Week 2 - G - Medium & Small Vessel Vasculitis - Kawasaki/polyarteritis nodosa (&Scarlet fever) and G.P.A/E.G.P.A/M.P.A/H.S.P

Question 1

What are the two main types of medium vessel vasculitis known as?

Answer 1

Polyarteritis nodosa (PAN) and Kawasaki Disease

Question 2

Where in the medium sized vessels does the necrotizing inflammatory lesions happen in polyaerteritis nodosa? What liver condition is often associated with polyarteritis nodosa?

Answer 2

In polyarteritis nodosa, the necrotizing inflammatory lesions occur at vessel bifurcations

Hepatitis B or hepatitis C is often associated with polyarteritits nodosa

Question 3

What is polyarteritis nodosa? * ie what kind of vasculitis * what does it cause

Answer 3

Polyarteritis nodosa is a necrotizing vasculitis that causes aneurysms and thrombosis in medium sized arteries leading to infarction in affected organs with severe systemic symptoms

Question 4

Symptoms of PAN depend mainly on location and severity of the arteritis and extent of secondary ischemia. Only one organ or organ system may be affected. What organs are typically affected by the vascular inflammation in polyarteritis nodosa?

Answer 4

The kidneys, skin, joints, muscles, peripheral nerves, and gastrointestinal (GI) tract are most commonly affected but any organ can be.

However, the lungs are usually spared.

Question 5

What are the presenting symptoms of polyarteritis nodosa?

Answer 5

Symptoms depend on the organ affected by the inflamaion of the arteries *

Kidneys - hypertension, haematuria, proteinuria

* Skin - purpurua, livedo reticularis, ulcers

* Joints - arthralgia

* Muscles - myalgia

* Peripheral nerves - mononeuritis multiplex (sensory and motor disturbances in greater than or equal to 2 peripheral nerves)

* GI - malabsorption, pain

Question 6

How is polyarteritis nodosa diagnosed?

Answer 6

Clinical findings

Biopsy of affected tissue

Arteriography if no clinically involved tissue is available for biopsy

Question 7

What is the treatment of polarteritis nodosa?

Answer 7

Treatment- control BP

Steroids for mild cases and immunosuppressants if severe eg cyclophosphamide

Question 8

What patient does Kawasaki disease typically affect?

Answer 8

Kawasaki typically occurs in children under the age of 5 and is a medium vessel vasculitis - inflammation weakens blood vessls leading to aneursyms (outpouching of the vessel)

Question 9

What are the characterisitc features of Kawasaki disease? (Clue- Warm CREAM)

Answer 9

Child (typically Asian) presents with fever lasting 5+ days + at least 4 of *

* Conjuncitvitis (non-exudative) *

* Rash - dequamative polymprophic rash on trunk

* Erythema palms and soles + swelling

* Adenopathy - cervical lymphadenopathy

* Mucous membrane - dry and strawberry tongue

Question 10

Restate the presenting features of Kawasaki disease? What is the worrying complication of Kawasaki disease?

Answer 10

Child (typically Asian /=5days and at least 4 of

* Conjunctivitis (non-exudative)

* Rash - desquamative rash on trunk

* Erythema on palms and soles

* Adenopathy - cervical

* Mucosal membrane - red and strwaberry tongue

Coronary artery aneurysms may develop and rupture or cause myocardial infarction

Question 11

What is the treatment of Kawaski disease?

Answer 11

Treatment is

High dose aspirin and high dose IV immune globulin (IVIG).

Coronary thrombosis may require fibrinolysis or percutaneous interventions. - DO AN ECHO

Question 12

What is another cause of strawberry tongue? What infection causes it?

Answer 12

Scarlett fever and toxic shock syndrome are other causes of strawberry tongue

Both conditions can be causes by group A b-haemolytic strep (aka streptococcus pyogenes)

Question 13

What typically precedes scarlet fever? What is the toxin released by streptococcus pyogenes that causes this fever?

Answer 13

Scarlet fever, a predominantly childhood disease, usually follows a pharyngeal streptococcal infection

Scarlet fever is caused by group A streptococcal strains that produce an erythrogenic toxin - causes lysing of RBCs and tissue cells

Question 14

How does scarlet fever present?

Answer 14

Sandpaper-like red rash develops on the skin (chest, axillae, behind the ears) usually into 2nd day of fever which will desquamate

Child has tender cervical lymph nodes and strawberry tongue

Question 15

What is the treatment of Scarlet fever?

Answer 15

Treatment is the same as for other GABHS infections - penicillin V (Phenoxymethylpenicillin)

Question 16

SMALL VESSEL VASCULITIS What can the small vessel vasculitis be divided into?

Answer 16

ANCA positive and ANCA negative small vessel vasculitis

ANCA positive = ANCA associated vasculitis (AAV)

Question 17

What are the four ANCA positive vasculitis? * Which two have granuloma formation? (A granuloma is a tiny cluster of white blood cells and other tissue)

Answer 17

Graulomatous ANCA positive vasculitis

• * Granulomatosis with polyangiitis (GPA) (aka Wegner’s syndrome)
• * Eosinophilic granulomatosis with polyangiitis (EGPA (aka Chrug-Strauss syndrome)

Non granulomatous ANCA positive vasculitis

• * Microscopic polyangitiis (MPA)
• * Renal limited vasculitis (RLV) - subset of MPA

Question 18

Which two vasculitis are associated with glomerulonephritis? How do you differentiate between the two?

