Cutaneous vasculitis by dr maria

CUTANEOUS VASCULITIS
By dr maria saeed
Pgr dermatology (CMH)
Rook’s
dermatology
chapter 102

DEFINITION
• Cutaneous vasculitis is inflammation of the blood vessel
walls usually resulting in palpable purpura

CLINICAL FEATURES
• History
• Presentation
• Clinical variants
• Differential diagnosis

HISTORY
• Full history
• Drug history
– Drugs purchased from pharmacies
– Or borrowed from relatives
– Herbal treatments
– Tonics and vitamins
– Drugs causing addiction
– Drugs taken for bodybuilding
– Drugs for sexual purposes
• Infection

• Questions about systemic disease:
i. Complications of vasculitis
ii. Potential malignant and infectious triggers
iii. Systemic features of systemic vasculitides
• Diseases with secondary vasculitis
including:
– Rheumatological diseases ( SLE)
– Thrombo‐occlusive disorders
– Inflammatory dermatoses.

PRESENTATION
• Painful
• Palpable purpura
• Non blanchable (Leakage of blood from the
vasculature into the interstitium)
• Painful ischaemia of the skin
• Haemorrhagic and necrotic lesions
• Erosions or ulcers
Cutaneous small‐vessel vasculitis
producing palpable purpura

• Ulcers may then become secondarily
infected.
• The ulcers may be slow to heal, even after
resolution of the vasculitis,due to:
– Venous stasis
– Malnutrition
– Anaemia
– Lymphoedema
– Prolonged infection or old age.

Cutaneous small‐vessel vasculitis
demonstrating a haemorrhagic vesicle
Ulcerated necrotic lesions in a livedo
distribution suggestive of
medium‐vessel disease

WHY VASCULITIS IS MORE COMMON IN LOWER LIMBS?
Increased pressure
in the venous
circulation
increases blood
vessel leakage
damage to the
vessel walls

Prolonged
standing
exaggerates
venous
hypertension
increases
blood leakage
and purpura
HOW PROLONGED STANDING CAUSED VASCULITIS IN LOWER
LIMBS?

The physical signs are determined to some extent
by the size of vessel involved

Systemic examination may reveal an underlying infection or
malignancy acting as a trigger for the vasculitis.

CLINICAL VARIANTS
• Petechiae : purpura less than 5 mm in diameter
• Ecchymoses : purpura larger than 1 cm
• livedo pattern: reticulate (like a net)

Petechiae Ecchymosis Livedo Reticularis

DIFFERENTIAL DIAGNOSIS
• Thrombo‐occlusive disorders
• Trauma
• Inflammatory dermatoses with disordered clotting
• Purpura due to prolonged running
• Neutrophilic disorders,
• Cellulitis (particularly in the elderly withedematous legs)
• Insect and snake bites

Cutaneous exposure
to cobra venom
cellulitis DVT

INVESTIGATIONS
2 main purposes
1. to establish if the vasculitis is primary or secondary
2. to demonstrate the presence of vasculitis involving
internal organs
• Skin biopsy in vasculitis, if needed, should be taken from a
fresh lesion less than 48 h old

MANAGEMENT
• Triggering drugs should be stopped
• Underlying infections should be treated
• Malignancy or associated rheumatological diseases should
be managed
• correction of venous stasis by elevation of the legs
• appropriate dressings in ulcerated areas and pain relief
should be given

SINGLE‐ORGAN SMALL‐VESSEL
VASCULITIS

Cutaneous
vasculitis
Small vessels
Single‐organ
(skin)
small‐vessel
vasculitis
Cutaneous
vasculitis with
systemic
diseases
immune
complex‐associate
d vasculitis
ANCA‐associated
vasculitis
Medium vessels
Polyarteritis
nodosa (PAN)
Kawasaki
disease
Large vessels
Giant cell
arteritis (GCA)
Takayasu
arteritis

1. Cutaneous small‐vessel vasculitis.
2. Erythema elevatum diutinum.
3. Recurrent cutaneous necrotizing eosinophilic
vasculitis.
4. Granuloma faciale.
SINGLE‐ORGAN SMALL‐VESSEL VASCULITIS

1.CUTANEOUS SMALL‐VESSEL VASCULITIS
• Cutaneous small‐vessel vasculitis (CSVV) is a single‐organ
vasculitis producing leucocytoclastic angitis of cutaneous
vasculature.

INTRODUCTION AND GENERAL DESCRIPTION
• Presence of 3 of the following 5 criteria have 84% specificity
for CSVV:
(i) Age greater than 16 years at disease onset.
(ii) History of taking a medication .
(iii) Presence of palpable purpura .
(iv) presence of a maculopapular rash.
(V) biopsy demonstrating granulocytes around an arteriole or venule.

• 15 to 30 persons per million
Incidence and
prevalence
• 36 and 56 years
Age
• Different regions have different
ratios
Sex
• condition is localized to the skin
may involve systemic vasculitis
Associated
diseases
EPIDEMIOLOGY

PATHOPHYSIOLOGY
Predisposing factors
• Idiopathic
• Certain Drugs
• Food allergies
• Bacterial infections
Pathology
• Segmental inflammation in an
angiocentric pattern
• Swelling of the endothelium
• Fibrinoid necrosis
• Extravasation of erythrocytes
• Infiltrate of neutrophils with
karyorrhexis of the nuclei
• Igm or complement C3
deposition

Leukocytoclastic vasculitis. (a) Low-magnification photomicrograph
showing perivascular infiltrates and fibrinoid deposits within the vessels of the
upperdermis.
(b) Higher magnification demonstrating nuclear dust, fibrinoid deposits,
vascular alteration and collagen degeneration
(a) (b)

(a) (b)
Leukocytoclastic (small vessel) vasculitis at (a) lower and (b) higher magnifications.
There is visible vascular wall damage with evidence of red blood cell extravasation, fibrinoid
change and extensive leukocytoclasis (nuclear debris from polymorphonuclear leukocytes)

CLINICAL
FEATURES
Presentation
• Lesions typically occur in areas prone to
stasis (ankles and lower legs )
• Sparing of intertriginous regions
• often asymptomatic
• pruritus, pain or burning
• systemic symptoms : fever, arthralgia,
myalgia and anorexia
• cutaneous manifestation of CSVV is palpable
purpura which may progress to
– papules
– nodules
– vesicles
– plaques, bullae or pustules
– ulceration, necrosis and post‐inflammatory
hyperpigmentation
History
•’crop’ lesions resulting
from exposure to an
inciting stimulus.
•New lesion formation
can continue for several
weeks .
•Resolve within several
weeks or a few months.
• Recurrence can occur.

