RHEUMATOLOGY Flashcards
What is Wegners Granulomatosis with polyangitis
Macroangiopathic vasculitis
Classically causes vasculitis in nose / airway and GN
-epistaxis
-arthropathy
-pulmonary haemorrhage
raised TLCO and kCO due to blood in airway with reduced He due to ventilation loss (restrictive picture)
-PR bleeding
-erosion of nasal septum causing saddle bridge
Diagnostic:
History
c-ANCA positive
Raised kCO and TLCO due to pulm heamorrhage
Differential:
Goodpastures - no sinus issues / epistaxis etc
churg strauss (p-anca)
Treatment:
Monitor renal function - HD or PD or transplant
plasma exchange
methyl pred+ rituximab / cyclophosphamide
Familial Mediterranean Fever
Autosomal recessive
- pyrexia
- recurrent peritonitis
assoc:
arthropathy
pleuritis / pericarditis
rash
last 2-3 days
mimics acue abdomen
laparatomy = NAD
COLCHICINE - GOOD PREVENTION
INDOMETACINE FOR PERICARDITIS
How should acute gout be managed
- Colchicine
- 500mcg BD renal dose
2.Allopurinol - may worsen acute gout
good for prevention
- Febuxostat - xanthine ox inhibitor like allopourinol but with worse CV incidence
- Rasburicase - urate oxidase
- reduce risk of gout in TLS e.g. whilst giving RCHOP
- TREAT HYPERURICAEMIA IN TUMOUR LYSIS
- ACCELERATES URIC ACID METABOLISM
What is Raynauds phenomenon
- idiopathic
- secondary raynauds
- SLE
- Sarcoid
- RA
- Scleroderma
Small vessel vasculitis in response to cold
Presentation: PAIN / BLUE –> RED
Peripheral vasoconstriction hands and feet leading to vlue discolouration in response to cold weather
Painful
Blanching erythema secondary to reperfusion + reperfusion injury
chronic: CHRONIC ISCHAEMIA Pulp atrophy nail fold telangiectasia in response to HIF1a arterial ulceration
What do you see cutaenously manifested in sarcoid
- lupus pernio
face ears limbs
Indurated red / black papules - cutaeneous sarcoid - cutaenous non cavitating granuolmas
- Epitheliod cells with sparce lymphocyte infiltrate marginally
- may show calcium deposition as well
- Sarcoid leads to hypercalcaemia due to ectopic production of 1a hydroxylase within granulomas = MORE ACTIVE VIT D3 = MORE CA ABSORPTION GUT + REDUCED EXCRETION DCT.
What are cold agglutinins
AI disorder presenting with haemolytic anaemia in response to cold weather
Abs opsonise and agglutinate resulting in AGGLUTININ MEDIATED ACROCYANOSIS -microocclusion -microangiopathic haemolysis -localised ischaemia
Warming does not stimulate reperfusion as in Raynauds.
What is Behcets disease?
Multisystem AI vasculitis
Can follow a relapsing remiting course
HLA B12/B51/B5
overlaps with chrons
- apthous ulcers
- abdo pain
- seronegative arthropathy
- weight loss
-systemic mucosal ulceration
90% oral apthous
70% genital
-Erythema Nodosum
(migratory panniculitis = inflammation of the fat cells)
- Thrombosis
- pathergy - abnormal scarring post trauma
20% vision loss
50% eye involvement
-anterior / posterior uveitis
-retinital vasculitis
CNS:
Can resemble MS
-sporadic lesions
-chronic meningoencephalitis.
-brainstem
4M motor N / motor p CST / MLF = ino (M+P) / med lemnisc
4S SNS (horners) / /spinothal / sensory V / cerebsopin /
(midbrain 3/4 pons 6M 578L medulla 9.10.11. L 12 M)
-basal ganglia - Parkinson plus syndrome
What is Jaccouds Arthropathy?
How might it present?
What is it associated with?
How is it managed?
