropathy (Hall et al., 1988). Plasma urea and creatinine may rise intermittently but this does not seem to be related to permanent renal impairment (Hall et al., 1988).
D-penicillamine should be stopped if over 1 gram of proteinuria occurs in a 24hour period. Even after the drug has been discontinued the proteinuria may persist for up to 21 months.
The appearance of haematuria may indicate rapidly progressive glomerulonephritis - for example, Goodpasture’s syndrome or SLE and can be lifethreatening requiring steroids and immunosuppressives. However, the presence of haematuria usually does not lead to serious complication and recurrent haematuria is quite common in RA patients without serious renal pathology (Leonard et al., 1987).
There have been cases of bronchiolitis obliterans reported (Day, 1994). Although this is a rare side effect it may be irreversible and present as dyspnoea late in therapy (Kay, 1986).
Myasthenia gravis. This rare complication may evolve after years of uneventful therapy and may take over a year to resolve (Kay, 1986).
Auto-antibodies may appear including anti-striated muscle antibody, anticentromere antibody and anti-glomerular basement membrane antibody. The latter is associated with the life-threatening complication of Goodpasture’s syndrome.
Drug-induced SLE usually resolves after stopping D-penicillamine. Pemphigus (oral involvement common) is dangerous and requires cessation of D-penicillamine, glucocorticosteroids and perhaps plasmapheresis.
D-penicillamine should be stopped if the following occur:
• Severe rash.
• Severe mouth ulcers.
• Autoimmune side effect.
• Platelets <150x109L
• Total white cell count <3.5 x 109 L
• Neutrophils <2x109 L
• Proteinuria > 1 gm/24 hours.
SULFASALAZINE EN THERAPY (SALAZOPYRIN)
Sulfasalazine is used in its enteric coated form (EN) as second line treatment for RA, spondyloarthropathies and reactive arthritis. To reduce nausea the drug should be commenced at 500 mg daily increasing by 500 mg daily at weekly intervals to the usual maintenance dose of 1 g twice daily. Incomplete responders sometimes require 1 g three times a day. It may take three to six months for a patient to respond to treatment with sulfasalazine. This preparation ranks with the antimalarials and auranofin as the best tolerated of the DMARDs and is a popular first choice of DMARDs amongst rheumatologists (Kay and Puller, 1992).
• Moderate renal impairment.
• May impair folate absorption.
• Pregnancy and breastfeeding.
• Hypersensitivity; sulfonamide/co-trimoxazole.
These are commonest in the first three months of therapy. Only 20-25% of patients need to stop treatment because of toxicity (Amos et al., 1986) and only about 5% of patients will experience potentially serious side effects (Farr, Scott and Bacon, 1986).
Commonest adverse effects are gastrointestinal and on the central nervous system. They include nausea, vomiting, malaise, anorexia, abdominal pain, dyspepsia, indigestion, headache, light-headedness and dizziness. If a patient experiences nausea the dose should be reduced to the previously tolerated dose and further increase should be attempted slowly. Make sure the patient is taking enteric coated tablets and administrating them on a full stomach. Anti-emetics may be required. With headaches again the dose should be initially reduced and further increases attempted slowly. If headaches are severe the patient may need to discontinue sulfasalazine.
Pyrexia is a rare side effect and can be considered only when other causes of raised temperature have been excluded.
This is relatively common and may manifest itself in a number of ways ranging from skin rash to fatal multi-organ involvement.
Rashes. If these are mild, treatment can be continued and the rash can be treated symptomatically. Skin rashes will occur within 5% of cases and take the form of a generalized pruritic maculopapular rash, urticaria or photosensitivity (Amos et al., 1986). If the rash occurs within the first two weeks of treatment then desensitization can be tried. Initially given in 1 mg doses sulfasalazine is built up over 25-56 days. Successful desensitization has been achieved in as many as 85% of cases in RA patients (Bax and Amos, 1986). Rarely severe reactions such as Stevens-Johnson syndrome or exfoliative dermatitis can occur. In the case of this happening all drugs should be stopped and urgent dermatological advice should be obtained. Rarely serum sickness occurs.
Most toxicity is allergic in origin from sulfasalazine. The commonest presentation is eosinophilic pneumonitis; symptoms include dyspnoea with fever, rash, weight loss, pulmonary infiltration on X-ray and reduced pulmonary function tests. Reduction of symptoms occurs following cessation of therapy (Tydd and Dyer, 1976).
Leucopenia in 1-5% of cases: It is most likely to occur in the first six months of treatment although it can occur at any time. It is the commonest potential serious side effect associated with sulfasalazine. It indicates the need for continued review particularly as early recognition with dosage reduction or cessation leads to reversal in most cases.
Thrombocytopenia is less frequent than leucopenia.
Agranulocytosis is rare but can develop rapidly and present with intercurrent infection. It has been recorded in association with a transient but marked plasmocytosis.
Mean cell volume (MCV): Sulfasalazine causes the erythrocyte MCV to rise. It inhibits folate uptake in the small bowel; however it would be rare to see folate deficiency at a dose of 2 g daily.
Abnormalities of red cell morphology: Morphological changes are due to oxidant damage resulting in red cell membrane abnormalities leading to low grade haemolysis (Pounder et al., 1973). The changes are reversible on discontinuation of therapy but this action would only be necessary if the haemolysis was causing a problem. Significant methaemoglobin can cause headaches and may require a dosage reduction.
Allergic hepatic responses to sulfonamides are well known; raised hepatic enzyme levels and eosinophilia may cause fever rash and hepatomegaly (Amos et al., 1986).
Granulomatosus hepatitis may occur necessitating discontinuation of therapy. Minor rises in hepatic enzyme levels during treatment occur in about 3% of cases but do not seem to be productive of severe hepatic reactions and treatment may continue (Puller, Hunter and Capell, 1987).
Reversible oligospermia. About 70% of men develop oligospermia and abnormal sperm motility (Birnie, Mcleod and Watkinson, 1981). Therefore this drug should be avoided in men wishing to have a family. This temporary reduction in fertility is reversible on stopping sulfasalazine treatment.
Miscellaneous. Sulfasalazine can cause orange staining of soft contact lenses. The urine can become bright orange. Rarely drug-induced lupus.
Sulfasalazine should be stopped if the following occur:
• Severe rashes.
• Severe headaches.
• Deteriorating liver function.
• Platelets <150x109 L.
• Total white cell count <3.5x 109 L.
• Neutrophils <2x109 L.
Methotrexate is an antimetabolite cytotoxic agent used in RA, psoriatic arthritis, myositis and vasculitis. It is given either orally, subcutaneously, intramuscularly or intravenously. Weekly doses are usually between 5 mg and 25 mg. Rarely the maximum dose can be 30 mg per week. The initial dose will vary depending on the severity of the condition and patient characteristics such as age, renal function and co-morbid conditions. It is preferable to use only one strength (2.5 mg) of tablets and patients should be reminded of the need to check the dose and strength of the tablets with each prescription. It is co-prescribed with folic acid, which may reduce the likelihood of side effects. Clinical effect is usually evident after two to three months but doses may need to be increased to maintain this effect. A chest X-ray is taken prior to starting treatment as pre-existing lung disease requires special attention. Any patient suspected of alcohol abuse is usually unsuitable for methotrexate therapy. Patients should be advised to limit their alcohol intake to well within national limits.
Patients with clinically significant renal impairment.
• Pregnancy and breastfeeding.
• Suspected local or systemic infection.
• Phenytoin, co-trimoxozole, trimethorpim-antifolate effect of methotrexate is increased.
• Probenecid, penicillin, azapropazone, NSAIDs-methotrexate excretion is reduced. Clinically significant interaction between NSAID and methotrexate is rare. All patients should be advised to avoid over-the-counter medications including aspirin and ibuprofen without the knowledge of the rheumatology team.
These are the most common side effects which include anorexia, nausea, dyspepsia, vomiting, diarrhoea and abdominal pain. It is recommended that the therapy is taken with food. Anti-emetics may be required on the day of methotrexate administration and the following 24-48 hours. If nausea and vomiting are problematic and doubts exist about absorption, methotrexate can be given intramuscularly.
Mouth soreness can present with or without ulceration (Kremer and Joong, 1986). The use of folic acid to minimize stomatitis has been recommended (Segal, Yaron and Tartakowsky, 1990). Minor ulcers can be treated symptomatically whilst major mouth ulcers may necessitate dose reduction or discontinuation.
Minor rashes can be treated symptomatically whereas severe rashes may necessitate discontinuation of methotrexate.
Leucopenia is the most common bone marrow toxicity from methotrexate (Kremer and Joong, 1986). This is usually managed by reducing the dosage of methotrexate. Anaemia and thrombocytopenia can also occur. Macrocytosis is a sign of toxicity and may precede bone marrow suppression. Pancytopenia is a rare but potentially fatal complication of methotrexate, which may develop suddenly and without warning signs (Lim, Gaffney and Scott, 2005). It can occur early within one to two months of commencing methotrexate possibly reflecting an idiosyncratic reaction (Lim, Gaffney and Scott, 2005) and more commonly later on in the patient’s experience reflecting a cumulative effect (Lim, Gaffney and Scott, 2005).
