Station 2/5 Flashcards
What HLA is associated with RA?
HLA DR1/DR4
Which joints are typically affected in RA?
Any small or large joint that has synovial fluid. This includes C1/C2, MCPs, PIPs (not typically DIPs), and larger joints such as wrist, elbow, shoulder, knee.
It is a symetrical, inflammatory deforming arthropathy with extra-articular manifestations.
What are the radiological features of RA?
Subluxation
Synovitis
Soft tissue swelling
Joint space erosion
Ulnar deviation
Peri-articular osteopenia
What are the extra-articular manifestations of RA?
Anaemia
Felty’s
Lung fibrosis, fibrosing alveolitis, pleural effusions, lung nodules
Ophthalmic - sicca (most common), iritis, chloroquine retinopathy
IHD (same risk as T2DM), Pericarditis, conduction defects
Skin - rheumatoid nodules (subcutaneous)
What treatments do you know of for RA?
- Bridging steroids for flares
Early DMARD’s - MTX +/- second agent, such as leflunomide, sulfasalazine
- Anti-TNF (Infliximab)
- Anti-CD20 (Rituximab)
- T-cell co-receptor blocker (Abatacept)
What are the complications of MTX?
- Marrow suppression
- Accidental overdose
- Hepatotoxicity
- GI side effects including ulcerative stomatitis
Contraindicated
1. Pregnancy
2. Breast-feeding
3. Active infection
4. Pleural effusion
5. Ascites
It is contraindicated in pregnancy and contraception is recommended for 6 months after discontinuation
How do you quantify a RA flare?
DAS28
1. Number of swollen/tender joints
2. Global pain score
3. ESR/CRP
What are the diagnostic criteria for RA?
ACR/EULAR
1. No. LARGE joints
2. No. SMALL joints
3. ESR/CRP
4. Anti-RF/CCP
5. >6/52
What are the characteristic hand signs of RA?
- Wrist subluxation
- Thickened synovium
- Ulnar deviation
- Boutoiniers (PIP flex.d)
- Swan neck (PIP ex.d)
- Z thumb (MP hyper-ext)
- Rheumatoid nodules (elbows)
- Arthroplasty scars
Talk me through examination of hands?
- Look for scars and deformimties
- Feel for warmth
- Assess muscle bulk
- Feel pulses
- Examine each joint in turn, counting tender/swollen joints
- Mobility: fist+release, prayer sign, upside down prayer sign
- Strength: OK, finger abduction, pincer grip
- Look at elbows
- Look at eyes (scleritis, episcleritis, scleromalacia)
What is the pattern of distribution of psoriatic arthritis, and how is it different from RA?
PsA usually affects smaller, distal joints and leads to dactylitis and juxta-articular new bone formation.
It also leads to enthesitis, nail changes, and skin psoriasis.
HLAB27 is associated with axial spondyloarthropathy
HLADR4 is associated with a RA type phenotype
How do you diagnose Psoriatic arthropathy?
CASPAR criteria can be used for early disease
- Psoriasis, or FHx
- Psoriatic nail changes
- Dactylitis
- Juxta-articular new bone formation
- Absent RF CCP
What is the pathophysiology of skin psoriasis?
- Non-contagious autoimmune condition that leads to excessive inflammation and damage to keratinocytes; thought to be mediated by T HELPER cells
- Dilated blood vessels = infiltration of immune cells and secretion of inflammatory cytokines eg TGFb IL12, IL17, IL23.
- Destruction of keratinocytes and hyperproliferation leading to thickened stratum corneum and keratinisation
- Skin bruises easily and reveals underlying dilated blood vessels
- Contrast with eczema which is an IgE mediated Type 1 hypersensitivity reaction
What are the radiographic features of Psoriatic arthritis?
- Juxta-articular new bone formation
- Arthritis mutilans (pencil in cup)
How do you treat PsA, and what are the key differences to treamtent of RA?
Early disease is managed with NSAIDs; DMARD’s commenced later.
DMARDs like MTX and leflunomide are effective for skin and joints. Hydroxychloroquine avoided due to skin flares. Steroids avoided due to flares of skin upon withdrawal
Local cortisone effective for enthesitis
Biologics for severe disease including
1. Anti-TNF (infliximab)
2. Anti-IL12/23 (ustekizumab)
3. PDE4 inhibitors (apremilast)
What nail changes do you see in PsA?
Transverse nail ridging
Pitting
Onycholysis
What is Koebner’s phenomenon?
Plaques over sites of trauma
What % of patients with Psoriasis develop PsA and vice verca?
10% of patients with psoriasis will develop arthritis
Some develop arthropathy before psoriatic skin changes
What important extra-articular manifestations of Psoriatic arthritis are you aware of?
With all spondyloarthropathies:
-aortitis
-aortic regurgitation
-iritis
-apical lung fibrosis
-colitis
-enthesitis (specific for spondyloarthropathies)
DDx from other spondyloarthropathies by more asymetry, and more peripheral joint involvement.
What patterns of joint involvement do you see in psoriasis?
