Inflammatory arthritis - Clinical Medicine Flashcards
Define polyarticular pain
Pain in at least 4 joints
List the classification of polyarticular pain, provide with examples
- Inflammatory Arthritis
- Rheumatoid Arthritis (RA)
- spondyloarthropathies (SpA)
- Peripheral e.g. Psoriatic
- Axial Spondyloarthritis
- Juvenile Idiopathic Arthritis (JIA)
- Crystal Arthritis
- Infection Related (usually transient – acute, self-limiting)
- Connective Tissue Disease
- Others (>100)
- Non-inflammatory Arthritis
* Osteoarthritis (OA) or Degenerative Arthritis (numerically the commonest type of polyarthritis) - Other – e.g., fibromyalgia
* Arthralgia – aching in joints without swelling.
Describe the characteristics of inflammatory arthritis
- Calor (heat), Rubor (redness), Dolor (pain), Tumor (swelling)
- Earling morning & inactivity stiffness (generally lasts more than 1 hr and averages 3hrs in treated RhA)
- Systemic symptoms (unwell, lethargy, weight loss, fever)
Why do we distinguish between inflammatory and non-inflammatory types
- Inflammatory is potentially more serious
- Many forms have systemic manifestations
- Early recognition and intervention improves outcome
a) List the common types of acute (self-limiting) inflammatory arthritis
b) What symptoms does it present with?
a)
- Infection related e.g., viral, bacterial
- Viral e.g. Rubella, Hep B or bacteria, STD, Streptococcus /
- Bacteria e.g., post-dysentery or STD (Reactive), Streptococcus, mycoplasma, Lyme disease (related to tick bites)
- Goes away by itself
b) Presents with sudden onset: fever and systemic upset, variable severity, 6-12 weeks duration
What are the common types of chronic inflammatory arthritis
- RhA (lasts more than 6 weeks)
- Spondyloarthropathy, SpA [conditions that are related with having inflammation of spine but don’t necessarily need to present with that or have it at a given time e.g., Psoriatic Arthritis, Axial SpA (inflammation of spine)]
- Crystal Arthritis – Gout, CPPD (calcium pyrophosphate deposition- pseudogout)
- Connective Tissue Disease e.g., Systemic lupus erythematosus (SLE), Polymyositis (inflammation of muscles), Scleroderma (hard, thickened areas of skin)
- Others e.g., Sarcoid (condition where inflamed cells clump together to make small lumps called granulomas), HPOA (Hypertrophic pulmonary osteoarthropathy)
Describe the patient assessment to diagnosing a patient with polyarticular pain
Assessing the patient:
- No single test
- Diagnosis established by: history, physical examination, lab tests, imaging studies
History
- Age
- Sex
- Mode of onset
- Severity of joint inflammatory: intensity, no. swollen joints
- Temporal pattern of joint involvement
- Distribution of joint involvement (small joint: MCP – RhA, DIP – OA) (Large joint: Spondyloarthitis-Hip, foot & crystal)
Laboratory investigations
- FBC (haemoglobin, white blood cells, platelets)
- ESR or CRP
- RF (Rheumatoid factor: non-specific), ANA (Anti-nuclear antibody- linked with connective tissue disorders), anti-CCP (linked with RhA), HLAB27 (linked with spondyloathropies (95% who have alkylating spondylosis are +ve)
- Uric acid
- Synovial fluid analysis
Radiology
- X-ray (normal in early disease)
- Ultrasound
- MRI
List the clinical features of seronegative spondyloarthropathies
Predominant features
- Presentation -Inflammatory back/buttock pain (95%+)
- Axial involvement
- Peripheral joint involvement
- Enthesitis
- High incidence of HLA-B27 but RF negative
Clinical features
- Uveitis
- Psoriasis
- Hip arthritis
- Psoriatic nail changes
- Dactylitis - inflammation (swelling) of fingers and toes
- Colitis
- IBD
Describe the epidemiology of spondyloarthropathies (SpA)
- Slightly less common than RhA
- Prevalence 0.5-1%
- *Caucaison > Asian > Afro-Caribbean = *Proportion to freq. of HLA-B27
Describe other causes of polyarticular pain, excluding inflammatory and non-inflammatory arthritis
Endocrine
- Hyperthyroidism
- Hypothyroidism
- Hyperparathyroidism
Malignancy
- Metastatic Cancer
- Multiple Myeloma
Chronic Pain Syndromes
- Fibromyalgia
Define Rheumatoid arthritis
Rheumatoid arthritis (RA) is a common autoimmune, inflammatory condition characterized by symmetrical swelling in multiple joints.
