Vasculitis Flashcards
(104 cards)
1
Q
What is polyarteritis nodosa?
A
a multisystem vasculitis characterized by segmental necrotizing vasculitis involving predominantly medium-sized blood vessels.
2
Q
PAN is more common in males
A
T - ratio of 1.5:1 M :F
3
Q
Associations with PAN
A
Infections
- HBV
- Group A strep
Inflammatory diseases (e.g. inflammatory bowel disease),
Malignancies (especially hairy cell leukemia)
Medications
- minocycline
VEXAS ( vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic)
4
Q
Genetic associaiton for children with PAN?
A
CECR1 gene
5
Q
Clinical presentation of PAN?
A
Constitutional symptoms - weight loss, fever
Arthralgia
Sensory and motor neuropahty (mononeuritis multiplex)
Myagias
Abdo pain
Renal involvement - renovascular HTN and renal failure
Orchitis
thrombotic microangiopathy or vasculitic arterial occlusion resulting in:
Stroke
Ischaemic cardiomyopathy
Mesenteric ischaemia –> bowel perforation
*lungs are spared
6
Q
PAN is associated with glomerulonephritis
A
False - it is ass with renovascular HTN and renal failure
7
Q
Poor prognostic factors for PAN
A
GI involvement, 1 year survival rate < 50%
8
Q
Cutaneous findings with PAN?
A
Tender erythematous nodules
Livedo Racemosa
Retiform purpura
Ulceration
Palpable purpura
Atrophe blanche
9
Q
A skin predominant form of Polyarteritis nodosa occurs in 30% of cases
A
false - only 10%
10
Q
Cutaneous PAN often progresses to systemic PAN
A
False - this is rare.
11
Q
Ix findings for PAN
A
No lab test is diagnostic
ANCA - negative
Leukocytosis
Thrombocytosis
ESR often elevated
HBV and HCV should be performed
12
Q
Histology of PAN
A
segmental necrotizing vascu-
litis of medium-sized muscular arteries
medium-sized vessels are located within the deep dermis and subcutaneous fat,
although overlying small blood vessels
and nearby fat lobules may be secondarily involved.
DIF, if performed, may show deposits of C3, IgM, and fibrin within or around vessel walls, but this is of uncertain significance.
13
Q
Differences between ANCA ass vasculitis and PAN?
A
ANCA = glomerulonephritis and pulmonary involvement, circulating ANCAs
PAN = renovascular HTN, lacks pulmonary involvement, ANCA negative
14
Q
Treatment of systemic PAN?
A
1st Line:
Oral corticosteroids - 1mg / kg / day
tapered over 6 months
Or Oral corticosteroids + plasmaphoresis + entecavir
One half of patients will acheive remission or cure with corticosteroids alone
Steroid spating agents:
- AZA
- MTX
- IVIG
- cyclophosphamide
15
Q
Rx of cutaneous PAN?
A
First Line:
- NSAIDs
- Corticosteorids (oral, topical, IL)
Second line:
- Dapsone
- Colchicine
- Aza
- MTX
Third line:
- pentoxyfyline
- HCQ
- IVIG
- MMF
- TNF inhibitors
16
Q
Ix for suspected Vasculitis?
A
Lesional skin biopsies (early lesions)
- Histology
- DIF
For CSVV - punch biopsy
For mediusm vessel - Ideally incisional, or deep punch (telescope) of a subcut nodules > reiform purpura > edge of an ulcer
Bloods:
- FBC and film
- UEC
- LFTs
- C3 / C4
- ANCA
- Cryoglobulins
- ANA, ENA, dsDNA, RF
- Hep B / C / HIV
- ASOT, anti DNA-ase B titres
- SPEP, age app malignancy screening
- pre-immunosupression screen
- G6PD (consider HLA 13:01 in chinese)
- Urinalysis
17
Q
Describe
A
18
Q
Is PAN more common in men or women?