- Asymetrical oligoarthritis (25%)
- Symmetrical polyarthritis rheumatoid pattern - HLADR4
- DIP arthritis (10%)
- Arthritis mutilans (aggressive and rare)
- Spondylitis +/- sacroilitis (HLAB27) in 40%!!!!!
What are the key differences between PsA and RA?
- Equal sex distribution (RA more common in women)
- Asymmetric
- Distal (with some exceptions)
- Enthesitis
- Spondylitis in 40%!
- Early bone deformity
- Majority RF / CCP negative
Steps of a knee exam
- Gait
- Erythema
- Patellar tap + sweep
- Feel joint lines
- Feel collaterals
- Feel for Baker’s cyst
- Active flexion
- Feel for crepitus
- Straight leg raise
- Knee hyperextension
- Sagging of knee when flexed 90 (PCL)
- Anterior drawer test (ACL)
- Test collaterals
- Alternative meniscal test (weight bear + twist)
- Patellar apprehension test
Steps of a hip exam
- Gait
- Test for pelvic tilt
- Palpate - GT, ASIS
- True vs. apparent leg length
- Assess for fixed flexion deformity
- Active abduction + adduction
- Passive abduction + adduction
- External hip rotation
- Internal hip rotation
- FABER
- FADIR
What do you know about mitral stenosis?
- AF
- PHTN
- Malar flush
- TAPPING apex beat (palpable first HS)
- Murmur = opening click in diastole: the earlier the click, the higher the pressure in the LA. This is followed by low pitched descrescendo-crescendo diastolic murmur heard best in expiration in left lateral with bell.
What are the causes of mitral stenosis?
- Rheumatic fever
- Congenital
- SLE
- Carcinoid syndrome
- Fabry’s disease
Which other condition can MS mimic?
LVSD. If the mitral valve area is <1, this can mimic LV failure when the LV is functionally normal
What are the complications of Mitral Stenosis?
LA dilation
Pul HTN + pulmonary oedema
Malar flush
What are the ECG / CXR findings in MS?
AF
LAH (bifid P in II)
LA dilation (biphasic or inverted P’s in V1-V2)
Double RHB
Splaying of carina
Orterners syndrome
Signs of severe pulmonary stenosis?
- Ejection click and systolic murmur heard loudest in pulmonary area
- Large v waves (TR)
- Widely split S2
- S4
Causes of PS?
Valvular
Congenital
Rheumatic
Noonan’s
Down’s Syndrome
Supravalvular
Williams
Rubella
Subvalvular
Fallot’s
What is wide splitting of S2?
During inspiration = more blood returns to chest = more volume in right heart = delayed emptying of RV = delayed Pulmonic valve closure.
When there is a problem with the right side of the heart this takes longer:
PS
RBBB
ASD
VSD
What is reverse splitting of S2 and what causes it?
LV stress = delayed LV emptying
S1 then P2 then A2. During inspiration, the split disappears as P2 and A2 come closer together.
Causes
LBBB
HOCM
Sev AS
WPW B (right accessory pathway)
What is the pathophysiology of HOCM?
Hypertrophic OBSTUCTIVE cardiomyopathy is evidence of an LVOT gradient
Clinical signs of HOCM?
- Prominent a due to septal bulging
- Double carotid impulse
- Reverse split S2
- MR (anterior motion of valve)
- Louder during Valsalva (reduced pre-load = reduced Starling = obstructed outflow)
Genetics of HOCM?
Autosomal Dominant
Several genes, all encoding sarcomeric proteins
Associated with Friedrich’s ataxia, Fabry’s, WPW
What are the ECG findings of HOCM?
- LVH criteria (S1+R6 >35mm)
- Deep antero-lateral TWI
- Deep infero-lateral Q waves
What must you avoid in HOCM?
Drugs that reduce pre-load as this accentuates the outflow gradient. EG nitrates, inotropes
Echo findings of HOCM?
MR - MR
SAM - systolic anterior motion of mitral valve
ASH - assymetric septal hypertrophy
Management of HOCM?
Amiodarone if AF
Beta-blockers
Cardioverter defibrillator
Dual chamber pacemaker
Endocarditis prophylaxis
What is the inheritence of Marfan Syndrome?
Autosomal Dominant mutation in fibrillin gene that codes for collagen
What do you know about the genetics of Ehler Danlos syndrome (EDS)?
AD, AR, denovo mutations in gene encoding for collagen III
Principally affects joints, blood vessels, heart, eyes
What are the complications of EDS?
- Joints = deformities, pain, impaired function
- Skin = easy bruising and fragility
- Heart = MVP, MR, AR, Aortic dissection, cardiac conduction abnormalities
- Vascular = haemorrhage
- GI = bleeding, diverticulae, diaphragmatic herniation, colonic rupture
- Eyes = glaucoma, retinal detachment
What do you know about Osteogenesis imperfecta?
