RA Flashcards
Define RA
Systemic symmetrical inflammatory destructive polyarthropathy
most likely autoimmune but aetiology not well known
Epidemiology of RA
more common in women
a/ highly w/ disability, mortality, high socioeconomic burden
most common age - 30-50
Risk factors of RA
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.
Describe of pathology RA
- 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
Describe physiology of RA
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
Symptoms a/w RA
Pain and stiffness
-stiffness >30 mins after sitting and in the morning
Redness and warmth
Loss of function
Limited movement
Difficulty sleeping
Signs aw RA
- 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
Define volar sublaxation of hand
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.
Define Boutonniere’s deformity
PIP flexion and DIP hyperextension
can occur in toes and fingers
Define Swan neck deformity
PIP hyperextension, DIP flexion
Z deformity?
occurs at thumb
Z shape of thumb
hyperextension of interphalangeal joints, flexion and sublaxation of MCP
How to distinguish Early RA from established RA
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
How does RA present in the foot?
- 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
What are the extraarticular manifestations ?
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
What is a result of vasculitis ?
splinter haemorrhage and necrotic areas at finger tips/around nails -> skin infarction
changes also seen in SLE, polyarteritis nodosa
Define Episcleritis
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
Define rheumatoid nodule/ olecranon
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
What occurs in the spine in RA
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
Describe pulmonary nodules
seen bilaterally in pulmonary parenchyma
same histological appearance as rheumatoid nodules
DISCRETE and identical to opacities seen in mets disease.
List the differential diagnoses for RA
osteoarthritis (Diff hand involvement) fibromyalgia post viral arthritis (rubella, hep B, erythrovirus) seronegative arthritis -ankylosing spondylitis -reactive arthritis -psoriatic arthritis -enteropathic arthritis
Difference between osteoarthritis and RA
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.
Recall the diagnosis for diagnosis of Ra
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)
List the radiological features of RA
pulmonary nodules
cervial spine- atlantoaxial sublaxation w pannus formation
erosive changes at joints
Distinguish RA from psoriatic arthritis
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
Define enteropathic arthritis
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
Define ankylosing spondylitis
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
Describe diagnostic investigations for RA
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
Describe investigations-screening for complications and aetiology
-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
Define principles of management of RA pt
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
What is the basis for giving pharmacological tx ?
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
Outline pharm and non pharm therapies , with examples
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
Describe drugs that cause symptomatic relief for RA
use, any concomitant drugs,adverse rx?
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
Describe therapeutic management of pt w RA
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
What important exercises are to be done by RA pts?
strengthening , aerobic and resistance exercises
What are the complications of RA?
Septic arthritis - Staph aureus ; tx w antibiotics
amyloidosis- chronic inflam causes build up of Serum amyloid A protein
atherosclerosis- accelerated by chronic inflam
What are some unmmentioned extraarticular manifestations a/w RA?
all manifestations stated above
bronchiolitis obliterans
mononeuritis multiplex
felty’s syndrome-splenomegaly, neutropenia
What are some poor prognostic indicators/
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
If commencing a biologic agent, what investigations should be done?
CXR and mantoux test ; screen for TB/Hep B
What are the causes of anemia in RA?
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
