Rheumatology Flashcards
Causes of gout?
DECREASED URATE EXCRETION
Drugs
Chronic kidney disease
Lead toxicity
INCREASED URATE PRODUCTION
Myeloproliferative/lymphoproliferative disorder
Cytotoxic drugs
Severe psoriasis
Lesch Nyhan syndrome?
Hypoxanthine-guanine phosphoribosyl transferase
deficiency
Inheritance = X-linked recessive
Features: gout, renal failure, learning difficulties,
head-banging
Drug causes of gout?
Thiazides, furosemide
Alcohol
Cytotoxic agents
Pyrazinamide
When to start allopurinol?
NEW GUIDANCE IS AFTER FIRST ATTACK
Tophi
Renal disease
Uric acid renal stones
Prophylaxis if on cytotoxics or diuretics
Starting allopurinol?
Initial dose of 100 mg od, with the dose titrated every few weeks to aim for a serum uric acid of
< 300 μmol/l
What foods are high in purines? (gout)
Liver, kidneys, seafood, oily fish (mackerel, sardines) and yeast
products
What causes pseudogout?
microcrystal synovitis caused by the deposition of calcium pyrophosphate
dihydrate in the synovium
Features of pseudogout?
Knee, wrist and shoulders most commonly affected
X-ray: chondrocalcinosis (linear calcification of the articular cartilage)
Joint aspiration: weakly-positively birefringent rhomboid shaped crystals
Risk factors for pseudogout?
Hyperparathyroidism
Hypothyroidism
Hemochromatosis
Acromegaly
Low magnesium, Low phosphate
Wilson’s disease
Criteria for RA diagnosis?
1. Morning stiffness > 1 hr (for at least 6 weeks) 2. Soft-tissue swelling of 3 or more joints (for at least 6 weeks) 3. Swelling of PIP, MCP or wrist joints (for at least 6 weeks) 4. Symmetrical arthritis 5. Subcutaneous nodules 6. Rheumatoid factor positive 7. Radiographic evidence of erosions or periarticular osteopenia
Antibody for RA?
Anti-CCP
X-ray findings in RA?
EARLY
- Loss of joint space (seen in both RA and osteoarthritis)
- Juxta-articular osteoporosis
- Soft-tissue swelling
LATE
- Periarticular erosions (osteopenia and osteoporosis)
- Subluxation
Poor prognostic features in RA?
Rheumatoid factor positive
Poor functional status at presentation
HLA DR4
X-ray: early erosions (in < 2 years)
Extra articular features e.g. Nodules
Female sex
Insidious onset
Anti-CCP antibodies
Extra-articular complications of RA?
Respiratory: pulmonary fibrosis, pleural effusion, pulmonary nodules, bronchiolitis obliterans,
methotrexate pneumonitis, pleurisy
Ocular: keratoconjunctivitis sicca (most common), episcleritis, scleritis, corneal ulceration,
keratitis, steroid-induced cataracts, chloroquine retinopathy
Osteoporosis
IHD: RA carries a similar risk to T2DM
Increased risk of infections
Depression
DMARDs in RA?
Methotrexate
Sulfasalazine
Hydroxychloroquine
Leflunomide
Monitoring and complications methotrexate?
Monitoring FBC & LFTs is essential due to the
risk of myelosuppression and liver cirrhosis. Other important side-effects include pneumonitis
Indication for TNF inhibitors in RA?
inadequate response to at least two DMARDs
including methotrexate
TNF inhibitors in RA?
Etanercept: subcutaneous administration, can cause demyelination
Infliximab: intravenous administration, risks include reactivation of
tuberculosis
Adalimumab: subcutaneous administration
STOP 2-4 WEEKS BEFORE SURGERY
Two other types of drugs in RA (not DMARDs or TNF inhibitors)
RITUXIMAB
Anti-CD20 monoclonal antibody, results in B-cell depletion
Two 1g intravenous infusions are given two weeks apart
Infusion reactions are common
ABATACEPT
Fusion protein that modulates a key signal required for activation of T lymphocytes
Leads to reduced T-cell proliferation and cytokine production
Given as an infusion
Features of Adult Still’s Disease?
