Rheumatoid Arthritis Flashcards
RA - Initial Mx
The management of rheumatoid arthritis (RA) has been revolutionised by the introduction of disease-modifying therapies in the past decade. NICE has issued a number of technology appraisals on the newer agents and released general guidelines in 2009.
Patients with evidence of joint inflammation should start a combination of disease-modifying drugs (DMARD) as soon as possible. Other important treatment options include analgesia, physiotherapy and surgery.
Initial therapy
in the 2009 NICE guidelines it is recommend that patients with newly diagnosed active RA start a combination of DMARDs (including methotrexate and at least one other DMARD, plus short-term glucocorticoids)
Patients with newly diagnosed rheumatoid arthritis and evidence of active exacerbation should be treated with methotrexate and another DMARD plus steroid. Options for other DMARDs include sulfasalazine, leflunomide and hydroxychloroquine. DMARD monothearpy is only used if the combination therapy is not appropriate. Biological agents such as infliximab is not used as a first line medication for patients with rheumatoid arthritis.
RA - DMARDs
DMARDs
methotrexate is the most widely used DMARD. Monitoring of FBC LFTs is essential due to the risk of myelosuppression and liver cirrhosis. Other important side-effects include pneumonitis, pulmonary fibrosis, mucositos
Other Examples of DMARDs
sulfasalazine
leflunomide
hydroxychloroquine (used if high titre ANA as sulfasallazinse = high risk of stevens Johnsons)
RA - TNF-Inhibitors
TNF-inhibitors
- the current indication for a TNF-inhibitor is an inadequate response to at least two DMARDs including methotrexate
- etanercept: recombinant human protein, acts as a decoy receptor for TNF-α, subcutaneous administration, can cause demyelination, risks include reactivation of tuberculosis
- infliximab: monoclonal antibody, binds to TNF-α and prevents it from binding with TNF receptors, intravenous administration, risks include reactivation of tuberculosis
- adalimumab: monoclonal antibody, subcutaneous administration
RA - Rituximab
Rituximab
- anti-CD20 monoclonal antibody, results in B-cell depletion
- two 1g intravenous infusions are given two weeks apart
- infusion reactions are common
RA - Abatacept
Abatacept
- fusion protein that modulates a key signal required for activation of T lymphocytes
- leads to decreased T-cell proliferation and cytokine production
- given as an infusion
- not currently recommend by NICE
RA - Later Mx
Current NICE guidelines recommend the starting of biologic therapy when the patient has been on at least two DMARDs, including methotrexate, reporting two DAS 28 scores of greater than 5.1 at least one month apart1. A short course of oral prednisolone may be appropriate for flares for symptomatic control. However, this is not an option if the patient does not wish to take any steroids. Intravenous pulsed steroids or long-term treatments are not appropriate. Regular COX-2 inhibitors are not recommended by NICE guidelines. NSAIDs are appropriate for short-term symptomatic control but only at lowest doses for as short a period as possible.
Example Question:
A 68 year old female diagnosed with rheumatoid arthritis four years ago presents gradually increasing tenderness in the small joints of both hands over the past 5 months. She continues to work as a legal secretary, involving significant amounts of time at a computer. She is currently on maximum doses of methotrexate and sulphasalazine on diagnosis and maintained on the same doses since. Her DAS score today is 5.8, it was 4.7 when you saw her in clinic last 1 month ago. What is the next management step?
> Continue methotrexate and sulphasalazine. Short-course oral prednisolone Stop current DMARDs. Start etanercept Stop current DMARDs. Start infliximab Admit for pulsed intravenous methylprednisolone Prescribe regular long-term celocoxib in addition to methotrexate and sulphasalazine
Late Onset RA - Diagnosis: Example Question
An 82-year-old gentleman was referred to the outpatients rheumatology clinic by his GP. He presented to his GP six weeks ago complaining of significant shoulder girdle stiffness. He felt weak and lethargic and complained of malaise. He also complained of pain and stiffness in both wrists, but especially his right wrist. The stiffness was worst in the morning, lasting an hour before easing off with activity. A trial of ibuprofen 400mg TDS alleviated his symptoms partially. On systems review, he denied any further symptoms, including the absence of weight loss, respiratory and urinary symptoms. He denied losing weight. He had previously been well, with a past medical history comprising of osteoarthritis of his knee joints, asthma and hypertension. He had never smoked and consumed eight units of alcohol per week.