Jaccouds Arthropathy
Reversible chronic non erosive deforming arthritis which typically follows repeated episodes of inflammation of the joint capsule and fibrosis that imposes traction afterwards
-ulnar deviation from mcp subluxation
ASSOCIATED
- SLE 5%
- POST RHEUMATIC FEVER
- SJORGENS
- PSORIATIC ARTHROPATHY
- ANKYLOSING SPONDYLITIS
- MIXED CONNECTIVE TISSUE DISEASE
MX: PAIN CONTROL physio Osteotomy Kirschner intramedullary wire for stability
What is Rheumatoid arthritis?
A common (1% of pop) autoimmune erosive symmetrical small and large joint arthropathy typically sparing the DIPJ.
It is set apart from other seronegative joint arthropathys like ankylosing spondylitis which affects primarily larger joints
It shares similarities with psoriatic arthropathy which has a typically varied presentation
The focus is on early diagnosis and early intervention to
How is Rheumatoid arthritis diagnosed?
Systemic signs
Scoring mech: - Im knacked (NACD)
NACD
Joint involvement
- Symmetrical
- Small and large joints
- Early morning stiffness
- RA rubbery nodules
- ulnar deviation of the MCP joints
- small tender effusions
- boutonnieres deformity - tendon sheath ruptute
- Swan neck - pipj and dipj tendon sheath rupture
- Z thumb
Neuro
Cervical myelopathy - Atlanto-axial subluxation = snap peg
Ulnar neuropathy - claw - paradox - more prox lesion worse deformity
Carpal Tunnel syndrome
SURGICAL SCARS Swansons arthrodesis of MCPJs Carpal Tunnel decompression Wrist Arthrodesis Ulnar styloidectomy Wrist synovectomy TENDON TRANSFER - follows line of tendon
EXAMINE FOR SPLENOMEGALLY / ANAEMIA
-Felty’s syndrome - splenomegally/ neutropenia / RA
RESP
pulmonary fiborsis
- secondary to RA or MTX
Renal
Amyloid
SCORING MECH - >6 = RA
NACD = number / Abs / CRP / duration
-Number of joints involved large = 1 1-3 small =2 4-10 small = 3 >10 = 5
-Serology:
High RF titre + Anti-CCP positive–3
Low RF titre + Anti-CCP positive–2
- CRP +ESR = 1
- Duration of symptoms >6/52 = 1
How is RA treated
DMARDS =MLSH Biologics =T(3 targets) =B
Aim is for early diagnosis and early treatment to induce remission and a state of disease quiescence
Physiotherapy to maintain mobility and ROM
DMARDS
- MTX
- Sulfasalazine
- Leflunomide
- Hydroxychloroquine
Biologics:
Anti-TNFa - INFLIXIMAB / ADALIMUMAB / GOLIMUMAB
TNF-R ANTAG - ETANERCEPT
PEG-FAB VS TNF-A- CERTILUZIMAB PEGOL
RITUXIMAB - ANTI-CD20 (no B cell Ab production)
ABATACEPT - CTLA-4 AGONIST (i Tcell acitvation)
TOCILIZUMAB - ANTI IL-6 - reduces TNF-a
Surgery - uncontrolled disease or disability
- arthrodesis - fusion
- arthroplasty - replacement
Analgesia
finger braces
Why is RA associated with anaemia
- Anaemia of chronic disease
- MTX
- UGIB secondary to NSAID use
FELTYS SYNDROME
RA / NEUTROPENIA / SPLENOMEGALLY
What are the side effects of MTX
Counselling needed
- pancytopenia
- hepatitis
- pulm fibrosis
- stomatitis
- anaemia
MOA:
Blockade of folic acid metabolic pathway / IL-1 inhibition / DNA synthesis / purine metabolism / thymidine synthesis / RNA synthesis
immunosuppression and opportunistic infection
need regular blood test to look for pancytopenia and trans-aminitis
Treat toxicity
FOLINIC ACID
MOA of MTX
CANCER?
RA?
Methotrexate is an antimetabolite of the antifolate type.