Describe the epidemiology of RhA
- Overall prevalence 0.8-1%
- Worlwide, F>M
- Increases with age
Describe the immunological abnormalities of rheumatoid arthritis
- T lymphocytes accumulate in synovium
- Synovium macrophages express peptide antigens on their cell surfaces in association with HLA class II molecules
- T-lymphocytes with appropriate receptors interact with the macrophages and both cell types become activated = IgG + anti-IgG (IgM) —> (IgG + IgM) Complex
- This activates complement system which activates the inflammatory cytokines
- This leads to the production of inflammation, excessive synovial fluid prodcution, cartilage destruction, bone destruction, stimulation of B-lymphocyte differentiation and maturation, increased antibody production and production of rheumatoid factor
Describe the risk factors for the development of RhA
- Cigarette smoking
- Obesity
- Immunisation
- Blood transfusion
- Previous termination of pregnancy
Describe the diagnostic classification critertia for RhA
- Joint involvement, symmetry
- Serology - RF/Anti-CCP
- Acute-phase reactant - CRP/ESR
- Duration of symptoms: >6 weeks
- Morning stiffness
Describe the general systemic features of RhA
Patients often feel generally unwell with RA, including low grade fevers, weight loss, and fatigue.
Describe the articular features of RhA
a)
- Symmetrical small joint - MCP, PIP, MTP, wrist
- Pain
- Stiffness - especially morning stiffness that lasts more than 30 minutes
- Swelling
Fingers and wrists
- Ulnar deviation of the fingers - results from MCP joint inflammation
- MCP subluxation - can occur, with the PIP joints drifting in an ulnar and solar (palmer) direction.
- Boutonnière (PIP flexion and DIP hyperextension)
- Swan-neck deformities (MCP flexion, PIP hyperextension & DIP flexion)
- Z-shaped thumb
Foot
- Hallux valgus
- Hammer toes
- MTP subluxation
Cervical spine
- Atlantoaxial subluxation - Inflammation and erosive disease, affecting the first cervical vertebra and stabilizing ligaments of the first two cervical vertebra, can result in atlantoaxial subluxation. The atlas slips forward on the axis, reducing the space around the spinal cord. This produces neck pain, which radiates to the occiput.
a) Describe the peri-articular features in RhA
Describe the extra-articular features/ manifestations of RhA
a)
- Carpal tunnel syndrome – causing pain, weakness and paraesthesia in the median nerve distribution of the hand.
- Tenosynovitis – typically of the flexor tendons in the hands, causing pain and swelling.
- Bursitis – typically of the olecranon (elbow) and sub-acromial (shoulder) bursae, causing pain and swelling.
b) Haematological
- Anaemia
- Splenomegaly including Feltys syndrome (triad of RA, splenomegaly and neutropenia)
- Amyloidosis
Dermatological
- RA nodules
- Raynad’ssyndrome
Opthalamic
- Keratoconjuctivits sicca (dry eyes)
- Epscicleritis and scleritis
Respiratory
- Pleural effusions - usually positive for RF
- Pneumonitis leading to pulmoanry fibrosis
Cardiac
- Pericarditis, mycarditis
Neurlogoical
- Peripheral neuropathy
Describe the radiological features of RhA
LESS
Loss of joint space
Erosions (juxta-articular)
Soft bone (osteopenia) / Periartciualr osteoporosis
Soft tissue swelling
Describe the investigations undertaken to diagnose RhA
- FBC
- Inflammatory markers - ESR and CRP
- RF - found 80% with RhA (non-specific as found in rheumatic and non-rheumatic disease)
- Anti-CCP
Why is RF for diagnosing RhA not the best?
