Multisystem disease

Question 1

Autoantibodies

1. SLE (Smooth double)
2. Limited Systemic sclerosis
3. Polymyositis (Joe Hart has shit muscles and shit lung - ILD)
4. Dermatomyositis (MIkel has shit skin+muscles)
5. Sjogrens syndrome (ROLO)
6. Diffuse Systemic Sclerosis (Kidney)
7. Diffuse Systemic Sclerosis (Lung)
8. Mixed Connective Tissue Disease (erosive arthritis and pulmonary artery hypertension)

Answer 1

1. ANA, Anti-Ds DNA, Anti-SM
2. Anti-centromere
3. Jo-1
4. Anti-Mi
5. Anti-Ro, Anti-La
6. Anti-RNA polymerase III
7. Anti-topoisomerase

K before L = R before T

8. RNP

Question 2

Sjorgens syndrome - F>M 9:1
Cause
Sx
Dx
Mx
Complications

Answer 2

Lymphocytic infiltration of exocrine glands either primary or due to SLE, RA, CTD

Dry eyes, dry mouth, parotid gland enlargement

Sx + ANA/RF/Anti-Ro-LA (ROLO) + Schirmers test (tear production) + high ESR but normal CRP

Eye drops etc

Risk of lymphoma

Question 3

Difference between type 2 and type 3 hypersensitivity reaction

Answer 3

Type 2 antibodies attack on fixed antigen
Type 3 antigen & antibodies that circulate all over the body

Type 2 is kind of like a sniper in action. You’ve got a set target and you’re sending a hitman (Ig) to do the damage…targeted damage, to targeted tissues! For example in goodpasture we just have kidney and lung involvement, nothing else.

Type 3 on the other hand is carpet bombing. You have immune complexes flying all over the place, activating complement and causing inflammation, and coagulation cascade activation and what not. The inflammation can happen pretty much anywhere where immune complexes go

Question 4

IBD
Sx
Examination
Ix

Answer 4

Bowel: Diarrhoea w/ blood/mucus, pain, urgency, tenesmus

Systemic: Fever, weight loss, joint pain, episcleritis, uveitis, angular stomatitis (Fe deficiency), swollen cheeks + lower lip + mouth ulcers = orofacial granulomatosis (also sarcoidosis)

O/E: Clubbing, apthous ulcers, erythema nodosum, pyoderma gangrenosum, conjunctivitis, seronegative arthropathy (ank spond, large joints)

Bloods: anaemia (low ferritin), high platelets, low albumin etc

Stool: Faecal calprotectin

Imaging: AXR to exclude toxic megacolon

Generally colonscopy is good for UC

Need upper and lower endocscopy with barium/capsule/MRI for small bowel

ASCA = Crohns
pANCA = UC

Question 5

Patients presents with swollen bottom lip, what do?

Answer 5

Biopsy:
Granuloma + multinucleated cells, lymphocytic infiltration = Crohns

Crypt abscesses + goblet cell deletion = UC

Question 6

Leg Sx in IBD

Answer 6

UC = Pyoderma gangremosum

Crohns = Erythema nodosum

Question 7

Sarcoidosis - Female 20s-40s
Pathology
Sx
Dx
Mx

Acute form

Answer 7

Non-caseating granulomas

Lung: Bilateral hilar lymphadenopathy + infiltrates > cor pulmonale + fibrosis

MSK: Lower limb arthritis, dactylitis

Other: Uveitis, heart block (annual ECG+/- echo)n fever, night sweats, weight loss

1. CXR + PFTs (Reduced DLCO) + ACE, hypercalcaemia (vit d from granuloma)
2. HRCT
3. Biopsy = Non-caseating granuloma with epithelioid + multinucleated giant cells

-caseating granuloma = TB

Acute:
Lofgrens Syndrome: Triad of Erythema nodosum + arthritis (bilateral ankle) + bilateral hilar adenopathy

Question 8

Reactive arthritis/Reiters syndrome
Arthritis following an infection, typically male returning from Thailand with STI, conjuctivitis and arthritis
Sx within and outside MSK

Answer 8

Usually starts with lower limb joints (toes, ankles, knees) but can affect anywhere

Also affects tendons and can cause dactylitis

Non MSK:
Conjuctivitis
Scaly rash over hands and feet = keratoderma blenorrhagica
Diarrhoea
Mouth ulcers
Urethritis discharge
Penis rash
Weight loss + fever

