Rheumatology Revision 4 Flashcards
Describe the basic pathophysiology of RA
current theory for the pathophysiology of RA is that exposure to an external trigger in a genetically predisposed individual leads to an abnormal, autoimmune response, which targets synovial joints resulting in chronic inflammation and joint damage
Following a suspected triggering event, there is development of self-citrullination: alteration of a positively charged arginine amino acid into the neutral citrulline
- The immune system then reacts to these citrullinated proteins, which is characterised by development of anti-cyclic citrullinated peptide (anti-CCP) antibodies.
Also get infiltration of synovial joints with immune cells and a subsequent pro-inflammatory response causing the classic synovitis
At joint level: synovial membrane hyperplasia, or ‘thickening’, which subsequently damages cartilage - called a pannus. There is subsequent boney loss, which manifests as localised and periarticular boney erosions.
Describe the clinical features of RA
Polyarthropathy:
- multiple joints affected, usually in symmetrical distribution; typically the small joints of hands or feet (MCP most common; PIP; MTP)
- On palpation of the joints, there will be tenderness and synovial thickening, giving them a “boggy” feeling.
- Morning stiffness lasting more than 30 mins
- Joint swelling
- Cervical (but not lumbar) spine can be affected
- Knees, ankle, hips and shoulders
- Pain on palpitation
Muscle atrophy:
- may see ‘guttering’ between extensor tendons in hands due to wasting of the interossei muscles
Systemic symptoms
- myalgia
- fatigue
- low-grade fever
- weight loss
- low mood
TOM TIP: Rheumatoid arthritis very rarely affects the distal interphalangeal joints. Enlarged and painful distal interphalangeal joints are more likely to represent Heberden’s nodes due to osteoarthritis.
Describe what is meant by a boutonniere and swan-neck deformity [2]
Boutonniere deformity:
- flexion at the PIP joint with hyperextension of the distal interphalangeal (DIP) joint
- caused by a tear in the central slip of the extensor components at the proximal interphalangeal (PIP) joint.
Swan-neck deformity:
- hyperextension at the PIP joint with flexion of the DIP joint
Boutonniere - same positions are buttoning up a shirt
Name two other hand signs of RA (asides from swan-neck and Boutonniere deformities) [2]
Name a foot sign [1]
Ulnar deviation at MCPs:
- subluxation of the MCP joints with deviation of the fingers towards the ulnar bone due to dislocation of flexor tendons and disruption of extensor tendons.
Z-deformity at wrist:
- hyperextension of interphalangeal joint of thumb in association with carpal bone rotation and radial deviation as well as ulnar deviation at MCPs
- deformity to the thumb
Hammer toes:
- compensatory flexion of the toes due to weakening and subluxation of surrounding tendons.
Describe why RA can lead to spinal cord compression [1]
Atlantoaxial subluxation occurs in the cervical spine.:
- Synovitis and damage to the ligaments around the odontoid peg of the axis (C2) allow it to shift within the atlas (C1).
Describe the extra articular manifestations of RA:
- occular [4]
- oral [2]
Ocular
* Keratoconjunctivitis sicca: refers to dry eyes. Seen in 10%. If accompanied with xerostomia (dry mouth) suggestive of secondary Sjögren’s syndrome.
* Episcleritis: inflammation of superficial layer of sclera
* Scleritis: more aggressive inflammation of the whole sclera
* Scleromalacia perforans
Oral
* Xerostoma (dry mouth): If accompanied with keratoconjunctivitis sicca (dry eyes) suggestive of secondary Sjögren’s syndrome.
* Oral ulcers
Describe the extra articular manifestations of RA:
- pulmonary [3]
- cardiac [4]
Pulmonary
* Interstitial lung disease
* Serositis: inflammation of serous membranes (i.e. pleural, pericardium, peritoneum)
* Costochrondritis
Cardiac
* Pericarditis: as part of serositis
* Myocarditis
* Non-infective endocarditis
* Increased risk of ischaemic heart disease
Describe the extra articular manifestations of RA:
- Renal [1]
- Neurological [3]
- Haemotological [3]
Renal
* Glomerulonephritis (uncommon in the absence of vasculitis)
Neurological
* Peripheral neuropathy: diffuse sensorimotor neuropathy or mononeuritis multiplex
* Entrapment mononeuropathies: carpal tunnel syndrome
* Cervical myelopathy: typically due to cervical spin involvement or atlantoaxial subluxation
Haematological
* Neutropenia: if combined with splenomegaly known as Felty’s syndrome
* Thrombocytopaenia or thrombocytosis
* Haematological malignancies
Describe 3 dermatological mainfestations of RA [3]
Rheumatoid nodules:
- most present skin complaint (20%). Found on extensor surfaces of upper limb at pressure points (e.g. elbow) as hard nodule. Composed of central fibrinoid necrosis with surrounding fibroblasts. Usually in seropositive patients.