Hepatoxicity defined as elevation of transaminase occurs within 69-89% of patients (Williams et al., 1985). These increases do not usually correlate with the development of cirrhosis. Liver fibrosis and cirrhosis can occur with normal liver enzymes and imaging findings. Current studies in patients with RA suggest that liver biopsies are not cost-effective for at least the first 10 years of methotrexate use in patients with normal liver function (Jones and Patel, 2001).
Hypersensitivity Reactions and Pneumonitis
Hypersensitivity reactions include rashes, fever and pneumonitis (Cannon et al., 1983). Methotrexate pneumonitis occurs in 1-6% of cases (Fuhrman et al., 2001). It is a potentially fatal hypersensitivity reaction most frequently seen within the first year of treatment (Kinder and Hassell, 2005). Many studies suggest that the incidence of pneumonitis is much higher in patients with pre-existing lung disease (Alarcon et al., 1997; Saravanan and Kelly, 2004). Pulmonary function tests may be a useful investigation to detect pre-existing lung disease as methotrexate pneumonitis tends to occur in 48% of patients with pre-existing lung problems (Grove and Hassell, 2001). If pre-treatment X-ray suggests abnormal shadowing it may be worth considering a high resolution computerized scan and pulmonary function tests. Airway obstruction may not be a contraindication to the use of methotrexate but the presence of interstitial lung disease is.
Acute renal decompensation and renal failure have been reported although rarely, and appear related to high dose therapy with concomitant NSAIDs with underlying renal disease (Thierry et al., 1989).
Methotrexate should be stopped immediately if infection is suspected. Significant mortality and morbidity can be associated with viral infections due to herpes zoster/varicella. Patients with a history of contacts with such viral infections need special advice and the consideration of treatment with anti-herpes zoster immunoglobulin.
Folic acid has been shown to reduce the likelihood of derangements of liver function tests (Vn Ede, Laan and Rood, 2001) as well as mucosal and gastrointestinal side effects (Ortiz et al., 2000). No consensus exists amongst specialists as to the optimal dose and timing of folate supplementation (Lim, Gaffney and Scott, 2005) and no studies have proven an unequivalent protective effect of folate supplementation on methotrexate-related haematological toxicity (Lim, Gaffney and Scott, 2005).
Folinic Acid Rescue
In suspected cases of methotrexate overdose or severe haematological toxicity, folinic acid can be given. The initial dose should be at least 20 mg given intravenously. Subsequent doses of 15 mg orally should be given at six-hourly intervals until the haematological abnormalities are improved.
Research suggests that continuation of methotrexate treatment does not increase the risk of infection or surgical complications in patients with RA (Bridges et al., 1991; Grennan et al., 2001).
Methotrexate should be stopped if the following occur:
• Major mouth ulcers.
• Severe skin rashes.
• Infection is suspected or present.
• Severe sore throat.
• Abnormal bruising.
• Acute pneumonitis.
• Deteriorating liver function - that is, AST, ALT greater than twofold rise.
• MCV .105fl -check serum B12, Folate and TFT.
• Platelets <150x 109 L.
• Total white blood cell count <3.5x 109 L.
• Neutrophils <2x109 L.
AZATHIOPRINE (IMURAN) THERAPY
Azathioprine is an immunosuppressant antimetabolite used in RA, psoriatic arthritis and in vasculitis. It is widely used to suppress transplant rejection. It is given orally in daily doses of up to 3 mg/kg. It can be used in combination with corticosteroids as a ‘steroid sparing agent’. It may take three to six months for patients to respond to treatment.
• Thiopurine methyl transferase deficiency.
• Older people with renal impairment.
• Localized or systemic infections with hepatitis B and C or a history of TB.
• TPMT deficiency - can be fatal.
• Aminosalicylates - for example, sulfasalazine contributes to bone marrow toxicity.
• Co-trimoxazole and trimethoprim can cause life-threatening haematoxicity (Norgard et al., 2001).
• Pregnancy and breastfeeding.
This includes nausea and vomiting; patients may have to reduce the dose and then increase again when symptoms settle. Anti-emetics may be required. It is advisable to take azathioprine on a full stomach.
Minor ulcers can be treated symptomatically whilst severe ulceration may necessitate stopping azathioprine.
This is rare but if occurs may be severe and require dose reduction or withdrawal.
The most important side effect is reversible marrow suppression (Luqmani, Palmer and Bacon, 1990). Macrocytosis is common but is not a sign of toxicity.
Long-term effects may include the induction of lymphoid tumours (Rosman and Bertino, 1973). In RA the azathioprine-related risk of lymphoma and non-Hodgkin’s lymphoma is confounded by an increased relative risk secondary to RA. Overall there appears to be a small added risk of developing malignancy when using azathioprine in RA (Frust and Clements, 1994).
Hypersensitive reactions occur early in treatment and may include headaches, confusion and aseptic meningitis.
Allopurinol can increase the myelosuppression of azathioprine. Allopurinol can inhibit the anticoagulant effects of warfarin. Azathioprine can reduce the absorption of some antiepileptic drugs.
Azathioprine should be stopped if the following occur:
• Platelets <150x 109 L.
• White cell count <3.5 x 109 L.
• Neutrophils <2x109 L.
• Deteriorating liver function > twofold rise in AST, ALT.
• MCV >105 - check serum folate, vitamin B12 and TSH.
• Abnormal bruising or severe sore throat.
CYCLOPHOSPHAMIDE (ENDOXANA) THERAPY
Cyclophosphamide is a cytotoxic alkylating agent used for immunosuppression in SLE, vasculitis, resistant rheumatic arthritis, polyarteritis nodosa, Wegener’s granulomatosis, myositis and as a steroid sparing agent. A daily oral dose of 1-2 mg/kg body weight is used, it may be given as pulsed intravenous or oral therapy. Cyclophosphamide reaches its peak of effectiveness after approximately 16 weeks and although remission may be maintained for several years on withdrawal of the drug the majority of patients will experience some recurrence of symptoms. Non- articular complications of RA such as interstitial lung disease, cutaneous ulcers and peripheral neuropathy may respond well to oral cyclophosphamide. Cyclophosphamide should be used with care in patients with diabetes as it may induce hyper- or hypoglycaemia.
• Avoid if possible in men and women of childbearing age. Otherwise offer gamete storage and ensure adequate contraception.
• Carry out a full infection screen including chest, urine testing and culture, joint examination, sinuses and perineum.
• Some rheumatology units advise patients on this therapy to minimize or stop alcohol consumption.
• Pre-treatment investigations include chest X-ray and a full blood count, including differential white count and platelets, electrolytes and liver function tests.
Minor ulcers can be treated symptomatically. Severe ulcers may necessitate stopping cyclophosphamide.
Nausea and Vomiting
If gastrointestinal intolerance occurs the patient may require anti-emetic therapy. It is advisable to take this treatment with food.
This is usually mild in dosages less than 100 mg daily.
Suppression of the immune system exposes patients to the risk of infections. This can be minor - for example, herpes zoster - or major - for example, septicaemia. There is also the increased risk of patients experiencing opportunistic infections.
Bladder toxicity is due mainly to the effects of acrolein on the urinary metabolite of cyclophosphamide. As well as causing haemorrhagic cystitis and bladder fibrosis it has been associated with bladder carcinoma. Therefore the occurrence of haemorrhagic cystitis is an indication for cessation of therapy. Haemorrhagic cystitis has been reported in about a third of subjects receiving oral cyclophosphamide daily (Baker et al., 1987). It is rare in patients receiving intermittent high dose intravenous cyclophosphamide therapy (Bacon, 1987), where it is often co-prescribed with Mesna which reacts specifically with the metabolite acrolein preventing urothelial toxicity. Patients should be advised to take at least 3 litres of fluid per day whilst taking cyclophosphamide therapy.
Kinlen et al. (1979) reports a relative risk of 12.8 for all cancers combined and a tenfold increase in bladder cancer for patients receiving at least three months of treatment with cyclophosphamide. There appears to be a relationship of total dose and duration of therapy with the incidence of malignancy (Baker et al., 1987). There is also an increased risk of leukaemia (Adamson and Seiber, 1981).
The risk of infertility, azoosperma and amenorrhoea with cyclophosphamide increases with higher dosages, longer duration of therapy and increased age in women (Schilsky et al., 1980). Infertility is not always reversible.
This can occur with therapy.
Abnormalities are detected by blood monitoring. Maximum effect on the marrow dose not occur until 5-10 days after dosage. Recovery is seen within 10-14 days. Macrocytosis is not inevitable but is a sign of toxicity and dosage reduction may be necessary.
Allopurinol can increase the myelosuppression of cyclophosphamide.
Cyclophosphamide should be stopped if the following occur:
• Severe mouth ulcers.
• Platelets <150x 109 L.
• Total white cell count <3.5 x 109 L.
• Neutrophil <2 x 109 L.
• Macroscopic haematuria or persistent confirmed macroscopic haematuria (infection excluded).