Arthralgia
Fever (noticeable at afternoon and evening)
Elevated serum ferritin
Rash: salmon-pink, maculopapular, pruritic
Lymphadenopathy
RF and ANA negative (but ANA 25% positive). Raised ESR and CRP
Leukocytosis and thrombocytosis
Age Adult still’s disease affects?
16-35
Organisms causing post-dysenteric reactive arthritis?
Shigella flexneri
Salmonella typhimurium
Salmonella enteritidis
Yersinia enterocolitica
Campylobacter
Organism causing post-STI reactive arthritis
Chlamydia trachomatis
Antibodies for palindromic arthritis?
Anti CCP, AKA
20-50 yrs
Cause of ‘recent-onset arthritis’’? Where does it affect? Blood test?
Parvovirus (exposure to kids with febrile illness)
Small hands joints, wrists, elbows, hips, knees, and feet are each affected in > 50% of cases
IgM - detection indicates recent infection, likely parvo
‘A’s of ank spond?
Apical fibrosis (CXR)
Anterior uveitis
Aortic regurgitation
Achilles tendonitis
AV node block
Amyloidosis
And cauda equina syndrome
Examinations in ank spond?
Reduced lateral flexion (earliest sign), forward flexion and chest expansion
SCHOBER’S TEST - line 10cm above and 5cm below back dimples, distance should increase >5cm in forward flexion
Investigations in ank spond?
X RAYS
Sacroilitis: subchondral erosions, sclerosis
Squaring of lumbar vertebrae
‘Bamboo spine’ (late & uncommon)
CXR
Apical fibrosis
SPIRO
Restrictive defect - fibrosis, kyphosis and ankylosis of costovertebral joints
Management of ank spond?
NSAIDs
Physiotherapy
Sulphasalazine may be useful if there is peripheral joint involvement - doesn’t improve spinal
mobility
TNF blockers such as etanercept and adalimumab
Seronegative spondyloarthropathies
Ankylosing spondylitis
Psoriatic arthritis
Reiter’s syndrome (including reactive arthritis)
Enteropathic arthritis (associated with IBD)
Pseudoxanthoma elasticum?
Autosomal recessive condition - abnormality in elastic fibres
Retinal angioid streaks
‘Plucked chicken skin’ appearance - small yellow papules on the neck, antecubital fossa and axillae
Cardiac: mitral valve prolapse, increased risk of ischemic heart disease
Gastrointestinal hemorrhage
Immunology SLE?
ANA positive (99% SENSITIVE)
20% are rheumatoid factor positive
Anti-dsDNA: HIGHLY SPECIFIC (> 99%), but less sensitive (70%)
Anti-Smith: MOST SPECIFIC (> 99%), sensitivity (30%)
Complement factor deficiency –> increased SLE risk
C3 and C4
HLA in SLE?
HLA B8
HLA DR2
HLA DR3
Monitoring in SLE
ESR: during active disease the CRP is characteristically normal - a raised CRP may indicate
underlying infection
Complement levels (C3, C4) are low during active disease (formation of complexes leads to consumption of complement) Low C4 is early marker for disease activity
Anti-DsDNA titers: used for disease monitoring disease activity (but not present in all patients)
SLE in pregancy?
Worse during prego and puerprium
Can cause neonatal LE
Complications = congenital heart block (anti-Ro)
Caues of drug induced lupus?
Anti-epileptics: phenytoin
Chlorpromazine
Hydralazine
Isoniazid
Minocycline
Procainamide
Features of drug induced lupus?
Arthralgia
Myalgia
Skin (e.g. malar rash) and pulmonary involvement (e.g. pleurisy) are common
ANA positive in 100%, dsDNA negative
Anti-Ro, anti-Smith positive in around 5%
Discoid lupus?
Younger females
Rarely progresses to SLE
Follicular keratin plugs
Erythematous raised, scaly rash; face, neck, ears, scalp
Heal with atrophy, scarring, pigmentation
Topical steroid cream, oral antimalarials (hydroxychloroquine), avoid sun exposure
Takayasu disease?
continuous or patchy granulomatous inflammatory process
involving macrophages, lymphocytes, and multinucleated giant cells which cause progressive occlusive
disease of the aorta and its branches
Rare in western world
Presentation of Takayasu disease?