Vasculitis skin rash:
- ulcers, digital gangrene, periungual infarcts, splinter haemorrhages
Pyoderma gangrenosum
How do you differentiate PsA to RA? [3]
- PsA often demonstrates an asymmetric oligoarticular pattern.
- Dactylitis (sausage digits) and enthesitis are also unique features of PsA that help differentiate from RA.
- Radiographic findings such as pencil-in-cup deformity or periostitis could aid differentiation; these are NOT typical for RA.
Which factors indicate a worse prognosis in RA?
Poor prognostic features
* rheumatoid factor positive
* poor functional status at presentation
* HLA DR4
* X-ray: early erosions (e.g. after < 2 years)
* extra articular features e.g. nodules
* insidious onset
* anti-CCP antibodies
Rheumatoid arthritis seen in adults of all ages
Which is the most common occular complication of RA? [1]
keratoconjunctivitis sicca
What are iatrogenic occular complications seen in RA? [2]
- steroid-induced cataracts
- chloroquine retinopathy
What is the difference between epi- and slceritis? [2]
episcleritis (erythema)
scleritis (erythema and pain)
HLA DR4
Lung fibrosis caused by rheumatoid arthritis typically affects the:
* Upper zone
* Lower zone
lower zones
DAS28
State why synovial joints are susceptible to inflammatory injury [2]
Presence of rich network of fenestrated capillaries
* Fenestrated capillaries: become more leaky so plasma and immune cells can enter synovial membrane and joint cavity
Limited ways it can respond
DAS28 is used to monitor RA; treat to target is the aim.
What DAS28 scores would indicate:
- disease remission [1]
- low severity [1]
- medium severity [1]
- high severity [1]
- disease remission: < 2.6
- low severity: 2.6 - 3.2
- medium severity 3.2 - 5.1
- high severity: > 5.1
Name this deformity seen in the hand associated with RA [1]
Describe the changes in hand position that occurs [2]
Describe the initial treatment plan for RA with MILD disease activity at initial presentation: not pregnant or planning pregnancy
1st Line: conventional DMARD:
- hydroxychloroquine - it is better tolerated and has a more favourable risk profile than other DMARDs
Consider: Corticosteroid
- Prednisolone
Consider: non-steroidal anti-inflammatory drug (NSAID)
- ibuprofen
NB: hydroxychloroquine: should only be considered for initial therapy if mild
BMJBP
State 5 side effects of corticosteroids
Osteoporosis; weight gain; DM; HTN
Methotrexate:
1. MoA?
2. Advantages [3]
3. Disadvantages [6]
MoA:
- Folic acid inhibitor (due to inhibition of dihydrofolate reductase) which stops cell proliferation; impacts rapidly dividing cells
Advantages:
- Inexpensive
- Oral or injection
- Well established safety profile
Disadvantages
- N&V
- Mouth sores
- Hair loss
- Liver toxicity
- Bone marrow suppresion
- Lung toxicity
How do you manage / monitor ongoing methotrexate; SSZ and LEF prescription? [3]
FBC and LFTs are to be monitored every 2 weeks for the
first 6 weeks (induction phase) and with any increased
dose, and then monthly for 3 months.
