Rheumatological Red Flags Flashcards
What are the usual clinical features suggestive of systemic inflammation?
Fatigue (disproportionate to the patient’s usual tiredness) in the presence of adequate sleep
Lethargy (not as productive as usual)
Insidious onset (rare for inflammatory conditions to present overnight)
Sometimes weight loss with or without anorexia or a low grade fever are associated
May be associated rashes, arthralgia
What is vasculitis? What is the mechanism of the clinical features seen in vasculitis?
Inflammation in the walls of the blood vessels (arteries and veins of all sizes)
Clinical features are a mixture of inflammatory and ischaemic/infarction organ dysfunction +/- damage as the lumen of affected vessels become narrowed when the walls become thickened
Which organs are typically involved in vasculitis?
Some syndromes manifest in one organ only (e.g. skin, kidney) but MOST involve multiple organs
What symptoms are common in a vasculitis with a multiple organ syndrome?
Limb girdle ache/stiffness in the mornings (especially around the shoulders)
Common large vessel vasculitides
GCA
Takayasu
NB Probably the same condition in different age groups (histopathologically similar)
List 2 medium vessel vasculitides
Kawasaki
Polyarteritis nodosa
(Medium vessel vasculitides are rarer)
79 year old woman, 4-week Hx of recurrent headaches (gradual onset)
No PHx of headaches
Associated features: jaw pain when chewing and talking on the phone, vision normal, 5 kg LOW, fatigue
Severe shoulder and hip stiffness (worse in the morning, i.e. inflammatory joint pain)
I.e. there are some systemic inflammatory symptoms and some localised ischaemic symptoms involving masseter muscles and scalp skin and muscles
DDx? Ix?
Polymyalgia rheumatica (PMR) with GCA
RA (but no arthritis)
Polymyositis (unlikely)
Hypo or hyperthyroidism (may present with myopathy)
Malignancy (may present with paraneoplastic syndrome)
Trigeminal neuralgia
Ischaemic cardiac pain
Ix: CRP, ESR
When should you suspect GCA?
Caucasian men and women (>55 years; almost exclusively Caucasian)
New headache
Jaw claudication
Unexplained fever, ESR >100mm/hr
PMR-type symptoms (i.e. limb girdle stiffness) In any patient with a Dx of PMR, esp when ESR remains elevated despite treatment with low dose steroids
Sudden monocular blindness (anterior ischaemic optic neuropathy, AION; can be transient initially)
Describe the symptom complex seen in GCA
Superficial headache, scalp tenderness, jaw and tongue claudication (common; ask if it hurts when brushing their hair)
Polymyalgia rheumatica with shoulder and hip girdle pain and morning stiffness (very common)
Fever and fatigue LOW AION, retinal artery occlusion (risk less than 1%)
Upper limb claudication (rare)
Cough, sore throat (very rare)
How common is it for a patient with GCA to have a visibly enlarged temporal artery?
Extremely rare; most patients with GCA have no obvious signs (although opthalmologists may observe blood vessel changes on careful fundoscopy)
List 9 complications of GCA by the vessels involved
Opthalmic/long ciliary arteries: blindness
Subclavian: arm claudication, absent pulses
Renal: renovascular HTN (angiotensin 2 mediated)
Aorta, esp ascending and thoracic: aortic valve incompetence, aneurysm rupture (late)
Coronary: angina pectoris, MI ICA: TIA, stroke
Vertebral: TIA, stroke Iliac: leg claudication
Mesenteric: bowel ischaemia
DDx for acute monoarthritis
Bacterial septic arthritis
Crystal arthritis (e.g. gout, pseudogout)
Subchondral bone lesion (e.g. #, osteonecrosis, osteomyelitis)
Haemarthrosis (e.g. trauma, haemophilia, anti-coag therapy)
Palindromic rheumatism
22 year old woman presents with 2/7 Hx of spotty rash over lower legs and buttocks
No fever or headache but has bouts of pain in her muscles, knees and ankles
O/E: palpable, purpuric rash over lower legs, afebrile, neck supple, knees and ankle joints normal, peripheral sensation normal, muscle strength and reflexes normal
Ix: urinalysis (dipstick) shows trace of protein (+1) and no blood
DDx?
