Histo: Connective tissue disease, amyloid, sarcoid, Immune related multisystem disorders

Question 1

Give an example of an autoimmune disease that is:

1. Organ-specific with a specific antigen
2. Organ-specific without a specific antigen
3. Multisystem disease

Answer 1

1. Organ-specific with a specific antigen: Pernicious anaemia
2. Organ-specific without a specific antigen: Primary biliary cirrhosis
3. Multisystem disease: Rheumatoid arthritis, Sjogren syndrome, SLE

Question 2

What are the main features of SLE?

Answer 2

• Serositis - note can cause pleuritic chest pain, abdo pain
• Oral ulcers
• ANA - Anti nuclear antibodies
• Photosensitivity
• Bloods - pancytopenia (low HB, low platelets, low WBC)
• Renal (proteinuria)
• Arthritis
• Immunological (anti-dsDNA)
• Neurological (psychiatric, seizures)
• Malar rash
• Discoid rash

NOTE: SOAP BRAIN MD

Question 3

What is ANA used for

Answer 3

Anti-nuclear antibody

Used as a screening test –> high sensitivity, low specificity

If -ve –> good at ruling out SLE
If +ve –> means it could be SLE among other things

the higher the titre –> the more +ve

Question 4

List three autoantibodies found in SLE. Which is most specific?

Answer 4

• Anti-dsDNA -
• Anti-smith (against ribonucleoproteins)
• Anti-histone - seen in drug-related SLE (e.g. hydralazine)

Question 5

How is anti-dsDNA measured?

Answer 5

• Incubate the patient’s serum with Crithidia Luciliae (protozoan)
• It has a big organism with dsDNA (kinetoplast) so if the patient has anti-dsDNA antibodies it will bind to the dsDNA in the kinetoplast

NOTE: it can also be measured with ELISA

Question 6

Describe the appearance of skin histology in SLE.

Answer 6

• Lymphocytic infiltration of the dermis
• Vacuolisation (dissolution of the cells) of the basal epidermis
• Extravasation of blood causes a rash
• Immunofluorescence will show immune complex deposition at the epidermis-dermis junction

Question 7

Describe the appearance of renal histology in SLE.

Answer 7

Glomerular capillaries are thickened (wire-loop capillaries) due to immune complex deposition.

NOTE: this can be visualised by immunofluorescence

Question 8

What is the name of non-infective endocarditis associated with SLE?

Answer 8

Libman-Sacks endocarditis

NOTE: the vegetation is made up of lymphocytes, neutrophils, fibrin etc.

Question 9

What is scleroderma/systemic sclerosis?

Answer 9

A condition characterised by excess collagen in the skin and fibrosis –> tight skin

Question 10

What is the localised form of scleroderma called?

Answer 10

Morphoea

Question 11

What are the two types of scleroderma? Name the antibodies that they are associated with.

Answer 11

• Diffuse - involves the trunk (anti-Scl70 antibodies (aka anti-topoisomerase))
• Limited - only affects distal to the elbows and knees (anti-centromere)

Question 12

What are the main features of limited cutaneous systemic sclerosis?

Answer 12

• Calcinosis - painful deposits at tip of fingertips
• Raynaud’s phenomenon
• Oesophageal dysmotility
• Sclerodactyly - tight skin over fingers
• Telangiectasia

CREST syndrome

Question 13

What pattern of ANA immunofluorescence is seen in scleroderma?

Answer 13

Nucleolar

Question 14

Describe the skin histology in scleroderma.

Answer 14

Increased depth and amount of collagen.

Question 15

Describe the vascular histology in scleroderma.

Answer 15

Intimal proliferation gives an onion skin appearance.

Question 16

What is a major consequence of vascular damage in scleroderma?

Answer 16

Renal hypertensive crisis - HTN + Acute renal failure

Need ACE-inhibitor

Question 17

What is mixed connective tissue disease?

