Revision Checklist Topics Flashcards
Rheumatoid arthritis - what antibodies are associated with this condition? What other blood tests may be raised?
What genetic mutations are associated with this condition?
Anti-Rheumatoid Factor and Anti-CCP antibodies. CRP, ESR and pV may also be raised. (NOTE - patients may still have RA and not have anti-CCP antibodies)
HLA-DR1 and HLA-DR4
Name some Rheumatoid deformities of the hands
Ulnar drift
Knuckle and wrist subluxation
Swan-necking
Boutonniere’s
Z-thumbing
Rheumatoid arthritis - what joints are typically affected and what time of day do they seem to be worst? How does activity affect these joints?
Hands - not DIPs
Feet
Sacral spine
C1/C2 - causing atlanto-axial subluxation
Less commonly, the shoulder and hip
Rheumatoid arthritis - other than pathology in the joints, where else might RA present?
Skin - rheumatoid nodules are commonly seen in areas of bony prominence e.g. eblows, heels, knuckles. Also may rarely see pyoderma gangrenosum, erythema nodosum, palmar erythema and atrophy of finger skin
Lungs - pulmonary fibrosis and pleural effusions
Heart and blood vessels - atherosclerosis, various forms of vasculitis, pericarditis, endocarditis, left ventricular failure etc.
Blood - anaemia
Kidneys
Eyes - episcleritis, scleritis
Liver - PBC, autoimmune hepatitis
Rheumatoid arthritis - investigations
Imaging
- Xray
- USS
- MRI (gold standard but expensive)
Serology (remember, may be negative for antibodies but still have RA!)
- Anti-rheumatoid factor, anti-CCP antibodies (best marker, co-relates with disease severity)
- CRP, ESR and pV
Rheumatoid arthritis - what scoring tools exist to grade extent and progression of disease?
EULAR Rheumatoid Arthritis Scoring Criteria - grades amount of joint involvement in small and large joints
DAS28 - monitors progression of disease
- >5.1 = active disease
- 3.2-5.1 = moderate disease
- 2.6-3.2 = mild disease
- <2.6 = remission (target for rheumatologists)
Rheumatoid arthritis - treatment
MTD review required to agree treatment plan
DMARDs within 3 months to prevent deformity
-
methotrexate is first line - 15mg/week initially, scale up to 25mg/week
- also need to give folic acid
- risk of pneumonitis and teratogenicity
- sulfasalazine
- Hydroxychloroquine (HCL) - doesn’t prevent erosions!
- Leflunomide
- Gold injections, azathioprine and others
If Methotrexate is insufficient alone, combine with other DMARDs. If no response after MTX and 2 or more other DMARDs, can use steroids as an adjucnt, and then Biologics
- prior to commencing Biologics, patients must be screened for TB!!!
Osteoarthritis - hallmark signs to look for on Xray
L - loss of joint space
O - osteophyte formation
S - subchondral sclerosis
S - subchondral cyst formation
Osteoarthritis - how do the symptoms of OA differ to those of RA?
What OA deformities may be seen on the hands, and how does this compare to the swelling seen in RA?
OA is gradual onset, taking months-years to develop
OA pain is mechanical, being worse on activity and at the end of the day, unlike RA which improves on activity.