DDx: infection (most likely due to very short Hx; possible Dx includes meningococcal infection), allergic drug reaction (e.g. OCP, Abx), vasculitis (LCP classically, or HSP)
If fingers or toes were involved, it could suggest an embolic phenomenon (micro-emboli)
Which vessels are typically affected in Takiyatzu’s vasculitis vs GCA?
Takiyatsu’s: aorta
GCA: temporal
What is the mechanism of the weight loss and fever?
IL-1, IL-6, TNF-a
Give 7 examples of small vessel vasculitides
ANCA-associated: GPA (granulomatosis with polyangiitis; Wegener), MPA (microscopic polyangiitis), EGPA (eosinophilic granulomatosis with polyangiitis; Churg-Strauss)
Immune complex: cryoglobulinaemic, IgA (Henoch-Schonlein purpura), HUV (hypocomplementaemic urticarial vasculitis), anti-GBM
What organs are of greatest concern RE involvement in vasculitis?
Kidney
Lungs
Cerebral (rare)
Give 2 examples of variable vessel vasculitides
Behcet
Cogan
ANCA
Anti-neutrophil cytoplasmic Ab
Describe the findings
Pathological specimen: inflamed vessel
Findings include red cell extravasation, lumen obliterated with thrombus, fibrinoid material deposited in the wall of the vessel (fibrinoid-type necrosis), and evidence of inflammation (inflammatory infiltrate)
Describe the findings and give a DDx
Lung granuloma with macrophages, giant cells and eosinophils
DDx: some forms of vasculitis (classically ANCA-associated), TB, sarcoidosis (rare)
What is the mechanism of jaw claudication in GCA?
Temporal artery biopsy in GCA: describe the findings
Segmental destruction of internal elastic lamina (arrow), and granulomatous vessel inflammation with giant cells (small arrows); inflammatory exudate extends into the intima, where there is fibrosis
Is temporal artery biopsy always positive in GCA?
No; can be negative as lesions can be patchy
If there is a good story for GCA but the biopsy is negative, patient should be treated anyway
Describe the relationship between GCA and PMR
Both are diseases of elderly Caucasians
Frequently occur synchronously or sequentially in same individual
PMR in >50% of GCA patients; 25% of PMG patients have co-existent GCA
Histological temporal arteritis has been documented in patients with no headache and clinically normal temporal arteries (very tricky!)
PET imaging shows increased aortic uptake in many patients with PMR who have no headache
Mx of GCA
Have a low index of suspicion (because there is a high risk of blindness!)
Commence prednisolone 40-60mg daily immediately and arrange temporal artery biopsy (changes will still be present within a week of treatment)
Decide what to do if biopsy is negative - usually steroids are rapidly tapered and stopped unless the pre-test probability of GCA is very high
Taper corticosteroids according to ESR or CRP
Provide fracture prevention therapy
Be alert to early (infection) and late (fractures, aortic aneurysms, hyperglycaemia) complications
When should “steroid sparing” drugs (e.g. methotrexate) be used for treatment of GCA?
If patients have been taking prednisolone 15mg daily for 6/12, consider steroid-sparing agents
Consider commencing steroid-sparing agents from onset if patient is diabetic
63 year old woman with a PHx of knee OA presents with 2/7 of severe R knee pain, swelling and redness
She is unable to sleep or walk due to the pain
O/E: febrile (38.5 degrees), resists passive movement of R knee, R knee has tense effusion
DDx?
Ix?
DDx: bacterial septic arthritis, crystal arthritis (gout, pseudogout), subchondral bone lesion (e.g. fracture, osteonecrosis, osteomyelitis), haemarthrosis (e.g. trauma, haemophilia, anticoagulation, therapy), palindromic rheumatism
Ix: arthrocentesis
63 year old woman with a PHx of knee OA presents with 2/7 of severe R knee pain, swelling and redness
She is unable to sleep or walk due to the pain
O/E: febrile (38.5 degrees), resists passive movement of R knee, R knee has tense effusion
Purulent synovial fluid is aspirated from the R knee joint and microscopy shows 60,000 neutrophils/mm, 2000 RBCs/mm, Gram positive cocci
Likely causative organism?