CANCER: HIGH DOSE
= antimetabolite / no purines / reduce DNA RNA synth
methotrexate competitively inhibits dihydrofolate reductase (DHFR) (binds folate)
DHFR catalyses the conversion of dihydrofolate to the active tetrahydrofolate for the de novo synthesis:
- nucleoside thymidine–>required for DNA synthesis
- folate is essential for purine and pyrimidine base biosynthesis,
Methotrexate, therefore, inhibits the synthesis of DNA, RNA, thymidylates, and proteins
RA: LOW DOSE
= TURN OFF Bcells / reduce costim / reduce IL-1 sensitivity
- inhibition purine metabolism, leading to accumulation of adenosine;
- inhibition of T cell activation and suppression of intercellular adhesion molecule expression by T cells;
- selective down-regulation of B cells; increasing CD95 sensitivity of activated T cells;
- inhibition of IL-1 to its cell surface receptor
What are the signs of Psoriatic Arthritis
Small and large joint SERO NEGATIVE + ASYMMETRICAL oligoarthropathy with a variable presentation associated with psoriatic skin changes preceding or developing after arthropathy onset
This develops in 5-10% of people with psoriasis
70% have psoriasis for >10 years before onset of arthritis
30% arthritis onset is before or at the same time
More common with nail involvement
onset 30-50
1st deg FMH = 50 fold increase risk
father PsA = risk x2 to child
male = female
Presentation:
- psoritic papular plaques - extensors + Koebner
- back pain - ASYMMETRICAL spondyloarthropathy - commoner men
- Symmetrical favours ANK SPOND - PR bleeding / altered bowel habit
- ASSOC CD + UC - Iritis
- Achilles Tendonitis
- Arthtiris mutilans / dipj / symmetrical small joint RA like /oligoarthropathy + effusion
- Dactylitis
- BILATERAL PLANTAR FASCIITIS
- NAILS
- pitting / onycholysis / transverse ridging / flaking /yellowing /
What are the 5 patterns of joint involvement in PsA
What are the HLA associations
RADOS
PsA is a SERONEGATIVE oligoarthropathy which typically causes large joint effusion and dactylitis
There are 5 types of presentation
1) RA like - symmetrical / persistently seronegative
- HLA DR4 (also CD)
2) ARTHRITIS MUTILANS
- very deforming
- joint telescoping
- joint destruction and finger shortening
- Dactylitis
3)DIPJ involvement
HLA B38 and 39
4)Oligoarthritis - asymmetrical + MASSIVE EFFUSIONS
5)Spondyloarthropathy - like ank spond but ASYMMETRICAL
HLA B27
How is PsA treated
Analgesia
Avoid steroids - acute flare on withdrawal
DMARDS MTX - mainstay leflunomide - joints and skin sulfasalazine - little skin effect hydroxychloroquine - AVOID AS MAKES SKIN WORSE
ACHILLES TENDINOPATHY
-Steroid injections = very good
Biologics
-Anti Tnf - inflix / adalimumab / golimumab = joint + skin
Joint differentials
DIPJ - HLA B38 AND 39
NOT RA
PsA - subtype
OA - erosive
Small joint symmetrical arthritis - HLA DR4
RA
PsA subtye RA like
Dactylitis - sausage fingers SARCOID Gout PsA Reactive arthritits
Explosive psoriasis + Joint involvement
-loss of Tregs - CD45 - think HIV
Spondyloarthropathy
- Ank spond
- PsA - HLA B27 TYPE
How can you differentiate PsA from RA
-RA may be sero positive - PsA always sero-negative
low or high RF
positive anti-ccp
- Cutaneous psoriatic plaques and pitting in PsA
- PsA Dactylitis - entire finger or toe inflammed
- DIPJ involvement in PsA subtype HLAB38 and 39
-Arthritis Mutilans PsA
telescoping
shortening
severe erosive arthritis
-RA symmetrical - PsA except RA type asymmetrical
How can you differentiate OSA from RA in xray
BOTH
narrowed joint space
bone cysts
RA symmetrical joint involvement subluxation juxta-articular osteopenia erosive arthropathy
OSA
osteophytes
osteosclerosis
What is SLE?
A common multi-organ involving auto immune ANA positive vasculitis which may present with arthropathy, vasculitic sequelae , glomerulonephritis and cutaneous features
What are the erosive arthropathies?
RA
PsA
Erosive OA
What are the non erosive arthropathies?