Ciclosporin A is a fungal metabolite of Trichoderma polysporum and Ciclocarpon leucidium. Studies have confirmed potent effects of this drug in several arthritic and other cell-mediated chronic inflammatory conditions (Cannon et al., 1990). It may be instituted at doses of 2.5 mg/kg/day given in 2 divided doses every 12 hours. The dose may be cautiously increased 25-50% every 2-4 weeks until a maximum of 4 mg/kg/day is reached assuming there are no adverse reactions. Ciclosporin is used in the treatment of RA and Behcet’s disease. Clinical improvements in patients receiving ciclosporin are associated with a reduction in C-reactive protein, d-1-acidglycoprotein and platelet counts but not rheumatoid factor or the ESR (Dougados, Awada and Amor, 1988). When ciclosporin is used in the treatment of rheumatic disease side effects are generally mild and reversible at low doses (Frust and Clements, 1994).
• Uncontrolled hypertension.
• Use of potassium sparing diuretics.
• Pregnancy and lactation.
• Grapefruit juice to be avoided for one hour after administration.
• Malignancy such as lymphomas.
• Uncontrolled hypertension.
• Renal and liver failure.
• Severe electrolyte imbalance.
• Suspected systemic infection.
Minor reactions - can include nausea and vomiting, tinnitus, tremor, paraesthesia and gum hyperplasia.
Major reactions - Nephroxicity. Ciclosporin should be avoided in patients with pre-existing renal disease. Increases in serum creatinine are common during ciclosporin immunosuppression. Ciclosporin therapy in doses of 10 mg/kg/day for even two months may lead to an irreversible loss of more than 10% of renal function in RA patients. Nephrotoxicity is dose-related (Berg et al., 1989). Longterm influences on renal function are significant even after cessation of the drug especially in view of the potential for apparent persistent impairment of creatinine clearance. A study by Tugwell et al. (1990) showed that although serum creatinine rose and creatinine clearance decreased over the period of ciclosporin administration the effects stabilized after four months with no further changes. After discontinuation of therapy serum creatinine fell to within 15% of baseline in all except two patients. Dosage reductions of 25-50% are required if serum creatinine increases above baseline by 30-50% or if hypertension cannot be controlled.
Hypertension has always been a factor predisposing to nephrotoxicity in RA (Shiroky et al., 1989). New onset hypertension has been reported in about one third of RA and psoriatic patients. Hypertension should be managed with beta blockers and ACE inhibitors; potassium sparing diuretics should be avoided because ciclosporin may cause hyperkalemia (Kowal, Carstens and Schinitzer, 1990). If hypertension is present prior to commencing ciclosporin the hypertension should be treated first before ciclosporin is introduced.
This can occur with higher dosages of ciclosporin and present with elevated hepatic enzymes and bilirubin.
Diltiazem, ketoconazole, rifampicin and phenytoin may all require adjustment of ciclosporin dose.
St John’s Wort decreases ciclosporin activity. Colchicine should be avoided and the dose of diclofenac reduced by 50%.
Ciclosporin should be discontinued if the following occur:
• Elevation of serum creatinine >30% from baseline on two consecutive occasions.
• Potassium rises to above the normal range.
• Raised blood pressure - diastolic 95mm Hg on two consecutive occasions.
• Ciclosporin levels are >300 mg/ml.
• Elevated hepatic enzymes - > twofold increase in AST or ALT or alkaline phosphatase from the upper limit of the normal range.
• Platelets <150.
• Abnormal bruising.
Chlorambucil like cyclophosphamide is a bifunctional alkylating agent. It is not a cytotoxic but is metabolized to phenylacetic acid - its principal and most active metabolite. It is given in an oral preparation. The intravenous preparation is unstable because of rapid hydrolysis. Chlorambucil can be commenced in doses of 0.1-0.2 mg/kg/day. Once response or toxicity has occurred it is suggested that a dose of 3-4 mg daily is adopted.
Chlorambucil has been used in patients with RA, vasculitis and connective tissue disorders, inflammatory eye disease and amyloidosis.
The advantages of chlorambucil therapy have to be balanced against the risk of inducing adverse effects. The most common toxicities with chlorambucil use are dose-related bone marrow suppression and infertility.
Bone Marrow Suppression
Cumulative bone marrow toxicity occurs regularly and often requires discontinuation of the drug.
Kahn et al. (1979) reported that leukaemias occurred in patients with RA who had received a total dose of at least 1 g of chlorambucil and who had been treated for at least six months. Luqmani, Palmer and Bacon’s (1990) review of the literature on patients receiving chlorambucil indicated that tumours occurred in less than 1% of patients. The majority of the malignancies were leukaemias with a particularly high incidence of acute myeloid leukaemia. It is not possible to exclude the part that the disease process itself plays in the likelihood of malignancies and Palmer and Denman (1984) found that patients with connective tissue disorders were more sensitive to the leukaemiogenic effects of chlorambucil than patients with other non-malignant conditions.
The risks of infertility, azoospermia and amenorrhoea increase with duration of therapy and high doses. Infertility affects men at a greater rate than women; irreversible azoospermia was regularly reported in men who received greater than 400 mg of chlorambucil. In post-pubertal females both gametogenesis and hormonal function are altered adversely and menopause occurs.
Phenylbutazone is not longer recommended or indeed available in many countries for the treatment of arthritis conditions due to the risk of marrow aplasia. Although it is still used in the United Kingdom, it is available only on hospital prescription for patients with ankylosing spondylitis and other spondyloarthropathies. Phenylbutazone is a NSAID but it may also affect the immune response (Furst, 1988). It is usually prescribed in dosages of 100-200 mg, two to three times a day. It should help with pain and swelling within a week but will take months before an immune response can be assessed.
Nausea and vomiting.
Skin rashes, mouth ulcers, stomatitis.
Central Nervous System
Headaches, dizziness and blurred vision.
Care must be taken when prescribing these tablets to patients with asthma or breathing problems as these conditions may be aggravated.
Phenylbutazone has fluid retaining properties.
Serious hepatocellular reactions have been reported (Benjamin et al., 1981) and hepatic clearance of drugs is reduced as phenylbutazone inhibits oxidase drug metabolism.
A range of haematological abnormalities have been reported. Long-term recipients may develop iron deficiency anaemia due to chronic blood loss from inflammation of the small intestine. Aplastic anaemia has been associated with the slow metabolism of phenylbutazone (Leyland et al., 1974) suggesting that this adverse effect is related to excessive concentrations of the drug. Thrombocytopenia, effects on platelet function, agranulocytosis, pancytopenia and haemolytic anaemia have also been noted but are still rare although can be fatal (O’Brien and Bagley, 1985).
Phenylbutazone interacts with oral anticoagulants, lithium, oral hypoglycaemic agents, phenytoin, methotrexate (causing pancytopenia probably due to retention of methotrexate due to inhibition of proximal renal tubular secretion), digoxin, aminoglycosides, probenecid and barbiturates.
Dapsone is best known as an anti-leprotic agent but it also has effects on the immune system and has been used for the treatment of RA and psoriatic arthritis. There is a delay of two to three months before onset of action but when successful it will reduce the ESR. The dosage is 50 mg daily for one week increasing then to 100 mg daily depending on the result of the haemoglobin. Occasionally patients may require 150 mg daily.
Minor side effects such as rashes and gastric upset can occur. Haematological - haemolysis occurs in all patients and gives a drop in haemoglobin of 1-2 g. This therefore requires monitoring before increases in dosage are considered. Patients also develop a pallor which is more marked than the drop in the haemoglobin would produce. It is worth warning patients that they will look pale. Patients of Mediterranean origin will require a G6PD estimation prior to starting treatment since massive haemolysis will occur if there is a deficiency in this enzyme. Agranulocytosis has been reported but is rare.
Minocycline is a broad spectrum antibiotic often prescribed in the treatment of acne. It has also been used in the treatment of RA. Its mode of action is not known but it is thought to be effective at inhibiting the pro-inflammatory enzyme metalloproteinase. It does not become fully effective for two to three months. The dosage is 100-300 mg twice daily.
An abnormal metallic taste can occur when first starting the treatment. Dizziness, nausea and diarrhoea have also been reported. The treatment is best taken with food.
Although severe side effects are rare a drug-induced lupus syndrome and hepatitis can occur that resolves on stopping but necessitates that treatment is monitored with a full blood count and biochemistry monthly and an anti-nuclear antibody six-monthly.
Minocycline should not be taken at the same time as antacids, calcium and iron preparations. A two-hour gap is required between administration of minocycline and these preparations.
If prescribed penicillin, leave off minocycline until the course of penicillin is completed.
Lefluomide is usually prescribed as a daily dose of 10-20 mg. It is common in the United Kingdom not to use a loading dose of 100 mg daily for three days although this practice is seen in other European countries (Maddison et al., 2005). Loading doses are associated with an increased incidence of side effects (Erra et al., 2003). On doses of 10 mg it will take over six months to reach a therapeutic level (Maddison et al., 2005). The recommended daily dose is 20 mg. In patients receiving other potentially hepatotoxic drugs, such as methotrexate, or who are renally impaired 10 mg is recommended (Maddison et al., 2005). Alcohol ideally should be avoided.
• Evidence of Hepatitis B or C infection.
• History of tuberculosis.
• Serious infections.
• Impaired liver function.
• Severe unexplained hypoproteinaemia.
• Renal impairment - moderate to severe.
Many adverse effects can be managed by reducing the dosage or by concomitant administration of symptomatic therapy (Maddison et al., 2005). If it is necessary to rapidly remove the drug from a patient’s system then a washout with cholestyramine will quickly reduce the plasma levels of the drug.