OA also affects the DIPs
OA also causes morning stiffness (like RA), but this lasts less than an hour
Where swelling in RA is soft and boggy, in OA there is usually no joint swelling and instead hard bony swellings are seen
Deformities seen in OA
- Bouchard’s nodes - bony lumps seen at the PIPs
- Heberden’s nodes - bony lumps seen at the DIPs
Osteoarthritis - investigations
History and examination to exclude primary inflammatory arthritis
FBC
Xrays (remember, LOSS)
Osteoarthritis - treatment options
Non-pharmacological
- education
- physiotherapy
- weight loss
- appropriate footwear and walking aids
Pharmacological
- analgesia
- paracetamol
- topical analgesics, compound analgesics
- NSAIDs
- pain modulators
- tricyclics (amitriptyline), anti-convulsants (gabapentin)
- Intra-articular steroids - ONLY for short term relief of symptoms
Surgery
- arthroscopic joint washouts, soft tissue trimming and loose body removal
- partial/total joint replacements
Paget’s Disease - most commonly affected areas
Pelvis
Femur
Lumbar vertebrae
Skull
(may rarely transform into a malignant bone cancer, however Paget’s itself does not spread from bone to bone)
Paget’s Disease - suspected causes and genetic associations
Viral triggers? RSV, Canine Distemper Virus, Measles
Genetic factors? SQSTM1, RANK, specific regions on chromosomes 5 and 6 implicated
Paget’s Disease - signs and symptoms
35% of patients are asymptomatic at time of diagnosis
Most common presentation is bone pain. Rarely, there may also be hearing and vision loss due to nerve compression
Associated conditions: osteoarthritis, heart failure (rare), kidney stones, raised ICP
Paget’s disease - what is usually the first clinical manifestation of the disease seen in bloods?
How is diagnosis confirmed?
Usually first clinical manifestation is raised Alk Phos, while calcium, phosphate, PTH and aminotransferase are typically normal
Imaging is done to confirm diagnosis - Pagetic bone has a characteristic appearance on Xray, and bone scans may be useful in determing severity and extent of the disease
Paget’s Disease - treatment
MTD required
Medication (purpose is to relieve bone pain and prevent progression of disease)
-
Bisphosphonates
- Alendronic acid
- Calcitonin
Surgery may be required
Diet and exercise also seem to play a role
PMR - what condition is commonly associated with Polymyalgia Rheumatica?
GCA (temporal arteritis) is often seen alongside PMR
PMR - signs and symptoms
Wide ranging, typically seen in older patients
Proximal myalgia and stiffness of the hip and shoulder girdles, especially in the morning, lasts for more than an hour and tends to improve as the day goes on
Constant fatigue, weakness and sometimes exhaustion
Lack of appetite, anaemia and a general, non-specifc flu-like illness may be seen
PMR - investigations
No specific test to diagnose PMR, need to exclude other conditions
CRP, ESR and pV may be raised
PMR - treatment
Patients typically respond very dramatically to low-dose steroids (e.g. prednisolone, 15mg/day), suddenly patients feel much better
This can be used as a diagnostic test!
Gradually reduce pred. dose over 18 months
Systemic sclerosis - what are the two classifications of this disease and what antibody is each associated with?
Limited - skin involvement tends to be confined to face, hands, forearms and feet. Organ involvement tends to occur later on
Diffuse Cutaneous- skin changes occur more rapidly and tend to involve the trunk. There is early significant organ involvement
Limited - anti-centromere antibody
Diffuse - anti-Scl-70 antibody, anti-topoisomerase, anti-RNA III polymerase
Diffuse Cutaneous Systemic sclerosis sees much earlier organ involvement than Limited, how might this present?
ILD
Renal crisis due to pulmonary hypertension
GI problems - dysphagia, malabsorption and bacterial overgrowth of small bowel
Inflammatory arthritis and myositis
What did Limited Systemic Sclerosis used to be known as?
What is a common complication of Limited SSc?
Used to be called CREST - calcinosis, Raynaud’s (seen in 90% of patients), Oesophageal dysmotility, Sclerodactyly, Telangiectasia
Pulmonary hypertension is a common complication
Systemic Sclerosis - treatment
No one overall treatment, need to manage the symptoms and complications
Raynaud’s/digital ulcers - CCBs (amlodipine, diltiazem, verapamil), iloprost, bosentan
If renal involvement - ACE inhibitors (-prils)
If GI involvement - PPIs (e.g. omeprazole), H2 receptor antagonists
If ILD - immunosuppression, usually w/ cyclophosphamide.
Need tight control of BP and regular monitoring and screening of organ function
SLE - what is it and who tends to get it more?
Systemic autoimmune disease, can affect any part of the body. Immune system attacks the body’s cells and tissues, antibody-immune complexes form and precipitate, causing further immune response
Who gets it?
