Rheumatology: Inflammatory Arthritis Flashcards
Rheumatoid arhthritis - examination findings [4]
- Soft-tissue swelling over the joints with tenderness.
- Joint deformities: swan-neck and boutonniere in the fingers, Z-thumb, ulnar deviation at the MCP
joints, radial deviation of the wrist joint, over-riding and hammer toes. - Rheumatoid nodules (~20% of patients):
◆ Firm, mobile and usually over pressure points.
◆ Consist of fibrinoid necrosis and palisading histiocytes. - Muscle weakness (due to disuse atrophy), tenosynovitis and bursitis.
Rheumatoid arthritis Investigations
- Synovial fluid analysis
Bloods - FBC: normochromic, normocytic or hypochromic microcytic anaemia, thrombocytosis, neutropenia associated with Felty’s syndrome
- Inflammatory markers (ESR and CRP): elevated, especially in acute flares.
- Auto-antibodies (RF and anti-CCP): anti-CCP has greater sensitivity and specificity than RF. Anti-
CCP can be detected several years prior to onset of RA - Renal, liver and bone biochemistry: to exclude other pathologies and prior to institution of medical
treatments.
Radiology
- Plain film radiography.
- Joint US examination.
- MRI of small joints of the hands and feet may help (e.g. peri-articular osteopaenia, erosions, joint
space narrowing), where plain films and US have been unremarkable.
Rheumatoid arhtritis extra-articular manifestations
skin, bone, haema, resp, cardio, ocular, renal, neuro
Rheumatoid arhtritis
Poor prognostic indicators [4]
- Presentation- insiduous onset, constitutional sx, poor functional state at 1y, social deprivation, high disease activity score on presentation.
- Demographic- female, smoking
- Biochemical - high inflammatory markers, shared epitope HLA-DRB*04 cluster. RF positivity with high titres (especially IgA RF) and anti-CCP.
- Radiological- early erosions
Synovial fluid in RA
- Inflammatory diseases may show yellow or green with decreased viscosity
- High WCC - neutrophilia, lymphocytosis
- Glucose may be low in RA as it is in bacterial infections.
RA Definition
Chronic autoimmune systemic illness
characterised by symmetrical peripheral arthritis
and other systemic features
RA diagnosis needs a score of x according to 2010 EULAR Classification
6 OR MORE out of 10
4 sub-categories of RA Classification/Criteria
In each sub-category, what would score high pointing to a dx of RA?
Joint Involvement (poly + small joints)
Serology (RF +ve, ACPA +ve)
Acute phase reactants (raised)
Duration of symptoms 6w
Epidemiology of RA
Gender
Prevalence
Peak age of onset
But may occur at any age from ____
F:M 3:1
1% of population
4th or 5th decade
But may occur at any age from 16 y
Aetiology RA
Genetic - closest association with specific amino acid sequences at positions ____ of _____
What are the susceptibility genes?
Environmental factors (2)
Genetic - closest association with specific amino acid sequences at positions 70-74 of DRb1
HLA DR1 and HLA DR4
Environmental factors:
Smoking
Chronic infection - peri-odontal disease
Pathogenesis RA
3 stages
Rheumatoid factor binding to IgG forming immune complexes
Not easily cleared
Activate complement - further inflammation
Activation of macrophages
RA Symptoms 4
Pain
Swelling
Loss of function
Systemic symptoms
Symptoms RA
- Systemic symptoms
- Non-specific (3)
Fatigue
Weight loss
Anemia
Which types of malignancy have higher incidence assoc with RA
Leukemia and Lymphoma
DAS28 score - how does it relate to RA?
What score represents clinical remission?
What score indicates eligibility for biology therapy
DAS28 score – monitor disease activity (disease activity score)
DAS<2.4 represents clinical remission
DAS>5.1 represents eligibility for biologic therapy
4 modes of management of RA
NSAIDS
DMARDS
Biologics
Corticosteroids
Name 4 DMARDs used in RA
Whats the gold standard DMARD drug
Methotrexate
Sulfasalazine
Hydroxychloroquine
Leflunomide
Name 5 drugs under ‘Biologics’ category of RA MX
TNF-alpha inhibitors Etanercept
IL-1 inhibitors Anakinra
IL-6 inibitors Tocilizumab
Anti-B cell therapy - Rituximab
Anti-T cell therapies - Abatacept
What are the extra-articular manifestations of RA? [4]
Extra-articular
- Rheumatoid nodules
- Increased risk of atherosclerosis
- Interstitial lung fibrosis
- Pleural effusions (SOB)
What is Felty’s syndrome? Why can it be dangerous?