What important AE do you need to monitor for with hydroxychloroquine tx? [1]
Retinal toxicity - requires regular eye exams
Also: gastrointestinal upset, skin rash
Describe the MoA [1] and AEs [3] of MMF
MoA:
- Inhibits enzyme used for de novo purine synthesis - effects T & B cells
AEs:
- GI upset
- Infections
- Bone marrow suppression
What do you screen for prior to starting methotrexate; SSZ and LEF tx? [3]
- FBC; UEs; LFTs
- Viral serology screen
- Baseline CXR - for MTX as can cause PF
- Baseline BP for LEF
What should you offer women prior to cyclophosphamide treatment? [1]
Egg harvesting treatment as causes infertility
Describe the MoA and side effects of cyclophosphamide
MoA:
- Alkylating agent - cross links DNA strands, leading to cell death
Effects:
- Bone marrow suppression
- Bladder inflammation - hamorrhagic cystitis
- Infertility
- N&V
Describe some of the unwanted effects of blocking TNFa
TNFa is essential for granuloma formation, organisation and maintenance - risk of TB reactivation AND increased risk of infection
Autoimmune reactions:
- paradoxical psoriasis (new onset or worsening)
- drug induced lupus
- MS or optic neuritis
Allergic reactions
HF exacerbations
Blood abnormalities (anaemia; neutropenia)
Liver toxicity
Increased risk of malignancies
What should you screen for prior to anti-TNF tx? [4]
FBC ++
Serology for HIV, HBV & HCV
CXR and TB Elispot
Exclude infections, pregnancy, malignancy, NYHA Class III/IV and EF < 50%
antibodies to antibodies
Can produce antibodies agaisnt
Name an anti-TNF that can be used in pregnancy [1]
Certolizumab
Name an anti-TNF that might cause less chance of infection [1]
Etanercept
Whats an overall JAK inhibitor MoA? [1]
JAKs are inside the cells (block the messages delivered by cytokines inside the cells)
There are different JAKs
Name an advantage of JAK inhibitors tx [1]
Can be taken orally (c.f. biologics are often infusions)
Name some side effects of JAK inhibitors [4]
Increased risk of serious infections - use in caution with > 65
Risk of MACE - caution with CVD
Malignancy - particularly increased risk of lymphoma and lunger cancer
Thrombotic events; GI side effects and anaemia
Describe the treatment pathway for RA
Which alternative drug should be used if pregnant or pregnancy planning? [1]
Sulfasalazine
How often do you perform blood tests for methotrexate monitoring? [1]
How do you assess response to methotrexate use? [1]
Assess using DAS28 = disease activity score of 28 joints
What needs to be checked before starting DMARDs?
Hepatitis B and C status, purified protein derivative (PPD), FBC, and LFTs need to be checked before starting DMARDs.
Describe the initial treatment plan for RA with MODERATE-SEVERE disease activity at initial presentation not pregnant or planning pregnancy
1st line cDMARD:
- methotrexate (primary option) with folic acid supplementation
- sulfasalazine (secondary option)
- hydroxychloroquine (secondary option)
- leflunomide (secondary option)
- bridged with corticosteroid - prednisolone for 2/3 months until methotrexate starts working
2nd line: Combination treatment with multiple cDMARDs
3rd line: bDMARDs
- etanercept (primary option)
- infliximab
- adalimumab
4th line: Rituximab
Double check with lecture
How do you treat a flare of RA? [1]
flares of RA are often managed with corticosteroids - oral or intramuscular
- methylprednisolone
Which RA medication has a risk of reactivating TB? [1]
Etanercept and also
adalimumab, infliximab, golimumab and certolizumab
Which RA medication has a risk of an infusion reaction? [1]
Rituximab
TOM TIP: The main biologics to remember are [3] (TNF inhibitors), and [1] (a monoclonal antibody that targets the CD20 proteins on the surface of B cells).
TOM TIP: The main biologics to remember are adalimumab, infliximab and etanercept (TNF inhibitors), and rituximab (a monoclonal antibody that targets the CD20 proteins on the surface of B cells).
They cause immunosuppression, increasing the risk of infection, certain cancers (e.g., skin) and reactivation of latent TB.
Describe the dosing regimen for methotrexate [1]
Methotrexate interferes with folate metabolism and suppresses the immune system. It is given once a week
Folic acid 5mg is taken once a week (on a different day to the methotrexate)
Describe the MoA of Leflunomide [1]
Name 5 side effects [5]
Leflunomide is an immunosuppressant medication that interferes with the production of pyrimidine.
Side effects:
* Mouth ulcers and mucositis
* Increased blood pressure
* Liver toxicity
* Bone marrow suppression and leukopenia (low white blood cells)
* Teratogenic (harmful to pregnancy) and needs to be avoided before conception in both women and men
* Peripheral neuropathy
TOM TIP: The unique side effects worth remembering are:
- Methotrexate [3]
- Leflunomide [2]
- Sulfasalazine [3]
TOM TIP: The unique side effects worth remembering are:
Methotrexate:
* Bone marrow suppression
* leukopenia
* highly teratogenic
Leflunomide:
- Hypertension
- peripheral neuropathy
Sulfasalazine:
- Orange urine
- male infertility (reduces sperm count)
TOM TIP: The unique side effects worth remembering are:
- Hydroxychloroquine [3]
- Anti-TNF medications [2]
- Rituximab [2]
Hydroxychloroquine:
- Retinal toxicity
- blue-grey skin pigmentation
- hair bleaching
Anti-TNF medications:
- Reactivation of tuberculosis
Rituximab:
- Night sweats
- thrombocytopenia
[2] are considered the safest DMARDs in pregnancy
Hydroxychloroquine and sulfasalazine are considered the safest DMARDs in pregnancy
3-monthly monitoring for MTX, SSZ, and LEF includes..? [5]
3 monthly FBC; ALT; AST; ALP; Albumin; U&Es
