Vasculitis

Question 1

Think [] if patients have multisystem features and are failing to respond to conventional therapies eg antibiotics for fevers, raised inflammatory markers and involvement of one or more vital organ system such as nerve, skin, kidney, lung

Answer 1

Think vasculitis if patients have multisystem features and are failing to respond to conventional therapies eg antibiotics for fevers, raised inflammatory markers and involvement of one or more vital organ system such as nerve, skin, kidney, lung

Question 2

The clinical features of vasculitis depend on both the size of the vessels involved (e.g. large, medium or small) and the location of the vessels involved (e.g. kidney, skin or gut vessels).

However, there are certain clinical features that are strongly suggestive of a vasculitic process. These features include: [4]

Answer 2

Palpable purpura:
- vasculitis classically causes ‘palpable purpura’ that is often referred to as a ‘vasculitic rash’. Purpura are small (3-10 mm) red/purplish skin lesions that are non-blanching (i.e. do not go pale when pressed) and occur due to damaged blood vessels. Suggest cutaneous involvement of vasculitis

Constitutional symptoms:
- refers to features such as fever, weight loss, and fatigue. Non-specific and simply suggestive of a systemic process (e.g. infection, cancer, inflammatory disorder). Need to be considered in the context of other features

Asymmetrical neuropathies:
- damage to the small blood vessels that supply peripheral nerves can lead to peripheral neuropathy with sensory and/or motor features. Typically cause mononeuritis multiplex or an asymmetrical polyneuropathy

Unexplained bleeding:
- patients with unexplained haemoptysis or haematuria is suggestive of a vasculitic process affecting the small vessels of the pulmonary and renal vasculature. This may be seen with many small-vessel vasculitides

Question 3

Describe the pathophysiology of polyarteritis nodosa (PAN) [3]

Answer 3

Inflammation of Medium-sized Arteries:
- The hallmark of PAN is necrotising inflammation of the medium-sized arteries, particularly the muscular and elastic type
- Immune Complex Deposition - in cases associated with HBV, immune complexes formed by the viral antigens and corresponding antibodies are thought to be deposited in the arterial walls, leading to inflammation and damage.

Ischaemia and Infarction:
- The inflammation and damage to the arterial wall can lead to stenosis or occlusion of the vessel, resulting in ischaemia and infarction of the downstream tissues.

Aneurysm Formation:
- The weakening of the arterial wall can lead to the formation of microaneurysms, which can rupture, causing haemorrhage.

Question 4

Describe the clinical features of PAN [+]

Answer 4

ZtF:
* Renal impairment
* Hypertension
* Cardiovascular events
* Tender skin nodules

PM:
* fever, malaise, arthralgia
* weight loss
* hypertension
* mononeuritis multiplex, sensorimotor polyneuropathy
* testicular pain
* livedo reticularis
* haematuria, renal failure
* perinuclear-antineutrophil cytoplasmic antibodies (ANCA) are found in around 20% of patients with ‘classic’ PAN

Question 5

Investigations for PAN?

Answer 5

There is no diagnostic laboratory test for PAN.

Biopsy is performed on a clinically affected organ to confirm the diagnosis.

Arteriography (mesenteric or renal) can be used as an alternative to biopsy to confirm the diagnosis (to minimise bleeding risk). It can reveal aneurysms and irregular constrictions in the vessels.

Chest radiography may be obtained to exclude other forms of vasculitis, which have greater involvement in the lungs.

Question 6

How would you differenitate PAN to atherosclerosis? [1]

Answer 6

Atherosclerosis can also cause infarctions in various organs, causing similar symptoms, with similar age of onset as PAN. They can be both differentiated on histology.

Question 7

Tx of PAN?

Answer 7

Induction of Remission
* Corticosteroids - Prednisolone at a dose of 1mg/kg/day (maximum 60 mg/day) is usually recommended. Tapered
* Cyclophosphamide: For patients with severe PAN or organ-threatening disease, cyclophosphamide is usually added. The typical dose is 2 mg/kg/day orally or 15 mg/kg intravenously every 2-3 weeks.