Women, 30 years
Fever, malaise, and weight loss;
neurological symptoms such as transient ischemic attacks; or vascular symptoms such as
claudication.
Cardiac - angina, heart failure, and aortic regurgitation.
Renal - mesangial proliferative glomerulonephritis
Most specific antibody in dermatomyositis?
Anti-Mi-2
What is PAN? What is it associated with?
vasculitis affecting medium-sized arteries with necrotizing inflammation leading to aneurysm formation
more common in middle-aged men
and is associated with hepatitis B infection
Features of PAN?
Fever, malaise, arthralgia
Hypertension
Mononeuritis multiplex, sensorimotor polyneuropathy
Hematuria, renal failure
Testicular pain
Abdominal pain (e.g. From mesenteric ischemia)
Perinuclear-antineutrophil cytoplasmic antibodies (pANCA) are found in around 20% of
patients with ‘classic’ PAN
Diagnostic criteria for PAN?
- Weight loss > 4.5 kg.
- Livedo reticularis
- Testicular pain or tenderness. (Occasionally, a site biopsied for diagnosis).
- Muscle pain, weakness, or leg tenderness.
- Nerve disease (either single or multiple).
- Diastolic BP > 90mmHg
- Raised urea/creatinine
- Hepatitis B positive (surface antigen or antibody).
- Abnormal arteriogram (angiogram)
- Biopsy of small/medium size artery (typically inflamed arteries).
Summary of vasculitides?
Large arteries - GCA, Takayasu’s arteritis
Medium arteries - PAN, Kawasaki disease
Small - Microscopic polyangitis, Wegener’s, Churg Strauss
Arterioles - HSP, Essential cryobulinaemic vasculitis, Anti-GBM antibody mediated disease
Features of Wegener’s Granulomatosis?
Upper respiratory tract: epistaxis, sinusitis, nasal crusting
Lower respiratory tract: dyspnea,
hemoptysis
Glomerulonephritis
•
Saddle-shape nose deformity
Also: vasculitic rash, eye
involvement (e.g. Proptosis), cranial
nerve lesions
Ix and Mx of Wegener’s?
Ix - cANCA +ve in >90%, CXR - sometimes cavitating lesions
Mx - Steroids, cyclophosphamide (90% response), plasma exchange
Median survival = 8-9 years
Features of Churg-Strauss syndrome?
ASTHMA + EOSINOPHILIA + NERVE LESION
Asthma, pulmonary esoinophilic infiltrate
Blood eosinophilia
Paranasal sinusitis
Mononeuritis complex
pANCA +ve in 60% - Anti myeloperoxidase antibody
What can sometimes precipitate Churg-Strauss syndrome?
Leukotreine receptor antagonists
What is HSP
IgA mediated small vessel vasculitis
Usually seen in children after infection
Some overlap with IgA nephropathy (Buerger’s disease)
Features of HSP?
Palpable purpuric rash (with localized edema) over buttocks, extensor surfaces of arms and legs
Abdominal pain, non-bloody diarrhea.
Polyarthritis
Features of IgA nephropathy may occur e.g. Hematuria, renal failure
What is thromboangiitis obliterans? (Buerger’s disease)
Small/medium vessel vasculitis –> inflammation and ulceration
No CA involvement
Occurs only in cigarette smokers
Presents with arterial ischaemia, progresses proximally, digit gangrene
Treatment is supportive, stop smoking
Bechet’s syndrome triad?
oral ulcers, genital ulcers and anterior uveitis
Thrombophlebitis Arthritis Neurological involvement (e.g. Aseptic meningitis) GI: abdo pain, diarrhea, colitis Erythema nodosum, DVT
Random stuff about Bechet’s?
Eastern mediterranean (Turkey)
Men > Women, 20-40 yeears
HLA B51, MICA6
Pathergy test is suggestive (puncture site following needle prick becomes inflamed with small pustule)
Manage with steroids and azathioprine
Antiphospholipid syndrome important point?