Although it is found in 80% of patients with RhA it is non-specific as it is found in rheumatic and non-rheumatic disease
a) Describe the HAQ disablitiy index
b) List the categories assessed
a)
- It is a measure of functional outome
- A total score can range from 0.-3.0, in 0.1 increments are higher scores indicate worse function
b)
- Dressing and grooming
- Arising
- Eating
- Walking
- Hygiene
- Reach
- Grip
- Activities
- Use of aids or devices or need for help from others
a) What is the DAS28
b) Describe its role in guding therapy in RA
a)
- DAS28 (Disease activity 2score 28) is a measure of disease activity in rheumatoid arthritis and the number 28 refers to the 28 joints that are examined in this assessment (excludes foot)
- Disease severity and the efficacy of treatment is often monitored using the DAS28 score, which includes CRP or ESR, the number of swollen or tender joints, and a patient questionnaire.
b)
- DAS scores below 2.6 indicate remission (i.e. free from symptoms).
- DAS scores between 2.6-3.2 indicate low disease
- DAS scores between 3.2-5.1 indicate moderate disease levels.
- DAS scores above 5.1 indicate high disease levels.
List the treatment options of RhA for mild, moderate and severe RhA
- NSAID’s (mild RhA)
- DMARD’s (moderate RhA)
- Corticosteroids
- Biologics (Severe RhA)
- Combination therapy (Severe RhA)
List the effective DMARDs used for RhA
- Methotrexte
- Hydoxychloroquine
- Leflunomide
- Ciclosporin
- Gold
- Azathioprine
- Cyclophosphamide
When is more aggressive treatment for RhA required?
More aggressive treatment if 2 or more DMARDs including methotrexate have failed and there is still active RhA
a) When is a patient eligible for biologic treatment?
b) List the possible biologics
a) To be eligible for biologic treatment response to 2 or more DMARDs including methotrexate must be proven inadequate
b)
- Anti – TNF
- Rituximab
- Abatacept
- Tocilizumab
- JAK inhibitors
Describe genetic factors of RhA
- The most significant genetic predisposing risk factor for RA is in variations of the human leucocyte antigen (HLA) genes.
- The most significant appears to be the HLA-DRB1 gene.
What are the classificaton of spondylarthrosis
- Axial spondylarthritis
- Ankylosing spondylitis
- Reactive arthritis
- Psoariatic arthritis
- Enteropathic arthritis
- Undifferenetiated spondyarthritis
List the SpA associated with HLA-B27
- Anylosing spondylitis
- Undifferentiated SpA
- Acute anterior uveitis
- Reactive arthritis
- Juvenile SpA
- Psoriatic arthritis
Over 95% of patients with radiolgraphic axial spondylitis are HLA B27. However we do not just screen for HLA B27. Why is this?
Although 95%+ patients with radiographic axial spondylitis are HLA B27 only 5% of patients who are HLA B27 postitive develop MSK symptoms
What are HLA B27 associated features?
- Uveitis
- Sacroiliitis
- Enthesitis
- Spondylitis
- Peripheral joint involvement
- Aortitis, valve disease, heart block
- Upper lobe fibrosis
- Skin disease - psoriasis, keratoderma, blanaitis
Describe the cinical features of inflammatory back pain (spondylitis)
- Gradual onset
- Early moning/rest stiffness
- Better with movement
- No radicular signs (no symptoms of a nerve being compressed)
- Usually at young(er) age
- Good response to NSAID
Describe the epidemiology of spondyloarthritis
- Age
- 10-20% aged 10-20
- Vast majority 20-40
- < 5% over 45
- Gender - F to M is 2:1
- Progression
What are all types of spondyloarthropathies genetically associated with?
Human leukocyte antigen (HLA) B27
Describe the epidemiology of ankylosing spondylitis (AS)
- AS amongst the Caucasian population is 0.5%–1%.
- M:F = 3:1
- Tends to be more severe in men.
- Usually develops in the teenage years and early adulthood, with a peak age of onset in the mid-20s.
- Presentations over the age of 45 years are rare.