Examination revealed an elderly gentleman who was systemically well. His temperature was 37.4ºC, heart rate 74 bpm, and blood pressure 138/78 mmHg. Examination of his musculoskeletal system revealed the presence of right wrist tenderness and slight swelling, as well as restricted active movements of his shoulders. Examination of his cardiovascular, respiratory, gastrointestinal and neurological systems was unremarkable.
Initial investigations by his GP revealed the following results:
ESR 55 mm/hr
CRP 58 mg/l
CPK 188 u/l (reference range 17-148)
PSA 2.6 ng/ml
Serum electrophoresis normal clonal pattern
Rheumatoid factor pending
Anti-CCP pending
Full antibody screen pending
Chest x-ray: normal heart and lung fields
Urine Bence Jones protein: negative
From the information so far, what is the most likely diagnosis?
Paraneoplastic syndrome > Late onset rheumatoid arthritis (RA) Polymyalgia rheumatica (PMR) Polymyositis Giant cell arteritis
Upon initial reading of this question, one may be tempted to suggest that polymyalgia rheumatica is the most likely diagnosis, given the history of the new onset girdle stiffness, malaise and raised ESR. However, there are important clues that exclude this. PMR would not account for the presence of synovitis on examination within this gentleman’s wrist, and it is unusual (though not unheard of) to have a raised CRP with PMR. There is no evidence to suggest the presence of a neoplasm, and one would expect a greater degree of muscle involvement as well as perhaps signs of motor weakness on examination with a suspected diagnosis of polymyositis. Therefore option 2 is the most appropriate answer.
CPK = Creatinine Phosphokinase
RA - Diagnosis
NICE have stated that clinical diagnosis is more important than criteria such as those defined by the American College of Rheumatology.
2010 American College of Rheumatology criteria
Target population. Patients who
1) have at least 1 joint with definite clinical synovitis
2) with the synovitis not better explained by another disease
Classification criteria for rheumatoid arthritis (add score of categories A-D;
a score of 6/10 is needed definite rheumatoid arthritis)
Key
RF = rheumatoid factor
ACPA = anti-cyclic citrullinated peptide antibody
A = JOINT INVOLVEMENT 1 large joint 0 2 - 10 large joints 1 1 - 3 small joints (with or without involvement of large joints) 2 4 - 10 small joints (with or without involvement of large joints) 3 10 joints (at least 1 small joint) 5
B = SEROLOGY (at least 1 test result is needed for classification)
Negative RF and negative ACPA 0
Low-positive RF or low-positive ACPA 2
High-positive RF or high-positive ACPA 3
C = ACUTE PHASE REACTANTS (at least 1 test result is needed for classification)
Normal CRP and normal ESR 0
Abnormal CRP or abnormal ESR 1
D = DURATION OF SYMPTOMS
< 6 weeks 0
> 6 weeks 1
RA - Diagnosis: Example Question
A 60 year old woman attended her General Practitioner and reported a three month history of bilateral shoulder muscle and bilateral hip girdle aches and pain. She also experienced stiffness affecting these areas that lasted for up to two hours each morning. These symptoms were limiting her day to day activities and were unresponsive to simple analgesics.
The patient denied symptoms of headache, visual disturbance or jaw claudication. Intermittent episodes of dry mouth and dry eyes had been present for several years. There was no history of unexplained skin rashes. Past medical history included coeliac disease diagnosed twenty years previously that was well controlled on a gluten-free diet. The patient was a non-smoker and drank alcohol only occasionally.
