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
What is Scerlodactyly?
Localised thickening of fingers and toes DISTAL TO MCPJ
INVOLVEMENT POST MCP IS BEYOND SCLERODACTYLLY AND IMPLIES MORE DIFFUSE INVOLVEMENT
specific Questions for specific CTD SLE questions Antiphos question Sjorgens question CREST question sceroderma Qs
SLE (RASH GANA) rash in the sun? Do you have any rashes? Joint pains - jaccouds SOB / chest pain Haematuria mononeuritis multiplex / gbs /psychosis / confusion apthous ulcers
Antiphos
stroke / mi / PE / VTE
DM
rash - heliotropic
muscle weakness / pain?
Features of SLE and Slceroderma
Sjorgens
dry mouth
dry eyes
joint pains - jaccouds
CREST
Skin changes when cold ? painful? ?ulcers?
Do you have difficulty swallowing / heartburn?
DIARRHOEA /DYSPHAGIA / DYSPEPSIA
What is scleroderma crisis
ONSET IN DIFFUSE CUTANEOUS SYSTEMIC SCLEROSIS
- associated Anti RNA pol 3
- associated with SCL70 = diffuse ILD
- Acute onset malignant HTN leading to acute renal failure / headache // blurred vision , seizures, CCF AMD microangiopathic haemolysis
How does dermatomyositis present?
Autoimmune process and associated with , CREST, SLE, malignancy (breast lung gynae / colorectal)
Causes degernation of collagen resulting in
- heliotropic (surrounding eyes) rash
- proximal muscle weakness
- GOTTRON’s PAPULES over DIPJ / MCPJ - violaceous papules
Abs:
Anti Jo
onset 40-60
more common in women
Atopic Eczema management
- topical steroids
- anti-histamines
- daily emollients
- topical calciuneurin inhibitors for refractive disease
RA disease treatment in pregnancy
DMARDS
MTX - terato
Leflunomide - terato
azathioprine - shown to be safe but not recommended
SULFASALAZINE and HYDROXYCHLOROQUIN are the current recommendation
TNF-a inhibitors - inflix / adalimumba and golimumab have been shown to be safe but are not yet recommended due to lack of longterm evidence
How do you treat MTX toxicitiy
- glossitis
- candidiasis
- macrocytic anaemia
- thrombocytopenia
- severe mouth ulcers
–> FOLINIC ACID
More efficacious than folic acid
75mg over 12 hours
6-12mg every 4 hours thereafter
If severe
Bicarbonate
fluids
Dialysis does not remove mtx
What are the diagnostic criteria for FIBROMYLAGIA
1990 ACR
Widespread pain for >3 months
Pain elicited by pressure of 4kg/cm2 in 11 areas
Psychological stress = > pressure points
Overlaps substantially with depressive disorders / anxiety and chronic fatigue
overlaps with regional pain syndromes - atypical CP / IBS / chronic pelvic pain / TMJ pain
How is Fibromyalgia treated
- psychotherapy
- pharmacotherapy for disordered sleep = tricyclics / melatonin / zopiclone
- graded exercise programs
What is Gout?
Polyarticular or monoarticular gout
- single or multiple hot effused joints
- restricted ROM due to pain
- attacks last 3-10 days
- first presentation monoarticular - big toe / ankle / foot arch
- 50% onset hallux–>90% involvement
- Diurnal variation - onset in night and worst in morning
- Olecranon bursitis
- scars from ulceration and sinus formation over joints
-Aspiration - needle shaped intracellular and extracellular crysals of monodosium urate
yellow crystals–>red aligned parrallel–>blue when aligned perperndicular (NEGATIVE BIREFRINGENCE)
PSEUDOGOUT: Calcium pyrophosphate (CPP) - short / rhomboidal - no colour change underpolarising filter
TOPHI: ACHILLES BEHIND PINNA ELBOWS FINGERS / TOES EXTENSOR FOREARM ALONG TENDONS
PODAGRA - foot torturer in greek mythology
HALLUX GOUT
Caused by precipitation of urate crystals within the joint space causing localised inflammation and pain with restricted movement
Gouty arthritis is the most common for of arthritis in men over 40
4x more common in men
Prevelance rises with age and serum urate concentrations
4 PHASES 1 Asymptomatic Hyperuricaemia 2 Acute Gout 3 Intercritical Gout 4 Chronic tophaceous gout
triggers: alcohol purine ingestion (shellfish)- concurrent azathioprine use will require AZA reduced dose will need to be considered to maintain IBD control and avoid excessive BM suppresion UGIB and ingestion of digested blood sepsis trauma dehydration
drugs: TZDs - LOW POTASSIUM aspirin theophyllin ciclosporin levodopa ethambutol
Risk factors CKD hypothyroid myeloprolif / lymphoprolife: high turnover DM DI hereditary hyperuriacaemia Sarcoid Psoriasis obesity
Allopurinol is a xanthine oxidase inhibitor which would normally facilitate breakdown of 6’mercaptopurine (active form of AZA and mercaptopurine) (also inhibits TPMT) - Therefore in IBD can use a low dose of thiopurine analogue and supplement wit allopurinol to have clinical effect
Mx:
Colchicine / pred / NSAIDs (naproxen NOT IBUPROFEN) in the acute setting
Allopurinol or febuxostat (XOI) after symptoms resolve for secondary prevention
RASBURICASE - recombinatn urate oxidase
Avoid precipitants - alcohol / caffeine / cheese
How is Gout best managed?