AD mutation usually in COL1A1/2 that codes for collagen I
This leads to
B: weak bones and atraumatic fractures
I: Eyes - blue sclera (loss of collagen = choroidal veins visible)
T: Teeth - dentinogenesis imperfecta
E: Ear: otosclerosis (conductive hearing loss)
Cardiac: Valvular disease - MVP, bicuspid aortic valve, AR/aortic root dilation
Rx:
1. Vit D/calcium/bisphosphonates
2. OT/PT
3. Hearing aids
4. Valve replacement/repair if needed
DDX blue sclera
- EDS
- Marfan
- OI
- Pseudoxanthoma elasticum
- Diamond Blackfan (Pure red cell aplasia)
What do you know about Pseudoxanthoma elasticum?
AD/AR ABCC6
Abnormal MINERALISATION of ELASTIN
Mid-dermal deposition of calcium that triggers a metabolic response
Dermis: Pseudoxanthoma plaques and plucked chicken) in axilla/groin/neck
Eyes: Angoid streaks (85%)
Heart: AR, MR, MVP
Vessels: Early plaques, CAD, PVD, HTN, Renovascular disease
GI: haemorrhage due to friable vessels
What is Systemic sclerosis?
Damage of endothelial vessels and the presence of certain environmental triggers leads to abnormal repair and fibroblast recruitment with ensuing damage to tissue. Triggers include CMV, PB19, silica, malignancies, and even some drugs like bleomycin.
This leads to thickening and ischaemia of tissue.
What patterns of systemic sclerosis do you know of, and how do they differ?
Limited cutaneous scleroderma affects the fingers and arms predominantly. Raynaud’s is the PC in 70%. Patients also develop calcinosis of the digits, Raynaud’s, Esophogeal dysmotility, Sclerodactyly, and Telangiectasia. CREST syndrome is associated with later internal organ (particularly lung) involvement, and carries a better prognosis. ANA (anti-centromere)
Diffuse scleroderma is associated with early internal organ involvement, and the mortality comes from lung fibrosis. The skin of the arm, face, neck, trunk and legs are involved. ANA (anti-Scl70)
What are the consequences of Systemic Sclerosis?
- GI: Oesophogeal dysfunction, dysphagia, malaborption, SIBO, PBC
- Skin: Raynaud’s, gangrene
- MSK: arthritis, osteopenia (malabrption)
- Renal: HTN, scleroderma renal crisis
- Resp: ILD, pleural effusions
- CVD: Restrictive cardiomyopathy, pericarditis, PHTN, conduction defects
How do you treat systemic sclerosis?
MDT - resp, cardio, renal, GI
Patient education, counselling, psychology (lots of uncertainty)
Symptom Control
PPI, rifaximin (SIBO)
Vasodilators
Dihydropiridine CCB like nifedipine, amlodipine - For Raynaud’s
Sildenfanil for PHTN
IV prostanoids for severe Rayanud’s/PHTN
Targeted
Immunomodulatory - MMF, Rituximab, Tocilizumab (IL-6). Stem cell transplant in high risk patients (this comes with a 10% mortality so need risk vs. benefit discussion)
Anti-fibrotic - Nintedanib
AVOID high dose steroids as this can precipitate renal scleroderma crisis
What is the usefulness of nailfold capilloroscopy in Systemic sclerosis?
The nailfold is one of the few places you can visualise capilaries. There is significant capillary dropout due to microangiopathy, with regeneration of poorly constructed vessels in systemic sclerosis/Raynauds
What are the diagnostic criteria for lupus?
ANA >1:80 and signs/symptoms/labs suggestive of lupus:
Labs: Anti-dsDNA, Anti-smith, Anti-cardiopilin, lupus anti-coagulant, low C3/C4
- Constitutional
- Neurological
- Mucocutaneous
- Photosensitivity
- MSK
- Serosal
- Renal
- Haematological
What are the classic skin features of lupus?
Discoid lupus (sun-exposed)
Malar rash on face sparing naso-labial folds
Painless mucosal ulcers
Tender small joints
What labs are needed to diagnose SLE?
ANA
Anti-dsDNA
Anti-Smith
AntiU1 RNP
Anti-Ro (strongly implicated in lupus of pregnancy)
Anti-La
Low complement
What pregnancy complications of lupus do you know?
Auto-antibodies can cross the placenta and lead to congenital heart block (Anti-Ro)
What are the renal manifestations of lupus?
6 different types of lupus nephritis, most common and most severe is diffuse proliferative lupus nephritis
How do you treat lupus?
Mainstay is hydroxychloroquine
+/- other DMARDs like AZA, MMF, calcineurin inhibtors (ciclosporin/tac)
Steroids for flares
ACEi if proteinuria
What are the systemic features of lupus?
Anaemia
Arthritis
Raynauds
Dermatomyositis
Discoid rash
Malar rash
Mouth ulcers
ILD, pleural effusions, pleurisy
pericarditis, Libman-Sacks endocarditis, PHTN
CNS involvement
Renal HTN, nephritis
Haematological - lymphadenopathy, splenomegaly
Eyes - Sjogren syndrome
What drug causes of lupus do you know?