Cutaneous small‐vessel vasculitis (CSVV
Vesicles in a dependent area on the foot.

Csvv in lower legs
Purpura on the thighs; there was similar
involvement on the lower legs.

Csvv in lower legs
CSVV progressing to blistering

The reticulate pattern on the leg
CSVV progressing to necrosis

CLINICAL VARIANTS
• Edema
• Livedo reticularis (cutaneous polyarteritis nodosa )
• Urticaria (urticarial vasculitis)

Complications and co‐morbidities
• Hyperpigmentation
• Haemosiderosis take months to resolve
• Ulcerated lesions may become infected adding to the
morbidity

INVESTIGATIONS
• The purpose of investigation is two fold:
I. to look for evidence of vasculitis in other organ systems
II. to look for evidence of a disease that is predisposing towards
CSVV, such as infection and malignancy
• Tests required
– blood testing,
– scanning
– organ biopsies

MANAGEMENT
First line
• Oral
prednisolone
30–80 mg once
daily, tapered
over 2–3 weeks
Second line
• Colchicine 0.6
mg twice daily
• Dapsone 50‐150
mg daily
Third line
• azathioprine(1–
2 mg/kg/day)
• methotrexate
(15–25
mg/week).

2.ERYTHEMA ELEVATUM DIUTINUM
• Erythema elevatum diutinum (EED) is a rare, chronic,
cutaneous eruption characterized by fibrosing plaques
with histological evidence of leukocytoclastic vasculitis

• Very rare
• only a few hundred cases
described
Incidence and
prevalence
• 40 and 70 years
Age
• Equally occurs in both
genders
Sex
EPIDEMIOLOGY

ASSOCIATED DISEASES
• Rheumatoid arthritis
• Coeliac disease
• Inflammatory bowel disease
• type 1 diabetes
• Hiv
• Streptococcal infections
• Syphilis
• Hypergammaglobulinaemia
• Iga monoclonal gammopathies
• Myelodysplasia
• Pyoderma gangrenosum
• Relapsing polychondritis
• Multiple myeloma

PATHOLOGY
Acute lesions of EED
• Fibrin deposition
• Eosinophils (upper and mid
dermis)
• Degree of edema and infiltration
into the dermis
• Unaffected collagen may be
present just under the epidermis
Chronic lesions of EED
• Angiocentric eosinophilic fibrosis.
• Capillary proliferation.
• Infiltration of macrophages,plasma
cells and lymphocytes
• Cholesterol deposits in histiocytes
and in the extracellular tissue.
• Dermal nodules of EED contain
spindle cells and fibrosis.

Erythema elevatum diutinum at (a) lower and (b) higher
magnifications.
There is a perivascular infiltrate containing neutrophils, with
leukocytoclasis and some perivascular fibrin deposition
(a) (b)

Erythema elevatum diutinum
on the hands.

Early non‐fibrotic lesions at a typical site on the knee
This patient also had EED on the hands, and pyoderma
gangrenosum

CLINICAL
FEATURES
Presentation
• Lesions typically occur in symmetrical
Fashion over the:
– Dorsa of the hands
– Knees
– Buttocks
– Achilles tendons
– Face and ears may also affected
• They are red‐violaceous, red‐brown or
yellowish papules, plaques or nodules
• Lesions are soft but eventually they
fibrose and later leave atrophic scars.
History
• Generally
asymptomatic
• Painful lesions

• DIFFERENTIAL DIAGNOSIS : Sweet syndrome
• Complications : rare
• Disease course and prognosis: last from 5 to 35 years, crops
of new lesions developing every few weeks to months.
• Investigations: IgA antineutrophil cytoplasmic antibodies
(ANCA)

MANAGEMENT
First line
• Dapsone
Second line
• Niacinamide
• High potency
topical
intralesional,
corticosteroids
• 5% topical
dapsone gel
Third line
• Other
therapies used
for CSVV

3.RECURRENT CUTANEOUS NECROTIZING
EOSINOPHILIC VASCULITIS
• vasculitis consisting of a predominantly centripetal
purpuric papular rash, angio‐oedema, peripheral blood
eosinophilia and an eosinophilic necrotizing vasculitis of
small vessels

• Very rare
• Few cases in literature
Incidence and
prevalence
• 17–81 years
Age
• Either sex may be affected
Sex
• connective tissue diseases
and with rheumatoid arthritis
Associated
diseases
EPIDEMIOLOGY

PATHOPHYSIOLOGY
• Histopathology shows fibrinoid deposition.
• Necrosis of small dermal vessels with an infiltrate of
eosinophils and absent or minimal leukocytoclasis.
• Small epidermal vesicles containing eosinophils.
• Eosinophil cytokines such as interleukin 5 (IL‐5).
• Neutrophil elastase is prominent around vessels, and mast
cell degranulation occurs.