A
1.5 : 1
M : F
19
Q
ANCA ass vasculitis - disease and antibody association
A
20
Q
A
21
Q
Acute haemorrhagic oedema is more common in Males (70%) compared to females (30%)
A
True
22
Q
Who does acute haemorrhagic oedema of infancy affect?
A
Children < 2 years old
Boys
23
Q
How can you distinguish between urticaria and urticarial vasculitis
A
Urticarial vasculitis:
Duration of lesion
Resolution with bruising
Pain
Brown lesion of diascopy
24
Q
Ix for urticarial vasculitis?
A
ANA
ENA
C3 / C4 / C1q solid phase assay
FBC
UEC - urinalysis
ESR
25
What is HUVS?
Hypocomplementemic urticarial vasculitis syndrome
A more severe form of hypocomplementaemic vasculitis characterised by
● Two major criteria:
(1) urticaria for 6 months; and
(2) hypocomplementemia
– plus –
● Two or more minor criteria:
(1) vasculitis on skin biopsy;
(2) arthralgia or arthritis;
(3) uveitis or episcleritis;
(4) glomerulonephritis;
(5) recurrent abdominal pain; or
(6) positive C1q precipitin test with a low C1q level.
26
How do you treat EED?
1st Line - Dapsone
Adjuncts:
- NSAIDs
- Nicotinamide
2nd Line:
- Tetracyclines
- Hydroxychloroquine
- Cochicine
27
How does granuloma faciale present?
Dermal, chronic dermatitis
characterized by red–brown to violaceous plaques or nodules.
The face is the most
common site of involvement and lesions are more often solitary than
multiple.
28
What is the surface of the skin described as in granuloma faciale?
Orange peel surface
29
Pathology of granuloma Faciale
Normal epidermus
Dermal infiltrate with a Grenz Zone
Diffuse, nodular, perivascular neutrophils, lymphocytes and plasma cells admixed with eosinophils
30
1st line treatment of Granuloma Faciale
TCI
TCI
Il steroids
31
Systemic treatment for granuloma faciale
Dapsone
Plaquenil
32
33
Physical therapy for granuloma faciale?
Cryosurgery
Electrosurgery
Surgical excision,
Dermabrasion, and
CO2 or pulsed dye laser therapy may be effective
Laser therapy targeting the prominent
vascular component (e.g. 595 nm pulsed dye laser, 532 nm potassium
titanyl phosphate laser) has led to improvement in a number of patients.
34
Normocomplementaemic vasculitis runs a benign and self limiting course
True
35
Hypocomplementaemic vaculitis has the following systemic associaitons:
- Nephritis
- lung disease
- Arthritis
- Splenomegaly
- Hepatomegaly
- Ocular
- Rare neurological invovlement
36
Epidemiology of urticarial vaculitis
F > M
Peak incidence = 4th decade
Rare in children
37
Associations with urticarial vasculitis
SLE
Srojrens
Hep B / C
EBV
Lyme disease
COVID 19
Haematological disorders
- thrombocytopaenia
- cyroglobulinaemia
Non hodgkins lymphoma
AML
CLL
IgA myeloma
38
Explain the pathophysiology of urticarial vasculitis
Type 3 hypersensitivity reaction
Intravascular antigen - Antibody complexes
complement activation
mast cell activation
Pro inflammatory cytokines
endothelial cell activation and damage
Neutrophil activation
39
Urticarial vasculitis predominantly affects postcapillary venules in the superficial dermis.
True
40
DIF findings of urticarial vasculitis
IgG, IgM and C3 within and around vessel walls and at the DEJ
41
Antibodies and antigens involved in HUVS?
IgG autoantibodies directed against the collagen-like region of C1q (anti-C1q) and low levels of
C1q[2].
42
Histology features of urticarial vasculitis?