- women more than men - 9:1
- higher prevalence in asians, afro-americans, afro-caribbeans and hispanic-americans
- uncommon in african blacks
- genetic factors
- increased incidence amongst relatives
- hormonal factors
- higher incidence in those with increased oestrogen exposure - early menarche, oestrogen-containing contraceptives and HRT
- environmental
- viruses e.g. EBV
- UV light
- Silica dust (cigarettes, cleaning powders, cement)
What important complication needs to be screened for in people with SLE?
Renal disease
SLE has a very varied clinical presentation. What are some of the features that may be seen, and what classification criteria exists to help diagnose SLE?
SLICC Classification Criteria for SLE - require 4 or more of the following (at least one clinical and one laboratory)
Clinical
- acute cutaneous lupus
- chronic cutaneous lupus
- oral or nasal ulcers
- non-scarring alopecia
- arthritis
- serositis
- renal complications
- neurological complications
- haemolytic anaemia
- leukopenia
- thrombocytopenia
Laboratory
- ANA
- Anti-DNA
- Anti-Sm
- Antiphospholipid antibody
- low complement
- Direct Coombs’ test
SLE - what are some of the general constitutional symptoms that may be experienced?
Fever
Malaise
Weight loss and poor appetite
Fatigue
SLE - what are some of the mucocutaneous and musculoskeletal signs associated with SLE?
Mucocutaneous
- Malar rash
- Alopecia
- photosensitivity
- discoid/subcutaneous lupus
- oral/nasal ulceration
- Raynaud’s
Musculoskeletal
- arthralgia
- myalgia
- inflammatory arthritis
- AVN of femoral head (related to steroid use?)
SLE - what are some of the renal, respiratory and cardiac symptoms associated with SLE?
Renal
- Lupus nephritis
Respiratory
- Pleurisy
- Pleural effusion
- Pneumonitis
- ILD
- Pulmonary embolism/Pulmonary hypertension
Cardiac
- Pericarditis
- Pericardial effusion
- sterile (non-infective) endocarditis
- accelerated ischaemic heart disease
SLE - investigations
Again, no one specific test
FBC may show anaemia, leukopenia and thrombocytopenia
Immunology
- anti-nuclear antibody (ANA) - positive in 95% of SLE but non-specific
- anti-dsDNA antibody - specific and varies with disease intensity
- anti-Sm - specific but low sensitivity
- C3/C4 levels may be low during active disease
Urinalysis to screen for glomerulonephritis
SLE - treatment
Dependent on manifestations, but requires MTD
Skin disease and arthralgia - HCL, topical steroids and NSAIDs
If inflammatory arthritis/organ involvement then immunosuppression via azathioprine or mycophenolate mofetil
Steroids may be used at a moderate dose as well, over the short term
Monitor for complications
Sjogren’s syndrome - what is it? Who gets it? What antibodies are associated?
Chronic autoimmune inflammatory disorder, characterised by diminished lacrimal and salivary gland function
Most commonly seen in women in their 50s and 60s
Associated with Anti-Ro and Anti-La
What potentially serious syndrome is associated with autoimmune diseases, in particular SLE?
How does it present clinically?
What immunological testing can be done to detect it? (3 specific markers)
Anti-phospholipid syndrome - venous and arterial thrombosis
Presents clinically with livido reticularis, prolonged APTT, thrombocytopenia and recurrent miscarriages
Can be screened for using antiphospholipid antibodies
- Anti-cardiolipin antibody
- Lupus anticoagulant
- Anti-beta 2 glycoprotein
Sjogren’s syndrome - how does it present clinically and how can it be diagnosed?
Typically causes sicca symptoms (dry mouth, dry eyes, vaginal dryness)
May also cause swelling of the parotid gland. Other symptoms include arthralgia and fatigue
Diagnosis is done via Schirmer’s Test (tests ocular dryness) and antibody testing for Anti-Ro and Anti-La antibodies
Sjogren’s syndrome - treatment
No specific treatment, management largely revolves around treating symptoms
Lubricating eye drops and saliva replacement products
Regular dental care is important as there is a high risk of dental microbial colonisation
Hydroxychloroquine (HCL, DMARD) can sometimes be useful in treating symptoms of arthralgia and fatigue
What is the treatment for anti-phospholipid syndrome?