CLINICAL
FEATURES
Presentation
• Recurrent pruritic papules .
• Urticarial lesions .
– Involvement of lower limbs
– Head and neck
• Angio‐edema of the face and extremities
• Raynaud phenomenon
History
• Pruritic papules over
the lower limbs

• Eosinophilic granulomatosis with polyangiitis
• Hypereosinophilic syndrome
• Episodic angio‐oedema with eosinophilia
• Dermatitis herpetiformis
• Wells syndrome
• Drug eruptions

• Clinical variants : connective tissue diseases
eosinophilic vasculitis, typically with hypocomplementaemia
• Complications : Ulceration and secondary infection of necrotic
lesions
• Disease course and prognosis: A good response to
corticosteroids
• Investigations: Investigations are guided by history and clinical
examination

MANAGEMENT
First line
• oral corticosteroids
Second line
• Systemic antibiotics
for secondary
infection and
ulcerated lesions

4.GRANULOMA FACIALE
• Asymptomatic cutaneous nodules
• occurring primarily on the face
• occasional extrafacial involvement. Granuloma faciale is
limited to the skin, without any systemic manifestations

• Recurrent, multiple,raised, discrete, smooth, greyish brown,
facial lesions.
• Histology demonstrated pleomorphic infiltrate with
predominant eosinophils but also polymorphs and plasma
cells.
• In the absence of any bony involvement, this was diagnosed
as an eosinophilic granuloma.

• Very rare
Incidence and
prevalence
• 40–60 year olds
Age
• commoner in males
Sex
• IgG4‐related disease
Associated
diseases
EPIDEMIOLOGY

PATHOPHYSIOLOGY
• The presence of plasma cells and igG deposition in and
around the dermal vasculature
• Indicating that granuloma faciale may be immune complex
mediated
• T cells in the tissue is variable.
• Numbers of CD4+ cells that stain strongly for IL‐2R
antibodies

PATHOLOGY
• upper half of the dermis with infiltrate of eosinophil and plasma
cells
• A band of normal collagen referred to as a ’Grenz’ zone typically
separates the inflammatory infiltrate from the epidermis and
pilosebaceous appendages.
• Nuclear dust (fragmented neutrophil nuclei) near capillaries.
• vascular changes (perivascular distribution of inflammatory cells) to
florid (leucocytoclastic vasculitis with fibrinoid necrosis).
• Perivascular storiform fibrosis and obliterative venulitis

Granuloma faciale. (a) Low‐magnification view showing perivascular
nodular infiltrates within the dermis. (b) At a higher magnification
the infiltrate shows lymphocytes, eosinophils and a few neutrophils
(a) (b)

CLINICAL
FEATURES
Presentation
• Soft and red‐brown nodules or plaque
• Smooth lesions
• With prominent follicular orifices
• Telangiectatic surface
• Scaling
• Lesions never ulcerate
History
• Lesions occur on the
face
•Extrafacial involvement
is uncommon
• Asymptomatic
• Itching, burning or pain

Granuloma faciale
Reddish brown plaque on the nose

Granuloma faciale
Close up of a facial plaque

• Clinical variants : Eosinophilic angiocentric fibrosis
• Differential diagnosis : Sarcoidosis
TB
Rarely EED
Cutaneous lupus erythematosus.
• Disease course and prognosis: resistant to treatment
• Investigations: biopsy
blood eosinophilia

SMALL‐VESSEL IMMUNE COMPLEX
ASSOCIATED VASCULITIS

1. IgA vasculitis.
2. Cryoglobulinaemic vasculitis.
3. Hypocomplementaemic urticarial vasculitis.
4. Antiglomerular basement membrane vasculitis
disease.
SMALL‐VESSEL IMMUNE COMPLEX
ASSOCIATED VASCULITIS

1.IgA vasculitis
• Previously called henoch–schonlein purpura
• Is an immune complex vasculitis characterized by iga1
dominant immune deposits.
• It often involves the skin and gastrointestinal tract, and
frequently causes arthritis.

ACR old criteria
(I) palpable purpura
(Ii) bowel angina
(Iii) age <20 years at onset
(iv) the presence of granulocytes
in the vessel wall
• Any 2 of the following 4 criteria could
be classified as IgA vasculitis.
Modified criteria
(i) diffuse abdominal pain
(ii) any biopsy demonstrating
predominant IgA deposition
(iii) any acute arthritis or arthralgia
(iv) renal involvement in the form of
haematuria or proteinuria.
• Any 1 of the following 4 features
in the presence of palpable
purpura classified as of IgA
vasculitis.

• In children :10–20/100 000
• In adults :1–1.5/100 000
Incidence and
prevalence
• ages 4 and 6 years
• Adult‐onset IgA vasculitis can occur at any age
Age
• Mild preponderance in males 1.8:1
Sex
• MEFV (familial Mediterranean fever) gene
Associated
diseases
EPIDEMIOLOGY

PATHOPHYSIOLOGY
• common in spring, autumn and
winter as compared with the
summer months
• Respiratory infections
• Streptococcal infections
Pathology
• Increased levels of IgA in the
serum (in 50% with active
disease).
• Circulating immune complexes
containing IgA .
• deposition of IgA in blood vessel
walls and in the renal
mesangium are associated with
IgA vasculitis.

IgA antibodies of HSP
• IgA1 rather than IgA2 is the main IgA subclass deposited
in skin lesions .
• Diminished glycosylation of the proline‐rich hinge region
of the IgA1 heavy chain
– allows IgA to be deposited in the mesangium.
– and in activating the alternative pathway of complement in IgA
making it more prone to forming macromolecular complexes.