Maintenance of Remission
* Azathioprine or Methotrexate: Once remission is induced, cyclophosphamide can be replaced with azathioprine (2 mg/kg/day) or methotrexate (15-25 mg/week) as maintenance therapy.
* Corticosteroids: Continue with a lower dose of corticosteroids and taper gradually.

Question 8

Answer 8

Hep B

Question 9

Answer 9

HTN

Question 10

Answer 10

a 55-year-old man who has had fever and malaise for the past few weeks develops a common peroneal nerve palsy. Bloods show the presence of hepatitis B surface antigen

Question 11

Answer 11

positive hepatitis B serology

Question 12

On imaging, typical findings in PAN are [] and []

Answer 12

On imaging, typical findings in PAN are multiple aneurysms and irregular constrictions of arterial vessels.

Question 13

Describe the typical presentation of Kawakasi disease [5]

Answer 13

Medium vessel vasculitis that presents in children

• High grade fever lasting > 5 days (normally resistant to antipyretics)
• Conjunctival injection
• Bright cracked lips
• Strawberry tongue
• Cervical lymphadenopathy
• Peeling, red palms
• Coronary artery aneurysms

Question 14

Management for Kawasaki disease? [3]

Answer 14

High dose aspirin
IV IG
Echo - used to screen for coronary artery aneurysms

Question 15

Name 4 forms of small vessel vasculitis [4]

Answer 15

Henoch-Schonlein Purpura
Microscopic Polyangiitis
Granulomatosis with Polyangiitis
Eosinophilic Granulomatosis with Polyangiitis

Question 16

Answer 16

A 2-year-old who has had a fever for the past 7 days is noted to have conjunctivitis, erythema and oedema of the hands and feet, cracked lips and a strawberry tongue

Question 17

Answer 17

Bright red, cracked lips and strawberry tongue

Question 18

Answer 18

child with fever, conjunctivitis, desquamating rash, cracked lips, strawberry tongue

Question 19

Answer 19

red palms of the hands and the soles of the feet which later peel

Question 20

Answer 20

Aspirin

Question 21

Answer 21

coronary artery aneurysm

Question 22

Answer 22

Intravenous immunoglobulin

Question 23

Describe what is meant by Granulomatosis with polyangiitis? [1]

Which antibody is most commonly associated with patients of GPA? [1]

Answer 23

GPA:
- cANCA systemic vasculitis that affects small and medium vessels

Question 24

Describe the basic pathophysiology of GPA

Answer 24

cANCA associated vasculitis - B cells produce due an autoimmune trigger

Causes vascular injury from cANCA deposits, and complexes formed after endothelial attachement causing release of more cytokines

Question 25

Describe the clinical presentation of GPA

Answer 25

Patients typically present with: **URTI** - sinusitis - saddle nose - due to nasal bridge collapse, - otitis media - nasal crusting **LRTI**: - Haemopytsis - Dysopnea and cough - Pleuritis - Pulmonary infiltrates **Neurological** - Mononeuritis simplex - Peripheral sensorimoto polyneuropathy - Cranial neuropathy **Petechiaie, purpura** **Glomerulonephritis** Consider granulomatosis with polyangiitis when a patient presents with **ENT, respiratory and kidney involvement**

Question 26

A 48-year-old male presents to the GP as he has recently coughed up small amounts of blood on several occasions. He has also noticed his nose is 'always blocked' and has had a few episodes of nosebleeds. Upon questioning, he admits that his clothes feel a little looser but he has not weighed himself. On examination, you notice a palpable rash on his lower legs. Based on the most likely diagnosis, which antibodies are most likely to be found in this patient's blood? Anti-CCP Anti-GBM Anti-dsDNA cANCA pANCA

Answer 26

**cANCA** This patient most likely has granulomatosis with polyangiitis (GPA) based on the history which includes ENT symptoms (rhinosinusitis and epistaxis), respiratory symptoms (cough and haemoptysis), and weight loss. Palpable purpura is also a common feature of GPA. cANCA is the antibody most commonly found in patients with GPA.