Mx:
Colchicine / pred / NSAIDs (naproxen NOT IBUPROFEN) in the acute setting
Allopurinol or febuxostat (XOI) after symptoms resolve for secondary prevention
RASBURICASE - recombinatn urate oxidase
Avoid precipitants - alcohol / caffeine / cheese
When are Gottron’s papules seen?
Indicative of dermatomyositis
What is Reactive Arthritis?
Spondyloarthritis presenting with triad:
urethritis / dysuria
uveitis
arthritis
Causes
E.Coli / shigella / salmonella Gastroenteritis
Chlamydia trachomatis
Chlamydia pneumoniae
Psoriatic like rash = chlamydia
Treat = cause
What is Carpal Tunnel Syndrome?
What conditions are associated with it?
CTS results from median nerve compression in the wrist affecting the median nerve distribution
- Thumb movements except flexor pollicis brevis
- thenar wasting
- 1st and 2nd fingers
- Tinnels and phalens sign positive
Associations: RA Hyperthyroid Hypothyroid Idopathic
Mx:
local consticosteroid
hand splint
median nerve decompression
EMG studies to confirm
What is seen on aspiration in Gout?
Needle shaped negative birefringence crystals
yellow at base
aligned to light = red
perpendicular to light = blue
WCC +++
no growth
What is seen on aspiration in pseudogout?
calcium pyrophosphate crystals
no birefringence
What is seen in HPOA
Clubbing
periosteal inflammation i.e. effusion similar to dactylytis but involves whole fingers
What is HPOA?
Hypertrophic pulmonary osteoarthropathy
How does osteomalacia present?
global joint pain
proximal weakness
What is Charcot Arthropathy?
Results in Charcot’s joint
- TYPICALLY PAINLESS DUE TO SENSORY PARAESTHESIA AND IMPAIRED PROPRIOCEPTIVE FEEDBACK
- GROSS DEFORMITY
XRAY
- loss of joint margin
- bony destruction
- significant and active remodelling
Rx:
immobilisation for 3-4 months
bisphosphonates
IRREVERSIBLE ONCE ESTABLISHED
Causes: DM Charcot Marie tooth - hereditary sensory and motor neuropathy - demyelinating / schwann cell damage - loss of sensation - pes cavus or pes planus - CMT is divided into the primary demyelinating neuropathies (CMT1, CMT3, and CMT4) and the primary axonal neuropathies (CMT2), with frequent overlap.
What is allopurinol’s effect on azathioprine?
Allopurinol is a xanthane oxidase inhibitor
XO converts 6 mercaptopurine to inactive metabolites
Inhibition of XO results in build up of active component 6 mercaptopurine
i.e. dose seen by tissue is much greater than dose prescribed.
What antibodies are present in mixed CTD
Anti-RNP
How does Cryoglobulinaemia present
Immunoglobulins that precipitate out of solution when exposed to cold temperatures causing microvascular complications
- purpuric rash
- polyarthralgia
- polyarthritis
- Raynauds
Abs:
ANA
RF - 90% present in Sjorgens and cryoglobulinaemia
low C3 - immune complex deposition
How can Pulmonary HTN be reduced in Sarcoidosis
Remember pulmonary sarcoid will cause bilateral hilar lymphadenopathy and basal pulmonary fibrosis
P.HTN is a significant cause of morbidity and MORTALITY -core pulmonale severe = PA pressure >40mmHg -PR -TR -peripheral oedema -OSA -T2RF -impaired ET
Treatment for sarcoid = improve QOL and slow progression
- Pulmonary rehab
- stop smoking
- Sildenafil to reduce Preload
- iloprost infusion
Longterm:
Pred
MTX
Why is arthritis associated with Hereditary Haemochormatosis
Presentation: 40M Skin pigmentation Diabetes Heart problems CLD Arthropathy
Arthropathy is due to CHONDROCALCINOSIS CALCIUM PYROPHOSPHATE DEPOSITION i.e. pseudo gout / chondrocalcinosis / chronic arthropathy Rhomboid crystals may be weakly positive birefringence
-High transferrin saturation >15%
raised serum ferritin >500
In PsA WHERE might you find hidden psoriasis?