Other IgA antibodies of HSP
• IgA ANCA
• IgA rheumatoid factor
• IgA anticardiolipin antibodies
• IgA antiendothelial cell antibodies (AECAs)

Inflammatory markers
• activation of several cytokines
• TNF‐α levels are increased
• IL‐6, IL‐8
• transforming growth factor β (TGF‐β)
• vascular endothelial growth factor (VEGF) levels
• Neutrophil activation
• elevated nitric oxide levels
• reactive oxygen species
• increased urinary leukotriene

IgA vasculitis at (a) lower and (b) higher magnifications. There is
perivascular leukocytoclasis and fibrin deposition, and eosinophils are
present.
(a) (b)

CLINICAL
FEATURES
Presentation
• Erythematous, urticarial papules, which
may evolve within 24 h into palpable
purpura with haemorrhage.
• Urticaria, vesicles, bullae
• Necrotic ulcers may develop
• A retiform pattern within lesions is
characteristic
• Typically involves the extensor aspects
of the limbs in a symmetrical fashion
– Elbows and knees
– Buttocks
– May also affect the trunk and face
History
• Purpura
• Arthralgia
• Abdominal pain
• Lesions usually fade
within 5–7 days
• Crops of lesions
can recur for a few weeks to
several months.

IgA vasculitis and systemic involvement
Common involvement
• Haematuria
• Proteinuria
• gastrointestinal bleeding
• Painful arthritis (frequently affecting the knees and ankles)
Less common manifestations
• orchitis (in 10–20% of boys)
• intussusception
• Pancreatitis
• neurological abnormalities
• Uveitis
• carditis

IgA vasculitis
Haemorrhagic vesicles present on the hand

IgA vasculitis
Vasculitis extending onto the arms.

• Clinical variants : gastrointestinal involvement and arthritis can occur
in the absence of skin disease
• Differential diagnosis :
– IgA nephropathy
– idiopathic thrombocytopenic purpura
– septic shock
– acute abdomen
– systemic lupus erythematosus.
• Disease course and prognosis: relapse is common
• Investigations: biopsy
immuno fluorescence
No laboratory tests are specific for IgA vasculitis

MANAGEMENT
• The treatment of IgA vasculitis is supportive
• self‐limiting
• Glucocorticoids
• Pulsed intravenous methylprednisolone
• ciclosporin A
• cyclophosphamide
• azathioprine and mycophenolate mofetil
Systemic glucocorticoid treatment may be effective in the treatment of
abdominal pain, arthritis and nephritis
• prednisolone 1 mg/kg/day for 2 weeks, tapering over a further 2
weeks.

2.CRYOGLOBULINAEMIC VASCULITIS
• Cryoglobulins are abnormal immunoglobulins.
• Precipitate spontaneously when serum is cooled to a temperature
below 37°c.
• Cryoglobulinaemia is the condition characterized by the presence of
circulating cryoglobulins.
• Cryoglobulins deposited as immune complexes.
• It is mainly the skin glomeruli and peripheral nerves that are
affected.

• Cryoglobulinaemic vasculitis is a small‐vessel vasculitis affecting the
skin, joints, peripheral nerves and kidneys.
• About 80% of cases are secondary to hepatitis C infection
• Other causes include
– B‐cell lymphoproliferative disorders
– autoimmune diseases
– Sjogren syndrome
– other viral disorders (hepatitis B, HIV)
– essential mixed cryoglobulinaemia.

Cryoglobulins may be divided into three main subtypes:
1 .Monoclonal immunoglobulin
usually IgG or IgM, accounts for about 10–25% of cases.
associated with:
– lymphoproliferative disease
– multiple myeloma
– Waldenstrom macroglobulinaemia.
2 .Mixed polyclonal (usually IgG) immunoglobulin and
monoclonal (usually igm‐κ) immunoglobulin, the latter having rheumatoid
factor activity, accounts for about 25% of cases.
3 . Polyclonal IgM with rheumatoid factor activity and polyclonal
IgG with antigenic activity account for about 50–65%

• Rare
Incidence and
prevalence
• In adults
Age
• HCV 80% cases
• Sjögren syndrome
• B‐cell lymphoproliferative disorders
Associated
diseases
EPIDEMIOLOGY

PATHOPHYSIOLOGY
• Cold and immobility may
precipitate acute episodes
• Causative organism: Hcv virus
• Environmental factors: Exposure
to cold and immobility,resulting
in cutaneous necrosis.
Pathology
• Cryoglobulinaemic vasculitis affects
capillaries, arterioles and venules.
• In the skin, it produces a pandermal
leucocytoclastic vasculitis that may
extend into the subcutis
• Eosinophilic periodic acid–Schiff (PAS)
positive globular immune complex
deposits.
• PAS‐negative intraluminal fibrin
deposits can be visualized
• Chronic lesions may become
granulomatus.

Changes in other organs due to cryoglobulins
• Membranoproliferative glomerulonephritis
• Immune complex deposition in the lungs causing
bronchiolitis obliterans organizing pneumonia.
• Vasa nervosa vasculitis causing a peripheral neuropathy.

CLINICAL
FEATURES
Presentation
• Myalgia, headache, fever and weight loss are
common
• Sensorimotor neuropathy and mononeuritis
multiplex
• Renal involvement (membranoproliferative
glomerulonephritis)
• nephrotic range proteinuria
• Raynaud phenomenon in connective tissue
disease
• Proliferative mesangial lesions or thrombotic
lesions may present
History
• Purpura
• Arthralgia
• weakness
’Meltzer’s triad

Multiple myeloma presenting as cryoglobulinaemic
vasculitis.

Differential diagnosis
• Cryoglobulinaemic vasculitis should be distinguished from
other causes of CSVV because corticosteroid therapy,
although sometimes necessary in the short term, may in
the longer term worsen the underlying infection that is
present in the majority of the cases.

COMPLICATIONS AND CO‐MORBIDITIES
• increased risk of myeloproliferative disorders,particularly
a B‐cell non‐Hodgkin lymphoma.
• fourfold greater in patients without hepatitis C
• Associated glomerulonephritis is common and important
and may be more frequent in those with hep c.
• In patients with hepatitis C‐induced disease, the
complications are those of liver involvement

DISEASE COURSE AND PROGNOSIS
• In patients with hepatitis C‐induced disease, the viral
disease will determine the prognosis.
• In patients without hepatitis C, renal involvement is
associated with greater morbidity.