Cholestyramine 8 mg is administered three times daily. Alternatively 50 mg of activated powered charcoal is administered four times daily. Duration of a complete washout is usually 11 days. The duration may be modified depending on clinical or laboratory variables.
Data from a US database (Emery et al., 2002) on the use of leflunomide by 40 000 RA patients indicated that gastrointestinal tract-related problems were the commonest reasons for stopping treatment. Problems experienced included diarrhoea, nausea, vomiting, oral mucosal disorders (e.g. aphthous stomatitis, mouth ulceration) and abdominal pain.
The prevalence of nausea is less in lefluomide than in patients taking sulfasalazine or methotrexate but the prevalence of diarrhoea is increased and should be treated, in the first instances, rather than stopping the drug. Daily doses of leflunomide 20 mg are associated with more nausea and diarrhoea than a daily dose of 10 mg.
In cases of ulcerative stomatitis, leflunomide administration should be discontinued. Minor rashes can be treated symptomatically but severe rashes will necessitate discontinuation of leflunomide. Severe dermatological toxicity has a higher prevalence than is seen in patients taking sulfasalazine or methotrexate (Maddison et al., 2005). Cases of Stevens-Johnson syndrome or toxic epidermal necrolysis have been reported.
The manufacturers recommend that blood pressure monitoring is carried out on patients taking leflunomide but hypertension does not appear to occur more often with this DMARD in comparison to other DMARDs such as methotrexate, except where loading doses have been used (Maddison et al., 2005).
Interstitial lung disease has been reported during treatment with leflunomide. Interstitial lung disease is a potentially fatal disorder, which may occur acutely during therapy. Pulmonary symptoms, such as cough and dyspnoea, should be investigated.
Pulmonary infiltration as an acute allergic reaction has been demonstrated in a small number of patients after commencing leflunomide.
Raised liver tests can occur and require monitoring; liver toxicity is more common in methotrexate that with leflunomide (Maddison et al., 2005). Rare cases of severe liver injury (some with fatal outcome) have been reported after drug treatment with leflunomide. Most cases occurred within six months and were associated with other risk factors for hepatotoxicity. Patients should be asked to limit alcohol intake well within normal limits at four to eight units a week.
It is recommended that patients on leflunomide have regular full blood counts although there is no data to suggest an increase in blood dyscrasias due to leflunomide (Maddison et al., 2005).
Leflunomide should be stopped if the following occur:
• Major mouth ulcers or skin rashes.
• Respiratory reactions.
• Liver function deteriorates - > twofold rise in AST, ALT.
• Platelets <150.
• Total white blood cell count <3.5.
• Neutrophils <2.
• Weight loss of >10% with no other cause identified.
• Severe persistent headaches.
• Severe sore throat.
• Abnormal bruising.
Mycophenolate mofetil is a potent reversible selective inhibitor of purine synthesis. It has been shown to inhibit T cell proliferation and antibody production by B cells. It is used in the treatment of systemic lupus erythematosus, scleroderma and vasculitis and after organ transplantation. Mycophenolate is usually taken in capsule form twice a day on an empty stomach. A typical dose may be 500 mg twice a day for four weeks; then, if tolerated, 1 g twice a day thereafter. Alcohol should only be taken in small amounts as it can affect the liver. Mycophenolate should not be taken with cholestyramine or antacids with magnesium or aluminium hydroxides as absorption may be reduced. If being used with azathioprine, lower doses should be used. Pre-treatment assessment includes FBC, urea and electrolytes, creatinine and liver function tests.
The most common side effects are sickness, diarrhoea, vomiting or abdominal pain. These side effects are usually dose-related and resolve on discontinuation of the drug. Severe neutropenia occurs in 0.5% patients receiving 1 g twice daily compared to 0.8% patients receiving azathioprine; it is most commonly seen within the first six months. There is a slight increase in the risk of skin cancer and patients should avoid exposure to strong sunlight and protect their skin with sunblock or sunscreen. Symptoms of allergy include wheezing, shortness of breath, swelling of the face, lips, tongue or throat. Urogenital reactions include sterile haematuria, urinary tract infection and renal tubular necrosis.
Reasons for Stopping Treatment
Mycophenolate should be stopped if the following occur:
• WBC<3.5 x 10/L.
• Neutrophils< 2.0 x 10/L.
• Platelets <150x 109/L.
• Rash or oral ulceration.
• Abnormal bruising or sore throat.
• Gastrointestinal disturbances - withhold until settle then reintroduce at a lower dose.
Table 3.5 Vaccines.
Poliomyelitis (IPV injected)
Haemophilis influenza type 2
Live vaccines (shown in Table 3.5) should be avoided in patients taking azathioprine, methotrexate, cyclophosphamide or high doses of corticosteroids. Patients on these medications should be considered for varicella-zoster immunoglobulin after exposure to chicken pox or herpes zoster and should be advised to avoid close contact with patients recently vaccinated with live polio vaccine because of the risk of infections from faecal excretion. Sulfasalazine, D-penicillamine, gold - in general vaccination are safe for patients on these therapies although is probably preferable to avoid live vaccines. Ciclosporin has a poor response to vaccines and patients should ideally have any appropriate vaccinations prior to therapy.
Patients planning a family will require advice and support from various members of the rheumatology team. Pregnancy and related issues such as breastfeeding must be addressed when patients are receiving a DMARD. It is necessary to be absolutely certain about the effects of the DMARD on the fetus as well as on lactation. One of the major concerns of any pregnant woman is the risk of congenital malformation due to drugs and this will cause even greater concern to the woman with rheumatoid arthritis (Richardson, 1992). The most vulnerable period of gestation is during embryonic and fetal development but many congenital abnormalities occur for reasons other than those that are drug-related. Spontaneous and serious malformations occur in 2-3% of all pregnancies and minor malformations occur in a further 6% (Oka and Vainio, 1966).
Women with rheumatoid arthritis often need to achieve disease suppression to increase their chance of conceiving. Adequate control of the disease will enable a woman to feel capable of bearing and raising a child. Decisions regarding the withdrawal of potentially toxic drug therapy need to be made in good time since many drugs can affect the vulnerable stages of embryogenesis. Women should discontinue teratogenic agents such as methotrexate, azathioprine and cyclophosphamide at least six months before attempting conception. Leflunomide, one of the newer DMARDs, has proven teratogenic and fetotoxic effects in animal studies and its active metabolite is detectable in plasma two years after discontinuation of the drug. Consequently the fetus could have in utero exposure to leflunomide up to two years after the end of treatment unless an oral cholestyramine regimen, 8 g 3 times daily for 11 days is administered to obtain undetectable plasmatic levels. The manufacturer recommends that for women of childbearing age ‘treatment with leflunomide must not be started until pregnancy is excluded and it has been confirmed that reliable contraception is being used’. Ideally all drug therapy should be avoided during pregnancy and lactation. The effects of drug therapy used in rheumatic disease are shown in Table 3.6 (Le Gallez, 1988).
In ankylosing spondylitis 80% of patients may experience a worsening of symptoms or no alteration of their condition during pregnancy (Le Gallez, 1988) and will require advice on coping with pain. This should include relaxation techniques, the application of hot and cold therapy and the use of diversional techniques. In RA 75% of women experience some remission of their condition during pregnancy but often return to disease status comparable with their pre-pregnant state within eight months of giving birth. Women who develop an exacerbation of their condition post-partum will need to recommence their suppressive drug therapy and individual advice from the rheumatology nurse will be required if the mother is breastfeeding.
Table 3.6 Drugs and pregnancy.
Can be taken during pregnancy
Avoid in first trimester, may cause cleft palate
Avoid during late pregnancy, may cause prolonged gestation and labour and increased blood
loss at delivery antepartum haemorrhage. May lead to premature closure of the ductus gloriosus
Considered safe when taken in low dosages (5-10 mg daily). If withdrawn within two months of labour steroid cover should be provided
Sulfasalazine: avoid in late pregnancy - neonatal janudice
Auranofin, D-penicillamine, mycophenolate mofetil and gold are all contraindicated Ciclosporin and sulfasalazine - use with caution
Hydroxychloroquine can be used in pregnancy but needs to be discussed with the rheumatologist
Leflunomide, methotrexate, cyclophosphamide and azathioprine are all teratogenic
Reliable contraception should be advised for all women receiving disease modifying anti-rheumatic drug therapy and all proposed pregnancies will need discussing on an individual basis with the rheumatology nurse. For those medications known to be teratogenic - for example, methotrexate, azathioprine, leflunomide, chlorambucil and cyclophosphamide - patients must have contraceptive cover and discontinue the drug for six months before trying for a family. In the case of leflunomide the manufacturers recommend that the drug should be discontinued for two years before becoming pregnant. If this waiting time is considered unpractical, prophylactic institution of a washout procedure may be advisable.