Answer 18

Both granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are associated with glomerulonephritis

Can differentiate between the two as MPA does not have granuloma formation

Question 19

What are the common shared symotoms of the different vasculitis? (not included RLV)

Answer 19

* Fever and weight loss

* A raised, non blanching purpuric rash

* Arthralgia/arthritis

* Mononeuritis multiplex

* Glomerulonephritis

* Lung opacities on x-ray

Question 20

What are the presenting features of GPA? Best way to think is the symptoms that related to each organ/system it affects

Answer 20

ENT symptoms- nosebleeds, recurrent sinusisits, nasal crusting and over time loss of nose cartilage

Respiratory symptoms - haemoptysis

Renal - haematuria / proteinuria due to glomerulonephritis

Question 21

What is the nasal deformity that occurs due to GPA?

Answer 21

Due to the loss of nasal cartilage due to ischaemia caused by GPA, there is the characteristic ‘saddle nose’ deformity that can be seen in these patients

Question 22

What may be seen on CXR in Wegener’s?

Answer 22

Cavitating lung lesions may be seen on CXR

Question 23

If proteinuria or haematuria is found on urinalysis, what needs to be carried out?

Answer 23

If these are present, consider carrying out a renal biopsy for the patient to understand the extent of the renal involvement

Question 24

What antibodies are tested for in GPA? What other vasculitis are these antibodies seen in?

Answer 24

Test for c-ANCA direct against PR3 * (cytoplasmic - anti-neutrophil cytoplasmic antibodies specific for serine proteinase 3)

c-ANCA PR3 antibodies are also seen in microscopic polyangiitis

Question 25

What is EGPA characterised by?

Answer 25

This condiiton is characterised by late onset asthma, rhinitis and a raised peripheral blood eosinophil count

As well as vasculitis affecting the lung, nerves heart and skin

Neurological symptoms such as mono-neuritis multiplex are common

Question 26

Which antibodies are found in EGPA? What other vasculitis are these commonly found in?

Answer 26

in EGPA P-ANCA directed against MPO

* (perinuclear-anti-neurtrophil cytoplasmic antiboies directed against myeloperoxidase)

p-ANCA MPO are commonly found in microscopic polyangiitis

Question 27

How does MPA present? What is the most important complication which occurs in up to 90% of patients?

Answer 27

MPA presents the similar to Wegener’s without the upper airway disease (no recurrent sinusitis or nasal deformity)

Will have Respiratory symptoms - haemoptysis

Renal - haematuria / proteinuria due to glomerulonephritis

Most important complication is the rapidly progressive glomerulonephritis

Question 28

What are the main differences between MPA and GPA? What antibodies are seen in bloods for MPA?

Answer 28

MPA - does not have granulomatous formation and does not affect upper airways

MPA - most commonly p-ANCA directed against MPO also c-ANCA directed against PR3 positive sometimes

Question 29

It is important to note that ANCA is negative in a small proportion of all these conditions so it cannot be relied upon solely to confirm the diagnosis What other investigations / tests are useful for confirming the diagnosis in a small vessel vasculitis?

Answer 29

ESR, PV and CRP and raised Anaemia of chronic disease is common.

U+E looking for renal involvement

Urinalysis (looking for renal vasculitis)

CXR

Biopsy of an affected area e.g. skin or kidney is often helpful in confirming the diagnosis

Question 30

What are most cases of ANCA associated vasculitis treated with?

Answer 30

Most cases of ANCA associated vasculitis require treatment with IV steroids and cyclophosphamide due to their aggressive disease course

Question 31

What is the acute immunoglobulin mediate ANCA negative small vessel vasculitis known as? It typically affects children Which immunoglobulin is it mediated by?

Answer 31

This is Henoch-Schonlein purpura (HSP)- it is an acute IgA mediated small vessel vasculitis

Question 32

Henoch-Schönlein purpura (HSP) is an acute immunoglobulin A (IgA)–mediated disorder characterized by a generalised vasculitis involving the small vessels of the skin, the gastrointestinal (GI) tract, the kidneys, the joints, and, rarely, the lungs and the central nervous system (CNS). How does HSP typically present? and in what age group?

Answer 32

HSP typically presents as

Child with a purpuric rash on the buttocks and lower limbs, with abdo pain and vomiting and joint pain

There may be glomerulonephritis It typically occurs in children aged 2-11 years

Question 33

What typically precedes HSP?

Answer 33

HSP is typically preceded by a respiratory tract infection of GI infection predating hte condition by about 2 weeks

Question 34

What is the most common bacterial infection to predate Henoch Schonlein purpura?

Answer 34

Group A beta haemolytic step infection - strep pyogenes infection

Question 35

What is the treatment for henoch schonlein purpura?

Answer 35

Usually self limiting with symptoms resolving in roughly 8 week - provide analgesia for symptomatic relief (paracetamol) (dont take NSAIDs as can harm the kidneys)

Corticosteroids may be given if severe or in adults