Rheumatology

Question 1

Rheumatoid Arthritis (1/3)
Describe the pathology and clinical features of RA. Include regional symptoms, and non-articular symptoms.

Answer 1

type III hypersensitivity, where a self-antigen causes immune response and production of auto-antibodies.
- self-antigens: most commonly TNF (also IFNy, RANKL, IL1, IL17)
- auto-antibodies: anti-citrullinated peptides (anti-CCPs: against post-translated arganine -> citrulline), and rheumatoid factor (RF: IgM/IgA against Fc of IgG)
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symmetrical arthritis usually in the small joints of the hands and feet. forms a pannus within the synovium, then bridging to form a fibrous ankylosis
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-> hands: swan-neck/Boutonierre, finger drop, sparing of the DIPs
-> shoulders: painful arc (impingement)
-> knees: varus/valgus, Baker cysts
-> feet: MTPjs, ulcers, calluses, valgus
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-> skin: rheumatoid nodules
-> vasculitis
-> lung fibrosis (peripheral), bronchiectasis, Caplan’s
-> TB (if anti-TNF therapy used)
-> cardiac (pericarditis, Raynaud’s, endocarditis)
-> eyes/mouth: sicca syndrome

Question 2

Rheumatoid Arthritis (2/3)
Give the American College of Rheumatology (ACR) scoring criteria of RA; the relevant score markers of DAS28; and the investigations that go alongside it.

Answer 2

Four criteria:
- joint involvement (score 0-5). max if >10 joints
- serology (score 0-3). max if titre is high
- acute phase reactants (score 0-1). abnormal CRP/ESR
- duration of symptoms (score 0-1). >6 weeks
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DAS28: <2.6 remission, <3.2 low disease activity, >5.1 active disease
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- blood count (ESR/CRP)
- serology (anti-CCP/RF). anti-CCP more specific
- X-ray, USS, MRI
- patient questionnaire

Question 3

Rheumatoid Arthritis (3/3)
Describe the treatment of RA along with the specific considerations for each DMARD.

Answer 3

NSAIDs (weak ibuprofen -> diclofenac -> naproxen -> celecoxib strong), consider + PPI
Avoid steroids >3 months (risk of osteoporosis), but use to dampen disease and allow DMARDs to kick in.
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- Methotrexate: give with folic acid. monitor blood count and liver biochemistry. give lung infection vaccines. must stop 6 wks before pregnancy (can give sulfasalazine)
- Sulfasalazine: can risk leucopenia or thrombocytopenia. is tolerated in pregnancy
- Hydroxychloroquine: can be used as an adjunct. rarely causes macular degeneration
- Leflunomide: good if methotrexate has failed. avoid in pregnancy (long half-life)
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Biologics if 2+ DMARDs failed. Anti-TNF therapy is very rare but screen or TB or cardiac failure.
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Physiotherapy, OT, podiatry, orthotomy, surgery for resistant cases.

Question 4

Give the main features of the four seronegative spondyloarthropathies (ankylosing spondylitis, reactive arthritis, enteropathic arthritis, psoriatic arthritis).

Answer 4

AS: lower back/buttock pain, usually in males.
- five key symptoms (4/5 are 80% sensitive): age <45; insidious onset; improvement with exercise; worse with rest; pain at night with improvement getting up.
- bamboo spine with positive Schober’s test
- NSAIDs, steroids (flares), biologics, physiotherapy
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REACTIVE: sterile synovitis after infection of GU or GU tracts. Commonly chlamydia, shigella, campylobacter
- acute, asymmetrical, lower limb
- can’t see (conjunctivitis), pee (circinate balanitis), or climb a tree (arthritis)
- consider septic until proven otherwise; aspirate then steroid injection
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ENTEROPATHIC: usually with IBD, asymmetrical oligoarthritis.
- NSAIDs, steroids, sulfasalazine
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PSORIATIC: x-ray ‘pencil in cup’ appearance
- arthritis mutilans (rare, telescopic fingers, emergency)
- treat as above, but avoid HCQ

Question 5

Give the main features of septic arthritis (presentation, investigation, and specific antibiotic therapies)

Answer 5

• sudden inflammation, held immobile by spasm. usually only one joint
• arthrocentesis for gram stain
• begin therapy before culture results. immobilize the joint and give empirical abx:
• – fluclox + sodium fusidate
• – erythromycin/clindamycin + sf (penicillin allergy)
• – fluclox + gentamicin (covers gm -ve in immunosuppressed)
• – teicoplanin + sf (MRSA likely)

Question 6

Give the main features of gout and pseudogout (pathology, presentation, and treatment).