Musculoskeletal disorders are a common cause of long-term disability in the United Kingdom, making up 15% of the workload of GPs (Martin, Meltzer and Eliot, 1998). Shared care is the management of the patient between the hospital team - consisting of the rheumatologists, specialist nurse, occupational therapist and physiotherapist - and the primary healthcare team (see Table 3.7). Drug therapy should be carefully planned between the rheumatologist and the general practitioner. The rheumatologist’s main role is to diagnose and establish a treatment plan to be followed in primary care or shared between primary and secondary care. The latter is the case with rheumatoid arthritis, as it is a progressive chronic disease. The specialist nurse acts as a resource for the patients, other professionals and for the primary healthcare team. The nurse is required to be a counsellor, educator and adviser on many aspects of rheumatoid arthritis, particularly drug therapy. Physiotherapists provide a whole range of treatments and aim to maintain and improve function, alleviate pain and motivate the patient to carry out regular exercises. The occupational therapist provides help and support with problems of daily living and is often instrumental in enabling the patient to develop coping strategies including pacing of activities, joint protection and self-management interventions including relaxation. The primary healthcare team provide health services outside the hospital. They consist primarily of the general practitioner, the practice nurse, the district nurse and the health visitor, all of whom provide valuable information about the patient’s family and home situation. They are often the first point of contact the patient makes. An analysis of the work practice nurses do showed they offered practical treatment, health promotion and disease management (Bryan, 1995). When each team complements the other and, provided there is communication and respect for each other’s roles, then good quality treatment should be available for all patients.
Table 3.7 Members of the shared care team.
• Practice nurse
• Occupational therapist
• District nurse
• Health visitor
• Social services
• Nurse specialist
According to Bryan (1995) practice nurses are isolated from colleagues and need a forum for the exchange of ideas, the updating of skills and the acquisition of new knowledge. In order to try and fill this need, education and opportunities for updating knowledge are provided by the hospital team in the form of study days, visits to the rheumatology unit and the team visiting the general practice. The practice team will then be able to support and advise patients, recognize when side effects require a change of treatment or when the patient would benefit from an early hospital appointment. The early identification of symptoms of the disease, the side effects of drug therapies, the interpretation of the blood results and their implications, plus the psychological effect of arthritis on the patient and their family are important requisites for managing the condition.
An evaluation of two study mornings for practice nurses delivered by a specialist nurse in the rheumatology department of a general hospital enabled clinical scenarios to be discussed, increasing the clinical knowledge and consequently reducing the number of telephone calls from practice nurses (Sigworth, 2004).
Nurses in the primary healthcare team can play an important part in alleviating confusion in the administration of drugs by using medication cards stating how and when patients are to take the prescribed dose (Figure 3.2). Pill dispensers are invaluable for patients with poor memory as they have compartments containing drugs for each day on a weekly basis. To obtain the maximum benefit, medicines should be taken in the correct way at the correct time. Some patients will have failing eyesight and be unable to read the instructions. Many pharmacists will print large labels to overcome this. Patients who have poor hand grip often cannot open the childproof bottles. It is helpful to liaise with the pharmacist who will provide screw tops or ring caps. Patients with reduced manual dexterity frequently can experience difficulties with blister packs. Eye drops also often present a problem. The pharmacist and the occupational therapist can help with the provision of aids to maintain independence. An increased number of tablets taken, and doses involved, often reduces concordance. Patients with poor memory may find drugs to be taken daily of more benefit. Patients with Sjogren’s syndrome can find swallowing tablets difficult. It may therefore be more appropriate to prescribe drugs in liquid form.
Figure 3.2 Medication card.
Many patients do not comply with the drug therapy as they are afraid of the side effects or of being dependent on a drug, particularly analgesia. Confusion often arises as many drugs have three different names, the brand, the pharmaceutical and the generic name.
Low patient adherence to therapeutic regimes is an obstacle to achieving therapeutic goals in arthritis management. Improvement of concordance is a prime goal of much patient education and counselling (Daltroy, 1993). This area will be discussed in greater depth in Chapter 4.
In GP surgeries most of the drug monitoring is carried out by the practice nurse, guided by protocols issued and agreed with the rheumatologist and GP. The Royal College of Nursing rheumatology forum has produced guidelines for nurses involved in
• The administration of intramuscular sodium aurothiomalate (see Appendix 3.B).
• The administration of intramuscular methotrexate.
The objective of these guidelines is to ensure that the patient receives the same standard of care and high quality service, independent of the setting in which they are nursed. The guidelines also provide the nurse with a framework for practice.
Helliwell and O’Hara (1995) found that the percentage of cases in which the standard monitoring protocol had been complied with within the GP practice was 26% for sodium aurthoimalate, 67% for sulfasalazine and 93% for methotrexate. (The discrepancy relating to the monitoring of sodium aurothiomalate concerned an annual chest X-ray requirement).
Havelock (1998), in an audit undertaken of shared care monitoring, found that the majority of patients were being adequately monitored, less than 2% of patients were not being monitored and a significant number of patients were actually receiving more blood tests than had been stated on the agreed protocols.
Close monitoring of second line drugs ensures their safe use and is a guide to their efficacy. To provide close communication between the general practitioner and the rheumatologist, shared care booklets are often issued to patients from the rheumatology department. The use of a patient-held booklet has been strongly endorsed by the British Society of Rheumatology, the British Health Professionals in Rheumatology and the National Patient Safety Agency. Such booklets can be used to record the blood results serially and monitor the urinalysis (where required) for the presence of blood and protein. This enables the rheumatology specialist to examine the trends of the haematological and biochemical results and the presence of abnormalities in the urine. This therefore helps the rheumatology specialist to decide whether to discontinue the drug or reduce the dose. Each book issued should have the contact number of the rheumatology department with which the patient or a member of the primary healthcare team can make contact for advice and support. Serious side effects can be avoided by the hospital team and the primary healthcare team explaining to the patients the necessity of having regular blood tests and reporting side effects early. In Helliwell and O’Hara’s study (1995) there was unanimous agreement by the GPs that shared monitoring cards were helpful. The GPs involved were prepared to keep them updated and were willing to follow suggested protocols. Havelock (1998) also found that this method of documentation worked well within both the primary and secondary care settings.
Computerized patient monitoring systems have been gaining popularity in rheumatology (Lee, Lenert and Kavanaugh, 2004) as they offer automized validation, improved data capture and immediate result availability (Buxton, White and Osoba, 1998; Velikova et al., 1999). Lee, Lenert and Kavanaugh (2004) suggest that patient outcome measures could also be completed by patients via a computer program, which would enable the clinician to receive the information required to access the efficacy of drug therapy at the optimal time and prevent the delay that often occurs as a patient waits for an outpatient appointment. Clinicians could then review and compare results with earlier visits and adjust medications accordingly ensuring patients achieve a therapeutic dose at the optimal time (Lee, Lenert and Kavanaugh, 2004).
GPs’ CONCERNS RELATING TO PRACTICE-BASED MONITORING
Anxieties over various aspects of GP-based drug monitoring included:
• Poor facilities for the collection and distribution of blood samples to the hospital laboratory.
• A perceived lack of time to perform domiciliary visits on those patients unable to attend the practice. One could argue that it may be more appropriate for a community practitioner - for example, a district nurse with expanded knowledge in the field of rheumatology - to carry out such visits.
• A lack of clarity regarding the responsibility for prescribing and monitoring drug therapy.
One practice cited by Helliwell and O’Hara (1995) was unwilling to monitor second line therapy due to a perceived lack of time to perform the necessary blood tests and a reluctance to accept the responsibility inherent within this practice.
PATIENTS’ EXPERIENCES OF DRUG MONITORING
Arthur and Clifford (2004a) compared the satisfaction of patients attending followup monitoring care within primary and secondary care locations. They found that whilst patients from both locations were satisfied with the care they received, those receiving specialist nursing care in the secondary care location were more satisfied. Empathy, specialism, information provision, technical aspects, time and continuity of care were identified as being important for patients attending monitoring clinics (Arthur and Clifford, 2004b), with the specialist nurse able to positively influence patients’ perceived ability to cope with their arthritis (Ryan et al., 2006).
At the heart of community care is the principle that services should support people in their own home and locality (Wolf, 1997). In certain chronic conditions shared management between the hospital and general practitioner is well established, especially in areas such as diabetics and asthma (Jones et al., 1991; Thorne and Russell, 1973).
The essential features of community clinics are that they are:
• In a location close to the patient’s home.
• Performed by a consultant specialist.
• Providing educational opportunities for GPs.
• Improving communication between the hospital and community staff (Helliwell, 1996).
Shared care should include:
• Effective communication between primary and secondary care teams.
• Shared documentation in the form of agreed guidelines.
• Ongoing support, education and training.
• An appreciation of both service commitments and difficulties (Barrett and Thomas, 1992).
Most GPs will have only a very small case load (often single figures of patients) of those requiring DMARDs. Therefore the practitioner is unlikely to be familiar with all aspects of this therapy including adverse effects. Although the NHS management executive has decreed that the doctor who has clinical responsibility for the patient should undertake the prescribing, there is a clear need for shared management in both the clinician’s and the patient’s interest. The British Society of Rheumatology (1992) has recommended the referral of all patients with RA to the hospital setting with the subsequent sharing of treatment between the hospital and general practitioner.
GPs feel confident managing the majority of musculoskeletal conditions within their surgery provided they have adequate support with: joint injection techniques, complex cases with poor outcome (including pain syndromes), access to physiotherapy and a multidisciplinary approach to pain control (Roberts, Adebajo and Long, 2002). GPs’ knowledge of their patients with RA in the areas of functional disability, social situation and involvement of health and social care professionals was very variable (Memel and Kirwan, 1999), with GPs significantly underestimating the functional disability of their patients. The education and training of GPs may not equate with the needs of musculoskeletal patients. A lack of confidence in managing rheumatological conditions is related to lack of experience and poor teaching (Lanyon, Pope and Croft, 1995). This situation is being addressed through the training of GPs with a specialist interest in rheumatology.