SLE arthropathy
Jaccouds
What are ACR criteria for diagnosing SLE?
RASH GANA
ANA for antibody most specific neuro and arthropathy
Rash 3
Apthous ulcers 1
Serositis 1
Haemolytic anaemia / leukopenia etc 1
GN 1
Antibodies 2
Neuro 1
Arthropathy 1
NEED 4 or more = 4/11
Malar Rash
Discoid Rash
Photosensitivity
Apthous ulcers
Non erosive arthritis - JACCOUDS
Serositis - pleural effusion / pericarditis
Glomerulonephritis
Neuro SLE = GBS / seizures / psychosis / T myelitis / INO/ mononeuritis multiplex
Haem = haemolytic anaemia / leucopenia /low plt
ANA positive - 95% >1:320
Anti-phospholipid (stroke tia mi retinal art / Anti - DsDNA - good for flares. low c3 c4
How might SLE present
Think:
Multi system
Cutaneous SLE. Neuropsychiatric SLE. GN SLE ? transplanted / PD scars? Heart failure - libman sacks endocarditis
Assoc:
Autoimmune ovaarian failure - secondary amenorhhoea
recurrent miscarriages -antiphospholipid
-Arthritis
non deforming jaccouds arthritis
-alopecia + mouth ulcers
scarring or non scarring
-opthalmoplegia or CN lesions
mononeuritis multiplex
-Malar butterfly rash or systemic discoid rash
-Haematuria
Lupus glomerulonephritis
-VTE + PE / stroke / MI / Retinal A occlusion early onset
Antiphospholipid syndrome
RECURRENT MISCARRIAGE + PRE-ECLAMPSIA
-Anaemia
haemolytic anaemia / leucopenia / thrombocytopenia
-Cardiac
NON INFECTIVE ENDOCARDITIS
LIBMAN SACKS ENDOCARDITIS - AR MR
CCF
-Neuro
Psychosis / GBS / seizures
-Myositis
MIXED CONNECTIVE TISSUE DISEASE OVERLAP
- SOB Pericarditis Pleural effusion (transudative) PE pulm fibrosis GBS Reaction to biologics - as ARDS
-Cushingoid
steroids
Causes of pulm fibrosis
VITAMIN C
APICAL
work:
silicosis
coal pneumoconiosis
Autoimmune
Sarcoid and other connective tissue disease
ank spond
infective
Allergic aspergillosis
TB
metabolic
Histiocytosis X
iatrogenic
Radiation
BASAL
Autoimmune
RA
MCD - sjorgens / SLE / scleroderma / dermatomyositis / polymyositis
Idopathic
IPF - AIP / DIP /
infective
bronchiectasis
What is Sjorgens Syndrome
Primary or Secondary - usually Secondary
AI process which destroys exocrine glands
Usually secondary to another AI process like RA or SLE
Primary Sjorgens is associated with a 40fold increased risk of Lymphoma
Due to parotid involvement differentials of swelling should include:
- Parotid cancer
- Lymphoma
- Sjorgens
- Mumps - parotitis
- sarcoid
How Does Sjorgens present
Dry eyes - XEROPHTHALMIA Dry Mouth - XEROSTOMA Bilateral parotid enlargement (blocked) -LOOK FOR EXCISION SCARS UNDER JAW LINE non erosive small joint arthropathy
What is Shirmers Test and how is it performed?
Test for lacrimation when sjorgens suspected
litmus paper crimped and hooked inside lower eyelid for for 5mm
expect to see tear migration >15mm = normal
How is Sjorgens diagnosed
- History
- Hx of CTD - Ra or SLE
- Abs - anti Ro / La
RF and anti-Ds DNA may also be positive
- Salivary gland biopsy is conclusive
What is the antibody profile in SLE?
Anti nuclear antigen is +ve in 95% at >1:320
Anti phospholipid may be present
Anti-Ds DNA if present good for monitoring activity
Anti-ENA may also be present
-Sm / Ro / La (THINK IS 2dary SJORGENS PRESENT)
How is SLE managed?
