Flashcards in Rheumatology Deck (103):
What is the definition of Rheumatoid Arthritis (RA)?
Symmetrical inflammatory arthritis affecting mainly the peripheral joints which if untreated can potentially lead to joint damage and irreversible deformities
Who is more commonly affected by rheumatological conditions, men or women?
What mediates RA?
A major histocompatibility complex class II allele human leukocyte antigen: HLA-DR4
What is the main structure involved in RA?
the synovium (lines joint capsules and tendon sheaths)
True or False, the first two joints of the spine, C1/C2 can be affected by RA
True, because they are lined by synovium
Which joints are preserved in synovitis of RA?
Distal interpharyngeal joints
What defines RA as early RA?
Less than 2 years since symptom onset
What tests should be done in RA?
Blood testing, inflammatory markers, autoantibodies and imaging (x-rays of hands and feet and US for signs of synovitis)
True or False, diagnosis of RA is dependent on detection of auto-antibodies
False, it is a clinical diagnosis
Which auto-antibodies are associated with RA?
Rheumatoid factor (not as specific) and Anti-CCP (very specific)
Which score is used to assess disease activity in RA, and what are the classifications based on results?
DAS 28 score ( >5.1 = active disease, 3.2-5.1 Moderate disease, 2.6-3.2 = low disease activity, <2.6 = remission)
What is the primary treatment for RA?
DMARDs: Methotrexate, with NSAIDs and steroids only as adjuncts in early stages while waiting for DMARDs to take effect
What are the first and second line DMARDs, and other options in RA?
Methotrexate and Sulfasalazine (alternatively Hydroxychloroquine, Leflunomide and combination therapy)
Why must a baseline CXR be taken with Methotrexate?
Risk of pneumonitis (allergic reaction in the lung)
What risks are there with Methotrexate?
Pneumonitis, liver function derangement, bone marrow suppression, tetrogenic effects
What is the starting dose of Methotrexate in RA?
15mg/week with rapid escalation until state of clinical remission is achieved (max 25mg/week)
What are examples of biologic agents?
Anti TNF agents primarily: Infliximab, Etanercept, Adalimumab, Certolizumab, Golimumab (or T cell receptor blockers, B cell depletes, IL-6 blockers or JAK 2 inhibitors)
What are the guidelines for biologic agent use in RA?
• Used when failure to respond to 2 DMARDs including Methotrexate and DAS 28 greater than 5.1 on two occasions 4 weeks apart.
• Methotrexate therapy is co-prescribed.
• Screen for latent or active TB , Hep B, C, HIV, Varicella zoster.
• Avoid live attenuated vaccines.
What are some complications of untreated RA?
Swan necking, Boutonnière's, calluses, atlante-axial subluxation
What is the definition off Osteoarthritis?
Progressive degenerative condition affecting joints due to gradual thinning of cartilage, loss of joint space and formation of bony spurs (osteophytes) - essentially 'wear and tear'
What is the pathogenesis of OA?
There is loss of matrix, release of cytokines including IL-1, TNF and mixed metalloproteinases as well as prostaglandins by the chondrocytes. Fibrillation of the cartilage surface and attempted repair with osteophyte formation then occurs (overstimulation of the bone)
What are some of the clinical signs of OA?
Heberdens nodes (bony enlargements at DIPs), squaring of thumb, osteophytes, effusions, crepitus at joints, varus/valgus deformities, restricted movement
What tests are done in OA?
Inflammatory markers, X-ray
** What are the main differences between RA and OA?
What is seen on x-ray in OA?
Loss of joint space, osteophytes, subchondral sclerosis and subchondral cysts (LOSS)
What are the pharmacological managements of OA?
Analgesia (eg. paracetamol), NSAIDs, Pai modulators (eg. tricyclics - amitriptyline, anticonvulsants - gabapentin), intraarticualr steroids
What are the surgical options for OA?
Arthroscopy (clear out joint) and joint replacement
Crystals of which type and form are seen in pseudo gout?
Calcium pyrophosphate crystals which are Rhomboids shaped and weakly positively birefringent
Crystals of which type and form are seen in gout?
Monosodium rate which are negative bifringement and needle shaped
Which level of serum uric acid defines hyperuricaemia?
> 7 mg/dL
What is the diagnostic criteria of gout, hyperuricaemia or crystal identification/radiographic findings?
Crystal identification/radiographic findings - not everyone with hyperuricaemia will develop gout
When does Chronic Polyarticular Gout occur?
If gout is left untreated
What is a tophi?
A deposit of crystalline uric acid and other substances at the surface of joints or in skin or cartilage, typically as a feature of gout
Which investigations are carried out in gout?
Inflammatory markers, WCC, X-ray (only see changes in chronic gout) and joint aspiration as the gold standard
What is the management of an acute attack of gout?
NSAIDs, colchicine or corticosteroids + other analgesics
What is used in the prophylaxis of gout?
What is Milwaukee shoulder?