(paradoxically) prolonged APTT + low platelets
Can be primary, or secondary to SLE
Features of antiphospholipid syndrome
Venous/arterial thrombosis
Recurrent fetal loss
Livedo reticularis
Thrombocytopenia
Prolonged APTT
Other features: pre-eclampsia, pulmonary hypertension
IN PREGNANCY - recurrent miscarriage, IUGR, pre-eclampsia, placental abruption, pre-term delivery, VTE
Management of antiphospholipid syndrome? and in pregnancy?
Initial VTE - warfarin (2-3) for 6 months
Recurrent VTE - lifelong warfarin (2-3, if on warfarin already then 3-4)
Arterial thrombus - lifelong warfarin (2-3)
PREGNANCY
Low-dose aspirin should be commenced once the pregnancy is confirmed on urine testing
LMWH once a fetal heart is seen on ultrasound. This is usually
discontinued at 34 weeks gestation
Features of Raynaud’s suggesting ulderlying CTD?
Onset after 40 years
Unilateral symptoms
Rashes
Presence of autoantibodies
•
Digital ulcers, calcinosis
Very rarely: chilblains (pernio) are itchy, painful
purple swellings which occur on the fingers and
toes after exposure to the cold. They are
occasionally associated with underlying connective tissue disease but this is rare
Recurrent miscarriages: This indicates SLE or antiphospholipid syndrome.
Secondary causes of Raynaud’s?
•
Connective tissue disorders: scleroderma (most common), rheumatoid arthritis, SLE with
bilateral symptoms
Leukemia
Type I cryoglobulinemia, cold agglutinins
Use of vibrating tools
Drugs: oral contraceptive pill, ergot
Cervical rib
Management of Raynaud’s symptoms?
Calcium channel blockers
IV prostacyclin infusions
Morphea?
Localised scleroderma
Small, violaceous or erythematous skin lesions –> enlarge to firm with hypo/hyper-pigmentation
Settle into waxy, white appearance with subsequent atrophy
Resolves within 3-5 years, can last up to 25
ANA rarely positive in localised scleroderma, in systemic subtypes it is always +ve
Psoriatic arthropathy?
Often precedes skin lesions - 10% with skin lesions develop arthropathy (M = F)
- Rheumatoid like polyarthritis (most common)
- Asymmetrical oligoarthritis (hands and feet)
- Sacroilitis
- DIP joint disease
- Arthritis mutilans (severe deformed fingers/hand - ‘telescoping’)
Management of Psoriatic arthropathy?
Tx as RA - but better prognosis
3 types of systemic sclerosis?
- Limited cutaneous
- Diffuse cutaneous
- Scleroderma
Limited cutaneous systemic sclerosis?
Raynaud’s first sign
Scleroderma in face and distal limbs mainly
ANTI-CENTROMERE ANTIBODIES
CREST SYNDROME
CREST syndrome?
Type of limited cuatneous systemic sclerosis
Calcinosis Raynauds Esophageal dysmotility Sclerodactyly Telangectasia
Malabsopriton secondary to bacterial overgrowth in sclerosed small intestine
Pulmonary HTN is late complication
Diffuse cutaneous systemic sclerosis?
Affects trunk and proximal limbs mainly
Anti SCL-70 antibodies
HTN, lung fibrosis, renal involvement
Poor prognosis
Scleroderma?
Without internal organ involvement
Tightening and fibrosis of skin
Antibodies for systemic sclerosis?
ANA positive in 90%
RF positive in 30%
Anti-SCL-70 antibodies associated with diffuse cutaneous systemic sclerosis
Anti-centromere antibodies associated with limited cutaneous systemic sclerosis
Management of systemic sclerosis?
Topical treatment for skin changes do not alter the disease course, but may improve pain and
ulceration.
NSAIDs
Limited benefit from steroids
Raynaud’s - nifedipine or other calcium channel
blockers. Dual endothelin-receptor antagonist (bosentan) may be beneficial.
Severe digital ulceration may respond to prostacyclin analogue iloprost
The skin tightness may be treated systemically with methotrexate and ciclosporin
Scleroderma renal crisis: ACE-I to control BP and delay progression to CRF
Active alveolitis is often treated with pulses of cyclophosphamide, often together with a small
dose of steroids
Dermatomyositis/Polymyositis?