Question 27

Describe the investigations used for GPA [3]

Answer 27

**cANCA positive in > 90%**, pANCA positive in 25% **chest x-ray**: - wide variety of presentations, including cavitating lesions **renal biopsy:** - epithelial crescents in Bowman's capsule

Question 28

What is the gold standard for dx GPA? [1] How else do you investigate? [3]

Answer 28

**Gold standard**: - **histopathological** **confirmation** of **necrotising granulomatous inflammation** in a biopsy sample from an affected organ, typically the lung or kidney. **Serology**: - cANCA - proteinase 3 (PR3) **Abnormal urinary sediement:** - microscopic haematuria or red cell casts **Pulmonary abnormalities**: - nodules, fixed infiltrates or cavities observable on chest radiograph.

Question 29

How do you differentiate GPA with eGPA?

Answer 29

eGPA presents more with **asthma and eosinophilia** **mononeuritis multiplex** is more common in **eGPA** In **EGPA**, **pulmonary** **infiltrates** are more **transient** vs GPA **Renal involvement** in EGPA tends to be **less** **severe** than in GPA, presenting as **mild proteinuria or microscopic haematuria** rather than **rapidly** **progressive** **glomerulonephritis**.

Question 30

Describe the management plan for GPA in life/organ threatening disease [+]

Answer 30

**Induction of remission:** - **First-line therapy:** **Methylprednisolone** **IV** for 3-5 days (followed by **oral** **prednisolone**) and **cyclophosphamide** for **3-6 months** - **Second-line therapy:** **Methylprednisolone** IV for **3-5 days** (followed by **oral** **prednisolone**) and **rituximab** **IV**. **Maintenance of remission** * **First-line therapy**: **Prednisolone** and **methotrexate** (with folic acid).; **Prednisolone and azathioprine** usually for 2 years following remission, but can vary.

Question 31

Describe the management plan for GPA in life/organ threatening disease [+]

Answer 31

**Induction of remission:** - **First-line therapy:** **Methylprednisolone** **IV** for 3-5 days (followed by **oral** **prednisolone**) and **methotrexate** for **3-6 months** - **Second-line therapy:** **Oral** **prednisolone** and **cyclophosphamide**; **Oral prednisolone** and **rituximab**. **Maintenance of remission** * **First-line therapy**: **Prednisolone** and **methotrexate** (with folic acid).; **Prednisolone and azathioprine** usually for 2 years following remission, but can vary.

Question 32

Describe the clinical presentation of eGPA

Answer 32

* **asthma** (late onset) * **blood** **eosinophilia** (e.g. > 10%) * **paranasal** **sinusitis** * **mononeuritis multiplex** * **pANCA** positive in 60%

Question 33

Lanham criteria This criteria is formed of three components, which all need to be met for the diagnosis of EGPA: [3]

Answer 33

* **Asthma** * **Peak peripheral eosinophil count >1500** cells/microL (>1.5 x10^9/L) * **Systemic vasculitis** (with ≥2 extra-pulmonary organ involvement)

Question 34

Mx for eGPA

Answer 34

**Induction**: - **prednisolone** at 0.5-1.0 mg/kg/day - **Methylprednisolone** 1g daily for three days may be used for more extensive disease. - **Cyclophosphamide**, which is an alkylating chemotherapeutic agent used in systemic inflammatory conditions, may be added for severe multi-system disease or an inadequate response to steroids. **Maintenance**: - This can be initiated after induction therapy to maintain disease remission over long periods of time. The choice of agents may include **azathioprine** or **methotrexate**, but there are many other options.

Question 35

Answer 35

**Epithelial crescents in Bowman's capsule**

Question 36

Answer 36

**rapidly progressive glomerulonephritis**

Question 37

Answer 37

rapidly progressing GN

Question 38

Answer 38

saddle nose

Question 39

Answer 39

GPA ## Footnote NB - eGPA has late onset asthma

Question 40

Answer 40

eGPA

Question 41

Answer 41

Churg-Strauss syndrome

Question 42

Answer 42

epithelial crescents in Bowman's capsule

Question 43

Answer 43

**rapidly progressive glomerulonephritis**

Question 44

Microscopic Polyangiitis is associated with which antibody? [1] The major autoantigens in microscopic polyangiitis are [2]

Answer 44

p-ANCA The major autoantigens in microscopic polyangiitis are **MPO and PR3.**

Question 45

Clinical features of microscopic polyangiitis?