Staph aureus (shows preferential joint localisation)
Beta-haemolytic Streptococci
Gram negative bacilli (including E. coli)
Streptococcus pneumoniae
Polymicrobial
N. gonorrhoea
NB Septic arthritis with bacteria such as these typically affect single and usually large joints (50% of cases are knee, other common sites include hip, shoulder, ankle, wrist, elbow)
What is palindromic rheumatism?
Rare episodic form of inflammatory arthritis; between attacks, the symptoms disappear and the affected joints go back to normal, with no lasting damage
RFs for joint sepsis
Very young or advanced age
Recent joint aspirate/injection, or penetrating injury
Portals for bacteraemia
Previous joint damage (e.g. OA, RA)
Corticosteroid therapy
DM
Chronic renal or liver disease
Immunodeficiency (e.g. hypogammaglobulinaemia, CLL, any cancer)
Prosthetic joints (don’t stick a needle into a prosthetic joint!!)
List 5 possible portals for bacteraemia
Skin ulcers
Bowel inflammation (e.g. diverticulitis)
Colonic biopsy
Dental work
UTI
Lower urinary tract instrumentation
What does a polyarticular arthralgia +/- tenosynovitis suggest about the aetiology of the presentation?
Suggests immune complex response to systemic infection (e.g. rubella, parvovirus, hepatiti B)
NB This is very rare and the patient will be very, very sick (ICU on inotropes sick)
Sick young adult (20-35), multiple joints infected, casual sexual activity and rash
Dx?
Possibility of disseminated N. gonorrhoea (disseminated gonococcal infection - DGI)
Infection of multiple joints contemporaneously is other quite rare; think immunosuppression (and disseminated MAC) or damaged joints
MAC
Mycobacterium avium complex
List 8 clinical features of septic arthritis
Fever, “septic” appearance
Joint pain (with no diurnal or activity variation)
Joint swelling
Heat over the affected joint
Erythema overlaying the joint
Loss of function
Pain on attempted joint motion (passive or active)
Rapidly progressive joint destruction on XR (within days or 1-2 weeks)
What conditions might staphylococcal joint sepsis co-exist with?
Endocarditis
Deep abscess (e.g. epidural space)
List some important diagnostic steps in a case of suspected septic arthritis
Always obtain synovial fluid for analysis ASAP
A low synovial WCC or the absence of a fever does not exclude infection, especially if the patient is immunosuppressed
Plain radiographs should be performed as a baseline and repeated at 1/52 if no Dx
MRI scan may be performed (sensitive and relatively specific)
FBE (neutrophilia is not specific)
Blood cultures are useful (50% of patients with non-gonococcal septic arthitis have positive blood cultures)
CRP is non-specific but useful if elevated
What features are diagnostic of septic arthritis on XR?
Demineralisation
Rapid articular cartilage loss
NB This is critical if cultures are negative!
Outline one hypothesis explaining Staph. aureus’ preferential joint localisation
Cna gene may determine adhesion to collagen
Mx of septic arthritis
Maintain high index of suspicion
Choose effective Abx based on age, clinical situation and Gram stain
Joint drainage is critical: closed needle drainage is rarely adequate, arthroscopic washout is preferred (and is mandatory for hip and shoulder joints, prosthetic joints and damaged joints in RA), and remember that yield of cultures is significantly reduced if Abx are given beforehand!
Analgesia (opioids usually required)
Initial rest followed by joint mobilisation
Consider associated infection (e.g. endocarditis)
Before cultures from arthrocentesis in septic arthritis become positive, which empirical Abx should be chosen and how long should they be continued?
