RA

Question 1

Define RA

Answer 1

Systemic symmetrical inflammatory destructive polyarthropathy
most likely autoimmune but aetiology not well known

Question 2

Epidemiology of RA

Answer 2

more common in women
a/ highly w/ disability, mortality, high socioeconomic burden
most common age - 30-50

Question 3

Risk factors of RA

Answer 3

gender-female
genetics- a/w HLADR4 and DR a/ alleles
shared epitope
environment - smoking which can interact with genes to increase the susceptibility up to 20 to 40 fold. The most likely mechanism for the environmental component is repeated activation of innate immunity by factors such as smoking: poor dental hygene and air pollution may be other features.

Question 4

Describe of pathology RA

Answer 4

• destruction of cartilage ( joint space narrows)
• bone erosion
• pannus formation- abnormal layer of fibrovascular tissue / granulation tissue
• synovitis- inflam of synovial membrane- plasma cells and lymphocytes present in surface of synovial villi - seen in nodular clusters

AUTOIMMUNE RX

Question 5

Describe physiology of RA

Answer 5

cytokine signalling pathways involved in RA
TNF alpha is secreted by macrophages (insitu and recruited) and lymphocytes. Induces other cytokines, mettaloproteinases, adhesion molecules etc. This causes the destructive effects of RA - synovitis and ultimately bone erosion and cartilage destruction

Question 6

Symptoms a/w RA

Answer 6

Pain and stiffness
-stiffness >30 mins after sitting and in the morning

Redness and warmth

Loss of function

Limited movement

Difficulty sleeping

Question 7

Signs aw RA

Answer 7

• symmetrical,deforming polyarthritis w typical pattern joint involvement (wrists, MCPs, PIPs, MTPs, then knees, ankles,shoulders, neck etc)
• tender, warm soft tissue swelling at joints
• typical deformities in established disease
• volar sublaxation of hand , Boutonniere’s deformity , Swan neck deformity , Z deformity
• extra-articular manifestations of RA- sicca syndrome, rheumatoid nodules

Question 8

Define volar sublaxation of hand

Answer 8

metacarpophalangeal (MCP) joint involves partial dislocation of the joint in which the proximal phalanx slips away from the metacarpal head and moves in the palmar direction.

Question 9

Define Boutonniere’s deformity

Answer 9

PIP flexion and DIP hyperextension

can occur in toes and fingers

Question 10

Define Swan neck deformity

Answer 10

PIP hyperextension, DIP flexion

Question 11

Z deformity?

Answer 11

occurs at thumb
Z shape of thumb
hyperextension of interphalangeal joints, flexion and sublaxation of MCP

Question 12

How to distinguish Early RA from established RA

Answer 12

Early RA- Symmetrical soft tissue swelling at MCP and PIP joints. No damage
DIPs spared

Established RA-Ulnar deviation at MCPJs,
Z deformity of thumb
Atrophy of intrinsic muscles
radial deviation at wrist

Question 13

How does RA present in the foot?

Answer 13

• metatarsalgia- inflam of ball of foot
• rheumatoid flat foot
• valgus hallux- aka bunions ; medial deviation of first metatarsals and lateral deviation of big toe/hallux
• collapsed metatarsal
• bunions and forefoot pain

Question 14

What are the extraarticular manifestations ?

Answer 14

eyes ( sicca syndrome- dry eyes and mouth, scleritis, sclermalacia perforans)
leg ulcers (vasculitis)
rheumatoid nodules
lung (pleural effusions and lung fibrosis, nodules)
compression neuropathies
GIT (gastritis and peptic ulcers)
osteoporosis
cardiac- (raised cholesterol or raised BP,accelerated atheroma; CVD , pericarditis)
renal- analgesic nephropathy,amyloid
haem- anaemia

Question 15

What is a result of vasculitis ?