Inflammatory disorder causing symmetrical, proximal
muscle weakness and characteristic skin lesions
Idiopathic, or associated with CTD or malignancy
Polymyositis = variant where skin manifestations not as prominent
Dermatomyositis features?
SKIN Photosensitive Macular rash over back and shoulder Heliotrope rash over cheek Gottron's papules - roughened red papules over extensor surfaces of fingers Nail fold capillary dilatation
OTHER Proximal muscle weakness +/- tenderness Raynaud's Respiratory muscle weakness Interstitial lung disease: e.g. Fibrosing alveolitis or organizing pneumonia Dysphagia, dysphonia
Ix in dermatomyositis?
Raised CK
EMG
Muscle biopsy
Anti-jo-1 not common in dermatomyositis, more common in polymyositis
ANA +ve 60%
Screen for malignancy
Familial mediterranean fever?
Recurrent polyserositis
Autosomal recessive - presents by second decade
Turkish/Armenian, Arabic descnet
Features of familial mediterranean fever?
Attacks typically last 1-3 days
Pyrexia (on-off)
Constipation/Diarrhea may occur with or after the fever
Abdominal pain (due to peritonitis) – many times appendectomy scar is seen due to multiple admissions due to abdominal pain
Pleurisy
Pericarditis
Arthritis
Nephrotic syndrome due to renal amyloidosis (that might even need transplantation)
Erysipeloid rash on lower limbs
Mx of FMF?
Attacks self-limiting, analgesia
Colchicine may reduce attack frequency
Relapsing polychondritis?
inflammatory condition that involves cartilaginous structures, predominantly those of the pinna, nasal septum and larynx
M + F, fifth decade
Features of relapsing polychondritis?
Fever, weight loss
sudden onsent ear pain, low hearing
mono/polyarthritis, back pain, myalgia
Mild epistaxis, saddle shaped nose
Redness of eyes (conjunctivitis, episclerits or scleritis)
Hoarse voice, recurrent resp infections
Mx of relapsing polychondritis?
(no specific test except raised ESR, CRP)
Steroids
Ix for other autoimmune diseases
Features of Sjogren’s syndrome?
Dry eyes: keratoconjunctivitis sicca
Dry mouth
Vaginal dryness
Arthralgia
Raynaud’s, myalgia
Sensory polyneuropathy
Renal tubular acidosis (usually
subclinical)
AT INCREASED RISK OF LYMPHOID MALIGNANCY (40-60 fold)
Ix in Sjogren’s?
Rheumatoid factor (RF) positive in nearly 100% of patients
ANA positive in 70%
Anti-Ro (SSA) antibodies in 70% of patients with PSS
Anti-La (SSB) antibodies in 30% of patients with PSS
Schirmer’s test: filter paper near conjunctival sac to measure
tear formation
Histology: focal lymphocytic infiltration (increased risk malignancy)
Also: hypergammaglobulinemia, low C4
Secondary Sjogren’s?
RA or other CTD (SLE) - develops about 10 years after onset
Causes avascular necrosis of hip? Ix?
long-term steroid use
chemotherapy
alcohol excess
trauma
Plain X-ray normal initially
MRI = gold standard
Mnemonic for SLE?
MD SOAP BRAIN
M alar rash
D iscoid rash
S erositis - pleurisy, pericarditis, pericardial/pleural effusions
O ral ulcers
A rthralgia - mainly peripheral joints
P hotosensitivity
B lood disorder - Pancytopenia, or individual cytopenia
R enal - SLE nephritis
A NA+
I mmunological markers - Anti-dsDNA, Anti-Sm, Antiphospholipid syndrome
N europsychiatrical: Psychosis, Seizures.
Paget’s disease Ix?
ALP raised, calcium phosphate normal
Other markers of bone turnover - procollagen type I N-terminal propeptide (PINP), serum C-telopeptide (CTx), urinary N-telopeptide (NTx), and urinary hydroxyproline
McArdle’s syndrome?
autosomal recessive type V glycogen storage disease
caused by myophosphorylase deficiency
this causes decreased muscle glycogenolysis
- muscle pain and stiffness following exercise
- muscle cramps
- myoglobinuria
- low lactate levels during exercise