Investigations
• Cbc
– The greatest care should be taken to ensure that the blood is transported to the
laboratory at 37°C to ensure that the tests are not falsely negative
• Rheumatoid factor
• Inflammatory markers will be elevated
• Urine analysis
• Renal biopsy
• Cutaneous biopsy

MANAGEMENT
• In patients with hepatitis C infection :
combination of glucocorticoids,antiviral therapy and
immunomodulatory agents
• non‐hepatitis C cryoglobulinaemic vasculitis :
little evidence for the management

3.HYPOCOMPLEMENTAEMIC URTICARIAL
VASCULITIS
• HUV is defined as vasculitis affecting small vessels (i.e. capillaries,
venules or arterioles).
• Accompanied by urticaria and hypocomplementaemia.
• Associated with anti‐C1q antibodies.

Introduction and general description
• Condition is very rare
• Persistant urticaria
Lesions lasting for longer than 24 h with circulating anti‐c1q autoantibodies.
• Arthritis
• Glomerulonephritis
• Pulmonary diseases
• Ocular diseases
• Leukocytoclastic vasculitis
• Abdominal pain are associated

• Rare
Incidence and
prevalence
• In 3os
• Few cases in childhood
Age
• Common in females
sex
• SLE
• pyogenic infections
Associated
diseases
EPIDEMIOLOGY

Pathophysiology
• HUV contains polyclonal IgG
with C1q precipitin activity
contained within the Fab
fragments.
• These IgG antibodies are
directed against the
collagen‐like region of C1q.
• resulting in a reduction of C1q
in the serum
• activation of the complement
pathway
Pathology
• Interstitial neutrophils
• deposition of immune
complexes.

CLINICAL
FEATURES
Presentation
• Cutaneous lesions of both the
hypocomplementaemic and
normocomplementaemic forms of UV are :
– erythematous indurated weals
– contain purpuric foci
– Angio‐oedema
– macular erythema.
– Livedo reticularis
– nodules ,bullae may be evident
History
• weals are painful
itchy, and persist
for more than 24 h
•weals resolve with areas of
discoloration
•Angio‐oedema

• SLE
• ocular inflammation
• angio‐oedema
• chronic obstructive pulmonary disease
• Pre‐bullous pemphigoid
• Erythema multiforme
• Sweet syndrome

• Cough or dyspnea may indicate :
– pleural and pericardial effusions
– emphysema or chronic obstructive pulmonary disease
• Renal symptoms
– Proteinuria or haematuria may indicate glomerulonephritis
– end‐stage renal failure
• Gastrointestinal symptoms
– (abdominal discomfort, nausea, vomiting and diarrhoea), arthritis
• Eye involvement
– episcleritis,
– uveitis, conjunctivitis,
– aseptic meningitis,
– Nerve palsies
– transverse myelitis.

INVESTIGATIONS
• Laboratory studies
• C3, C4 and antinuclear antibody (ANA)
• ESR
• Biopsy

MANAGEMENT
First line
• systemic
corticosteroids
Second line
• dapsone (100–200
mg once daily)
• colchicine (0.6 mg
twice to three times
daily)
• hydroxychloroquine(
200 mg once to twice
daily)
Third line
• cyclophosphamid
e
• mycophenolate
mofetil

4.ANTIGLOMERULAR BASEMENT MEMBRANE
VASCULITIS DISEASE
• Affects glomerular capillaries or pulmonary capillaries, or both
• With GBM deposition of anti‐GBM autoantibodies
• Lung involvement causes pulmonary haemorrhage
• Renal involvement causes glomerulonephritis with necrosis and
crescents

• 0.5 cases/million population
per year
Incidence and
prevalence
• in children
• in the third and seventh
decades
Age
• In children (M:F ratio is 1 : 2)
• In adults(M : F ratio of 1.9 : 1)
sex
EPIDEMIOLOGY

PATHOPHYSIOLOGY
• The condition is due to immune
complexes composed of
autoantibodies
• directed against the NC1
domain of the a3 chain of type
IV collagen .
• The distribution of this
molecule restricts the
condition to the lung and
kidney.
PATHOLOGY
• Peri vasculitis and anti‐IgM and
C3 antibodies at the basement
membrane zone in cutaneous
lesions.
• Genetics
• in a pair of identical twins
• Environmental factors
• common in late spring and
early summer

CLINICAL
FEATURES
Presentation
• other features:
– chest signs
– heart Pallor
– Oedema
– murmurs
– hepatomegaly
– Discrete, erythematous, macular lesions on the
instep of the foot
History
Presenting features :
–Haemoptysis
– fatigue
–dyspnoea
– cough

Clinical variants
Respiratory features predate renal disease by up to a year in two
thirds of cases, and there may be a gap of up to 12 years.
Disease course and prognosis
Untreated outcome is very poor, with near 100% mortality.
With treatment 1‐year survival depends on early renal function
there is 100% survival if the serum creatinine is <500 μmol/L, but
65%survival in dialysis‐dependent cases.