Another crystal arthropod with hydroxyapatite crystal deposition in or around the joint
True or False, Connective Tissue Diseases are diseases of the connective tissues
False (I know, don't even get me started). They are autoimmune multi system diseases
What are etiological factors in SLE?
Genetics, increased oestrogen exposure, viruses eg. Epstein-Barr, UV light and silica dust
What is the pathogenesis of SLE?
Primarily due to loss of immune regulation. Involves increased and defective apoptosis, due to defective clearance of nuclear material acting as auto antigens
What likely causes renal disease in SLE?
Likely due to deposition of immune complexes in mesangium
What are the requirements for diagnosis of SLE?
At least 4 of the clinical criteria (at least 1 clinical and 1 lab/immunological or biopsy proven lupus nephritis)
What are the main symptoms of SLE?
Main symptoms: fatigue (main), fever, malaise, poor appetite, weight loss
What is Anti-phospholipid syndrome?
An autoimmune, hypercoagulable state caused by antiphospholipid antibodies
What are the clinical signs of Anti-phospholipid syndrome?
Venous and arterial thrombosis, Recurrent miscarriage, Livido reticular rash and prolonged clotting time
Which auto-antibody is most specific for SLE, and which others are useful?
Anti-Double Stranded DNA is the most specific, but not everyone who has SLE has it. Anti- nuclear (ANA) and Anti-ENA (anti-Ro, Anti-Sm and Anti-RNP) are also useful
Which auto-antobdy is associated with anti-phospholipid syndrome?
What is the first test in SLE to test for other organ involvement?
True or False, C3/4 (complement) and Anti-dsDNA vary with disease activity
True, complement falls with increased activity, while anti-dsDNA increases
**What is the pharmacological management of SLE?
NSAIDs, simple analgesia, anti-malarials (hydrochloroquine), steroids (as low as possible) and immunosuppressives - with potential for biologics
What is the treatment for anti-phospholipid syndrome?
Lifelong anti-coagulation and lifestyle factors
What is Sjogren's Syndrome?
CTD - Chronic inflammatory and auto-immune disorder characterised by diminished lacrimal and salivary gland secretion (sicca complex).
Which auto-antibodies are associated with Sjogrens?
Anti-Ro and Anti-La
What is Schemer's test?
Used in Sjogren's Syndrome and determines whether the eye produces enough tears to keep it moist. Uses paper strips inserted into the eye for several minutes to measure the production of tears.
What are the 2 types of systemic sclerosis?
Limited/localised and diffuse
what are primary features of limited systemic sclerosis?
Pulmonary hypertensions + CREST (Calconosis, Raynaud’s, Esophageal dysmotilty, Sclerodactyly, Telangiectasia)
Which antibodies are associated with systemic sclerosis?
Anti-centromere antibodies (limited) and Anti-Scl-70 (diffuse)
What are polymyositis, dermatomyositis, inclusion body myositis and polymyalgia rheumatic all examples of?
What is the main clinical feature of polymyositis and dermatomyositis?
What is the main difference between polymyositis and dermatomyositis?
Dermatomyositis involves skin changes as well eg. Gottren's sign (papule over dorsal hands), Heliotrope rash (purply rash around eyes) and Shawl sign
What is the definitive test for polymyositis/dermatomyositis?
Muscle biopsy (would see perivascular inflammation and muscle necrosis)
What is the pharmacological managements for polymyositis/dermatomyositis?
Glucocorticosteroids, Immunosuppresion, IV immunoglobulin - Rituximab in resistant disease
What is the main difference between Inclusion Body Myositis and Polymyositis?
IBM causes distal muscle weakness, while polymyositis is proximal. IBM also responds more poorly to treatment, more gradual onset, affects older people and is asymmetrical (polymyositis is symmetrical)
True or False, Polymyalgia Rheumatica (PMR) only occurs in older people
True, almost exclusively occurs in >50y
What are the main differences between PMR and polymyositis?
The main symptoms are pain and stiffness in PMR, rather than weakness in polymyositis
What condition can occur with PMR?
Temporal arteritis/Giant Cell Arteritis
What is the treatment of Temporal arteritis/Giant Cell Arteritis?
Low dose steroids
What is Fibromyalgia? (And what is it not?)
A chronic pain syndrome diagnosed by the presence of widespread body pain (criteria being at least 11/18 tender points). It is NOT inflammatory
What is the tests for Fibromyalgia?
Trick question (soz, not soz) - there are no tests
What is IPEX Syndrome?
Immune dysregulation, Polyendocrinopathy, Enteropathy and X-linked inheritance syndrome (catchy). A rare genetic disorder of immune dysregulation, characterised by overwhelming systemic autoimmunity
Which mutation causes IPEX syndrome, and why is this?
FOXP3 gene mutation - which is essential for the development of regulatory T cells
IPEX syndrome is a failure of peripheral tolerance, what is this?