Describe the pathology and radiology of ankylosing spondylitis
- Outer fibres of vertebral discs become inflamed
- Destructive osteoitis and repair leads to squaring of the anterior contour of the vertebra
- Ossification leads to formation of syndesmophytes (bony bridges)
- Leads to bamboo spine on x-ray. May also see odema and erosions (due to inflammation)
Describe the criteria/clinical signs for ankylosing spondylitis/axial SpA
First symptom onset at age 45 years or younger
- Sacrolitis
- Low back pain and morning stiffness for at least 30mins for > 3 months
- Symptoms improves with excercise but isn’t relieved by rest
- Symptoms relieved by NSAIDs
- Limitation of motion of the lumbar spine in both the sagittal and frontal planes
- Limitation of chest expansion
Describe the extraskeletal/articular features of ankylosing spondylitis
4 A’s
- Acute anterior uveitis (iritis)
- A ortic incompetence/ascending aortitis
- A pical lung fibrosis
- A myeloidosis
Also
- Psoriasis
- Inflammatory bowel
- Peripheral joint involvement
- Lung, heart, renal complications and osetoprorsis usually late (> 20 years)
Describe the investigations for ankylosing spondylitis
- FBC
- ESR/CRP - usually elevated
- Serelogical tests for RF -ve
- MRI / x-ray of sacroiliac joints
- Genotyping for HLA B27 is not required for diagnosis but may be useful where doubt exists.
Describe the radiological features (MRI and x-ray) of ankylosing spondylitis
MRI
- ‘Squaring’ of vertebrae
- Formation of syndesmophytes
- Bamboo spine - severe
X-ray of sacroiliac joint
- Joint loss of cortical margins, widening of the joint space, sclerosis, ‘squaring’ of vertebrae
In addition to Regional Examination of the Musculoskeletal system (REMS). What other examintions may be useful to help diagnose ankylosing spondylitis and why?
- Sacroiliac squeeze test - sacroiliac joints are often tender and pain can be produced by applying pressure to the joints
- Schober test - mobility of the lumbar spine is reduced
- Lateral flexion of spine
Describe the treatment of axial/ankylosing spondylitis
- Physiotherapy
- Excercise
- NSAIDs
- DMARDs - more severe cases and peripheral joints
- TNF only for active axial disease
Describe the treatment for axial spondyloarthritis
- NSAIDs
- Excercise
- Limited DMARD use
- Anti-TNF
- secukinumab (axial spondyloathritis only)
- BASDAI (determines effectiveness of drug being used to treat), BASMI (assesses spinal mobility), BASFI (assesses functional limitations)
What should patients suffering from any spondyloarthrpathy be warned about and advised if they develop a painful red eye or have visual disturbance?
- Patients suffering from any spondyloarthropathy should be warned of uveitis causing blindness
- Be advised to seek urgent medical help if they develop a painful red eye or have visual disturbance.
a) What is reactive arthritis?
b) Where do the triggering infections begin?
c) Is there always a preceding infection
a) A sterile joint inflammation that develops after a distant infection
b) Throat, urogenital, GI
c) No
Describe the risk factors of reactive arthritis
- Male gender
- HLA B27 positive
- Preceding sexually transmitted or gastrointestinal infection (chlamydia, shigella, yersinia)
Name the bacterial infections that are most commonly associated with reactive arthritis when the distant infection is in the:
a) GI
b) Urogenital
c) Others
a) Salmonella, shigella, yersinia, campylobacter
b) Chlamydia, Neisseria
c) Meningococci, streptococci, borrelia viruses
Describe the pattern of arthritis in reactive arthritis
Tends to be peripheral arthritis (usually affects the large joints of the arms and legs, including the elbows, wrists, knees, and ankles) beginning 1-4 weeks after infection, commonly an asymmetrical oligoarthritis but may be polyarticular/ monoarticular, usually affecting larger joints in lower limb
Axial arthritis, particularly of sacroiliac joints and lumbosacral spine is another presentation
Describe the extra-articular features of reactive arthritis
- Constitutional symptoms including fever, weight loss, lethargy
- Enthesitis manifesting as Achilles tendonitis or plantar fasciitis
- Painless mucosal ulcers
- Keratoderma blenorrhagica - Dark maculopapular rash on palms and soles
- Ocular inflammation including conjunctivitis and anterior uveitis
- Urethritis and sterile dysuria, inflammation of bladder and prostate may cause cystitis and prostatitis
- Circinate balanitis (painless ulceration of glans)
- Aphthous ulcers in the mouth
- Erythema nodosum
What would you find on examiantion of a patient with reactive arthritis?
- Red and warm
- Shifting pattern
- Dactylitis
- Low back pain in chronic disease
What is Reiters syndrome?