Answer 15

splinter haemorrhage and necrotic areas at finger tips/around nails -> skin infarction
changes also seen in SLE, polyarteritis nodosa

Question 16

Define Episcleritis

Answer 16

inflam of episclera ( located between conjunctiva and connective tissue layer which all forms the sclera/white of the eye) occurs in superficial layers of the nasal portion of the eye- causing tenderness and discomfort

Question 17

Define rheumatoid nodule/ olecranon

Answer 17

A large subcutaneous nodule is located on the extensor surface of the forearm near the elbow. Rheumatoid nodules may be fixed or movable and are usually nontender
a/w high titres of rheumatoid factor - occurs in 20% of pts

Also seen w/ SLE and mixed connective tissue disease

Question 18

What occurs in the spine in RA

Answer 18

cervical spine involved
altlantoaxial sublaxation with pannus formation

Example:
separation between the anterior arch of C1 and the odontoid process of greater than 2.5 mm indicating subluxation

disc narrowing from C3-C7 w osteophyte formation can occur

Question 19

Describe pulmonary nodules

Answer 19

seen bilaterally in pulmonary parenchyma
same histological appearance as rheumatoid nodules
DISCRETE and identical to opacities seen in mets disease.

Question 20

List the differential diagnoses for RA

Answer 20

osteoarthritis (Diff hand involvement) 
fibromyalgia
post viral arthritis (rubella, hep B, erythrovirus) 
seronegative arthritis 
-ankylosing spondylitis
-reactive arthritis
-psoriatic arthritis
-enteropathic arthritis

Question 21

Difference between osteoarthritis and RA

Answer 21

OA is defined as joint stiffness caused by loss of cartilage between joints due to wear and tear, while RA stems from an autoimmune attack on joints
Bony enlargement can be seen in distal and proximal interphalangeal joints. The changes in proximal interphalangeal joints (Bouchard’s nodes) and distal interphalangeal joints (Heberden’s nodes) are common findings in degenerative joint disease of the hands. These changes are more frequently found in women after menopause and often show a genetic predisposition.

Question 22

Recall the diagnosis for diagnosis of Ra

Answer 22

2010 ACR/EULAR criteria
-definite diagnosis of RA is due to presence of synovitis in at least 1 joint and absence of alternative reason for synovitis occurring.

AND

-at least 6/10 in 4 domains
;number and site of joints involved (large joints, small joints)
;serological abnormality (ACP or RF)
;symptoms lasting more than 6 weeks
;acute phase response (CRP/ESR above ULN)

Question 23

List the radiological features of RA

Answer 23

pulmonary nodules
cervial spine- atlantoaxial sublaxation w pannus formation
erosive changes at joints

Question 24

Distinguish RA from psoriatic arthritis

Answer 24

both autoimmune and causes inflam arthritis(pain, swelling, stiffness) but psoriatic has diff joint distribution and involves skin- psoriatic skin lesions

Psoriatic affects only one side of body and can affect back and pelvis (as well as toes and fingers) unlike RA which more so impacts smaller joints and bigger joints like elbow, shoulder, knee, ankles and is bilateral

Question 25

Define enteropathic arthritis

Answer 25

Enteropathic arthritis, or EnA, is a form of chronic, inflammatory arthritis associated with the occurrence of an inflammatory bowel disease (IBD), ulcerative colitis and Crohn's disease

Question 26

Define ankylosing spondylitis

Answer 26

a form of spinal arthritis, chiefly affecting young males, that eventually causes ankylosis(stiffening and immobility of joint due to fusion) of vertebral and sacroiliac joints

Question 27

Describe diagnostic investigations for RA

Answer 27

Clinical presentation is key to diagnosis other ancillary tests: RF- IgM autoantibody against FC fragment of IgG - low specificity anti CCP- 98% specific -- predicts more aggressive and erosive disease course seronegative -antibodies negative seropositive-antibodies +ve