Answer 45

**fever** **palpable purpura** **rapidly progressive glomerulonephritis** - raised creatinine, haematuria, proteinuria **Diffuse alveolar haemorrhage** **Respiratory** (25-55%): haemoptysis, **pulmonary** **haemorrhage**, pleural effusion, oedema ## Footnote pANCA (against MPO) - positive in 50-75% cANCA (against PR3) - positive in 40%

Question 46

How do you differentiate MPA and PAN? [2]

Answer 46

**PAN**: - **usually** **no** **lung** involvement, strong link with **Hepatitis** **B**, only involves small to medium **arteries** (not venules or capillaries)

Question 47

Tx for **severe** MPA? [+]

Answer 47

**Induction**: - 1st line: **cyclophosphamide** (CYC) with high dose steroids. Therapy is continued for **3-6 months** then switched to less toxic maintenance once remission achieved - **Adjunct** **plasma** **exchange** in patients with **severe renal failure** (creatinine >500 µmol/l) or life-threatening manifestations **Maintenance**: for 24 months - 1st line: low dose steroids with azathioprine (**AZA**) or **MTX** - If patients refractory to AZA and MTX or contraindications to use: **MMF** or **leflunomide**

Question 48

Tx for **non-****severe** MPA? [+]

Answer 48

**Induction**: - High dose steroids with either methotrexate (**MTX**) or mycophenolate mofetil (**MMF**) **Maintenance**: for 24 months - 1st line: low dose steroids with azathioprine (**AZA**) or **MTX** - If patients refractory to AZA and MTX or contraindications to use: **MMF** or **leflunomide**

Question 49

**[]** is a complication of **cyclophosphamide** treatment: 5% risk after 10 years and 16% risk after 15 years.

Answer 49

**Bladder cancer**: a complication of cyclophosphamide treatment: 5% risk after 10 years and 16% risk after 15 years.

Question 50

**[Complication]** patients have a nine-fold increased risk of mortality and a higher risk of relapse in MPA

Answer 50

**Alveolar haemorrhage**: patients have a nine-fold increased risk of mortality and a higher risk of relapse

Question 51

Define Henoch-Schonlein purpura (HSP) [1]

Answer 51

**HSP** is an **acute immune complex-mediated small vessel vasculitis,** characterised by the classic tetrad of **rash, abdominal pain, arthritis/arthralgia, and glomerulonephritis**

Question 52

Describe the pathophysiology of HSP

Answer 52

**Type III** immune complex-mediated **hypersensitivity** **reaction**, characterised by the **tissue deposition of IgA-containing immune complexes** within affected organs **due to antigenic stimulus** (such as infections, drugs, or toxins) IgA antibody immune complexes **deposits** in **vascular** **walls**, stimulating **complement activation** Immune complex deposition causes **vessel** **necrosis** which results in **organ-specific symptoms.**

Question 53

In HSP, immunofluorescence studies show [3] within the walls of involved vessels.

Answer 53

Immunofluorescence studies show I**gA, complement component 3 (C3), and fibrin deposition** within the walls of involved vessels.

Question 54

Describe the typical presentation of HSP What is the typical tetrad? [4] Other manifestations?

Answer 54

Usually **preceded** by a history of a **preceding viral or bacterial upper respiratory tract infection (URTI)** **Classic tetrad:** * Palpable purpura * Arthritis/arthralgia * Abdominal pain * Renal disease **Other manifestations:** * Typically **symmetrically distributed, non-blanching palpable purpura**, especially on the **lower legs, buttocks, knees and elbows.** * **Arthralgias/arthritis (80%)** The **knees** and **ankles** are most often affected. * **Gastrointestinal symptoms** (50-75%): N&V; bloody stools or melena. **Intussusception** and **bowel infarction** common * **Renal**: causes **IgA nephritis**; symptomatic **haematuria** and/or proteinuria) to severe (i.e., **rapidly progressive nephritis, nephrotic syndrome, and renal failure**).