Endothelial cell damaage and swelling
Fibrin deposits in the affected post capillary venules
Neutrophil (or lymphocyte) predominant perivascular infiltrate
Leukocytoclasis
erythrocyte extravasation
+/- Eosinophils
43
Triggers for urticarial vasculitis
Idiopathic
Drugs
- cimetidine
- diltiazem
- Procarbazine
- potassium iodine
- fluoxetine
- procainamide
- etanercept
infection
- Hep B / C
- EBC
- COVID-19
- Lyme disease
Physical factors
- exercise and sun exposure
44
Clinical features of urticarial vasculitis
Recurrent wheals
Typically painful
Last > 24 hours
Resovle with PIH
+/- constitutional sx (fever, malaise, MSK, fever)
+/- angiooedema (51 - 70%)
+/- Arthralgia
*occasional bullae, raynauds, livedo*
45
Clinical featurs of Hypocomplementaemic urticarial vasculitis?
Same cutanoeus presentation
GI features - nausea, vomiting, abdo pain, intestinal bleeding or diarrhoea
Pulmonary symptoms - cough, dyspnoea or haemoptysis and occasionally the development of chronic obstructive pulmonary disease
46
Clinical variants of urticarial vasculitis
NUV - normocomplentaemic (80%)
HUV - hypocomplementaemic
HUVS - hypocomplentaemic UV syndrome (5%)
47
Hypocomplementaemia urticarila vasculitis is often associated with long duration, systemic symptoms and underlying disease such as lupus erythematosus.
True
48
Antibodies in HUVS?
Anti-C1q anti-bodies
49
Diagnostic criteria for HUVS?
urticarial vasculitis of more than 6 months’ duration with the following diagnostic criteria:
(i) biopsy-proven vasculitis;
(ii) arthralgia or arthritis;
(iii) uveitis or episcleritis;
(iv) recurrent abdominal pain;
(v) glomerulonephritis; and
(vi) decreased C1q or presence of anti-C1q autoantibodies
50
DDx of urticarial vaculitis
CSU
Schnitzler syndrome
51
90% of patients with HUVS develop SLE
False - 50%
52
Life threatening complications of HUVS?
COPD
Laryngeal angio-oedema
53
Ix for urticarial vasculitis
Bx
FBC and film
UEC + UA +/- UCR
LFTs
ESR
CRP
ANA
ENA
dsDNA
ANCA
Complement profile (C1q, C3, C4 and anti c1q abs)
TFT and Thyroid antibodies
Hep B / C / HIV
SPEP
+/-
CXR
PFTs
Opthal exam
54
Treatment of Urticarial vasculitsi
Depends on severity:
H1 blockers
Oral corticosteroids
Dapsone
Colchicine
Hydroxychloroquine
HUVS / HUS
- Immunosupression (MTx, MMF, CyA, Aza)
- Plamaphoresis
- IVIG
55
Histology of EED
Acute lesions- see photo.
Chronic lesions:
angiocentric eosinophilic fibrosis, capillary proliferation and infil-
tration of **macrophages,** **plasma cells** and **lymphocytes.**
Cholesterol deposits in histiocytes and in the extracellular tissue (the latter in a pattern that has been termed ‘extracellular cholesterolosis’) may
be present in older lesions [18]. Dermal nodules of EED contain spindle cells and fibrosis [19].
56
Associations with EED
1. AI conditions - IBD, Coeliac, RA
2. Infections - **HIV**, strep, HBV, HBV, Syphillus
3. IgA monoclonal gammopathy or myeloma
4. Myelodysplasia
4. PG
5. Polychondirtis
6. Medications
57
Streptococcal infections predispose to IgA vasculitis, and antistreptolysin O titre positivity confers a 10-fold risk of IgA vasculitis
T
58
58
What is the main cause of cryoglobulinaemic vasculitis?
HCV - in 80%
59
Describe the pathogenesis of cryoglobulinemic vasculitis.
Immune complexes containing cryoglobulins deposit in small vessels, especially in cold-exposed areas, activating complement and recruiting inflammatory cells, leading to leukocytoclastic vasculitis.
60
List common causes of cryoglobulinemic vasculitis.
Hepatitis C (most common), hepatitis B, autoimmune diseases (e.g., SLE, Sjogren’s), lymphoproliferative disorders.
61
What are the clinical skin manifestations of cryoglobulinemic vasculitis?