Answer 17

A condition characterised by the overlap of several connective tissue diseases (SLE, scleroderma, polymyositis and dermatomyositis)

Question 18

how does dermatomyositis and polymyositis present

Answer 18

proximal muscle weakness + tenderness - affects shoulder + pelvic girdle
can progess to respiratory muscle involvement
Can also get interstitial lung disease

dermatomyositis –> skin manifestations as well:
heliotrope rash in perioorbital
gottron’s papules

Question 19

what are the bloods in polymyositis and dermatomyositis

Answer 19

raised CK

ANA +Ve

Anti-Jo-1
Anti-Mi-2

Question 20

What ANA immunofluorescence pattern is seen in mixed connective tissue disease?

Answer 20

Speckled

Question 21

What is dermatomyositis?

Answer 21

A condition characterised by proximal muscle pain and weakness, high CK and skin changes (e.g. Gottron’s papules - purple rash across the knuckles)

Question 22

What is sarcoidosis of the skin called?

Answer 22

Lupus pernio

Question 23

List some features of sarcoidosis.

Answer 23

• Arthritis
• Lupus pernio
• Erythema nodosum
• Bilateral hilar lymphadenopathy
• Pulmonary fibrosis
• Lymphadenopathy
• Inflammation of layers of the heart
• Uveitis
• Meningitis
• Hepatitis, cirrhosis
• Bilateral parotid enlargement

Question 24

What is the pathological hallmark of sarcoidosis?

Answer 24

Non-caseating granuloma

Question 25

What is a granuloma?

Answer 25

* A collection of activated macrophages (aka histiocytes) * The macrophages are sometimes described as epithelioid macrophages * Some macrophages will fuse to form multinucleated giant cells - with horseshoe nucleus

Question 26

What is caseating vs non-caseating

Answer 26

caseating has necrosis inside of it

Question 27

Which investigations are useful in sarcoidosis?

Answer 27

* Hypergammaglobulinaemia * High ACE * Hypercalcaemia (due to extra-renal production of 1-alpha hydroxylase by macrophages --> activates vitamin D)

Question 28

What criteria is used to classify vasculitides based on the size of the vessel?

Answer 28

Chapel Hill Criteria | These are primary, can be secondary e.g. to lupus or infection

Question 29

What is polyarteritis nodosa? What are its main features?

Answer 29

* A necrotising arteritis which is focal and sharply demarcated * It heals by fibrosis and mainly affects the renal and mesenteric vessels * May present with gut ischaemia or renal impairment * It produces a rosary beads appearance on angiography due to multiple aneurysms

Question 30

Which condition is polyarteritis nodosa associated with?

Answer 30

Hepatitis B

Question 31

What is a characteristic feature of vasculitis on clinical examination?

Answer 31

Palpable purpuric rash

Question 32

How is termporal arteritis diagnosed and treated?

Answer 32

* High ESR * High dose prednisolone

Question 33

What will be seen on temporal artery biopsy in temporal arteritis?

Answer 33

Lymphocytic infiltration of the tunica media Granuloma with multinulceate giant cells

Question 34

What is Kawasaki disease? What are the main clinical features?

Answer 34

* A medium vessel vasculitis * Conjunctivitis * Rash * Adenopathy * Strawberry tongue * Hands and feet rash * Fever \> 38 degrees for \> 7 days * Coronary artery aneurysms

Question 35

What are the main features of granulomatosis with polyangiitis?

Answer 35

* **ENT** - nosebleeds, sinusitis, saddle nose * **Lungs** - haemoptysis, SOB * **Kidneys** - haematuria

Question 36

Which antibody is associated with granulomatosis with polyangiitis?

Answer 36

cANCA - against proteinase 3

Question 37

What are the main features of eosinophilic granulomatosis with polyangitis?

Answer 37

* Asthma * Eosinophilia * Vasculitis

Question 38

Which antibody is associated with eoisinophilic granulomatosis with polyangitis?

Answer 38

pANCA - against myeloperoxidase