Question 28

Describe investigations-screening for complications and aetiology

Answer 28

``` -FBC, U&E, LFTs May show normocytic normochromic anaemia U&E and LFTs should be normal unless result of drug toxicity or complications -ESR/CRP Elevated -Plain film radiographs Diffuse joint space narrowing Periarticular joint margin erosions may be present in carpal bones, ulnar styloid, MCPs, and MTPs -Joint aspiration Leukocyte count > 2000 WBC/mm3 -If trying to rule out other differential diagnoses Uric Acid ANA SPEP ```

Question 29

Define principles of management of RA pt

Answer 29

Patient education Symptomatic relief Prevent joint destruction Early use of DMARDs as soon as diagnosis made Maintain and maximize function Decrease morbidity and mortality Minimise medication-related toxicity and complications

Question 30

What is the basis for giving pharmacological tx ?

Answer 30

Goal is to suppress inflammation, treat pain and prevent or minimise disability Aggressive early DMARD use prevents disability & improves prognosis Bad prognosis RA should be treated early and aggressively

Question 31

Outline pharm and non pharm therapies , with examples

Answer 31

NSAIDS, corticosteroids DMARDS (Conventional) - methotrexate, sulfasalazine,leflunomid, hydroxychloroquine DMARDS(biological) - anti TNF agents, anti IL6 agents, anti B cell agents, T cell activation inhibitors -med management and monitoring needed Non pharm -MDT management Rheumatologist, RA nurse, GP, physiotherapist, Occupational therapist, social worker, dietician, orthopaedics, orthoptist/chiropodist Annual vaccinations

Question 32

Describe drugs that cause symptomatic relief for RA use, any concomitant drugs,adverse rx?

Answer 32

NSAIDs - helps relieve night pain and morning stiffness;; consider concomitant PPI - aspirin, ibruprofen, celebrex -Gi bleed Corticosteroids- IM, intra-articular and oral (oral used to induce remission) consider concomitant vit D, calcium and bisphosphonates if on corticosteroids for more than THREE months Adverse reaction- secondary osteoporosis, increased fracture risk oral- prednisolone high dose short term low dose <10mg daily - long term used for relieving symptoms w active RA

Question 33

Describe therapeutic management of pt w RA

Answer 33

DMARDs Methotrexate- antimetabolite effects dihydrofolate reductase onset of action - 2-3 months concomitant use of folic acid if needed side effects; mouth ulcers, hepatotoxicity, pulmonary fibrosis, GI- nausea, bone marrow suppression, B12/folate deficiency -monitor every 3 months U&E, LFTs, FBC BEWARE if pt has liver disease, alcohol use, renal impairment ``` sulfasalazine combo of 5ASA and sulfapyridine safe for use during pregnancy use 3-6 months for 50% pts risk of leucopenia and thrombocytopenia thus blood monitoring necessary ``` hydroxychloroquine - can be used alone / with another DMARD can cause retinopathy rare leflunomide - prevents pyrimidine production in lymphocytes given to pts if METHOTREXATE FAILED can cause self limiting diahrrea BIOLOGIC TNF inhibitors - adalimumad, infliximab, etanercept (self administered SC injection) These are more expensive thus used after at least 2 conventional DMARDS failed; can be given with methotrexate Side effects-- precipitate heart failure, reactivation of latent TB and Hep B , rare cause of demyelination Tocilizumab - anti IL6 monoclonal antibody - given weekly injection subcutaneously/infusions Abatacept- prevents T cell activation ; subcutaneous weekly injections Rituximab-anti CD19 B-lymphocyte cytotoxic antibody- given as intermittent course of infusions every 6-12 months

Question 34

What important exercises are to be done by RA pts?

Answer 34

strengthening , aerobic and resistance exercises

Question 35

What are the complications of RA?

Answer 35

Septic arthritis - Staph aureus ; tx w antibiotics amyloidosis- chronic inflam causes build up of Serum amyloid A protein atherosclerosis- accelerated by chronic inflam

Question 36

What are some unmmentioned extraarticular manifestations a/w RA?

Answer 36

all manifestations stated above bronchiolitis obliterans mononeuritis multiplex felty's syndrome-splenomegaly, neutropenia

Question 37

What are some poor prognostic indicators/

Answer 37

``` Older age & lower educational level Female sex Symmetrical small joint involvement Morning stiffness >30 mins >4 swollen joints Cigarette smoking Co-morbidities CRP >20 g/dL Positive RF and anti-CCP antibodies ```

Question 38

If commencing a biologic agent, what investigations should be done?

Answer 38

CXR and mantoux test ; screen for TB/Hep B

Question 39

What are the causes of anemia in RA?

Answer 39

Anaemia of chronic disease Macrocytic anaemia from folate/B12 deficiency Felty’s syndrome Drug induced / pancytopaenia ( Methotrexate, GOLD, Penicillamine) Anaemia from GI bleed from NSAID use