Positive anti-histone antibodies, negative anti-dsDNA. Resolution of effects upon cessation. F:M 1:1 (cc SLE F:M 9:1)
OCP
Hydralazaine
Procainamide (most common)
Carbamazapine
Phenytoin
Chlorpromazine
Tetracyclines
What are the cardinal features of ankylosing spondylitis?
- Stiffening of vertebral bodies with ensuing inflammation. Also involves eyes and blood vesels.
Can involve C1/C2 leading to atlando-axial subluxation - Seronegative arthropathy
- Strongly associated with HLA-B27 MHC class I
- Primarily affects the intervertebral and facet joints of the spine, and the sacro-iliac joint.
- Inflammation draws in fibroblasts that deposit fibrin which limits movement. Eventually osteoblasts lay down new bone which leads to immobility.
What are the non-spine features of ank spond?
- Anterior uveitis
- Aortic regurgitation
- AV conduction defects
- Enthesitis
- Apical fibrosis
- Ank spond is a rare cause of amyloidosis
Treatment of Ank Spond
- NSAIDs
- Excercise
- DMARD’s in severe cases
- Biologics such as anti-TNF (adalimumab, etanercept) and anti-IL17
- Rarely, surgery (spinal surgery is usually avoided)
What is osteomalacia?
Faulty bone mineralisation caused by low Vit D, low Calciun, low phosphate.
In children this leads to rickets, in adults it leads to softening of the bones due to poor mineralisation
How do PTH and Vit D regulate calcium?
Vit D is activated in the liver (25OH) then kidneys (1OH)
1,25VitD is responsible for re-absorption of calcium in the kidneys, and increased calcium/phosphate reabsorption in the gut.
PTH stimulates bone resorption to release calcium into the blood. It also stimulates phosphate renal excretion and calcium gut absoroption.
What are the signs of ostemalacia?
Bone fragility
Prox muscle werakness
Muscle spasms (low ca)
X ray - looser zones
Labs
Low Vit D, Low calcium, raised ALP (trying to stimulate bone actiivty). Low calcium stimulates PTH which stimulates phosphate excretion.
Low Vit D, Low Ca, Low Pho
Raised ALP and raised PTH
What is the pathophysiology of Paget’s disease?
- Excessive bone remodelling This leads to skeletal deformities nad fractures. Can involve one bone, or the entire skeleton
Might have an infective/genetic component, and most frequently seen in men of northern latitudes
Three phases
1) Lytic phase
2) Blast phase
3) Sclerotic phase - disorganised and fragile bone
Leads to
-Kyphosis
-Pelvic assymetry
-Bow legs
-Arthritis
-Optic, Vestibulocochlear nerve entrapment
-High output cardiac failure
Diagnosis
1. Skeletal signs
2. Raised ALP, rest bloods normal
3. Bone biopsy
Rx:
1. Symptom control
2. Bisphosphonates
3. Surgery
What is osteoporosis and how is it different from osteomalacia?
Balance tips towards bone breakdown
Leads to reduced number of osteoid units, however the cells are functionally normal and there is preserved mineralisation (in contrast to osteomalacia where there is reduced mineralisation)
What are risk factors for osteoporosis?
Post-meonopauseal
Low calcium
Alcohol
Smoking
Steroids
Thyroxine
Senile osteoporosis
Reduced gravity/weight bearing excercises
What is the FRAX score?
10-year fracture risk score. If FRAX comes out intermediate, a DEXA is recommended.
Components of FRAX score include Age, sex, ethnicity, prev fracture history, RA, DM, alcohol, secondary osteoporosis, and family history.
What is the T / Z score?
Compares the density of the long bones to matched controls.
What is osteopetrosis?
Inherited dysfunction of osteoclasts that leads to reduced burn turnover and disproportionate osteoblast activity. Can be AR or AD.
-Fractures due to poorly flexible bones
-Extramedullary haematopoeisis
-Nerve compression
How is Ank Spond disease activity assessed?
Bath index of disease severity
10 point score
>4 = active disease
How do you assess disease severeity of acute flares in UC?
Truelowe and Witts
Mild: <4 stools a day
Mod: 4-6 stools a day, no sys upset, CRP <30
Sev: >6 and any signs of systemic upset
What are the indications for surgery in a flare of IBD?
- Refractory to medical therapy
- Any evidence of dilatation on imaging
- Any evidence of fistulating disease
What are the endoscopic differences between Crohns and Ulcerative colitis?
UC is superficial
Crohns is full thickness (trans-mural)
UC affects the large bowel exclusively (with backwash ileitis)
Crohns can affect the entire GI tract
Crohns will have skip lesions (normal tissue)
UC does not have skip lesions
Crohns can affect the terminal ileum exclusively
UC always starts in the rectum and progresses proximally
Crohns - aphthous ulcers, cobblestone appearance
UC - crypt abscesses
Are there concerns for malignancy in IBD?
Yes, if there is colitis there is concern for CRC, particularly in UC
After 10 years - index surveillance colonoscopy to detect early pre-malignant changes; further colonoscopy depending on risk level at that stage.
What is the pathophysiology of psoriasis?