Answer 6

Gout caused by deposition of uric acid within/around joints; fault in metabolism or excretion (90% idiopathic). Negatively birefringent
- asymptomatic hyperuricemia -> sudden, acute excruciating pain (usually 1st MTP) with a tophus -> asymptomatic intercritical period
- rapid response to NSAIDs / colchicine
- Lifestyle modification (especially beer reduction and diet change with low purines)
- allopurinol used for frequent attacks, but must be used >1 month after acute attack
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Pseudogout is calcium pyrophosphate deposition. Similar to gout. Treatment with aspiration (helps pain, weakly +ve birefringent), and NSAIDs/colchicine

Question 7

Briefly describe tumours of the joint.

Answer 7

• ganglion: well-defined, firm, transilluminates
• cyst: herniation of synovium (e.g. Baker cyst)
• tenosynovial giant cell tumour:
• – diffuse (large joints)
• – localized (small joints)
• bursitis: fluid usually subsides, but leaves a thickened bursal sac. problems can arise from scarring

Question 8

Describe the pathology, presentation and treatment of diseases of the neuromuscular junction.

Answer 8

myasthenia gravis -> autoantibodies against the ACh receptors, associated with complement and thymus abnormalities.
fluctuating weakness that worsens with exertion and over the course of the day. diplopia (double vision) and ptosis (drooping) common, respiratory muscle weakness rare but life-threatening
main treatment - inhibition of AChE, immunosuppression, or thymectomy for thymus pathology
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Lambert-Eaton - inhibits release of ACh from the synapse. weakness of extremities. underlying malignancy in 50%. treat by causing depolarization by other methods and/or immunosuppresion
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- botox prevents release of ACh
- curare blocks ACh receptors

Question 9

Give the main features of the inflammatory myosites (dermatomyositis, polymyositis) - pathology, presentation, investigation, and management.

Answer 9

dermatomyositis
proximal muscle weakness, skin changes (telangiectasis, heliotrope rash, Gottron papules, and deposition of complement in nails, eyelids, and gums). can involve resp, cardio, GI systems
CD8+ T cell mediated
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polymyositis
similar to dermatomyositis, without skin features
associated with anti-Mi2, -Jo1, -P155/P140
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investigation
bloods (creatinine kinase, aminotransferases, LDH, adolase, ERP/CRP, autoantibodies), electromyography, MRI, biopsy, and malignancy screens (CXR, mammography, abdo USS, urine microscopy)
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management
exercise programme + bed rest. prednisolone then steroid sparing agents

Question 10

Give the major features of Becker/Duchenne muscular dystrophy (pathology, natural history, differences between the two, and treatment).

Answer 10

• x-linked recessive (males > females), affecting dystrophin protein (which binds actin and dystrophin glycoprotein complex, DGC)
• Duchenne: normal at birth, clumsiness walking, pseudohypertrophy, requiring a wheelchair at about 10. joint contractures, scoliosis, respiratory/cardiac function impaired leading to death at 25-30
• Becker: later in life, some form of dystrophin, near normal life expectency
• supportive Mx (physio, splintage) and surgical correction to assist wheelchair sitting (e.g. scoliosis)

Question 11

Give the major features of fibromyalgia (symptoms and presentation, and potential treatments).

Answer 11

chronic pain syndrome, often with psychological factors (which make pain worse in a viscous cycle)

• treat problems with anxiety, depression, employment, personal relationships, and dependence
• widespread pain, disrupted and unrefreshing sleep, tiredness, and predictable tender point pattern
• clearly explain the diagnosis (not arthritis, no cure but manageable)
• amytriptyline, pregablin, paracetamol, tramadol, gabapentin may help. CBT recommended

Question 12

Give the major features of large vessel vasculitis (giant cell arteritis, and polymyalgia rheumatica).

Answer 12

PMR: pain and stiffness in shoulder and neck, hips, and lumbar spine. worse in the morning lasting 30 mins - hours. 1/3 develop constitutional symptoms
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temporal artery biopsy, but do not wait for results to start treatment (risk of blindness). 12-18 months of steroids
-> PCR: 10mg prednisolone
-> GCA: 60-100mg prednisolone
use bisphosponates in long term steroid use

Question 13

Give the major features of Kawasaki disease (pathology, presentation, treatment).

