Rheumatology Revision 2

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

positive hepatitis B serology

Question 10

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

Answer 10

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

Question 11

Describe the typical presentation of Kawakasi disease [5]

Answer 11

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 12

Management for Kawasaki disease? [3]

Answer 12

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

Question 13

Name 4 forms of small vessel vasculitis [4]

Answer 13

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

Question 14

Answer 14

Bright red, cracked lips and strawberry tongue

Question 15

Answer 15

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

Question 16

Answer 16

Aspirin

Question 17

Answer 17

coronary artery aneurysm

Question 18

Answer 18

Intravenous immunoglobulin

Question 19

Describe the clinical presentation of GPA

Answer 19

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 20

Describe the investigations used for GPA [3]

Answer 20

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 21

What is the gold standard for dx GPA? [1]

How else do you investigate? [3]

Answer 21

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 22

How do you differentiate GPA with eGPA?

Answer 22

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 23

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

Answer 23

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 24

Describe the clinical presentation of eGPA

Answer 24

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

Question 25

Lanham criteria

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

Answer 25

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

Question 26

Mx for eGPA

Answer 26

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 27

Answer 27

Epithelial crescents in Bowman’s capsule

Question 28

Answer 28

rapidly progressing GN

Question 29

Answer 29

GPA

NB - eGPA has late onset asthma

Question 30

Microscopic Polyangiitis is associated with which antibody? [1]

The major autoantigens in microscopic polyangiitis are [2]

Answer 30

p-ANCA

The major autoantigens in microscopic polyangiitis are MPO and PR3.

Question 31

Clinical features of microscopic polyangiitis?

Answer 31

fever

palpable purpura

rapidly progressive glomerulonephritis
- raised creatinine, haematuria, proteinuria

Diffuse alveolar haemorrhage

Respiratory (25-55%): haemoptysis, pulmonary haemorrhage, pleural effusion, oedema

pANCA (against MPO) - positive in 50-75%
cANCA (against PR3) - positive in 40%

Question 32

How do you differentiate MPA and PAN? [2]

Answer 32

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

Question 33

Tx for severe MPA? [+]

Answer 33

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 34

Tx for non-severe MPA? [+]

Answer 34

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 35

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

Answer 35

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

Question 36

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

Answer 36

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

Question 37

Define Henoch-Schonlein purpura (HSP) [1]

Answer 37

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

Question 38

Describe the pathophysiology of HSP

Answer 38

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 39

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

Answer 39

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

Question 40

Describe the typical presentation of HSP

What is the typical tetrad? [4]
Other manifestations?

Answer 40

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 41

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

Answer 41

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

Question 42

How would you differentiate ITP from HSP? [3]

Answer 42

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

Question 43

Give notable indications for hospitalisation in HSP [5]

Answer 43

• 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

TOMTIP NSAIDs should not be used in patients with active gastrointestinal bleeding or glomerulonephritis because of their effects on platelets and renal perfusion.

Question 44

Define Takayasu’s arteritis [1]

Answer 44

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

Question 45

Which vessels does takayasu’s arteritis mainly affect? [2]

How does it affect these vessels? [1]

Answer 45

Aorta
Pulmonary arteries

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

Question 46

Describe the typical patient of TA [1]

Answer 46

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 47

Describe the clinical presentation of TA

Answer 47

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 48

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

Answer 48

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

Question 49

Managment of TA? [2]

Answer 49

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 50

Answer 50

intermittent claudication

Question 51

Answer 51

granulomatous thickening of the aortic arch

Question 52

Answer 52

absent radial pulse