Anticoagulation is the mainstay of treatment for those with an episode of thrombosis
LMWH can be used in patients with recurrent loss of pregnancy (NB - warfarin is teratogenic!!!)
What connective tissue disease are anti-RNP antibodies associated with?
What is the treatment?
Mixed Connective Tissue Disease - defined condition with features of various other connective tissue diseases
As with other CTDs, management varies with presentation - CCBs may help with Raynaud’s, and immunosuppression may be required if there is significant muscle or lung disease
Fibromyalgia - what is it and who most commonly gets it?
Unexplained condition causing widespread muscle pain and fatigue. Thought to be the result of a disorder in central pain processing or a syndrome of central pain sensitivity. Patients tend to have a lower threshold to pain and of other stimuli (temp., smells, noises etc.)
May be a primary condition, or associated with other autoimmune conditions (25% of patients have RA, 50% have SLE)
Most commonly seen in young to middle-aged women, although it can affect anyone
Fibromyalgia - signs and symptoms
Persistent, widespread pain, typically at specific points on the body (pain points can be used in diagnosis)
Fatigue, disrupted and unrefreshing sleep
Cognitive difficulties
Multiple other unexplained symptoms - depression, anxiety, functional impairments etc.
Fibromyalgia - investigations and management
No specific tests to diagnose fibromyalgia, instead need to exclude other conditions. Fibromyalgia diagnosis made on clinical basis
Mainstay of treatment is for the patient to learn how best to self-manage their condition, and also important to validate the patient’s concerns, express empathy and give advice regarding graded excercise and activity pacing
Atypical analgesia including tricyclics (amitriptyline) and gabapentin/pregabalin may be of some use
What are some of the signs and symptoms of Giant Cell Arteritis? How is it treated?
Symptoms
- Visual disturbances
- Headache
- Thickening non-pulsatile temporal artery
- Jaw claudication
- Scalp tenderness
- Consitutional symptoms
Treatment
- if no visual disturbances - 40mg Prednisolone
- if visual disturbances - 60mg Prednisolone ASAP!
- doses are gradually tapered over 2 years - most patients will have resolved
Polymyosititis and Dermatomyositis - what are they and who gets it?
Poly - idiopathic inflammatory arthropathy causing symmetrical proximal muscle weakness
Derm - clinically similar to the above, but with associated cutaneous features
Both are more common in women (2:1) and usually seen in 20+ year olds. Peak is between 40-65
Poly/Dermatomyositis - signs and symptoms
Both
- symmetrical proximal muscle weakness in upper and lower limbs
- insidious onset
- some patients complain of myalgia
- dysphagia seen in approx 1/3rd of patients
- ILD seen in 5-30% of patients
Specifically Derm
- shawl-like rash over shoulders
- Gottron’s papules on the hands over MCPs and PIPs
- Heliotrope rash seen on the face
- also a risk of malignancy (seen in 25% of patients)
Poly/Dermatomyositis - investigations
Inflammatory markers often raised, as is serum CK
Autoantibodies - ANA, Anti-Jo-1 antibodies, Anti-SRP
MRI may be useful
Muscle biopsy is crucial to exclude other rarer muscle diseases
Name some seronegative inflammatory arthropathies. What HLA type are patients with these conditions typically positive in?
Ankylosing spondylitis
Psoriatic arthritis
Reactive arthritis
Enteropathic arthritis
Patients are usually HLA-B27 positive
Ankylosing spondylitis - what is it and who gets it?