Answer 13

childhood disease, usually < 4 years
dense transmural inflammatory infiltrate of the coronary vessels; can cause aneurysm, thrombosis, or MI. leads to heart disease
fever, redness/edema of palms and soles, conjunctival and oral erythema, desquamative rash, cervical node enlargement
single dose IV immunoglobulin, followed by aspirin

Question 14

Give the major features of the small vessel vasculidities (key symptoms, antibodies, management).

Answer 14

symptoms are practically identical (sinuses, pulmonary, renal) -> sinusitis, haemoptysis, fibrosis, glomerulonephritis, haematuria. Late-onset asthma is also present in EGPA.
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immunosuppression or local treatment

Question 15

Lupus (1/3)

Describe the pathology of SLE.

Answer 15

autoimmune disease which affects women 9:1, and can affect virtually any organ.
main antibodies are nuclear (ANAs):
- anti-dsDNA (double stranded DNA),
- anti-Sm (smith),
- anti-RNA
- anti-B2-glycoprotein I (lupus anticoagulant, which actually coagulates in vivo)
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complement and IgG deposit in tissues and cause lesions (type III hypersensitivity); low serum levels of complement

Question 16

Lupus (2/3)

Describe the systemic symptoms of SLE.

Answer 16

Mnemonic - RASH OR PAIN

• rash (malar butterfly rash, livedo reticularis, ulcers, Raynaud’s)
• arthritis (pain, not swelling, and myalgia)
• serositis -> lungs (fibrosis, pleuritis, pulmonary HTN), heart (pericarditis, Libman-Sacks, murmurs)
• haematology (sclerosis, anaemia, thrombocytopenia)
• ocular (episcleritis, conjunctivitis, optic neuritis)
• renal disease (lupus nephritis)
• photosensitivity
• ANA antibodies,
• immunoglobulin Anti-dsDNA
• neuro (psychosis, seizures)
• ## constitutional (fever, fatigue, weight loss)Don’t have to name these! Essentially the same as above.
  clinical and immunologic categories:
  clinical (non-scarring alopecia, acute/chronic cutaneous, oral/nasal ulcers, arthritis, serositis, renal, neurologic, anaemia, leukopenia, thrombocytopenia)
  –
  immune (ANA, anti-dsDNA, anti-sm, lupus anticoagulant, low complement)

Question 17

Lupus (3/3)

Describe the management of SLE.

Answer 17

general
lifestyle, avoidance of excessive sun, mx cardio, NSAIDs, topical steroids (cutaneous lupus)
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immunosuppression
high dose oral: renal, cerebral, severe haematology
steroid sparing: cyclophosphamide, mycophenolate mofetil, azathioprine
biologics: refractory disease
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hydroxychloroquine used in all

Question 18

Give the major features of Sjogren syndrome (pathology, symptoms, diagnosis, and management).

Answer 18

• immunologic destruction of salivary and lacrimal glands, usually with RF, anti-Ro, -La, -SSA, -SSB
• associated with other rheumatological disease, or may be triggered by a virus (HTLV, HIV, hep C)
• symptoms: blurring of vision, burning, itching, and thick secretions from eyes, xerostomia
• diagnosis: lip biopsy (also, Schirmer tear test, Rose-Bengal staining, and immune lab tests)
• artificial tears and saliva
• HCQ can reduce fatigue and arthralgia, but monitor eyes. steroids rarely needed (only systemic)

Question 19

Give the major features of systemic sclerosis (classification, pathology, regional symptoms, investigation, and management).

Answer 19

CREST: calcinosis, Raynaud’s, esophageal dysmotility, sclerodactyly (beak nose, tight stretched skin), telangiectasis
other symptoms of diffuse;
MSK - similar to RA without joint destruction
renal - deposition, HTN, renal failure
lungs - pHTN and fibrosis
heart - pericarditis, effusion, arrythmia
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- work/hobbies (e.g. vinyl, silica etc)
- FBC (anaemia? renal disease?)
- urine microscopy, barium swallow
- CXR, hand x-ray, CT (lung fibrosis)
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do not use steroid except for in lung fibrosis
- education, counselling, family support
- Raynaud’s (ACEi/ARBs - paradoxically help renal disease, CCBs)

Question 20

Give the key features of anti-phospholipid syndrome (antibodies, symptoms, and management).

Answer 20

antiphospholipid antibodies (aPL)
- anti-cardiolipin
- anti-B2-glycoprotein I (lupus anticoagulant)
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ischaemic stroke, DVT, miscarriage, thrombocytopenia, chorea, migraine, epilepsy, valvular heart disease, livedo reticularis,  renal impairment
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long term anti-coagulation (warfarin)
aspirin and LMWH (pregnancy)