Random rearrangement of TCR a and b chain gene segments occurs in developing T cells and B cells, which gives rise to hugely diverse B cell and T cell populations, allowing for recognition of millions of different antigens. However this can result in auto-reactive cells.
Specific tolerance mechanisms are required:
• Removal of self-reactive lymphocytes in primary lymphoid tissues (central tolerance)
• Inactivation of self-reactive lymphocytes that escape central tolerance (peripheral tolerance)
What do HLA genes code for?
Human Leukocyte Antigens aka MHC (associated with many autoimmune diseases)
What are the 4 main potential mechanisms of autoimmune disease?
1) Molecular mimicry 2) Antigen sequestration (antigens are hidden from the body) 3) Unrelated bystander activation (with large infections, other cells can become overwhelmed and activate) 4) Super-antigens (eg. Supertoxins, which can un-specifically activate a wide range of T and B cells)
What is the definition of hypersensitivity reactions?
Immune response that results in bystander damage to the self, usually exaggerations of normal immune mechanisms
What type of hypersensitivity reaction is SLE?
Type III - Immune complex mediated
What type of hypersensitivity reaction is RA?
Type IV - Delayed type hypersensitivity
**What are the clinical features of SLE?
What is the pathogenesis of RA?
Type IV hypersensitivity response, characterised initially by infiltration of synovium by self-reactive CD4+ T cells with secondary involvement of activated B cells and auto-antibodies
What are Sponyloarthropathies?
Family of inflammatory arthritides (arthritis involvement) characterized by involvement of both the spine and joints, principally in genetically predisposed (HLA B27 positive) individuals
What are the 4 main spondyloarthropathies?
Ankylosing spondylitis, Enteropathic arthritis, psoriatic arthritis and reactive arthritis
What is Ankylosing spondylitis and what is the hallmark joint affected?
Chronic systemic inflammatory disorder that primarily affects the spine. Hallmark: Sacroiliac joint involvement (sacroiliitis)
What tests can be used for Ankylosing Spondylitis?
Tagus/occiput to wall and modified Schoeber's test
True or False: Rheumatoid factor is negative in Psoriatic Arthritis
What is Reactive Arthritis?
Infection induced systemic illness characterized primarily by an inflammatory synovitis
What is Reiter's Syndrome?
A form of reactive arthritis, characterised by the triad: Urethritis, conjunctivitis/uveitis/iritis, arthritis
What is Enteropathic Arthritis?
Arthritis associated with inflammatory bowel disease eg. Crohn’s, Ulcerative colitis
Which gene are sponyloarthropathies associated with?
What are key shared features of sponyloarthropathies?
- Sacroiliac and spinal involvement
- Enthesitis: inflammation at insertion of tendons into bones eg Achilles tendinitis, plantar fasciitis…
- Inflammatory arthritis:
- Dactylitis (“sausage” digits)- inflammation of entire digit
What is vasculitis?
Inflammation of blood vessels, often with ischemia, necrosis, and organ inflammation.
What are causes of small vessel vasculitis divided into?
Those associated with anti-neutrophil cytoplasmic antibody (ANCA) and those which are not
What are the 2 main causes of large vessel vasculitis? What is the main difference and similarity between the 2?
Takayasu arteritis (TA) and Giant Cell arteritis (GCA). TA affects those under 40, while GCA generally affects those over 50. Both conditions are characterised by granulomatous infiltration of the walls of the large vessels.
What are the main symptoms of Temporal arteritis?
unilateral temporal headache, scalp tenderness and jaw claudication.
What are the 2 main causes of Medium Vessel Vasculitis?
Polyarteritis nodosa and Kawasaki disease
What is Polyarteritis nodosa characterised by and what is it associated with?
Necrotizing inflammatory lesions that affect arteries at vessel bifurcations, resulting in microaneurysm formation and aneurysms. It is associated with Hep B
What are the 3 main small vessel vasculitides?
Granulomatosis with polyangiitis (GPA) (Wegener's granulomatosis), Eosinophilic granulomatosis with polyangiitis (EGPA) (Churg-Strauss syndrome) andMicroscopic polyangiitis (MPA)
What is Granulomatosis with polyangiitis (GPA) (Wegener's granulomatosis)?
Granulomatous inflammation of respiratory tract, small and medium vessels where necrotising glomerulonephritis common.
What is Eosinophilic granulomatosis with polyangiitis (EGPA) (Churg-Strauss syndrome), and how does it differ from GPA?
Eosinophilic granulomatous inflammation of respiratory tract, small and medium vessels. Main difference from GPA is that it is associated with asthma
What do small vessel vasculitides GPA, EGPA and MPA all have in common in terms of immunology?
All associated with anti-neutrophil cytoplasmic antibodies (ANCA)
What is the management for localised/early ANCA-associated vasculitis?
Methotrexate + steroids
What is the management for generalised/systemic ANCA-associated vasculitis?
Cyclophosphamide + steroids
What is the management for refractory ANCA-associated vasculitis?