Question 55

Investigations for HSP: Why would you perform a coagualation study and what would you expect to see? [2]

Answer 55

Should be **normal** in **HSP**. Helps in ruling out other diagnoses such as **thrombocytopenia**

Question 56

How would you differentiate ITP from HSP? [3]

Answer 56

**ITP**: - **arthralgias** and **abdominal** **pain** are uncommon. - The **platelet level** is **low** in **ITP** but **normal** in **HSP**

Question 57

Describe the management of HSP [1]

Answer 57

The majority of patients with HSP recover spontaneously

Question 58

Give notable indications for hospitalisation in HSP [5]

Answer 58

* Inability to maintain adequate hydration with oral intake * Severe abdominal pain * Notable gastrointestinal bleeding * Altered mental status * Renal involvement (elevated creatinine), hypertension, and/or nephrotic syndrome ## Footnote **TOMTIP** NSAIDs should not be used in patients with active gastrointestinal bleeding or glomerulonephritis because of their effects on platelets and renal perfusion.

Question 59

Answer 59

IgA mediated small vessel vasculitis

Question 60

Answer 60

palpable purpuric rash over buttocks

Question 61

check that you have done temporal / giant cell arteritis in other notes

Question 62

Define Takayasu's arteritis [1]

Answer 62

**Takayasu's arteritis** is a rare, idiopathic, chronic inflammatory disease characterised by **granulomatous** **inflammation** of the **aorta** and its **major** **branches**.

Question 63

Which vessels does takayasu's arteritis mainly affect? [2] How does it affect these vessels? [1]

Answer 63

**Aorta** **Pulmonary arteries** Causes **swelling** and **aneurysms** OR become **blocked** and **narrowed** - causes reduction in pulses and BP in limb: **pulseless disease**

Question 64

Describe the typical patient of TA [1]

Answer 64

A stereotypical presentation of Takayasu's arteritis often involves a young woman under the age of 40 who presents with systemic symptoms such as fever, malaise, night sweats, and weight loss. These non-specific symptoms may precede vascular manifestations by months or even years.

Question 65

Describe the clinical presentation of TA

Answer 65

Features depend on the organs affected. **Pulses** - **Pulselessness**: Diminished or absent pulses in one or more extremities is a hallmark feature. - **Blood** **pressure** **discrepancies** between limbs **Claudication**: - Patients may experience limb claudication due to reduced blood flow, particularly in the upper extremities. **Bruits** **Hypertension**: - **Renal artery stenosis can lead to secondary hypertension**. This is frequently resistant to conventional antihypertensive therapy. **Neurological and visual disturbances** **Aortic regurgitation**: - Involvement of the ascending aorta can lead to dilation and subsequent aortic valve insufficiency.

Question 66

What is the preferred imaging modality for Takayusu arteritis? [1]

Answer 66

**MRI Angiography (MRA):** - MRA provides detailed images of both the vascular lumen and surrounding structures without ionising radiation.

Question 67

Managment of TA? [2]

Answer 67

**Inducing remission:** - **Oral** **prednisolone** (1mg/kg/day) is usually first line. - Steroids should be given alongside **low dose aspirin (75mg daily).** **Immunosuppressive agents** (utilised when patients relapse during steroid tapering) * Methotrexate (given with folic acid). * Azathioprine. * Mycophenolate mofetil. * Cyclophosphamide.

Question 68

Answer 68

intermittent claudication

Question 69

Answer 69

granulomatous thickening of the aortic arch

Question 71

Answer 71

A 30-year-old woman from Singapore presents with headache, malaise and myalgia. On examination the blood pressure is 160/100 mmHg, the right radial pulse is difficult to palpate and a carotid bruit is noted

Question 72

Answer 72

**absent radial pulse**