scalp i.e hairline
gluteal cleft
naval
flexor tendon synovitis
How does hydroxyapatite arthritis present
Usually female
Usually monoarthritis
Usually glenohumeral joint
aspirate:
blood
hydroxyapatite crystals
VERY DESTRUCTIVE ARTHRITIS
What DMARD for RA is safe in pregnancy? What does NICE recommend?
Treatment should continue through pregnancy especially given the immuno changes that come i.e. tolerance
MTX / Leflunomide = teratogenic
Sulfasalazine = FIRST CHOICE
Azathioprine = Safe but not first choice
Infliximab = data shows no increased morb / mort but not yet approved by NICE for pregnancy
What is Felty’s Syndrome?
How does it present and how is it managed?
RA + splenomegally +neutropenia
50s
female
longstanding RA >10 years
Think as a differential in a patient with RA on MTX
i.e. not simply MTX tox = folinic acid resuce
Rx: pulse methylpred cyclophos switch DMARD - leflunomide / sulfasalazine / azathioprine SPLENECTOMY IF FAILS TO RESPOND
What is bronchopulmonary aspergillosis and what are its sequelae?
Manifests as EEA
- Driver is allergen to aspergillus
- Raised eosinophil count - Th2 response
- Raised aspergillus IgG
Aspergillus can seed in old TB cavities Can become invasive aspergillus Pulmonary haemorrhage Form a gravity dependent aspergilloma pulmonary fibrosis - apical Can also cause bronchiectasis due to chronic poor drainage
(CAUSES Bronchiectasis = TONNES - CONGENITAL = CF / YOUNGS (middle Age + bronchiectasis, rhinosinusitis and reduced fertility. / A1 ANTI-TRYPSIN / Kartageners - Primary ciliary dyskinesia / TOXIN - Recurrent aspiration / COPD / Traction bronchiectasis (pulmonary fibrosis splints open airay) / IMMUNO - HIV +LEUKAEMIA +SCID /MECHANICAL - obstruction / carcinoma / granuloma - sarcoid wegners tb )
Treatment Fostair - formeterol / fluticasone OR Seretide - salmeterol / fluticasone Pred for wheeze if active ITRACONAZOLE pulmonary rehab
SLOW PROGRESSIVE IN MOST CASES
What is the greatest adjuvant to smoking cessation?
BUPRIOPION AND VARENICLINE
single agent = 20-30% cessation
double agent up to 44% cessation
Willpower alone = 2-4% cessation
nicotine replacement lozenges / gum = 10%
How might Pneumocystitis Jirovecci present on CXR
Bilateral crackles
pyrexia and T1RF
leukopenia
CXR:
interstitial shadowing
basal cystic changes
CYSTS AS ANY BULLAE TYPE DISEASE AN RUPTURE CAUSING PTX - 10%
How is PCP diagnosed?
AIDS defining illness
CD4<200
also:
SCID / any immunosuppressed
Diagnosis: History CXR - interstitial shadowing + cystic lower zone changes BAL - fungus immunofluorescence and BAL
How is PCP Treated?
long term prophylaxis:
Co-trimoxazole
HIV ART/HAART compliance and CD4>200
Acute:
Prednisolone
Co-trimoxazole
What joints are particularly at risk to AVN
Humeral head –> almost all humeral neck fractures
Femoral head –> intracapital fractures
Scaphoid
SLE presentation
Chronic and intractable hip pain
90% progress to bilateral <12 months
Antiphospholipid
Gauchers storage disease
MRI best modality
Mx:
non weight bearing to prevent the colpase of the the femoral head and secondary OA
Surgical deompression
Hemi Arthroplasty
How is osteoporosis managed
T Score
How does gonococcal arthritis present?
dermatitis / polyarthritis / tenosynovitis / urethritis
Pustulous eruptions
Scaly pustular plaques
nail pitting
single joint disease above others - hot swollen (septic joint)
Mx:
Ceftriaxone
Azithromycin
NSAIDs
What is first line for septic arthritis?