The triad of athritis, conjuctivitis and uveitis following a bacterial infection
Describe the investigations for reactive arthritis
Bloods - FBC (WBC may be elevated), Urea and electrolyte, LFT, CRP and ESR (may be significantly elevated), RhF, urinalysis, blood cultures
Serological tests - autoantiboy and antiobdies against salmonella, complobacter, chlamydia, gonorrhea and neisseria, may help identify causative organism
Synovial fluid - examined for gram stain,polarised light microscopy and culture
Culture (+ exclude ongoing infection) - Faeces, urine, urethra, cervical, throat, blood/serology e.g., autoantibody
X-rays
HLA-B27 association
When investigating a patient with suspected reactive athritis what results would you expect in:
a) FBC
b) RhF
c) Urinalysis
d) Autoantibody
a) Slightly elevated WBC
b) Usually negative
c) May show sign of infection/protein in urine
d) Expect to be negative (sernonegative spondyloarthropathy)
Describe the management of acute reactive arthritis
- Treat any underlying infection with antibiotics
- Analgesia
- NSAIDs
- Corticosteroid joint injections +/- systemic steroid
- Rest
Describe the management of chronic reactive arthritis
- NSAIDs for athralgia
- DMARDs
Describe the prognosis of reactive athritis
- Usually good
- Self-limiting in weeks
- Recurrences - at least 60% of those affected will experience a further epsiode
- Eye/urogenital symptoms may recur
What are the differential diagnosis of reactive arthritis
- Septic arthritis
- Crystal arthritis
- Psoriatc spondyloarthropathies
Describe the features in the history and examination of someone with psoriatic arthritis
- Rash or family history or rash - typically on extensor surfaces
- Occult rash should be looked for on the scalp, behind the ears, umbilicus and natal cleft
- Nail changes include pitting, yellowing, ridges or onycholysis
- Enthesopathy including achilles tendonitis
Describe the patterns of presentation of psoriatic arthritis in joints
- Asymmetrical oligoarthritis 30-40%
- Symmetrical polyarthritis (indistinguishable from RhA) 30%
- Distal arthritis involving DIP joints 10-15%
- Spondylitis +/- sacroliitis10-20%
- Arthritis mutilans/dactylitis <10%
a) What are radiological changes of psoriatic arthritis?
b) How and where do these radiological investigations affect most?
a)
- Pencil-in-cup deormity
- Erosions (with proliferation of the adjacent bone)
- Ankylosis (fusion of bones)
- New bone formation at entheses
- Sacroilitis
- Resorption of the terminal phalanges
- Periositis
b) Radiological chages are symmetrical and target the small joints of the hands and feet, particularly the DIP joints
Describe the prognosis of psoriatic arthritis
- Generally good
- Joint function perserved in most cases
- Chronic, destrcuctive and deforming arthritis may occasionally develop
Describe the treatment for psoriatic arthritis
- NSAIDs
- DMARDs e.g., Sulfasalazine, methotrexate, lefflunomide and cyclosporin A
- Biologics e.g., anti-TNF, usekinumab (monoclonal antibody)
- Physiotherapy/OT/Education
a) What is enetropathic arthritis
b) What are the two inflammatory bowel disease it is associated with?
c) What symptoms is it identical to?
a) Arthritis occuring with inflammatory bowel disease (IBD),
b) Ulcerative colitis and Crohn’s disease
c) Ankylosing spondylitis
Describe the clinical features of enteropathic arthritis
Axial arthritis (spondylitis and sacroilitis)
- Gradual onset of lower back pain and stiffness, worse in the morning, improves with exercise
Peripheral arthritis
- Asymmetric, oligoarticular arthritis, predominantly of the lower limbs
- Often transient and migratory joint inflammation
Enthesopathy
- Achilles tendonopathy, patellar tendonopathy, plantar fasciitis
Extra-articular manifestations
- Bowel symptoms to include abdominal pain, diarrhoea, weight loss, blood/ mucus in faeces
- Pyoderma gangrenosum and erythema nodosum
- Aphthous ulcers in the mouth
- Anterior uveitis
- Systemic symptoms including fever in a flare of disease
a) Describe the investigations for enteropathic arthritis and the findings
b) What should you do if you suspecta patient of IBD?
a)
- Blood tests - ESR/CRP (likely to be raised), HLA-B27 (supports diagnosis but do not confirm/exclude)
- X-rays -normal
- MRI - spinal imaging may show changes similar to ankylosing spondylitis (Squaring of vertebrae and syndesmophytes creating a “bamboo spine”)
b) ff IBD suspected, faecal calprotectin and inflammatory marks tested and patient referred to gastroenterologist
Describe the management of enteropathic arthritis
Treatment of IBD is the priority and will help with active peripheral arthritis
- Corticosteroids and sulfaslazine improve bowel and joint disease
- Anti-TNF biologics
Why is shared care of patient from GPs (primary care) and hospitals (secondary care) needed?