INVESTIGATIONS
• ANCA may be positive
• antinuclear antibody is usually negative.
• Specific testing is to anti‐GBM antibodies

MANAGEMENT
First line
• corticosteroids,
cyclophosphamide and
plasma exchange
Second line
• Dialysis if renal failure
• Respiratory support in
pulmonary hemorrhage

SMALL‐VESSEL ANCA‐ASSOCIATED
VASCULITIS

SMALL‐VESSEL ANCA‐ASSOCIATED
VASCULITIS
1. Microscopic polyangiitis
2. Granulomatosis with polyangiitis (wegners granulomatosis)
3. Eosinophilic granulomatosis with polyangiitis

1.MICROSCOPIC POLYANGIITIS
• Microscopic polyangiitis (MPA) is a necrotizing vasculitis, with few
or no immune deposits
• Necrotizing glomerulonephritis is commmon
• Pulmonary capillaritis often occurs
• Granulomatous inflammation is absent
• MPA was grouped with polyarteritis nodosa, and the two terms
were often used interchangeably
 They are united by their association with antibodies directed
against proteinase 3 (PR3) and myeloperoxidase (MPO)

• annual incidence of MPA
is 2.5–10/million
Incidence and
prevalence
• Age over 65
Age
• No predilection is seen
sex
• White people are
commonly affected
Ethnicity
EPIDEMIOLOGY

PATHOPHYSIOLOGY
• ANCA can induce degranulation of
neutrophils primed by TNF‐α
• Primed neutrophils exhibit MPO
on their surface
• The MPO ANCA can induce a
respiratory burst leading to :
– degranulation
– release of toxic oxygen radicals
– intracytoplasmic enzymes
– which may lead to vascular
inflammation
PATHOLOGY
• Segmental vascular necrosis.
• Neutrophils and monocytes
permeate vessel walls
• Causing leukocytoclasis
• The accumulation of fibrin and
haemorrhage
• Focal segmental
glomerulonephritis
• Glomerulosclerosis
– suggestive of the duration of disease
and dictates the renal impairment.

Genetics
No culprit genes have been definitely identified, but the
geographical distribution of the disease is suggestive of a
genetic influence.
Environmental factors
Farming may be associated with MPA
Associated diseases
No associations are known

CLINICAL
FEATURES
Presentation
• 40% of patients have palpable purpura
• Mouth ulcers
• necrotic lesions on the fingers or toes
• splinter haemorrhages
• livedo reticularis can all be present
• 80% of patients will have renal involvement
• progressive glomerulonephritis
• pulmonary haemorrhage
• Peripheral neuropathy
History
Presenting features :
constitutional symptoms
– fever
– weight loss
– myalgia
– arthralgia
present for several weeks before
the onset of the pulmonary
and renal disease

CLASSIFICATION OF SEVERITY
The European Vasculitis Society has classified disease severity:
Localized :
Upper and/or lower respiratory tract disease without
any other systemic involvement or constitutional symptoms.
Early systemic :
Any, without organ‐threatening or life‐threatening disease.
Generalized :
Renal or other organ‐threatening disease,serum creatinine <500 μmol/L.
Severe:
Renal or other vital organ failure; serum creatinine >500 μmol/L.
Refractory :
Progressive disease unresponsive to glucocorticoidsand cyclophosphamide.

• Other ANCA‐associated vasculitis
• polyarteritis nodosa
• Peripheral eosinophilia, extravascular eosinophils,
• Nasal or paranasal sinus involvement,
• Endobronchial involvement
• Granulomas on a biopsy
• Fixed pulmonary infiltrates
• Cavitating nodules on a chest x‐ray
• Asthma
• mastoidal or retro‐orbital disease

•renal failure
• life‐threatening pulmonary haemorrhage
•Pulmonary haemorrhage
•coronary artery disease
•hypertension.
At 5 years, there is a 16% incidence of
Cardiovascular events (myocardial infarctions, cerebrovascular accidents or
coronary revascularization procedures)
MPO ANCA positivity confers a higher risk of cardiovascular events compared with
PR3 ANCA positivity.
Relapse is common and increases with time.
8% at 18 months
34% at 70 months.
Survival at 12 months is 82–92%, falling to 45–76% at 5 years.

INVESTIGATIONS
• Laboratory markers
• Urine analysis
• ANCA test
• Chest x‐ray
• CT chest
• Biopsy of kidney

MANAGEMENT
• Immunosuppressive therapies including oral or
intravenous glucocorticoids.
1. Remission induction
2. Relapsing and refractory disease
3. Remission maintenance

REMISSION INDUCTION
Pulsed intravenous cyclophosphamide (15 mg/kg every 2–3weeks)
daily oral cyclophosphamide (2 mg/kg/day)
Oral prednisolone in a dose of 1 mg/kg/day, to a maximum of 60 mg/day, is commonly used as
an adjunct to cyclophosphamide, with the aim of reducing the dose to 15 mg/day at 3 months
Plasmapheresis may have a role in saving the kidney
1 g methylprednisolone intravenously per day for 3 days can be added to speed up the
induction of remission

RELAPSING AND REFRACTORY DISEASE
• rituximab 375 mg/m 2 per week for 4 weeks is
superior to pulsed intravenous cyclphosphamide

REMISSION MAINTENANCE
Post‐cyclophosphamide: Due
to the cumulative toxicity of
cyclophosphamide
• Azathioprine (2 mg/kg/day) is
preferred to maintain remission.
• switch over can happen either at
the end of:
– six pulses of intravenous
cyclophosphamide
– or after 6 months of oral
cyclophosphamide.
Post‐rituximab:
rituximab should be used at
• 4–6 monthly intervals over the
long term as a remission
maintenance agent.

2.GRANULOMATOSIS WITH POLYANGIITIS
• Necrotizing granulomatous inflammation
• Involving the upper and lower respiratory tract
• Affecting predominantly small to medium vessels (e.G. Capillaries,
venules, arterioles, arteries and veins).
• Necrotizing glomerulonephritis is common.

• The ANCA‐associated vasculitides are a group of
conditions
• characterized by their association with the presence of
antibodies directed against PR3 and MPO.
• PR3 and MPO are intracytoplasmic enzymes of
neutrophils.