Abnormal immunological response in the epidermal layers that leads to excessive inflammation and damage to the skin. This is mediated by dendritic cells acting as antigen presentation cells and T cells that release inflammatory cytokines including TNF, IL17, IL23
How do you assess disease severity in psoriasis?
Psoriasis area and severity index (PASI), and body surface area involved
What environmental triggers for psoriasis do you know?
Trauma
Sunburn
Stress
Smoking
Alcohol
Beta haemolytic strep
Drugs (Lithium, ACEi’s, beta-blockers, NSAID’s, terbinafine, anti-malarials)
What are the primary treatments for psoriasis?
Moistuirsers and emollients
Potent top steroid + top Vit D (calciptriol) - 4 week courses
If no improvement, can use top Vit D BD
Coal tar (inhibits DNA synthesis)
Dithranol (inhibits DNA synthesis)
Phototherapy (UVB, or UVA + psoralen)
Systemic treatments including MRX, ciclosporin, biologics (ustekinumab, adalimumab, infiliximab)
What variants of psoriasis do you know?
Plaque
Pustular
Guttate
Palmoplantar
Erythrodermic
Inverse psoriasis (flexor surfaces)
What is Auspitz sign?
Stripping of skin in psoriasis reveals underlying hypertrophied dermal capillaries
What is Koebner phenomenon?
Plaque forms over sites of trauma
What genes are implicated in NF?
NF1 on chromosome 17
NF2 on chromosome 22
Both these genes are TSG’s. Their absence leads to the fibrous tumours arising from the nerves - fibromas
What are the cutaneous manifestations of NF1?
Neurofibromas - cutaneous bumps under skin
CAL’s (>6)
Axillary/groin freckling
Lisch iris nodules
What are the manifestations of NF2?
Schwannomas (acoustic neuromas)
Meningiomas
Cataracts
Retinal hamartomas
Less frequent skin manifestations
Other than skin and nerve involvement, what other organs can be affected in NF?
Lungs - apical fibrosis
Heart - restrictive cardiomyopathy
Spine - scloliosis
Adrenal - phaeo
Kidneys - Renal artery stenosis
What are the responsible genes in Tuberous Sclerosis?
TSC1 and TSC2. Both are inherited in an autosomal dominant manner, and their absence leads to uncontrolled mTOR activity. This leads to benign tumours throughout the body (made up of various cell types) and an increased lifetime risk of cancer
Which organs are most often affected in Tuberous Sclerosis?
Brain - gliomas, epindymomas, astrocytomas
Skin - angiofibromas (face), subungal fibromas, ash leaf spots, Shagreen patches
Kidneys - angiomyolipolas (can bleed)
Lungs - lymphangioleiomyomatosis (cysts)
Eyes - reintal hamartomas.
What investigations need to be sent from an LP for suspected meningitis?
- Cell count and differential
- Protein, glucose, lactate
- Gram stain and culture
- Viral studies
Bacterial meningitis
Raised WCC, pred Neutrophils
High protein
Low glucose
Positive gram strain
Viral meningitis
Raised WCC, pred lymphocytes
Normal/High protein
Normal glucose
Viral PCR+
Comps of bacterial meningitis
- Severe morbidity
- Deafness
- Blindness
- Cognitive impairment
- Vascular - amputations due to sepsis
What are the manifestations of hereditary haemorrhagic telangiectasia?
Skin - telangiectasia
Mucus membranes - epistaxis
GI - bleeding
Lungs - AV malformations
CNS - SAH, migraines, spinal AV = paraparesis
Liver - can lead to liver failure due to AV malformations
What is your differential for telangiectasia?
Systemic Sclerosis
SLE
HHT
Mitral stenosis
Polycythaemia
Carcinoid syndrome
What organs can be affected in acromegaly?
Soft tissue - hands, feet, face
Face: macroglossia, prominent supraorbital ridge, prominent jaw
Cardiac - cardiomyopathy, IHD, HTN
Endocrine - T2DM
Visual impairment - bitemporal hemianopia
Rx for Acro?
Surgery
RT
Octreotide (somatostatin analogues)
Pegvisimont (GH receptor antagonist)
OSA symptom scoring criteria
STOP-BANG questioniarre
Epworth (>11)
OSA Diagnostic test?
Overnight polysomnography for apnoea hypopnea index
What is the reason OSA leads to daytime somnolensce?
Overnight arousal and frequent waking leads to poor quality of sleep and fatigue
What is the pathophysiology of dermatomyositis?
- Typically involves skin and muscle tissue
- Abnormal immune response and activation of the complement system that leads to recruitment of the membrane attack complex (MAC).
- Due to molecular mimicry, the MAC recognises self-antigens as foreign and leads to cell lysis
- Soluble antigens released from cell lysis that are in the blood deposit in carious blood vessels and this eventually leads to tissue hypoxia due to activation of the MAC complex
What are triggers for dermatomyositis?
Genetic: HLADR3/DR5
Environment: Cocksackie virus, cancers
Which cancers are associated with dermatomyositis?
An underlying malignancy is found in 20-25% of cases of dermatomyositis.