Examination revealed mild muscular tenderness across the shoulder and hip girdles although with no other inflamed or tender joints. Cardiovascular and respiratory examination was unremarkable.
Blood tests requested by her GP demonstrated an elevated ESR of 65. A diagnosis of PMR was made and a course of 20 mg prednisolone daily prescribed. However 6 weeks later the patients symptoms had not significantly improved and she was referred to rheumatology clinic. Repeat blood tests and other investigations are listed below.
Haemoglobin 110 g / dL White cell count 8.9 * 109/l Neutrophils 7.8 * 109/l Platelets 456 * 109/l Urea 6.2 mmol / L Creatinine 87 micromol / L Sodium 138 mmol / L Potassium 4.1 mmol / L Ferritin 180 ng / mL Erythrocyte sedimentation rate 75 mm / h Rheumatoid factor Negative Connective tissue ANA Negative Anti-CCP antibodies 58 EU (reference < 20) Creatinine kinase 89 U / L (reference 5-130)
X-ray hands: minor degenerative change in multiple inter-phalangeal joints of both hands; no evidence of erosive arthropathy
What is correct diagnosis?
Polymyalgia rheumatica > Rheumatoid arthritis Polymyositis Sjorgren's syndrome Systemic lupus erythematous
Rheumatoid arthritis can present with a polymyalgic syndrome prior to clinically detectable sinovitis. In this case this is suggested by the lack of response to trial of prednisolone and the positive anti-CCP antibody. Observational studies have shown a greater clinical and laboratory response to steroids in polymyalgia rheumatica than polymyalgic onset rheumatoid arthritis. Anti-CCP antibodies are rarely present in polymyalgia rheumatica but are strongly associated with rheumatoid arthritis.
Sjorgren’s syndrome and SLE are unlikely given the lack of anti-nuclear antibodies. Polymyositis is excluded by the normal CK.
RA - Complications: Example Question
A 62-year-old lady is seen in the rheumatology clinic. She was diagnosed with rheumatoid arthritis 16 years ago. Her symptoms were relatively well controlled with a combination of methotrexate 20mg once per week, folic acid 5mg once per week and azathioprine 100mg once per day until the last few months when she complained of increasing joint pain with stiffness. Since then her methotrexate dose was gradually titrated to the current dose of 25mg per week. She reported that her joints were less painful and stiff in the morning. Unfortunately, she was also complained of increasing tiredness with an increasing quantity of respiratory tract infections, requiring antibiotics twice in the last six months. She also noted that she bruised more easily of late.
Examination revealed a slender 62-year-old systemically well lady. She was haemodynamically normal and afebrile. Cardiovascular and respiratory examinations were unremarkable, and abdominal examination revealed a mass arising from the left upper quadrant. Clinical examination of her joints revealed no evidence of synovitis or swelling.
Routine blood investigations prior to attending clinic were as follows:
Hb 115 g/l MCV 84 fl Platelets 82 * 109/l WBC 3.5 * 109/l Neutrophils 1.6 * 109/l Lymphocytes 1.0 * 109/l Eosinophils 0.9 * 109/l
Na+ 141 mmol/l
K+ 3.9 mmol/l
Urea 7.0 mmol/l
Creatinine 81 µmol/l
Bilirubin 12 µmol/l
ALP 99 u/l
ALT 13 u/l
Albumin 39 g/l
What is the single most likely cause of the clinical and haematological abnormalities?
Myelodysplastic syndrome Chronic lymphocytic leukaemia Marrow aplasia secondary to drug therapy > Felty's syndrome Myelodysplasia
Felty’s syndrome is a complication of Rheumatoid Arthritis (RA). It consists of a combination of rheumatoid arthritis, neutropaenia and splenomegaly, and tends to affect RA of longstanding duration. The main differential diagnosis is drug-induced marrow aplasia; however, this would not easily account for the presence of splenomegaly.