- Cost incentives to prescribe or not
- GP’s may not be familiar with the medicine
- Need guidance to ensure patient’s aren’t caught in the middle and get the medicines they need
- Hospital need to provide enough medicine to allow GPs time to generate a prescription
- More work for patients to get their prescription if hospitals tell patients to get medicines from GP
What is treat to target (T2T)?
Designed to drive optimal control of RhA, practical approach to promote and guidance to achieve optimum control in RhA
a) List the medicines used in RhA that have shared care
b) List the medicines not used in RhA that have shared care
a)
- Methotrexate
- Sulphaslazine
- Leflunomide
b)
- Ciclosporin
- Mycophenolate
- Mofetil
- Denosumab
What patient information should you give about shared care
- Describe the principles of shared care
- Describe the benefits and issues that arise with shared care
- Describe the GMC guidance with respect to shared care
- Disuss the role of the MDT in rheumatology and how this benefits patient care
a) What happens when a patient under shared care is stable?
b) What are the advantages of this?
a)
- GP picks up ongoing prescribing and monitoring
- Patient remains under specialist care but seen less often once stable
b)
- Easier for patient to get prescriptions close to home
- Easier for blood monitioring
- Easier access to surgery than hospital appoinmtents
List the members of the wider multidisciplinary team (MDT) in rheumatology
- Pain managment team
- OT
- Physiotherapist
- Clinical and health psychologists
- Podiatry/biomechanics
- Orthopaedic surgeons
Describe how a suspected inflammatory case goes from primary to secondary care
- Urgent referral of patients with inflammatory arthritis to reduce risk of irreversible damage
- See senior doctor (history, examination, comorbidities, investigations, managment plan)
- Treat to target (T2T) to ensure disease remission
- Refer nurse practioners for eductaion and initial monitoring
Describe the role of the rheumatology specialist nurse
- Key role in implementing the T2T principles
- Undertaking education, escalation, review, telephone clinics
- Aim of escalation clinic is to induce clinical remission/low disease activity or timely referral for further treatments by seeing patients monthly
- Ongoing support for patient
- Managed by an agreed protocol
Describe the role of the pain managment team
- Polypharmacy
- Help patients who find it difficult to reduce/stop analgesia
- Manage acute to chronic pain (pathways)
- Help patients with the multifactoral causes and psychological causes of a
- Experts in understanding the mechanisms and managment of pain
Describethe role of the physiotherapist in MDT rheumatology
- Joint examination and joint count
- Range of movement, msucle wasting
- Excercise programme
- Treatments: wax terapy, excercises, hydrotherapy, ultrasound, acupuncture
- Joint education
- Promote self-managment
Describe the role of occupational therapists
- Joint prevention and alternative ways of doing tasks to make activites easier and less painful
- Conserve energy
- Relaxation and stress
- Splints, Insoles
- Home visists: possible and aids to support self-managment and improve independence
Describe the role of clinical and health psychologists in the wider MDT of rheumatology
- Mental health: anxiety, depression, poor coping strategies
- Behaviour and psychological infulences/interactions with health, symptoms and daily functioning
- Disease managment srategies
- Lifestyle impact
- CBT
- Counselling
Describe the difference between osteoarthritis and inflammatory in terms of the site, onset, associated symptoms, timing, exacerbating/relieving features, co-morbidities, family history
Methotrexate
a) Indications of use
b) Routes
c) Dose
d) What should you co-prescribe with methotrexate and why?