• 3–10/million per year
Incidence and
prevalence
• In children:14 years
• in adults : 50–59 years
Age
• affects males and females
equally
sex
• White people are commonly
affected
Ethnicity
EPIDEMIOLOGY

PATHOPHYSIOLOGY
• ANCA can induce degranulation of
neutrophils primed by TNF‐α
• Primed neutrophils exhibit MPO
on their surface
• The MPO ANCA can induce a
respiratory burst leading to :
– degranulation
– release of toxic oxygen radicals
– intracytoplasmic enzymes
– which may lead to vascular
inflammation
PATHOLOGY
• Perivascular lymphocytic
infiltrates.
• Leukocytoclastic vasculitis and/or
granulomatous inflammation
• Farming and occupational solvent
exposure

Granulomatosis with polyangiitis. (a) There is extensive leukocytoclastic
vasculitis involving the entire dermis. (b) Note the extensive area of
collagen degeneration,destruction of vessels and mixed inflammatory
infiltrate.
(a) (b)

at lower (c) and higher (d) magnifications There is a necrotizing vasculitis with
fibrin deposition, red blood cell extravasation and a granulomatous reaction.
(c) (d)

CLINICAL
FEATURES
Presentation
• palpable purpura
• digital infarcts
• tender subcutaneous nodules
• papules
• vesicles
• petechiae
• non‐specific ulcers
• pyoderma gangrenosum
• Nodular or papulonecrotic lesions occur:
– On the extremities
– on the face and scalp
• Oral ulcers are the second most common
mucocutaneous sign
History
Classic triad :
– Skin involvement
– Respiratory tract
– Kidneys
These features are not always
present early in the course of
the disease.

Granulomatosis with polyangiitis. (a) Cutaneous infarction. (b) Digital
infarction
(a)
(b)

Clinical presentation
• ’malignant pyoderma’ may actually have had lesions secondary to GPA.
• upper respiratory tract is commonly affected with:
– otitis media
– epistaxis
– rhinorrhoea
– sinusitis.
– A saddle nose deformity may result from necrotizing granulomas of the
nasal mucosa
• Lower respiratory signs and symptoms include :
• cough
• dyspnoea
• chest pain
• haemoptysis
• Nodules, which may be cavitating, may be visible on CXR
Cont:

X‐ray showing bilateral nodules.

80% upper or lower respiratory tract symptoms.
77% will eventually develop glomerulonephritis
73% nasal, sinus, tracheal or ear involvemnt.
40% will eventually manifest skin findings.
18% Renal disease is initially presents.
13% cutaneous manifestations and oral ulcers.

Granulomatosis with polyangiitis
Ulcerated lesions of cutaneous small‐vessel
vasculitis

Larger ulcerated lesions with background vasculitis

Deep skin ulcer in a person with nasal symptoms

Granulomatosis with polyangiitis must be differentiated from the
other types of AAV.
• In Eosinophilic granulomatosis with polyangiitis:
Destructive upper respiratory involvement and severe glomerulonephritis are
unusual which typically has asthma and eosinophilia, along with paranasal
polypoidal involvement.
• Microscopic polyangitis:
MPA has predominant renal involvement and is more likely to be associated with
MPO ANCA

Classification of severity :
The European Vasculitis Society has classified disease severity in
AAV as below:
• Localized .:
Upper and/or lower respiratory tract disease without
any other systemic involvement or constitutional symptoms.
• Early systemic :
Any, without organ‐threatening or life‐threatening disease.
• Generalized . Renal or other organ‐threatening disease; serum
creatinine <500 μmol/L.
• Severe . Renal or other vital organ failure; serum creatinine
>500 μmol/L.
• Refractory . Progressive disease unresponsive to glucocorticoids
and cyclophosphamide.

Complications and co‐morbidities:
Granulomatosis with polyangiitis or its treatment (especially
cyclophosphamide)
has a twofold increase in the risk of cancer including :
– acute myeloid leukaemia
– bladder cancer
– non‐melanoma skin cancers
GPA also predisposes to increased cardiovascular morbidity

• Remission can be achieved in up to 90% of patients.
• At 2 years , the relapse rate is between 18% and 40%.
• Untreated GPA has a 1‐year mortality of 83%; the survival of
treated disease at 1 year is >80%.
• End‐stage renal disease occurs in 7% at 12 months.
• Rising to 14% at 5 years and 23% at 10 years.

MANAGEMENT(first line)
localized disease
• Methotrexate (15–25
mg/week) in conjunction with
oral prednisolone 1 mg/kg/day
tapering to about 15 mg/day at
3 months.
non‐localized disease
• Cyclophosphamide can be used in
a daily oral 2 mg/kg/day dose for
6 months.
• Or as pulsed intravenous 15
mg/kg/pulse every 2–3 weeks for
six pulses.
• Oral prednisolone in a dose of 1
mg/kg/day,to a maximum of 60
mg/day, is commonly used as an
adjunct to
• cyclophosphamide, with the aim
of reducing the dose to 15 mg/
day at 3 months

MANAGEMENT
SECOND LINE
• contraindications to
cyclophosphamide
• with rituximab 375 mg/m2 per
week for 4 weeks.
THIRD LINE
• Patients with refractory
disease to cyclophosphamide
and glucocorticoids
• can be treated with rituximab
375 mg/m 2 per week for 4
weeks
• 15‐Deoxyspergualin
• intravenous immunoglobulin in
persistent disease

Intravenous cyclophosphamide has the advantage of a lower cumulative
dose and a lower risk of adverse events, but carries a greater risk of relapse
Remission maintenance
• Due to the cumulative toxicity of cyclophosphamide, azathioprine (2 mg/kg/day) is
preferred to maintain remission.
• The switch‐over can happen either at the end of six pulses of intravenous
cyclophosphamide or after 6 months or oral cyclophosphamide.
• Methotrexate
• leflunomide
• Mycophenolate mofetil.
• In patients where rituximab is used to induce remission, current
thinking suggests that this should used at 4–6‐monthly intervals.