Community clinics run by a rheumatologist in a GP’s surgery demonstrated increased patient satisfaction and greater patient access to a specialist, in comparison with traditional outpatient clinics, but only a slight improvement in health benefits (Bond et al., 2000). Whilst patients’ own costs were lower, NHS staffing and treatment costs were more expensive per patient in outreach than outpatient clinics (Bond et al., 2000).
The advantages of community clinics cited by both the GP and the specialist included:
• Improved patient access to the specialist (Bailey, Black and Wilkin, 1994).
• Patient convenience.
• Shorter waiting time for first appointment.
• Fewer non-attenders.
• Improved communication between GP and the specialist.
Patients in Helliwell’s (1996) study reported experiencing a greater satisfaction with their consultants than their counterparts attending a hospital-based clinic. Patients attending the community clinic stated that their questions were always answered.
POTENTIAL PROBLEMS WITH CONSULTANT-BASED COMMUNITY
• Infrequent follow-up intervals (if the specialist attends every four to six weeks then follow-up consultations are delayed).
• Increase in GP administrative costs and time.
• Many consultants working within the community have a minimal number of support staff, and the time spent travelling will reduce the number of patients seen per session (Barnyl et al., 1990; Bond et al., 2000).
• The opportunity for education as a result of personal contact between the consultant and GP is often infrequent due to GPs engaging in busy surgeries of their own (Helliwell, 1996). In a survey by Bailey, Black and Wilkin (1994) GPs were in attendance at only 5% of outreach clinics.
• Case mix disruptions may occur and the consultant is not available for other clinical practices whilst in the community (Walker, 1994). Although fewer patients were seen in the community clinic with a higher old/new ratio than the hospitalbased clinic, Helliwell (1996) found no difference in the case mix data between the two healthcare settings.
In Norfolk a weekly rheumatology nurse practitioner clinic was established in the general practice to provide the following range of services (Mooney, 1996):
• Physical assessment of joints.
• The monitoring of the safety and efficacy of drug treatment.
• Initiation and interpretation of clinical laboratory data.
• Referrals to the multidisciplinary team.
• Liaison between the patient and other healthcare professionals.
The patients were highly satisfied with this service provision. This finding was in accordance with work carried out by Hill (1997). Patients who were allocated to a nurse-led clinic within the outpatient setting were more satisfied with their overall care when compared to a similar group of patients attending the consultant clinic. Mooney (1996) concludes that the reported patient satisfaction could be attributed to the improved continuity of care the patients were receiving, coupled with the length of consultation time the patient spent with the nurse.
The nurse practitioner clinic in the doctor’s surgery also had other benefits. These included:
• The provision of disease education for patients and the opportunity to discuss issues with the nurse.
• Less travelling for patients as the clinic was located in a more convenient setting with no parking fees.
• The patients experienced a continuity of care in their management.
• The rheumatology nurse practitioner acted as an advocate between the practice, rheumatologist and patient thereby enhancing and improving communication.
• Early referral could be made to other healthcare professionals.
• If necessary quicker access to a rheumatologist was available and appropriate investigations could be carried out before referral.
• The number of outpatient visits to the hospital rheumatology clinics was reduced.
• The provision of specialist advice could be given in a familiar environment.
• General practitioner visits for rheumatological complaints were reduced (Mooney, 1996).
Dargie and Procter (1993) established a nurse-led arthritis clinic in the health centre in which they worked. One of the primary objectives of this development was to provide an easily accessible service for the assessment, support, education and monitoring of treatment for patients with arthritis and their families. Additional advantages that Mooney (1996) cites included a focus on prevention rather than crisis management. The two individuals involved (a district nurse and a practice nurse) also felt they were able to make full use of their nursing skills which enhanced their own job satisfaction. Potential disadvantages in the provision of this much-needed service were the lack of community services in some areas - for example, physiotherapist and occupational therapist. The extra time commitment required to provide such a service could also be viewed as a disadvantage in economic terms but the pay-off was that patients received a service that was tailored to their individual needs.
The advantage of community clinics to the patient include convenience whilst maintaining a high standard of care from a specialist practitioner. For the hospital one of the benefits is the devolution of some of the care to general practice, creating the scope for more new patients to be seen in the hospital setting (Helliwell and O’Hara, 1995).
Hewlett et al. (2000) evaluated the clinical efficacy, cost and acceptability of a shared care system of patient or GP-initiated review in patients with RA. Patients were randomized to either shared care with their GP (no routine hospital review but rapid access on request) or traditional hospital care (regular planned outpatient review usually three- to four-monthly). Patients (or their GPs) in the shared care group could request review by any member of the rheumatology team via the nurserun telephone helpline. Patients in the study appeared representative of a hospitalbased RA population with moderate inflammatory activity, pain and disability. Patients who declined to take part were older and more affected by their arthritis. Results showed no clinical deterioration and some clinical benefit in the shared care group, which was achieved at a 33.5% cost saving, with both patients and GPs experiencing greater satisfaction and confidence in the system (Hewlett et al., 2000).
As is often the case in the management of many chronic conditions, it is the primary healthcare team who are responsible for the early diagnosis and continuing care of patients with established osteoporosis (Brennan, 1996). Osteoporosis is a silent disease that can affect all age groups. Symptoms are not usually present until a fracture occurs, often as a result of minimum trauma. Bone is a living tissue and is being continually regenerated. Cells, called osteoclasts, destroy bone and eat away areas of bone, whilst other cells, called osteoblasts, are bone builders and follow the osteoclasts filling in and repairing the bone. When this process becomes imbalanced, more bone will be destroyed than is being replaced; then osteoporosis results with bones becoming thinner and more brittle. Peak bone mass is generally achieved between the ages of 25 and 36. Following this peak, bone mass then decreases by 0.3% a year. When women reach the menopause, however, bone is lost more rapidly and may be as much as 5% per year over a 10-year period. Thus 1 in 3 women and 1 in 12 men are likely to sustain a fracture related to osteoporosis by the age of 90 years (Peel and Eastell, 2004).
CLASSIFICATION OF OSTEOPOROSIS
Osteoporosis falls into two categories, primary and secondary. Primary osteoporosis is caused by ageing, the menopause and impaired adult peak bone density.
Secondary osteoporosis accounts for 40% of cases in women and 60% of cases in men. It is caused by:
• Anorexia and bulimia.
• Amenorrhoea for more than six months.
• Premature menopause in women (whether surgical, natural or radiation-induced).
Table 3.8 Foods rich in calcium.
225 mg calcium
Silver top milk
Bread white — 1 slice
Bread wholemeal — l slice
• Excessive exercise - for example, ballerinas and athletes.
• Lifestyle factors - smoking and excessive alcohol.
• Dietary factors - for example, lack of calcium and vitamin D (Table 3.8 shows food groups rich in calcium).
• Gut malabsorption and chronic liver disease.
• High dose corticosteroid therapy (over 7.5 mg daily).
• Heparin therapy.
• Genetic links.
• Cushing’s syndrome.
• Primary hyperparathyroidism.
It is important that the primary healthcare team recognize those individuals who are potentially at risk and discuss with them preventive strategies or management of the condition.
RISK FACTORS FOR OSTEOPOROSIS FRACTURE
Risk factors do not have adequate sensitivity or specificity to identify people at risk and measurement of bone mineral density is needed to quantify an individual’s risk of fracture (Peel and Eastell, 2004).
Risk factors for osteoporosis:
• Female sex.
• Increasing age.
• Early menopause (before 45 years).
• High alcohol intake.
• Physical inactivity.
• Low body mass index.
• Heredity (Peel and Eastell, 2004).
Risk factors that act independently of bone mineral density (Peel and Eastell, 2004):
• Prevalent low trauma fracture, particularly vertebral fractures.
• Family history, particularly of maternal hip fracture.
• Current smoking habit.
• Low body weight.
• Increasing age.
INVESTIGATIONS FOR OSTEOPOROSIS
• X-rays: radiography has an essential role in identifying fractures. However, standard radiographs cannot be used to diagnose osteoporosis on the basis of apparent osteopenia. The appearance of osteopenia on plain X-rays depends on the dose of X-ray used, volume of soft tissues and other variables, in addition to the bone density itself.
• Dual energy X-ray absorptiometry (DEXA) scanning: this is considered to be the gold standard technique for measuring bone density. Typically scans are taken at the proximal femur and spine. The radiation dose to the patient from this procedure is small, approximately one tenth of a chest X-ray. A T score and a Z score is reported. The T score is the number of standard deviations above/below the peak adult (premenopausal ) mean. The Z score is the number of standard deviations above/below the age-matched mean. For every one standard deviation fall in bone density, fracture risk approximately doubles. DEXA scanning is useful for measuring bone density in patients with risk factors in whom results will affect management. This form of scanning may be unreliable in the presence of skeletal deformities - for example, scoliosis or degenerative changes.
Once considered to be the gold standard in the treatment of osteoporosis, HRT now only has a role in the treatment of menopausal symptoms such as hot flushes or in women who have undergone an early menopause. Due to concerns in the increased risk of breast cancer and cardiovascular events it is no longer thought to be appropriate to use HRT in the management of osteoporosis.