Question 9

Extra-cutaneous features of psoriasis

Answer 9

Arthritis
Nail pitting
Onycholysis (separation of nail from nailbed)
Uveitis
Butterfly rash

Question 10

Endocrine dermatology

1. Striae, skin atrophy, acne
2. Hyperpigmentation in palmar creases and buccal
3. Periorbital oedema, dry skin, loss outer eyebrows
4. Pretibial myxoderma, acropachy (clubbing), exophthalmos

Answer 10

1. Cushings
2. Addisons
3. Hypothyroid
4. Hyperthyroid

Question 11

Metabolic dermatology

1. Sun blisters, facial hirsutism
2. Tendon xanthomas
3. Eruptive xanthomas
4. Acanthosis nigricans (armpit velvet), NECROBIOSIS LIPOIDICA (shin), candida
5. Tophi/periarticular urate

Answer 11

1. Porphyria
2. Familial hypercholesterolemia
3. High TGs so Familial Hypertriglyceridemia and to a lesser extent Remnant hyperlipidaemia
4. Diabetes
5. Gout

Question 12

Haematological dermatology

1. Neutrophilic dermatosis
2. Pyoderma gangresnosum
3. Mycosis Fungoides

Answer 12

1. High neutrophils in the lesion, often associated with haem malignancy but also Sweet’s syndrome
2. IBD (more UC), haem, RA, wegeners
3. Cutaneous T cell lymphoma

Question 13

Infective dermatology

1. Red macular morbilliform rash, kopliks spots, profrome featuring 3C’s (coryza, cough, conjunctivitis)
2. Vesicular viral rash
3. 1’ chancre 2’ palms/soles 3’ gumma (nose ulcer)
4. Erythema chronicum migrans ‘target lesion’
5. Purpuric/vasculitis rash

Answer 13

1. Measles virus
2. chicken pox / shingles
3. Syphillis
4. Lyme disease
5. Meninigits

Question 14

Inflammatory dermatology

1. Erythema nodosum
2. Urethritis, uveitis, arthritis + psoriasiform rash (circinate balanitis + keratoderma blenorrhagica)
3. Oral & genital ulcers, uveitis (triad), also lesions at injury site
4. Lupus pernio (nose nodule)
5. Photosensitive discoid plaques, butterfly rash, livedo reticularis
6. Photosensitivity, vascular changes - nailfold changes and livedo and vasculitis
7. CREST (Calcification, Raynauds, Esophageal dsymotility, Sclerodactyly, Telangiectasia)
8. Dermatitis herpatiformis

Answer 14

1. Sarcoidosis, crohns (IBD), TB, behcets, idiopathic and strep are most common
2. Reactive arthritis
3. Behcets
4. Sarcoidosis
5. SLE
6. CTD
7. Limited systemic sclerosis (diffuse is more widespread with nailfold changes)
8. Coeliac - very itchy!

Question 15

Paraneoplastic dermatology

1. Acanthosis nigricans
2. Dermatomyositis

Answer 15

1. Black velvet
2. Proximal weakness, heliotrope rash (red panda eyes), Gottrens sign (scales along fingers), muscle biopsy + Anti-Jo + Anti-Mi

Question 16

Nutritional dermatology

1. Scurvy
2. Pellagra

Answer 16

1. Vitamin c deficiency: Corkscrew hairs, perifollicular haemorrhages, bleeding gums!
2. Vitamin B3 Niacin deficiency: Dermatitis (photosensitive), diarrhoea, dementia

Question 17

Genetic dermatology

1. Pseudoxanthoma elasticum
2. Neurofibromatosis type 1

Answer 17

1. Arterial aneurysms, angioid streaks, elastomas (plucked chicken
2. Multiple café au lait spots, neurofibromas, axillary freckling (pathognomic), Lisch nodules (iris)

Question 18

What does Vasculitis feature that is not present in thrombosis? Thus differentiating the vasculitic rash

Pathophysiology of vasculitis

Answer 18

PALPABLE and RAISED purpura.
Blisters
Purple/blue edge to ulcers.
Livedo reticularis

Type 3 hypersensitivity reaction causing immune complexes to deposit in endothelium of vessels > immune response attacks self

Question 19

Giant cell arteritis (LARGE VESSEL)
Pathology
Sx
Dx

Answer 19

Commonest LARGE vessel vasculitis
F>M >55yrs

Jaw claudication, temporal headache, scalp tenderness, PMR symptoms, visual loss, pale retina/optic disc on fundoscopy