Benzylpenicillin and flucloxacillin
Drug induced lupus
commonest manifestation Cutaeneous rash which is photosensitive \+VE ANTI-HISTONE ABS \+VE ANA \+VE RF -VE ds DNA Normal C3 and C4
i.e appears like inactive lupus but cutaenous photsensitivity
causes:
HYDRALAZINE
SULFASALAZINE
CAPTOPRIL
RX:
low dose steroid
stop drug
What antibody is associated with CTD
Anti-RNP antibodies
How does Wegners Granulomatosis with Polyangitis present and what is the initial management
Granulomatous and necrotising systemic vasculitis of medium and small calibre vessles not associated with raised eosinophils.
Presentation: Necrosis of nasal septum and bridge = SADDLE BRIDGE Epistaxis Pulmonary Haemorrhage GN Cavitating chest lesions
C-ANCA positive PR-3
(CHURG STRAUSS + microscopic polyangitis =P-ANCA MPO)
Immediate Mx:
Pulsed IV methyl pred + cyclophosphamide / ritux
Biologics:
Rituxumab - non inferior to cyclophosphamide
Remission rate is only 75%
Chronic:
Oral pred + steroid sparing DMARD
Steroid bridges to get steroid sparing agent to a therapeutic level
e.g. MTX
Azathioprine or Mercaptopurine (need TPMT level - low TPMT = avoid)
Infliximab
Prophylactic co-trimoxazole
How Can UC and CD be differentiated based on ANCA?
80% UC is positive for atypicaly ANCA - ANCA-X Vs 20% of CD
What is ANCA
Antineutrophil cytoplasmic antibodies
Abs directed against neutrophils
C and P denote where Ab found
C = cytoplasm
P = perinuclear
MPO or PR3 are the targets
C-ANCA is always targeted at PR3
P-ANCA is always targeted at MPO
What do ECG leads correspond to?
1 LAT AVR V1 septal V4 ant
circumflex LAD RCA
High Lat LV ant/septal Ant LV
2 INF AVL: LAT V2 septal V5 Lat
RCA circumflex LAD circumflex
INF LV High Lat LV ant/septal Lat LV
3 INF AVF: INF V3 ant V6 Lat
RCA RCA RCA circumflex
INF LV INF LV Ant LV Lat LV
Signs of AS?
Carotid upstroke LVH and heave Reversed splitting on second heart sound - delayed A2 syncope = severe SOBOE poor pulse volume syncope on exertion SVT / Vt secondary to LVD
How can Aortic valve status be confirmed post ECHO in LVF
LVF may cause an underestimate of the valve pressure gradient and valve surface due to impaired contraction and impaired force of contraction(FALSE LOW)
For this reason it is better to go on : DOBUTAMINE STRESS ECHO
Severe AS = rise in trans-aortic pressure on dobutamine stimulation with same valve area i.e. a true estimate
If the pressure falls and valve area increases then estimate was likely a false low estimate
An increase in EJF of over 20% is associated with a much better prognosis post TAVI
What is morphoea?
What is it associated with?
Morphoea is a localised area of skin thickening which can be isolated or form part of the manifestation of limited or diffuse systemic sclersis or CREST
(calcinosis / raynauds (ANA / RO / LA) / GI / sclerodact / telangiectasia)
Typically linear thick plaques that become atrophic hypo or hyperpigmented over new damaged tissue tight and itchy skin on head - morphoea en coup de sabre white striae
Mx:
topical or oral steroid
phototherapy
MTX
What anti-bodies are associated with Dermatomyositis?
Anti-jo
onset 40-60 2:1 F associated cancer - lung breast uterine stomach rectum -precedes cancer 40% -concurrent 20% -30% post neoplasm
- Gottrons papules
- heliotropic rash
What antibody is likely positive in CREST with renal involvement?
Anti-RN pol III
increased risk of scleroderma renal crisis
REDUCED RISK PULM FIBROSIS
Anti-SCL70
increased risk of PULM FIBROSIS
Anti-topoisomerase -1
ILD + renal involvement
What is anti-topoisomerase-1 ab associated with?
systemic sclerosis
ILD and renal involvement
What is anti-centromere antibody associated with
limited cutaenous sclerosis
RF for P.HTN
NOTE ILD AND RENAL INVOVLEMENT VERY RARE IN LIMITED DISEASE
What reduces mortality in scleroderma renal crisis
Ramipirl
76% survival at 1 year Vs 15% without
What is of symptomatic benefit in treatment of raynauds
Amlodipine
How is lupus nephritis treated?
Prednisolone + cyclophosphamide or mycophenolate
Rtiux no use
MTX onset too slow
How is aknylosing spondylitis managed?
Regular analgesia and pain relief
physio and mobiisation
Atni-TNFa = ETANERCEPT / ADALIMUMAB / GOLIMUMAB
STEROID INJECTIONS for sacroilitis and enthetesis
Bisphosphonates for osteoporosis