Chronic inflammatory condition if the spine and sacroiliac joints. Leads to eventual fusion of the intervertebral joints and SI joints (bamboo spine)
Males more commonly affected (3:1), typically between 20 and 40 yrs old
Ankylosing spondylitis - signs and symptoms
Typically patients complain of spinal pain and stiffness. There may also be a development of knee/hip arthritis
Stiffness is worse in the morning and improves with exercise
Over time, there is a loss of lumbar lordosis and increased thoracic kyphosis, resulting in a question mark spine
Associated conditions: anterior uveitis, aortitis, pulmonary fibrosis and amyloidosis
Ankylosing spondylitis - investigations
Lumbar flexion can be assessed using Schober’s Test
X rays may show sclerosis, fusion of the SI joints and bony spurs from the vertebral bodies, bridging the intervertebral discs resulting in bamboo spine appearance
90% of patients will be HLA-B27 positive
Ankylosing Spondylitis - treatment
Physiotherapy and exercise
NSAIDs - either non-selective (Ibuprofen, naproxen) or COX-2 inhibitors (diclofenac). COX-2 selective are apparently safer for the upper GI tract
Anti-TNFalpha therapy for more aggressive disease
DMARDs - typically have no effect on spinal disease but may be useful for treating secondary joint problems
Psoriatic arthritis - what additional signs may be seen in a patient with this condition, other than standard arthritic symptoms?
Patients usually have nail changes - pitting, onycholysis (lifting of nail from nail bed)
5% of patients develop a particularly severe and destructive form of the disease known as arthritis mutilans
Psoriatic arthritis - treatment
Similar to RA - methotrexate is first line, and continue to add DMARDs until Biologics become necessary
Enteropathic arthritis - how does this come about?
Inflammatory arthritis invoving peripheral joints and sometimes the spine. Affects patients suffering from inflammatory bowel disease (e.g. Crohn’s and UC)
10-20% of patients with IBD suffer from some kind of joint pain
Reactive arthritis - how does it come about and what is the triad of symptoms exhibited by some patients?
Inflammation of large joints 1-3 weeks following infection, typically a genitourinary infection (chlamydia, gonorrhoea etc.) or GI infection
Reiter’s syndrome
- Urethritis
- Uveitis
- Conjunctivitis
Reactive arthritis - management
Typically self-limiting but chronic and frequent relapses are seen in 15-30% of cases
Treatment is aimed at the underlying infectious organisms and symptomatic relief. DMARDs may be used in chronic cases
Seronegative inflammatory arthropathies - typical presentation common to diseases in this group
Inflammation/arthritic disease of the spine (spondyloarthropathy)
Asymmetric oligoarthitis
Sacroiliitis, uveitis, dactylitis (inflammation of fingers) and enthesopathies (inflammation of tendonous insertions into bone e.g. achilles)
Raised CRP and ESR, and HLA-B27 positive
Gout - how is it caused?
Deposition of urate crystals within a joint, usually with high amounts of hyperuricaemia (either due to undersecretion or overproduction).
Uric acid is the final compound in the breakdown of purines in DNA metabolism
(Hypoxanthine > Xanthine > Uric acid)
(Xanthine oxidase is involved in both of the above conversions)
Gout - signs and symptoms
What is the number one differential when Gout is possible?
Classically presents with a red, hot, swollen and intensely painful joint, usually occuring during the night and lasting for 7-10 days
Can affect any joint, but is typically seen in the first MTP
Gouty tophi may also rarely appear - painless accumulation of uric acid in lumpy nodules on the hands.
Number one differential that MUST be excluded is SEPTIC ARTHRITIS!
Gout - investigations
Definitively done through analysing a sample of fluid from the affected joint, taken via arthrocentesis.
Uric acid crystals appear under polarised microscopy as needle-like with a strong NEGATIVE birefringence
Blood tests to assess for hyperuricaemia may also be useful, but uric acid levels in blood can be raised and a patient may still never develop gout
Gout - treatment (acute and longer term)
Acute attack - NSAIDs (colchicine for patients that cannot tolerate NSAIDs), corticosteroids, opioid analgesics
Longer term - allopurinol targets xanthine oxidase and can prevent attacks, however should only be started after an acute attack has settled as it may result in another flare of the disease
Pseudogout - what causes it and who is it more commonly seen in?
Caused by accumulation of calcium pyrophosphate crystals in cartilage and other soft tissues (chondrocalcinosis)
Exact cause is unknown
While Gout is typically seen in people (more commonly men) in their middle ages, Pseudogout typically affects older people
Pseudogout - treatment
Management is the same as with Gout (NSAIDs/Colchicine, steroids and opioid analgesics), however Allopurinol won’t do anything as the Xanthine pathway is not involved in Pseudogout.