High ESR
USS temporal artery - ‘halo’ sign
Biopsy is GOLD STANDARD
Consider CT-PET scan if no sure where is affected

Question 20

Takayasu arteritis (LARGE VESSEL)
Pathology
Sx
Dx

Answer 20

F>M <40yrs
Phase 1: Inflammatory
Phase 2: Absent pulses in arms + Claudication due to stenotic lesions + aneurysms + bruits

Angiography of aorta and branches

Diagnostic = CT-PET scan

Question 21

Polyarteritis Nodosa (MEDIUM VESSEL)
Pathology
Sx
Association

Answer 21

Affects branches of aorta so pain when eating - mesenteric angina

Associated with Hep B

Question 22

Kawasaki disease (MEDIUM VESSEL)
Pathology
Sx

Answer 22

Children <5yrs

3 Phases:
Affects coronary arteries
Fever >5 days
Strawberry tongue
Conjunctivitis
Groin rash
Thrombocytosis

Question 23

ANCA associated vasculitis
Microscopic polyangiitis
Churg Strauss (eosinophilic)
Wegener's
Differentiating features

Answer 23

Wegeners’ features ELK: ENT (saddle nose deformity + chronic sinusitis), Lung (nodules) and Kidney (cresenteric/sclerosing RPGN) and cANCA and saddle nose deformity

MPA has pANCA and MPO antibodies, but biopsy reveals a lack of granulomatous inflammation formation and the upper respiratory tract is spared

Churg-Strauss features peripheral neuropathy and cardiac issues, eosinophilia and asthma and pANCA

Question 24

Immune complex associated vasculitis
HSP/IgA vasculitis
Anti-GBM
Differentiating features

Answer 24

IgA has the triad of abdo pain, arthritis and purpura and usually affects children. Features C3 and IgA deposits

Anti-GBM only really affects kidney and lung whilst obviously Anti-GBM features Anti-GBM antibodies

Question 25

SLE Sx Dx criteria Disease associations

Answer 25

``` Mouth ulcers on hard palate is pathognomonic Jaccoud arthropathy (ulnar deviation + MCP subluxation) ``` Lesser known Sx in criteria: Non-scarring alopecia, pleuritis, haemolytic anaemia, low WCC or platelets, neurology ie psychosis, photosensitivity, rash, arthritis, renal ANA, Anti-DNA, Anti-SM, low complement, direct coombs test to detect autoantibodies on RBCs (unless in presence of haemolytic anaemia) OR biopsy proven nephritis + ANA or dsDNA Pericarditis (Saddle shaped ST elevation) Renal disease

Question 26

Nailfold capillaroscopy

Answer 26

Abnormal in secondary Raynauds (CTD causes etc) Normal in primary Raynauds

Question 27

Antiphospholipid Dx

Answer 27

The diagnostic criteria require one clinical event, i.e. thrombosis or pregnancy complication, and 2 of the following 3 months apart: Anti-β2 glycoprotein I Anti-cardiolipin Lupus anticoagulant Lupus anticoagulant antibodies paradoxically prolongs APTT despite its clotting effects thus this is just an artefact. Hence its name saying anticoagulant despite being pro-coagulant

Question 28

Systemic sclerosis classification

Answer 28

Localised is purely skin. Systemic is skin and organs. Two types: 1. Limited: CREST + pulmonary hypertension + hands/face rash. Anti-centromere. spares kidney 2. Diffuse: Rapidly progressing and rash affects larger area of proximal trunk/skin and more organs. Interstitial lung disease. Anti-RNA polymerase = kidney. Anti-topo = lung

Question 29

Systemic sclerosis complications and Ix

Answer 29

Pulmonary fibrosis - HRCT Pulmonary hypertension - ECHO + R heart catheter Gastric antral vascular ectasia aka watermelon gut = iron def - Endoscopy

Question 30

Three things which can induce Raynauds

Answer 30

Smoking Beta blockers cold temps

Question 31

Systemic sclerosis monitoring

Answer 31

PFTs: ILD is restrictive, PAH is reduced TLCO Echo: Estimate PASP (pulmonary artery pressure) Renal: BP and urine dip - VERY IMPORTANT SCREENING TEST if suspect multisystem disease

Question 32