These are typically ovarian, lung, breast
What are the clinical manifestations of dermatomyositis?
Skin:
Gottrens papules
Heliotrope rash
Malar rash
Shawl sign
Hypertrophy of cuticles
Non-scarring alopecia.
Palmar hyperkeratosis (mechanics hands).
Photosensitive skin changes.
Muscles:
Prox weakness
Atrophy
Dysphagia
Resp muscle weakness
Lungs:
Fibrosing alveolitis
Organising pneumonia
What investigations would you perform for suspected dermatomyositis?
- FBC UE
- CK
- ANA, Anti Jo1, Anti SRP, Anti M2
- Muscle bx
- Directed screening for underlying malignancy
DDx for Raynaud’s
- RA
- SS
- Lupus
- Dermatomyositis
- Polymyositis
- Myeloproliferative disorders
- Hep B/C
- Thoracic outlet syndrome
- Atherosclerosis
- Carpel tunnel
- Hypothyroidism
- Drugs (beta blockers, cyclosporin)
What are the differences between Raynaud’s disease (primary) and Raynaud’s phenomenon (secondary)?
Primary - <40y
No associated systemic features
NO nailfold capillaries
Never necrotic
Normal ESR
Normal ANA
What drugs can cause Raynaud’s?
Betablockers
OCP
Ciclosporin
Chemo
Treatment for Raynaud’s
CCB’s
Prostacyclins
Nitrates
Categorise lymphomas
A silly system, but commonly classified as Hodgkin’s (Reed Sternberg B-cells) and non-Hodgkins.
Non-Hodgkins includes:
High-grade
Lymphoblastic (behaves like ALL)
B-cell (Burkitt’s, DLBCL, Mantle cell, Follicular)
How do you stage Hodgkin’s lymphoma?
Ann-Arbour staging
1. Single node
2. More than one node, same side of diaphragm
3. Above and below diaphragm
4. Extra-nodal
B symptoms at ant stage
What is the treatment for Hodgkin’s lypmphoma?
ABVD
Adriamycin
Bleomycin
Vincristine
Doxarubicin
What is the main treatment for hight grade NHL?
R-CHOP
Ritux
Cyclophosphamide
Hydroxydaunorubicin
Oncovincristine
Pred
and then maintenance Rituximab
What are the three cardinal features of anti-phospholipid syndrome?
- Thrombocytopenia (antibodies against platelets)
- Recurrent miscarriages
- Arterial (stroke) and/or venous clots (DVTs)
- Livedoreticularis
Can APS co-exist with other conditions?
APS can either be primary, or associated with other conditions such as SLE, other autoimmune and lymphoproliferative disorders
What specific tests will you perform in suspected APS?
Autoimmune screen
anti-cardiolipin
Anti-beta2glycoprotein 1
anti-phospholipid
Lupus anticoagulant
How do you treat APS?
Primary thromboprophylaxis - low dose aspirin
Secondary thromboprophylaxis - warfarin (INR 2-3, increased to 3-4 if clot on warfarin)
What causes for strokes in young patients do you know off?
- Extra-cranial - neck hyperextension
- Vasculitis
- Cardiac - embolic (mxyoma, endocarditis, valvular pathology, AF)
- Substance misuse - cocaine, methamphetamine
- APS
- Familial hyperlipidaemia
- Sickle cell disease
- Rare metabolic/mitochondrial causes such as MELAS
Causes for erythema nodosum?
STREP THROAT!
TB
Sarcoid (Lofgren’s)
Myeloproliferative disorders
IBD
Behcet’s
Drugs (OCP, penicillin, sulphonylureas)
Describe erythema multiforme
Immune mediated mucocutaneous condition characterised by target lesions +/- mucosal involvement.
Start as distal papules that spread proximally, later forming target lesions (concentric rings of colour variations)
What causes erythema multiforme?
HSV
CMV, EBV, influenza, COVID-19
Medications - OCP, penicllin, carbamazapine
Vaccinations
SLE
Sarcoidosis
Malignancy
Mycoplasma pneumonia - now considered a distinct entity
Name some systemic causes for livedo reticularis
APS
PRV
SLE
PAN
GPA/EGPA
Walendenstrom’s
Cholesterol embolism
What conditions are commonly associated with vitiligo?
Apolecia areata
Hashimotos
Graves
Addisons
Hypoparathyroidism
DM
IPF
PBC
Pernicious anaemia
Atrophic gastritis
What do you know about bullous pemphigoid?
Bullous = Basement
Autoimmune type 2 hypersensitivity reaction against hemidesmosomes that anchor basal cells to basal membrane
IgG targets BPAG1+2. This leads to mast cell degranulation and inflammation
Genetic component and environmental triggers (furosemide, penicillamine, NSAIDs, abx)
Nikolsky sign negative (no intraepidermal splitting)
Rx topical and sytemic steroids
What do you know about Pemphigous Vulgaris?