Palpable purpura, petechiae, ulcers (especially on lower legs), livedo reticularis, Raynaud phenomenon, and cold-induced lesions.
62
What laboratory findings support a diagnosis of cryoglobulinemic vasculitis?
Low C4, presence of cryoglobulins, elevated RF, positive HCV serology (type II), and immune complex deposition on biopsy.
63
What is the cornerstone of treatment for cryoglobulinemic vasculitis?
Treat the underlying cause (e.g., antivirals for HCV), with immunosuppression (e.g., corticosteroids, rituximab) for severe or refractory cases.
64
Explain the immunopathogenesis of PAN.
Medium-vessel vasculitis characterized by transmural necrotizing inflammation; often associated with immune complex deposition, particularly in HBV-related cases.
65
Differentiate between systemic PAN and cutaneous PAN.
Systemic PAN involves visceral organs (renal, GI, nervous, cardiac), while cutaneous PAN is limited to skin, with nodules, ulcers, and livedo reticularis.
66
Describe classic angiographic findings in PAN.
Microaneurysms, stenoses, and irregular vessel narrowing in renal, mesenteric, or hepatic arteries.
67
What histologic findings are typical of PAN?
Transmural inflammation with fibrinoid necrosis in medium-sized arteries; absence of granulomas.
68
Outline the first-line treatment approach for systemic PAN.
High-dose corticosteroids ± cyclophosphamide. For HBV-associated PAN: antivirals, short steroid taper, and plasmapheresis.
69
What are the histopathologic stages of EED?
Early lesions show leukocytoclastic vasculitis with neutrophilic infiltrate; late lesions demonstrate dermal fibrosis, capillary wall thickening, and lipid-laden macrophages.
70
Which laboratory tests are essential to assess for underlying causes in EED?
Serum protein electrophoresis (SPEP), immunofixation (for monoclonal gammopathy), HIV serology, and hepatitis B/C screening.
71
Describe the distribution and morphology of EED lesions.
Symmetric red to violaceous papules, plaques, or nodules on extensor surfaces; may become yellow-brown, ulcerated, or fibrotic over time.
72
What is the most effective treatment for EED and its mechanism?
Dapsone; inhibits neutrophil chemotaxis and reduces oxidative damage.
73
What systemic diseases are most commonly associated with EED?
IgA monoclonal gammopathy, HIV, autoimmune diseases (e.g., RA, IBD), and hematologic malignancies.
74
Describe the pathogenesis of cryoglobulinemic vasculitis.
Immune complexes containing cryoglobulins deposit in small vessels, especially in cold-exposed areas, activating complement and recruiting inflammatory cells, leading to leukocytoclastic vasculitis.
75
List common causes of cryoglobulinemic vasculitis.
Hepatitis C (most common), hepatitis B, autoimmune diseases (e.g., SLE, Sjogren’s), lymphoproliferative disorders.
76
What are the clinical skin manifestations of cryoglobulinemic vasculitis?
Palpable purpura, petechiae, ulcers (especially on lower legs), livedo reticularis, Raynaud phenomenon, and cold-induced lesions.
77
What laboratory findings support a diagnosis of cryoglobulinemic vasculitis?
Low C4, presence of cryoglobulins, elevated RF, positive HCV serology (type II), and immune complex deposition on biopsy.
78
What is the cornerstone of treatment for cryoglobulinemic vasculitis?
Treat the underlying cause (e.g., antivirals for HCV), with immunosuppression (e.g., corticosteroids, rituximab) for severe or refractory cases.
79
What are the types of cryoglobulinemia and their immunologic profiles?
Type I: monoclonal Ig (usually IgM or IgG), associated with lymphoproliferative disorders. Type II: mixed (monoclonal IgM with RF activity + polyclonal IgG), commonly associated with HCV. Type III: polyclonal IgM + polyclonal IgG, seen in autoimmune diseases.
80
How is cryoglobulin level measured and what are pre-analytical considerations?
Blood must be kept warm until clotting; serum is then cooled to precipitate cryoglobulins. Precipitate is quantified and characterized.