Simple analgesics such as paracetamol and non-steroidal anti-inflammatory drugs are sometimes beneficial for chronic pain in osteoporosis. Opiates (e.g. morphine) and calcitonin are sometimes given for the intense pain of a vertebral fracture. If chronic pain is not managed then the patient becomes less active, more helpless and isolated, and self-esteem is greatly reduced. Non-pharmacological management of pain is shown in Table 3.9.
Bisphosphonates act to block the action of osteoclasts. They are poorly absorbed from the gut and readily bind to other agents in the gut and must be taken on an empty stomach.
This is the first of the bisphosphonates to be used commonly in osteoporosis. Due to the risk of osteomalacia, 400 mg is taken daily for two weeks every three months, with the option of taking calcium supplements for the remaining weeks. It must be taken with water in the middle of a four-hour fast to ensure adequate absorption.
Contraindications for this drug are severe renal impairment, hypocalcaemia, hypercalcinuria, pregnancy and lactation.
Cyclical etidronate reduces bone loss from the spine and vertebral fracture risk in post-menopausal women with osteoporosis (Peel and Eastell, 2004).
ALENDRONATE SODIUM (FOSAMAX)
It is taken as a single 5-10 mg daily dose. There is now an option to take one 70 mg tablet per week. Patients should swallow a 10 mg tablet when getting out of bed in the morning half an hour before any food and with a 7oz drink of plain water. It is important that patients should stand or sit for at least 30 minutes after taking the tablet, after which the first beverage, meal or medication of the day may be taken. Antacids can affect the absorption of this drug. Contraindications are patients with significant renal impairment, pregnancy, breastfeeding women, abnormalities of the oesophagus or upper gastrointestinal problems. The side effects include nausea, dyspepsia and diarrhoea. Treatment is continued long term. Alendronate prevents bone loss from vertebral and non-vertebral sites and decreases the risk of spine and hip fractures (Peel and Eastell, 2004).
Table 3.9 Pain management (non-pharmacological).
• Pacing activities
• Joint protection techinques
• Aids and adaptation
• Use of heat — for example, heat pads
• Massage (aromatherapy)
• Diversional therapy
• Transcutaneous electrical nerve stimulation (TENS) machine
Risedronate. Risedronate is taken daily as a 5 mg tablet. It should be taken with water 30 minutes before the first drink, food or medication of the day in the middle of a four-hour fast and not before going to bed. Risedronate prevents bone loss from the vertebral and non-vertebral sites and decreases the risk of spine and hip fractures (Peel and Eastell, 2004).
In 2005, NICE issued guidelines on the secondary prevention of osteoporosis and recommended the use of bisphosphonates for post-menopausal women who had already experienced a fracture.
Selective estrogen receptor modulators (SERMs). These are synthetic compounds that stimulate oestrogen receptors of bone tissue and work in a similar way to HRT. Oestrogen receptors of breast and endometrial tissue are not engaged and so it is considered that this treatment will not increase the risk of breast or endometrial cancer. Raloxifene is a commonly used SERM. It has been shown to reduce the risk of vertebral fractures but has not been shown to reduce the risk of non-vertebral fractures (Peel and Eastell, 2004). Like HRT raloxifene is associated with small increases in the number of thrombo-embolic events but is associated with a reduction in the number of new cases of breast cancer (Peel and Eastell, 2004).
Calcitonin inhibits osteoclast activity slowing the breakdown of bone. It can be given as subcutaneous injections or as a nasal preparation that is associated with fewer side effects. Nausea, vomiting, diarrhoea and dizziness have been reported. Calcitonin has been shown to reduce the risk of vertebral fracture. It has analgesic properties that may be useful in the acute management of vertebral fracture (Peel and Eastell, 2004).
CALCIUM (1000-1200 mg DAILY)
Calcium supplementation may be considered where dietary calcium intake is deficient or in cases of malabsorption. It has a less marked effect on fracture reduction than the other antiresorptive agents but it is usually well tolerated (Peel and Eastell, 2004).
Vitamin D is required to facilitate calcium absorption. Most people achieve their vitamin D requirement by the action of sunlight on their skin, in addition to that obtained from food. A French study in nursing homes showed that 800 iu of vitamin D3 and 1.2 g of elemental calcium daily reduces the risk of hip fracture by 43% (Chapuy et al., 1992). There is no evidence that vitamin D and calcium supplementation decreases spine bone loss or the incidence of vertebral fracture. A combination of calcium and vitamin D should be considered in all elderly patients who are housebound or in residential care (Peel and Eastell, 2004).
Calcitriol is an active form of vitamin D which increases calcium absorption from the gut and decreases calcium excretion. It is used when there is active vitamin D deficiency which may be the cause of diminished bone mass. Patients should be monitored for hypercalcaemia whilst taking calcitriol. Calcitriol reduces postmenopausal bone loss and reduces spinal and extra-spinal fractures (excluding the hip).
FORMATION STIMULATING AGENTS
Fluroide dramatically increases bone mass but evidence of fracture prevention is inconclusive and the therapeutic window is narrow. Consequently it is rarely used in the United Kingdom (Peel and Eastell, 2004).
Parathyroid Hormone (PTH)
Intermittent injections of recombinant parathyroid hormone have recently been licensed in the United Kingdom (Peel and Eastell, 2004).
Teriparatide (Forsteo) is almost identical to human parathyroid hormone. It stimulates osteoblast production and is used to reduce vertebral fractures. It is administered as a daily subcutaneous injection.
STRONTIUM RANELATE (PROTELOS)
Is licensed for post-menopausal women with osteoporosis to reduce the risk of vertebral and hip fracture. It works by suppressing the action of osteoclasts and stimulating osteoblasts. It is administered in powder form mixed with water, taken daily in the evening, in the middle of a four-hour fast. Unlike bisphosphonates,
strontium ranelate has very few gastrointestinal side effects; nausea and diarrhoea can occur on commencement of treatment but are usually mild and short-lived. There is a slight increased risk of blood clots and it would not be recommended to patients already at risk from thrombolytic events.
For optimum bone health a well-balanced diet is recommended with adequate calcium and vitamin D (see Table 3.8). Calcium requirements change throughout life and an adequate intake is particularly important during childhood, adolescence, pregnancy and lactation. Excessive caffeine, salt and fibre can hamper absorption or increase calcium excretion.
Smoking should be discouraged. Smoking alters oestrogen metabolism resulting in a reduction in the biologically active oestrogens which are beneficial to bone health. Women smokers tend to have an earlier menopause. Smokers also tend to have a lower body weight.
Alcohol intake should remain moderate. Excessive alcohol intake has a detrimental effect on bone turnover and formation; it can also effect calcium metabolism.
Weight bearing exercise can increase bone formation, improve muscle strength and coordination. Exercise must be sustained as bone loss will resume once exercise stops. Exercise can also improve coordination and reduce the likelihood of falls. Three sessions of 20-minute exercise weekly are required. Excessive exercise will have a negative effect and increase the risk of osteoporosis due to low body weight and the effects on the hypothalamic-pituitary-gonadelaxis.
Nurses have an input in fall prevention by improving awareness, identifying these who might be at risk and addressing risk factors such as poor eyesight, non-supportive footwear, reduced mobility and unsafe situations in the home environment.
The primary healthcare team play a valuable preventative role, especially with regard to osteoporosis, emphasizing the importance of a healthy lifestyle from the cradle to the grave. They often have a good relationship with the patients because they see them for a multitude of conditions. The more the practice healthcare team are involved with the hospital care team the better for patients with chronic disease. The efficacy of this arrangement requires continuous audit, with each practice reviewing how it can improve. There are variations in the quality of care of chronic conditions. It is the responsibility of the primary healthcare team, with the support of the rheumatologist and their team, to ensure the continuity of complex care which is offered to the rheumatology patient. What is regarded as routine in the rheumatology clinic may be rare to the GP. It is therefore important that the appropriate information be given to the patient on ward discharge and after clinic appointments, and to the GP with a diagnosis and details of medication and treatment. A network of support and communication between rheumatology services, the rheumatology team, the district nurses, the practice nurses and other community-based services will ensure consistent, clinically effective management of the patient and their rheumatoid disease. It is important that the practice nurse team uses the rheumatology nurse practitioner in a coordinating role as a resource and advisor. Management of arthritis is a long-term partnership between the patient and the primary and secondary healthcare team.
Information Sheet (arc 2005)
The Rheumatology Nurse Specialist
WHAT IS IN THIS LEAFLET?
This leaflet contains information about the role of the rheumatology nurse specialist in helping you with your arthritis.
WHAT IS A RHEUMATOLOGY NURSE SPECIALIST?
The rheumatology nurse specialist is a trained nurse who has special experience in looking after the physical, emotional and social needs of patients with arthritis. These nurses have different titles, such as clinical nurse specialist, rheumatology nurse practitioner or liaison rheumatology nurse. Rheumatology nurse specialists work with people with rheumatoid arthritis and with people with other rheumato- logical conditions, such as scleroderma, osteoarthritis, fibromyalgia and lupus.