Triad of:
RA
Splenomegaly
Granulocytopenia
Can lead to life-threatening infections
X-ray of RA
Early [3]
Late [3]
soft tissue swelling, juxta-articular osteopenia, loss of joint space
Late changes: bony erosions, subluxation, complete carpal destruction
L – loss of joint space
E – erosions
S – soft tissue swelling
S – soft bones (osteopenia)
What finding would you see on FBC
Increased platelets
DMARDs
Indications for prescribing [1]
How long before patient should expect symptomatic benefit [1]
Best results with? [3]
SE [3]
How to counter this side effect [1]
Should be started within 3 months of persistent symptoms
Can take 6-12w for symptomatic benefit
DMARD monotherapy +/- a short-course of bridging prednisolone (NICE, 2018)
SE: immunosupression, pancytopenia, neutropenic sepsis so regular FBC monitoring
DMARDs side effects
Methotrexate [3]
Sulfasalazine [3]
Leflunomide [4]
Hydroxychloroquine [1]
Methotrexate - pneumonitis, oral ulcers, hepatotoxicity
Sulfasalazine - rash, decreased sperm count, oral ulcers
Leflunomide - teratogenicity, oral ulcers, increased BP, hepatotoxicity
Hydroxychloroquine - Bull’s eye retinopathy
Biologics
First line? When is this indicated? [2]
Second line? [2]
Third line? [2]
- TNF alpha inhibitors - after failure of 2 DMARDs and DAS28>5.1
- Anti B-cell therapy - after failure of DMARDs and TNF alpha inhibitor
- IL6 inhibitior - after failure of TNF alpha and anti-B cell therapy
SE profile of biologics [5]
Serious infection eg reactivation of TB, Hep B
Worsening heart failure
Hypersensitivity
Blood disorders
Reversible SLE-type illness may evolve
Palindromic RA
Presentation of joint inflammation [2]
Episodic and sequential moving from one joint to another
Hours-days then symptom-free periods that last days-months
MOA Methotrexate
- a competitive inhibitor of dihydrofolate reductase (DHFR), DHFR catalyses the conversion of dihydrofolate to the active tetrahydrofolate.
- Folate is needed for nucleoside thymidine production (required for DNA synthesis) and for purine and pyrimidine base biosynthesis.
- In RA, methotrexate has further inhibitory actions on T- and B-cell function.
- Biologic DMARD use mandates a careful screening process prior to treatment initiation including screening for:
◆ Mycobacterial infections: if active, requires treatment. Prophylactic anti-TB therapy for those with potential latent disease (e.g. past history of TB or abnormal CXR).
◆ Hepatitis B and C and HIV: hepatitis B vaccination is offered to high risk patients. Influenza and pneumococcal vaccinations given prior to biologic DMARDs (unless contraindicated).
◆ Malignancy: caution is warranted in patients with previous malignancy and premalignant conditions
(e.g. Barrett’s oesophagus, cervical dysplasia). The risk for specific skin cancers (e.g. malignant melanoma) should be discussed, and preventative skin care and surveillance offered.
Anti-tumour necrosis factor (TNF) treatment must be discontinued if malignancy is confirmed.
Anti-TNF therapy is contraindicated in patients with:
◆ Multiple sclerosis and used with caution with other demyelinating diseases.
◆ NYHA grade 3 or 4 cardiac failure (see Table 3.39) and used with caution in patients with mild
cardiac failure (NYHA grade or 2).
Which HLA is RA associated with?
DR4
Especially Felty’s syndrome
What is Felty’s syndrome?
RA
Splenomegaly
Neutropaenia
Psoriatic arthritis
Genetic factors [3]
- Family history of psoriasis or psoriatic arthritis (PsA) in 40% of patients.
- Increased frequency of psoriasis and PsA in monozygotic and dizygotic twins.
- Increased frequency of HLA-B13, B17, B27, B38, B39, DR4, DR7 and Cw6.
Psoriatic Arhtiritis
Which genetic association may be protective
◆ HLA B22 may be protective.