- Pred long term - may be cushingoid as in RA / PsA
- steroid induced DM2
2.DMARDS MTX hydroxychloroquine MMF Cyclophosphamide (esp lupus nephritis)
3, biologics
Rituximab - anti cd20
IVIg for flares
plasmaphoresis
- anticoag if antiphospholipid
Warf - antag vit K
Rivarox / apix / - renal biopsy
ACEi for protein urea
transplant - TAVI
- iron for haemolytic anaemia
- physio for jaccouds arthropathy
- specialist
stroke
mi / vte
pulm fibrosis - apical OR if secondary to MTX basal
pleural effusion - Percutaenous drain / pleurodesis
Pericardial effusion - pericardiocentesis
10 cosmetic
Wigs if scarring alopecia
- counselling
support groups
PT and OT input
How would you counsel a patient with SLE re: children
Conveying exact genes for SLE is rare
increased risk compared to background population
medication counselling
STOP MTX as teratogenic
STOP WARF as teratogenic
STOP Carbemazepine as teratogenic
azathioprine and hydroxychloroqione ok
How can you monitor SLE activity?
- Urine - protein and blood / casts / biopsy
- Anti-Ds DNA - levels correlate to disease activity
- FBC - cytopenias
- LFTs - Transaminitis
- Low C3 low C4
- haematuria
What are the risks associated with cyclophosphamide?
1 Immunosuppresion
Reactivation of latent TB / HCV / HBV / CMV / EBV
Acceleration of undiagnosed HIV
Opportunistic infection due to BM suppression
PCP
CMV or EBV or HTLV-1
THEREFORE PROPHYLACTIC COTRIMOX
2.Small risk of increased cancer.
- Hemorrhagic cystitis
TAKE ORAL MESNA PRIOR TO INFUSION
Conjugates toxic urinary metabolites to reduce the risk. - infertility
What is systemic sclerosis? How is it different from Scleroderma? Can scleroderma present in any other way?
Systemic form of scleroderma
Multi organ involving CTD characterised by skin thickening and joint deformity
CREST no longer really applies therefore:
- systemic sclerosis - CREST
- limited cutanoues - not all CREST fulfilled - e.g. gastroenteropathy + pulm fibrosis + morphoea
Look for
- small tight mouth / beaked nose
- tight shiny skin
- sclerodactyly deformity
- morphoea - Limited cutaenous SS or DcSS
- calcium deposition - CREST
- ulcers over fingers - raynauds
- hair loss and scarring alopecia
- telangiectasia (CREST)
artificial tears / saliva = Sjorgens
Remember CTD do cross over
-SLE may also feature here
(RASH G-ANA) rash malar discoid photo / apthous / serositis / haemolytic / GN / ANA / Abs / Jaccouds arth)
-E.g MCTD - SLE + scleroderma + myositis
3 presentations:
Raynauds
Localised scleroderma aka morphoea
linear scleroderma well circumscribed
Tight hard skin
en coup de sabre - scalp scerloderma
Systemic Sclerosis - 3 types
-Limited cutaeonus systemic sclerosis =any non CREST
Diffuse morphoea face / below elbows and knees but spares trunk - typically get pulm fibrosis and gastroenteropathy
Pulm fibrosis types - usually SCL70 +VE
- CREST - term no longer used (true systemic sclerosis)
Calcinosis - isolated hypercalcaemic deposits not unlike sarcoid granulomas (due to ectopic a1 hydroxylase production)
Raynauds
Eosphagial dysmotility / dilatation / achalasia
Scleroderma / sclerodactyly
Telangiectasia
Dysmotiity extends to all bowel - bacterial overgrowth / malabsorption / weight loss and diarrhoea
pulmonary fibrosis -->p.HTN and CCF UIP - usual int pneumonia = crap - 2.5-5 years NSIP = non specific int pneumonia GOOD STEROID RESPONSE MORT 12-14 years
-Diffuse cutaenous systemic sclerosis
Whole body morphoea
SCL70 +VE - risk of severe ILD
Anti-RNA pol 3
RISK OF SCLERODERMA RENAL CRISIS
- in event of renal crisis treat BP with RAMIPRIL - Better outcome mortality - 76% survival at 1 year Vs 15%
- amlodipine is good for BP control regarding raynauds but does not alter mortality in renal crisis