81
Which complement component is characteristically low in cryoglobulinemic vasculitis?
C4 (often markedly decreased)
82
What is the role of rituximab in treating cryoglobulinemic vasculitis?
Targets CD20+ B-cells to reduce cryoglobulin production; used especially in HCV-related or refractory disease.
83
What complications may arise from untreated cryoglobulinemic vasculitis?
Glomerulonephritis, peripheral neuropathy, systemic vasculitis, skin ulcerations, and progression to lymphoma.
84
Explain the immunopathogenesis of PAN.
Medium-vessel vasculitis characterized by transmural necrotizing inflammation; often associated with immune complex deposition, particularly in HBV-related cases.
85
Differentiate between systemic PAN and cutaneous PAN.
Systemic PAN involves visceral organs (renal, GI, nervous, cardiac), while cutaneous PAN is limited to skin, with nodules, ulcers, and livedo reticularis.
86
Describe classic angiographic findings in PAN.
Microaneurysms, stenoses, and irregular vessel narrowing in renal, mesenteric, or hepatic arteries.
87
What histologic findings are typical of PAN?
Transmural inflammation with fibrinoid necrosis in medium-sized arteries; absence of granulomas.
88
Outline the first-line treatment approach for systemic PAN.
High-dose corticosteroids ± cyclophosphamide. For HBV-associated PAN: antivirals, short steroid taper, and plasmapheresis.
89
What neurologic symptom is highly suggestive of PAN?
Mononeuritis multiplex—due to vasculitis of vasa nervorum.
90
How does renal involvement in PAN differ from other vasculitides like MPA?
PAN causes infarction and hypertension without glomerulonephritis; MPA often presents with glomerulonephritis.
91
Which mutation is associated with familial PAN?
CECR1 (ADA2 deficiency) mutation.
92
What are GI manifestations of PAN and why are they concerning?
Abdominal pain, nausea, GI bleeding, or infarction; mesenteric ischemia can lead to perforation.
93
What non-angiographic diagnostic criteria are used in PAN?
American College of Rheumatology (ACR) criteria include weight loss, livedo reticularis, testicular pain, myalgias, mononeuritis multiplex, diastolic BP >90 mmHg, elevated BUN/creatinine, hepatitis B, arteriographic abnormalities, biopsy with PMNs in arterial wall.
94
What are the histopathologic stages of EED?
Early lesions show leukocytoclastic vasculitis with neutrophilic infiltrate; late lesions demonstrate dermal fibrosis, capillary wall thickening, and lipid-laden macrophages.
95
Which laboratory tests are essential to assess for underlying causes in EED?
Serum protein electrophoresis (SPEP), immunofixation (for monoclonal gammopathy), HIV serology, and hepatitis B/C screening.
96
Describe the distribution and morphology of EED lesions.
Symmetric red to violaceous papules, plaques, or nodules on extensor surfaces; may become yellow-brown, ulcerated, or fibrotic over time.
97
What is the most effective treatment for EED and its mechanism?
Dapsone; inhibits neutrophil chemotaxis and reduces oxidative damage.
98
What systemic diseases are most commonly associated with EED?
IgA monoclonal gammopathy, HIV, autoimmune diseases (e.g., RA, IBD), and hematologic malignancies.
99
What cytokines are thought to be involved in the pathogenesis of EED?
IL-1, IL-8, TNF-alpha contribute to neutrophil recruitment and chronic inflammation.
100
What are differential diagnoses for EED?
Granuloma faciale, Sweet syndrome, rheumatoid nodules, necrobiosis lipoidica, sarcoidosis.
101
How can EED be differentiated from Sweet syndrome histologically?
EED shows vasculitis and fibrosis in chronic lesions; Sweet lacks true vasculitis and is more edematous.
102
What can lead to treatment resistance in EED?
Failure to treat associated systemic diseases like monoclonal gammopathy or HIV.
103
Why should EED patients undergo regular hematologic evaluation?
To monitor for progression of monoclonal gammopathy to myeloma or lymphoma.