Name some benign bone tumours (7)
Which ones are painful?
Osteochondroma - most common, produce bony outgrowth covered by cartilaginous cap. Most commonly around epiphysis of long bones, especially the knees
Enchondroma - intramedullary and usually metaphyseal cartilaginous tumour. Usually asymptomatic but may cause pathological fracture and classically occur in small tubular bones of the hands and feet
Simple bone cyst - unicystic fluid-filled neoplasm, likely due to a growth defect in the physis. Seen around the metaphysis of long bones. Like encondromas, typically asymptomatic but may cause pathological fractures
Aneurysmal bone cyst - in contrast to above, contains lots of chambers filled with blood or serum. Locally aggressive causing cortical expansion and destruciton. USUALLY PAINFUL
Giant cell tumour - locally aggressive, predilection for metaphyses. Most commonly seen in knee and distal radius. ALSO PAINFUL, and may cause pathological fractures
Fibrous Dysplasia - usually occurs in adolescence, genetic mutation results in lesions of fibrous bone tissue and immature bone. Can affect any bone, but head and neck most common. Involvement of head of femur can result in Shepherd’s Crook deformity
Osteoid Osteoma - small area of immature bone surrounded by intense sclerotic halo. Most commonly at head of femur, diaphysis of long bones and veretbrae during adolescence. INTENSE, CONSTANT PAIN, worse at night
Name that benign bone tumour!
“Most common, produce bony outgrowth covered by cartilaginous cap. Most commonly around epiphysis of long bones, especially the knees”
Osteochondroma
Name that benign bone tumour!
“Intramedullary and usually metaphyseal cartilaginous tumour. Usually asymptomatic but may cause pathological fracture and classically occur in small tubular bones of the hands and feet”
Enchondroma
Main clinical difference between Simple bone cysts and Aneurysmal bone cysts?
Aneurysmal bone cysts are painful
Name that benign bone tumour!
“Locally aggressive, predilection for metaphyses. Locally destructive, destroying the cortex of bone. Most commonly seen in knee and distal radius. PAINFUL, and may cause pathological fractures. Characteristic “soap bubble” appearance on Xray”
Giant cell tumour
Name that benign bone tumour!
“Usually occurs in adolescence, genetic mutation results in lesions of fibrous bone tissue and immature bone. Can affect any bone, but head and neck most common. Involvement of head of femur can result in “Shepherd’s Crook” deformity. Patients with this condition usually also have other significant problems e.g .endocrine disorders”
Fibrous Dysplasia
Name that benign bone tumour!
“Small area of immature bone surrounded by intense sclerotic halo. Most commonly at head of femur, diaphysis of long bones and veretbrae during adolescence. INTENSE, CONSTANT PAIN, worse at night “
Osteoid osteoma
Name some malignant bone tumours (4)
These are very rare - which group more commonly gets them?
Osteosarcoma - most common PBT, malignant tumout that produces bone. Majority of cases associated with the tumour suppressor Retinoblastoma gene
Chondrosarcoma - cartilage-producing PBT, typically found in the pelvis and proximal femur. Tends to occur more in OLDER age groups
Fibrosarcoma
Ewing’s Sarcoma - often seen in teens and tend to occur in long bones, especially femur. Radiologically desrcibed as onion-skin pattern, and associated with t11;22 transolcation involving the Ewing Sarcoma gene (EWS)
Younger age groups get PBTs more commonly. Not uncommon in adults, but usually the result of metastatic spread from elsewhere
Name that malignant bone tumour!
“most common PBT, malignant tumout that produces bone. Majority of cases associated with the tumour suppressor Retinoblastoma gene”
Osteosarcoma
Name that malignant bone tumour!
“cartilage-producing PBT, typically found in the pelvis and proximal femur. Tends to occur more in OLDER age groups “
Chondrosarcoma
Name that malignant bone tumour!
“often seen in teens and tend to occur in long bones, especially femur. Radiologically desrcibed as onion-skin pattern, and associated with t11;22 transolcation involving the Ewing Sarcoma gene (EWS)”
Ewing’s Sarcoma