People with arthritis have many different needs. For this reason, most hospital rheumatology departments have a team of health professionals to look after all aspects of your care. The team itself may vary from hospital to hospital but generally will include a rheumatology nurse specialist, a physiotherapist and an occupational therapist (see arc leaflets A Mind Map on the Rheumatology Department, Physiotherapy and Arthritis and Occupational Therapy and Arthritis).
Some rheumatology nurse specialists have received special training which allows them to act in an ‘extended role’. This involves some tasks usually done by doctors, such as carrying out an examination of your joints, reviewing and requesting investigations, performing joint injections and making changes to your treatment as required. The rheumatology nurse specialist will work closely with the consultant rheumatologist and, when necessary, will discuss your care with one of the rheumatology doctors.
HOW CAN YOU BE REFERRED TO A RHEUMATOLOGY NURSE SPECIALIST?
People with arthritis are often referred to a rheumatology nurse specialist when a diagnosis has been made by their consultant rheumatologist and the drug treatment has been agreed on. Some rheumatology departments also offer an open system, where patients can request to see the rheumatology nurse specialist (usually if a problem arises between appointments).
HOW CAN A RHEUMATOLOGY NURSE SPECIALIST HELP YOU?
Helping You Learn About Your Condition
The diagnosis of arthritis or a related condition can lead to a mixture of emotions. These may include anger, bewilderment, fear and anxiety. A detailed explanation about what the diagnosis means can reduce anxiety and fear. The rheumatology nurse specialist will listen to your particular concerns (e.g. ‘Can I carry on working?’) and provide information and support during periods of adjustment.
The rheumatology nurse specialist will explain what symptoms the arthritis can cause, and will work with you to reduce their impact. This often involves a process known as goal setting. Here problems are identified - for example, pain - and a plan is drawn up to help you manage the problem. This plan may include using a combination of methods, such as painkillers, exercises and pacing techniques. Verbal information will often be supported by written information (such as arc booklets), which enable you to learn at your own pace. The booklets can be shared with family members so that your family can also become involved in your care. If appropriate, the rheumatology nurse specialist can also spend time with your family discussing their concerns.
When you are first diagnosed you will probably see the rheumatology nurse specialist on an individual basis so that you can receive advice and support which is specific to your individual needs. You may have the opportunity of joining a patient education group if there is one in your area. These groups provide you with the option of learning from other people who have arthritis as well as developing new coping skills - for example, relaxation to reduce muscle pain. Most programmes will have input from other members of the rheumatology team, including physiotherapists and occupational therapists.
Helping You Learn About Drug Treatments and Monitoring Needs
Drug treatment plays a key role in the management of rheumatoid arthritis and related conditions. Some drugs - for example, non-steroidal anti-inflammatory drugs (NSAIDS) help reduce pain and stiffness. Other drugs, known as disease modifying anti-rheumatic drugs (DMARDs - see arc leaflet Drugs and Arthritis), dampen down the arthritis itself. These drugs require regular ‘monitoring’ blood tests and some need regular blood pressure and urine testing. The rheumatology nurse specialist will provide you with information before you start taking any DMARDs so that you are fully involved in your treatment. This may include:
• The benefit of the drug.
• How to take the drug.
• Whether to continue with other tablets.
• What to do if you forget to take a dose.
• Side effects and what to do if they occur.
• Any special instructions - for example, avoid alcohol.
• Monitoring requirements.
• Contact telephone number.
The rheumatology nurse will also arrange for your drug treatment to be monitored in a hospital clinic or at your GP surgery.
Offering Telephone Support
In some rheumatology departments, rheumatology nurse specialists run a telephone advice line to provide you (and health professionals, including GPs) with easy access to a nurse who knows about you, your condition and your treatment.
Involving Other Members of the Rheumatology Team
When the rheumatology nurse specialist assesses you, they might identify a problem which another member of the team may help with. For example, it may be that you are having difficulties opening jars and you would benefit from an assessment by an occupational therapist. The rheumatology nurse specialist will be able to make arrangements for you to be seen by the occupational therapist or other members of the rheumatology team.
Providing Emotional Support
Having arthritis can have a major effect on how you feel about yourself, your mood, your job and your relationships with other people. The rheumatology nurse specialist can provide expert help and support to improve your confidence, mood and relationships.
GUIDELINES FOR NURSES ON THE USE OF AND ADMINISTRATION OF SODIUM AUROTHIOMALATE IN RHEUMATOID ARTHRITIS
What is Sodium Aurothiomalate?
Sodium Aurothiomalate (intramuscular gold) belongs to the group of drugs known as slow-acting anti-rheumatic drugs (SAARDs). These drugs suppress clinical and laboratory markers of disease activity and are thought to slow the progression of the disease but the precise mode of action is unknown. Unlike non-steroidal anti-inflammatory drugs (NSAIDs) which produce an immediate therapeutic effect, SAARDs are unlikely to produce any benefit before 12 weeks and often take as long as 24 weeks before improvement is attained.
Indications for Using Sodium Aurothiomalate
Sodium aurothiomalate is used in cases of active rheumatoid arthritis.
Females who are pregnant or are breastfeeding should not be given intramuscular gold. Likewise those who have gross renal or hepatic disease, history of blood dyscrasias, exfoliative dermatitis or systematic lupus erythematosus.
Administration and Dosage of Sodium Aurothiomalate
The drug is given by deep intramuscular injection, followed by gentle massage of the area. An initial test dose of 5-10 mg is usually given and if there are no adverse reactions (skin rash or hypersensitivity), weekly injections of 20-50 mg are administered until a response occurs. Most patients will feel no benefit until they have received a total dose of 500 mg-800 mg. Once in remission and providing they do not experience any side effects, patients are usually maintained on a dose of 50 mg administered monthly, but the physician may vary the dose according to the activity of the disease. If no major improvement has occurred after reaching a total dose of 1000 mg (excluding the test dose) the treatment is usually discontinued, although sometimes weekly injections of 100 mg for five weeks are given.
Side effects occur in approximately 30% of patients and can appear at any time during the course of the treatment, even after the patient has been successfully treated with sodium aurothiomalate for many years. They are mostly mild, but up to 5% experience severe reactions which are potentially fatal.
Skin reactions are perhaps the most common of the side effects to intramuscular gold and are usually mild, However, if they do develop, the injection should be withheld and their presence should always be reported to the physician as they may be the forerunners to severe gold toxicity. This side effect occurs most commonly after a total cumulative dose of 300-400 mg.
Rashes may be localized or general and range from minor reactions to major skin lesions. They can mimic almost any skin eruption.
Pruritus or ‘itching’ is quite common and is often first felt between the fingers.
Stomatitis and mouth ulcers can develop in some patients. Pharyngitis should raise the question of leucopenia. Patients sometimes complain of a metallic taste in the mouth which although unpleasant is not a permanent side effect.
Thrombocytopenia, neutropenia, agranulocytosis and fatal marrow suppression can develop but the latter is rare. Bruising, particularly around the shins, can be the first indication of thrombocytopenia. A fever and sore throat can indicate the presence of agranulocytosis.
Eosinophilia may be an indication of developing toxicity but does not always necessitate stopping gold.
The drug manufacturer recommends that a full blood and platelet count is taken before each injection is given and this should be meticulously adhered to. These results should be recorded sequentially. A sudden fall in platelet or white cell count outside normal limits may be reason for the physician to suspend treatment. A fall on three consecutive occasions, even if within normal limits, should also be reported as the physician may wish to suspend or modify the treatment.
Blood dyscrasias are most likely to happen when between 400 mg and 1000 mg of intramuscular gold has been given but can occur at any time during treatment.
Proteinuria develops in about 10% of patients but is severe in less than 2%.
A gradual increase in protein concentration is more significant than a single result and so, if protein is detected, do not give the gold but ask the patient to return a few days later for a retest. If the protein persists, consult the physician and it may be necessary to estimate the amount of protein excreted in 24 hours by a more accurate measure than use of dipsticks.
If blood and protein are present, eliminate the possibility of a urinary infection by collecting a midstream urine specimen; if the MSU is negative, the physician may decide to stop the gold.
Rarer Side Effects
Rarer side effects include peripheral neuritis, alopecia and colitis. A small number of patients may experience flushing, nausea or vertigo after an injection.
THE NURSE’S RESPONSIBILITY WHEN GIVING SODIUM AUROTHIOMALATE
Before beginning the gold injections, you should discuss the treatment with the patient. This should include an explanation of what the treatment is for, how it is to be given, how the treatment will help and what side effects may occur. It is also important to make sure that the patient knows where the treatment and monitoring will take place, and who they should contact if they are unable to attend or if they experience any problems. It is always helpful to provide written information to the patient as a backup to this verbal explanation.
Before Each Injection
• Inspect the skin for rashes and ask if any pruritus has been experienced.
• Ask the patient if they have experienced any soreness of the throat, developed mouth ulcers or loss of taste.
• Ascertain that blood has been taken for a full blood count.
• Check that the prescribing doctor has seen and approved the results of the previous blood tests.
• Inspect the skin for bruising.
• Inquire if the patient has experienced any undue bleeding such as epistaxis or bleeding gums.
• Ask the patient if they are experiencing any flu-like symptoms.
• Record the dose given, haematology and urinalysis results, the presence of any unwanted effects and any action taken on the patient’s gold card.
If the monitoring reveals any adverse effects, withhold the gold and report the symptoms to the doctor.
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