``` Diffuse systemic sclerosis RENAL CRISIS Antibody Pathology Cause Sx Mx ```

Answer 32

Renal issues more associated with Anti-RNA Acute sclerosis of blood vessels in kindey = renal crisis Steroids often precipitate ``` Malignant hypertension High renin Azotemia Microangiopathic hemolytic anaemia flash pulmonary oedema Seizures ``` ACEi may be protective

Question 33

Polymyositis Sx Dx

Answer 33

Proximal symmetrical muscle weakness in 50-60s 1. Elevated Creatinine Kinase, AST/ALT, LDh and anti-Jo (check for ILD) 2. EMG or MRI can show oedema which can then help guide site for muscle biopsy 3. Definitive diagnosis = muscle biopsy - endomysial infiltrates

Question 34

Dermatomyositis Pathognomonics What association? Muscle biopsy result

Answer 34

Gottrens papules - lichenoid rash on fingers extensor surface + Dilated nailfold capillaries Very strong link with malignancy + smoking Perivascular infiltrate

Question 35

Livedo reticularis is seen in?

Answer 35

Antiphospholipid syndrome SLE Rheumatoid arthritis Mixed connective tissue disease

Question 36

Myasthenia gravis diagnosis test

Answer 36

Tensilon test

Question 37

Always do what test when talking about multisystem vasculitis type conditions?

Answer 37

ALWAYS do urinalysis as prognosis is often determined by renal involvement

Question 38

Eponymous syndromes 1. Felty's 2. Caplan's 3. Lofgrens 4. Bechets 5. Burkitts 6. Cowdens 7. DiGeorge 8. Fanconi anaemia 9. HSP 10. Kallmann 11. Li-Fraumeni 12. Marfan 13. Prader-Willi 14. Sjogrens 15. Stevens-Johnson 16. Von Hippel-Lindau 17. Wilsons

Answer 38

1. RA + neutropenia + splenomegaly 2. RA + pneumoconiosis (pulmonary nodules) 3. Bilateral hilar lymphadenopathy + arthralgia + erythema nodosum (sarcoidosis) 4. Small vessel vasculitis with orogenital ulcers 5. Caused by EBV/HIV 6. PTEN mutation. hamartomas on mucus membranes 7. Ch22deletion + cleft palate + cardiac issues 8. Hereditary cause of pancytopenia/AML/bone marrow failure 9. Purpura + abdo pain + arthritis + IgA deposition 10. Failure to thrive + anosmia + infertility 11. Sarcoma, breast, leukaemia and adrenal gland tumours 12. AD tall CTD 13. Ch15deletion due to genomic imprinting gone wrong + always hungry 14. Dryness 15. Cell death causes epidermis to separate from dermis 16. Tumour supressor gene dysfunction, may cause pheochromocytoma & renal cell carcinoma 17. High urinary copper, low ceruloplasmin

Question 39

A 43-year-old female, Ghanaian anthropology lecturer presented to her GP complaining of a facial rash, dry eyes and mouth, oral ulceration, alopecia, raynauds and inflammatory joint pain in the hand and wrist. On examination, she had a butterfly rash, oral ulcers on the hard palate and ++ proteinuria. Bloods were performed. Which combination of blood tests would indicate the most active Systemic Lupus Erythematosus?

Answer 39

High titre ANA (1:640), elevated anti-dsDNA, low C3 and C4 complement, lymphopaenia

Question 40

When does titre become significant? 61 year old cleaner. Her right hand has been blue for last 3 months and in last 4 weeks both arms and hands have become swollen and feel warm. Her face is swollen and she feels dizzy and breathless. ANA -ve, ENA negative, Capillaroscopy normal. ?

Answer 40

>1:60ish (speckled pattern = lupus) SVC obstruction due to thoracic malignancy

Question 41

Difference between reactive and malignant (lymphoma) lymphadenopathy?

Answer 41

Reactive is usually just in one area and is mobile Cancerous lymphadenopathy is firm and diffuse

Question 42

Which LFT can be raised in myositis?

Answer 42

ALT

Question 43

Diagnose dermatomyositis, whats next step in management? Start high dose immunosuppression immediately. Refer to dermatolology to get a diagnosis for the rash. Arrange for Occupational Therapy and Physiotherapy to do a home visit and consider fitting a stair lift Arrange a malignancy screen to include CT chest abdomen pelvis, mammography, tumour markers Arrange pulmonary function tests & echo

Answer 43

Arrange a malignancy screen to include CT chest abdomen pelvis, mammography, tumour markers DERMATOMYOSITIS = high risk of malignancy