RA: Complications
Rheumatoid arthritis: complications
A wide variety of extra-articular complications occur in patients with rheumatoid arthritis (RA):
respiratory: pulmonary fibrosis, pleural effusion, pulmonary nodules, bronchiolitis obliterans, methotrexate pneumonitis, pleurisy
ocular: keratoconjunctivitis sicca (most common), episcleritis, scleritis, corneal ulceration, keratitis, steroid-induced cataracts, chloroquine retinopathy
osteoporosis
ischaemic heart disease: RA carries a similar risk to type 2 diabetes mellitus
increased risk of infections
depression
Less common
Felty’s syndrome (RA + splenomegaly + low white cell count)
amyloidosis
Bronchiolitis obliterans is an inflammatory obstruction of the lung’s tiniest airways, called bronchioles. The bronchioles become damaged and inflamed by chemical particles or respiratory infections, particularly after organ transplants, leading to extensive scarring that blocks the airways
Keratoconjunctivitis sicca (KCS) is a condition that is also commonly referred to as “dry eye.” The medical term means inflammation of the cornea and surrounding tissues from drying.
RA - Medication SE: Example Question
A 53 year old has just been diagnosed with rheumatoid arthritis whilst having a severe flare. She is started on methotrexate 15mg once weekly, folic acid 5mg once weekly, hydroxychloroquine 200mg BD, naproxen 250mg TDS and prednisolone 15mg OD. She returns one month later complaining of mouth ulcers, what should be done?
Hb 142 g/l Platelets 225 * 109/l WBC 6 * 109/l Na+ 136 mmol/l K+ 4.2 mmol/l Urea 4 mmol/l Creatinine 95 µmol/l Bilirubin 6 µmol/l ALP 105 u/l ALT 92 u/l
Admit for IV methylprednisolone Stop methotrexate, hydroxychloroquine and naproxen Increase folic acid to two days a week Stop hydroxychloroquine and discuss with rheumatology > Stop methotrexate and discuss with rheumatology
According to BSR guidelines, if new oral ulceration starts whilst a patient is on methotrexate then it should be withheld initially and discussed with the specialist team. In this case the alanine transaminase (ALT) is not two times the upper range of normal so that does not affect your decision. Often the folic acid is increased to six days a week (apart from the day of methotrexate) to mitigate side effects.
Hydroxychloroquine and naproxen are not associated with oral ulceration.
RA - Mx: Methotrexate
Methotrexate is an antimetabolite which inhibits dihydrofolate reductase, an enzyme essential for the synthesis of purines and pyrimidines
Indications
- rheumatoid arthritis
- psoriasis
- acute lymphoblastic leukaemia
RA - Mx: Methotrexate SE
Adverse effects mucositis myelosuppression pneumonitis pulmonary fibrosis liver cirrhosis
According to BSR guidelines, if new oral ulceration starts whilst a patient is on methotrexate then it should be withheld initially and discussed with the specialist team.
RA - Mx: Methotrexate and Pregnancy
Pregnancy
women should avoid pregnancy for at least 3 months after treatment has stopped
the BNF also advises that men using methotrexate need to use effective contraception for at least 3 months after treatment
RA - Mx: Prescribing Methotrexate
Prescribing methotrexate
methotrexate is a drug with a high potential for patient harm. It is therefore important that you are familiar with guidelines relating to its use
methotrexate is taken weekly, rather than daily
FBC, U&E and LFTs need to be regularly monitored. The Committee on Safety of Medicines recommend ‘FBC and renal and LFTs before starting treatment and repeated weekly until therapy stabilised, thereafter patients should be monitored every 2-3 months’
folic acid 5mg once weekly should be co-prescribed, taken more than 24 hours after methotrexate dose
the starting dose of methotrexate is 7.5 mg weekly (source: BNF)
only one strength of methotrexate tablet should be prescribed (usually 2.5 mg)
avoid prescribing trimethoprim or cotrimoxazole concurrently - increases risk of marrow aplasia