6/52 broad spectrum (e.g. flucloxacillin)
Give 6 examples of ANCA-negative SVVs
Hypersensitivity vasculitis (many causes including drug reaction)
HSP
Rheumatic disorders (e.g. SLE, RA, Sjogren’s disease)
Mixed cryoglobulinaemia (hep C, rarely HIV or cancer)
Infection (hep C, hep B)
Malignancy (leukaemia, lymphoma, myelodysplastic syndromes)
Describe the clinical spectrum of Sx which may be seen in small vessel vasculitides
Constitutional: fevers, night sweats, malaise
Myalgias, arthralgias and/or arthritis
Rashes: palpable purpura (more specific), non-palpable purpura (less specific), urticaria
Nail-fold or digital infarcts
Mononeuropathy multiplex (e.g. foot drop; due to small vessel ischaemia of nerves, can be irreversible if not treated promptly)
Upper respiratory tract: sinusitis, epistaxis
Lungs: haemoptysis, diffuse alveolar haemorrhage
Haematuria (may look “smoky” in colour), microhaematuria or proteinuria on dipstick (glomerulonephritis) - can affect kidneys quickly and progress to ESKD within days!
List 3 ANCA-associated SVVs
Microscopic polyangiitis (MPA)
Granulomatosis with polyangiitis (GPA; Wegener’s)
Churg Strauss syndrome (CSS)
Can you have an ANCA-negative ANCA-associated vasculitis? How?
Yes; right story but ANCA-negative
Happens in GPA in particular - patient should have biopsy if there is a convincing story
How can meningococcus present dermatologically?
Meningococcaemia may present with purpuric rash in absence of fever or symptoms and signs of meningitis
How can staphylococcal bacteraemia present dermatologically?
Palpable purpura may occur in staphylococcal septicaemia, usually associated with deep infection (e.g. endocarditis, septic arthritis, vertebral osteomyelitis, epidural abscess, etc)
How can subacute bacterial endocarditis present dermatologically?
Palpable purpura, splinter haemorrhages
List 5 other SVV mimics
Thrombocytopaenia purpura
Arterial thromboembolism
Cholesterol microemboli (rarer)
Malignancy (rarer)
Calciphylaxis (rarer)
What is thrombocytopaenia purpura?
Very low platelet count (<10,000)
Usually due to immune-mediated platelet destruction (ITP)
How can arterial thromboembolism mimic SVV?
Showers of tiny emboli
May be due to proximal arterial aneurysm, atherosclerosis or anti-phospholipid syndrome
How can cholesterol microemboli mimic SVV?
Older patients with atherosclerotic vascular disease, occur downstream from plaque dislodged during angiography
What malignancies can mimic SVV?
Myxoma
Myelodysplastic syndrome
Cancers with paraneoplastic syndrome
What is calciphylaxis?
HyperPTH in ESKD
What is the gold standard Ix for Dx of a vasculitide?
Tissue sample: biopsy!!
Suspected vasculitide: important Ix and their rationales?
FBE: normocytic anaemia and/or thrombocytosis suggests inflammatory process, thrombocytopaenia suggests ITP
Blood film: look for fragmented RBCs and high RDW suggesting intravascular haemolysis
Acute phase reactants (ESR, CRP)
Albumin: negative acute phase reactant (can fall quickly)
UEC
Septic workup: blood cultures, MSU, CXR, multiplex PCR for meningococcus/pneumococcus
MSU microscopy: “glomerular” or dysmorphic RCC, red cell casts suggest glomerulonephritis (consider renal biopsy)
MSU culture: urinary sepsis
Echocardiogram: essential for any febrile patients with heart murmur, prosthetic valves or PPMs
Skin (punch) biopsy: select fresh lesions for Gram stain, culture and H&E immunostaining (usual pattern is LCP; can get IgA deposits in HSP; immune complexes are absent in AAV)
Ix for systemic involvement (based on likelihood of organ involvement): tissue biopsy (provides direct evidence; choose biopsy site based on clinical involvement and lowest risk of complications, with common sites including skin, kidney and liver), angiography (useful if clinical suspicion of medium vessel vasculitis e.g. PAN), lung CT or pulmonary function tests, nerve conduction tests for neuropathy
Mx of suspected vasculitis (e.g. pt presents with palpable purpura)
Consider infection early
Obtain Hx of drug exposure
Rapid assessment important to avoid organ damage
Tissue usually required to establish Dx
Treatment involves removal or treatment of triggering cause (e.g. hep C, drugs)
Reserve high dose corticosteroids and immunosuppression for systemic/extensive disease (if there is evidence of end organ damage, consider methylprednisolone)
Rituximab
Monoclonal Ab against the protein CD20, which is primarily found on the surface of immune system B cells