e) Contraindications
f) Cautions
g) Interactions
h) Side-effects
i) Pregnancy/breast feeding
j) Hepatic impairment
k) Renal impairment
l) Monitoring requirements
a) RhA, Severe Crohn’s disease, psoriasis
b) Oral, IM, SC
c) 7.5-25mg once a week
d) Folic acid supplements because methotrexate is anti-folate (inhibits folate metabolism)
e) Active infection, immunodeficiency syndromes
f) GI toxicity, liver toxicity, pulmonary toxicity
g) Trimethoprim and septrin (anti-folate can lead to bone marrow failure), Amoxicillin, aspirin,
h) Immunosuppresion - bone marrow failure (Low WBC, platelets and anaemia so why regular blood monitoring is rquired), diarrhoea, fatigue, vomiting, GI discomfort, headaches, drowsiness, appetite decreased, infections - rash (herpes, shingles), pulmonary complications/fibrosis
i) Avoid in pregnancy and discontinue in breast-feeding - tetratogenic
j) Avoid in severe hepatic impairment
k) with caution in renal impairment
l) FBC (for bone marrow suppression - thrombocytopenia, cytopenia, anaemia, leucopenia, agranulocytosis) , renal and liver function tests repeated every 1-2 weeks until therapy stabilised (for hepatoxicity) , chest x-ray (can cause pneumonitis/pulmonary fibrosis), advice patients to be on contraception (for tetratogenicity)
Sulphasalazine
a) Indications of use
b) Routes
c) Dose
d) Cautions?
e) Side-effects?
f) Pregnancy/breast milk?
g) Hepatic impairement?
h) Renal impairment?
i) Monitoring requirements?
a) Rha, Crohn’s disease
b) Oral, rectal
c) Tablet/syrup: 1-2g 4x a day
d) Acte porphyrias, G6PDdeficiency, history of allergy, asthma attack, maintain adequate fluid intake
e) Myleosuppresion, rthralgia, cough, nausea, diarrhoea, dizziness, fever, GI discomfort, Oral ulcers, headache, vomiting, haematological (lower WBC/platelet count, Skin reactions (rash), decreased sperm count
f) Safe in pregnany as long as they’re taking adequate folic acid and caution in breast feeding
g) Caution in hepatic impairment
h) Caution but avoid in severe renal impairment
i) Monitor renal function
Leflunomide
a) Indications of use
b) Routes
c) Dose
d) Cautions?
e) Side-effects?
f) Pregnancy/breast milk?
g) Hepatic impairement?
h) Renal impairment?
i) Monitoring requirements?
a) RhA
b) Oral
c) 10-20mg daily
d) Anaemia, history of tuberculosis, impaired bone-marrow function, leucopenia, thromobocytopenia
e) Abdominal pain, appetite decreased, diarrhoea, dizziness, GI discomfort (Similar side effects to methotrexate and sulphasalazine), headache, vomiting
f) Avoid in pregnancy and breast feeding
g) Avoid in hepatic impairment
h) Avoid in moderate to severe renal impairment
i) FBC before treatment and every 2 weeks for 6 months then every 8 weeks + blood pressure as it can cause hypertension
Hydroxychloroquine
a) Indications of use
b) Routes
c) Dose
d) Cautions
e) Side-effects
f) Pregnancy/breast feeding
g) Hepatic impairement
h) Renal impairment
i) Monitoring requirements
a) RhA and connective tissue disease
b) Oral
c) 200-400mg daily
d) Acute poryphyria, Diabetes (may lower blood glucose)
e) Retinopathy, abdominal pain, appetite decrease,diarrohea, nause, skin reactions (rash), vomiting, vision disorders
f) Safe but try avoid in pregnancy and use with caution in breast feeding
g) Use with caution in hepatic impairment
h) Use with caution in renal impairment
i) No need for blood monitoring but some eye monitoring may be required (for the rare complication of hydroxychloroquine-induced retinopathy)
Describe the side effects of biologic therapy (e.g., etanercept, infliximab, adalimumab)
- Immunosuppresion
- Reactivation of TB
- Allergic reaction, reaction at infusion site
a) What are biosimilar drugs?
b) Why are they used to treat inflammatory conditions e.g., RhA?
c) What are new patients and exisiting paient asked to since the increased use of biosimilardrugs?
d) Provide 4 examples of biosimilar drugs
a) Biosimilars are copy drugs similar to biological drugs that has already been authorized (the biological reference medicine), hence similar but not identical
b) Cost savings and NICE/DoH approved
c) New patients offered tehm and exisiting patients asked to switch
d) Inflixima, Etanercept, Rituximab, Adalimumab
What is the mechanism of action of etanercept?
Anti-tnf (TNF receptor)
What is the mechanism of action of rituximab?
anti-C20 (depletes B-cells)
Why can Folic Acid not be taken on the same day as Methotrexate?
To avoid interference with the therapeutic action of Methotrexate.