Autoimmune type 2 hypersensitivity reaction against intra-epidermal desmosomes that hold keratinocytes together in the stratum spinosum layer
Can either affect mucosal cells only (Desmoglein 3) or skin+mucosal cells (Desmoglein 1+3)
Histologically there is tombstoning (intra-epidermal disruption of keratinocytes)
Nikolsy sign positive (lateral pressure causes a split between upper and lower layers of epidermis)
Rx: topical and oral steroids, rituximab, oral rinses with lidocaine
What do you know about Peutz Jegher’s syndrome?
Autosomal dominant mutation in the TSG STK11 that is expressed throughout the GI tract and also various other tissue including skin, breast, lung, ovaries, testicles
Leads to the development of hamartomas in the GI tract that can become malignant. These can lead to bleeding and obstruction.
Skin manifestations include flat mucocutaneous melanocytic macules on the mucosal surfaces and also palms and soles
Risk of GI, breast, lung, ovarian, testicular cancer
What is necrobiosis lipoidica?
Typically affects young female diabetic patients
It is also associated with hypertension, thyroid disease and obesity
It is a disorder of BLOOD VESSELS
Starts as a red papule, becomes a plaque, and then slowly enlarges to a yellow patch with a red rim
Can ulcerate and turn into a squamous cell cancer
What is pyoderma granulosum?
Extremely painful
Rapidly enlarging tender full-thickness ulcer with blue borders
Non-infectious neutrophilic dermatosis
More common in over 50’s
Frequently associated with autoimmune conditions such as IBD, RA, GPA
Rx: Urgent immunosupression
What do you know about colorectal cancer genetics?
- Lynch Syndrome (AD, MSH2, MLH1, MSH6, PMS2)
- FAP - Chr5, autosomal dominant - large bowel polyposis syndrome
- Gardener’s - variant of FAP (5q21) - CRC, skull osteomas, epidermoid cysts, thyroid cancer
Talk me through the Wells DVT score
Paralysis
Cancer
Immobilised
Prev DVT
Is an alternative diagnosis as likely?
Calf swelling, leg swelling, collaterals, tenderness along deep venous system, pitting oedema
1 = D-Dimer
>=2 Doppler
Talk me through the Wells PE score
DVT
Cancer
Immobilised
Prev DVT
Is PE as equally likely as other diagnosis
HR
Haemoptysis
1 = D-Dimer
>2 = CTPA/VQ
What are the components of a thrombophilia screen?
- Factor V Leiden
- Prothrombin mutation
- Protein C
- Protein S
- Anti-thrombin III (rare but aggressive)
Drug history (OCP)
Are there any scoring criteria you can use to risk stratify patients for inpatient/outpatient Rx for PE?
PESI Score predicts 30-day mortality and takes into consideration history, and clinical findings
What are contraindications for thrombolysis of PE?
Intracranial disease/bleed
Ischaemic stroke (<3mo)
Brain/spine surgery (<3mo)
Internal bleeding
Coag disorder
Recent head trauma
VQ vs. CTPA risks to pregnant pt?
Both have radiation - CTPA radiation comes from the X-rays, VQ radiation comes from the dye.
CTPA = higher dose of X-ray radiation to breast tissue
VQ = higher dose of dye-ionising radiation to fetus, but still very small amounts
Do you know the inheritence of Retinitis Pigmentosa?
AD, AR, X-linked recessive, and 30% are de novo.
Do you know of any syndromes involving retinitis pigmentosa?
Kearn Sayre: Mitochondrial. Ophthalmoplegia+cerebellar ataxia.
Usher: AR. Sensosineuronal deafness.
Refsum: Ataxia+muscle wasting.
Alport: X linked recessive. Type IV collagen. Haematuria+GS+SN deafness.
What are the clinical features of diabetic retinopathy?
Non-Proliferative
Microaneurysms
Blot haemorrhages
Hard exudates
Soft exudates
Venous beading
Mild - microaneurysm
Mod - microaneurysm and other signs
Sev - involves all 4 quadrants
Proliferative - neovasc
What is the treatment of proliferative diabetic retinopathy?
If disease involves fovea = anti-VEGF (benralizumab)
If disease does not involve fovea = laser photocoagulation
What are the clinical features of hypertensive retinopathy?
1: Silver wiring
2: AV nipping
3: flame/blot haemorrhages and hard exudates
4. Papilloedema
What is the pathophysiology of retinal vein occlusion?
Arterial compression - usually retinal vein BRANCHES
Thrombus - usually the central retinal vein
What are the clinical signs and symptoms of a retinal vein occlusion?
- Acuity
- RAPD
- SWOLLEN disc (ddx optic)
- Retinal haemorrhages (stormy sunset)
- Might develop neovasc an acute angle closure glaucoma
What are the causes of a retinal arterial occlusion?
The retinal artery is a terminal branch of the ophthalmic artery. Its occlusion can produce retinal infarction.
Can be:
1. Embolic
2. Rapid raised IOP
3. GCA
4. Profound hypotension
5. Vasospasm
6. Hypercoagulable states
What are the signs and symptoms of retinal artery occlusion?
- Sudden painless visual loss
- Pale retina
- Cherry red spot on fovea (choroidal arteries unaffected)
- RAPD
What is the treatment for central retinal artery occlusion?
- Occular massage
- IV acetazolamide/anterior segment paracentesis (reduce IOP)
- Treat underlying factor
What are the risk factors for macular degeneration?
Age
FHx
Smoking
Poor nutrition
Myopia
What are the clinical signs of macular degnereation?
Dry: Drusen + atrophy
Wet: Neovascularisation in choroid
What are the symptoms of macular degeneration?
Central visual loss
Distortion
What is the treatment for macular degeneration?
Anti-VEGF (ranibizumab)
What are the clinical findings of anterior uveitis?
- Red
- Painful
- Asymetric pupil
What conditions is uveitis associated with?
- Ank Spond
- Behcet’s
- MS
- Infections: HSV, TB, HIV
What are the risk factors for acute angle closure glaucoma?
Asian, short axial eyeball, Age, pupillary dilation
What are the symptoms of acute angle closure glaucoma?
Extreme pain
Blurred vision
Haloes
Red eye
Mid-dilated or fixed dilated pupil
Corneal oedema
Raised IOP
What is the treatment for acute angle closure glaucoma?
Topical betablockers/pilocarpine
IV acetazolamide
Peripheral laser iridotomy (hole in iris)
What is keratitis?
Inflammation of the cornea
Site threatening emergency
Caused by infection (bacterial, fungal, viral) or inflammation (blepharitis induced irritation)
Ix - slit lamp and fluorescein = corneal ulcer
Scleritis vs. episcleritis?
- Both associated with inflammatory conditions such as IBD and RA
- Scleritis is painful, episcleritis is not
- Both look pretty similar
- Scleritis is associated with photophobia and gradual decrease in visual acuity
- In episcleritis, injected vessels are mobile with gentle pressure and will blanch with phenylephrine drops
- Scleritis needs oral NSAID’s /steroids, most cases of episcleritis can be managed conservatively
What do you know about deQuevarian’s thyroiditis?
Typically post a viral illness
Phase 1: Lymphocytic infiltration: Hyperthyroidism, raised ESR
Phase 2: euthyroid
Phase 3: Hypothyroidism for weeks-months
Phase 4: Back to normal
Ix: Thyroid scintigraphy: globally reduced uptake of I131
Rx:
Self-limiting
Pain control - NSAIDs
Steroids if hypothyroid
What classes of diabetic drugs do you know for patients with T2DM?
- Biguanide: increase liver and muscle insulin sensitivity (metformin)
- SGL-2 inhibitor: Inhibits re-absorption (dapaglifozin).
- DPP4 inhibitors: reduce breakdown of incretins (sitagliptin, linagliptin). Caution if hx pancreatitis/pancreatic cancer. Can use linagliptin in renal impairment
- Sulphonylureas: Increase insulin secretion (glizlazide) - risk of hypo’s
- Pioglitazone: PPAR-gamma activator = more glucose transports - risk of fluid retention, osteoporotic fractures, and bladder cancer
What are the complications of spina bifida?
- Urinary stasis + recurrent infections
- Lower limb spasticity
- Hydrocephalus
- Arnold-Chiari malformations
- Recurrent meningitis
- Syrinx
Which malignancies are associated with acanthosis nigricans?
Gastric (most strongly)
What conditions are associated with acanthosis nigricans?
- T2DM
- Obesity
- PCOS
- Acromegaly
- Cushing’s
What are the features of Williams syndrome?
- Spotaneous microdeletion
- Mild intellectual impairment
- Characteristic facies with broad forehead
- Supravalvular aortic stenosis
Steroids in ascending order of potency
- Hydrocortisone (Mild)
- Betamethasone 0.025%
- Fluticasone/Betamethasone 0.1%
- Clobetasol
What is the pathophysiology of eczema?
Allergen enters the dermis and triggers a Type I hypersensitivity reaction. On repeat exposure there is IgE mediated mast cell degranulation.
Self-perpetuating cycle of skin breakdown, skin dryness, and itching.
What are the treatments for eczema?
- Identify triggers
- Moisturise skin
- Steroids
- Topical tacrolimus
- Immunosuppresion
- UV radiation
Causes of galacotthoea?
Physiological (pregnancy)
Prolactinoma
Exercise, stress
Acromegaly (1/3 of patients)
PCOS
Hypothyroidism (Raised TRH stimulates prolactin release)
Drugs (metoclopromide, domperidone, haloperidol, rarely SSRI’s)
Sickle cell
AR
HBB gene (beta globin)
Remember HbA is composed of a2b2
Low haptoglobin (intravasc haemolysis)
Scleral icterus, jaundice, bilirubin gallstones
Bone marrow hyperplasia - enlarged skull
Hepatomegaly (extramedullary haematopoiesis)
Autosplenectomy (R/O Strep, haemophilius, Neisseria, Salmonela)
Chest syndrome
Renal necrosis
Priapism
Rx: Prophylaxis, treat infections early, pain relief, hydroxyurea (increases gamma globin = ^ HbF)