3.EOSINOPHILIC GRANULOMATOSIS WITH
POLYANGIITIS
• It is an eosinophil‐rich and necrotizing granulomatous inflammation
• Involving the respiratory tract
• Necrotizing vasculitis predominantly affecting small to medium vessels.
• There is an association with asthma and eosinophilia.
• ANCA is more frequent when glomerulonephritis is present

• asthma sufferersmay be up to 67/million
per year
• incidence is 1–2.5 per million
Incidence and
prevalence
• in adults : aged 15–70 years
Age
• Male predilection
sex
• Atopy,particularly with asthma and allergic
rhinitis
Associated
diseases
EPIDEMIOLOGY

PATHOPHYSIOLOGY
• Th1 and Th17 responses are
seen
• Th2 responsible for
eosinophilic activation, and
prolonged eosinophil survival
• Eosinophilic and neutrophilic
degradation
• B‐cell involvement
PATHOLOGY
• 3 key histopathological
features:
• Eosinophilic infiltration of
tissue
• Formation of extravascular
granulomas in visceral and
cutaneous tissues
• Vasculitis involving both
arteries and veins.

Genetics
HLA‐DRB4 (Halo Nevi and Polyarticular Juvenile Idiopathic Arthritis)
Environmental factors
Environmental allergens are associated with more severe
asthma.

CLINICAL
FEATURES
Presentation
• Infiltrated nodules (on the scalp or limbs)
are the most common skin manifestations.
• Livedo reticularis
• Necrotizing livedo (i.E.Retiform purpura)
• Migratory erythema
• New‐onset raynaud phenomenon
• Aseptic pustules or vesicles
• Infiltrated papules
• 50–70% of patients have vasculitic skin lesions,
most commonly on the lower limbs
History
First phase:
Asthma with allergic rhinitis
and nasal polyps.
Second phase:
Peripheral and tissue
eosinophilia.
Third phase:
Affect almost all organ
systems

Relatively subtle vasculitis on the legs in eosinophilic granulomatosis with
polyangiitis. The patient also had eosinophilia and rapidly developed a
mononeuritis multiplex.

• ACR criteria :4 of the
following 6 features in order
to differentiate
(i) Asthma
(Ii) eosinophilia greater than 10% on
a differential white blood cell
count.
(Iii) mononeuropathy
(Iv) pulmonary infiltrates on chest
x‐ray.
(V) paranasal sinus abnormality
(Vi) a biopsy demonstrating
extravascular eosinophils.
• Lanham criteria:
1. Asthma
2. Peripheral eosinophilia
3. Systemic vasculitis in 2 or
more extrapulmonary organs.

• Remission is common in EGPA and achieved in >90% of
patients
• Relapse rates rise from 10% at 12 months to 20% at 4
years
• Survival is better than in the other AAVs.

INVESTIGATIONS
• Peripheral blood eosinophilia
• Inflammatory markers
• IgE
• ANCA (antineutrophil cytoplasmic antibodies)
• CXR
• CT scan of paransal sinuses
• Urine test
• biopsy of the affected organ

MANAGEMENT
• There are no randomized controlled trials of any treatment
for EGPA.
• treatment comes from open labelled trials and

Remission induction
Localized disease
• Prednisolone 1 mg/kg/day
• 35% will suffer a relapse
• the addition of methotrexate
20–25 mg/week,without
organ‐ or life‐threatening
involvement
Systemic disease
currently preferred regimen
• Intravenous pulsed
cyclophosphamide 15
mg/kg/pulse at 2–3‐weekly
intervals (six pulses)
• with oral prednisolone 1
mg/kg/day (maximum 60 mg).

REMISSION MAINTENANCE
Post‐cyclophosphamide: patients are switched to azathioprine
2mg/kg/day.
Post‐methotrexate . Remission is maintained by continuing
methotrexate long term.
Post‐rituximab . There is very little information on postrituximab
• use rituximab according to clinical need rather than every 6 months.

MEDIUM‐VESSEL VASCULITIS
1. Polyarteritis nodosa and cutaneous polyarteritis
nodosa
2. Kawasaki disease

1.POLYARTERITIS NODOSA
• (PAN) is a rare necrotizing arteritis of medium or small arteries
without glomerulonephritis and without vasculitis in the arterioles,
capillaries or venules.
• It is not associated with ANCAs
Cutaneous PAN (cPAN) is a single‐organ vasculitis
• affecting the skin. It is better termed cutaneous arteritis.

• incidence is 1–2.5 per million
Incidence and
prevalence
• peak age is between 40 and 60 years of age
Age
• No specific predilection
sex
• Hepatitis B
Associated
diseases
EPIDEMIOLOGY

PATHOPHYSIOLOGY
PATHOLOGY
• Neutrophilic inflammatory
infiltrate
• an eosinophilic ring of
fibrinoid necrosis.
• consisting predominantly of
lymphocytes and histiocytes.
• Complement and IgM
deposits in vessel walls of
lesions of cutaneous arteritis
PREDISPOSING FACTORS
• Viral infections
– hepatitis B virus
– Epstein–Barr virus
– erythrovirus (parvovirus B19)
– Cytomegalovirus.
• streptococcal infections
• erythrovirus (parvovirus B19)
• Mycobacterium fortuitum

CLINICAL
FEATURES
Presentation
• Dermal or subcutaneous nodules are most
commonly located:
– On the distal lower extremities near the malleoli
– And may extend proximally to the thighs,
buttock, arms or hands.
• Tenderness associated with the nodules, which
may ulcerate
• Necrotizing livedo reticularis
• Retiform purpura
• Gangrene of the digits
History
cutaneous manifestations are
the most striking feature
of the disease

Cutaneous polyarteritis nodosa
Erythematous lesions on the leg.

Nodules and ulceration on the leg

Ulcerating lesions on the leg

Livedo of the leg

• Adult onset Still disease (AOSD)
• ANCA‐associated vasculitis
• Cutaneous arteritis

• Gastrointestinal tract
• Renal
• Heart
• Central nervous system
Their involvement are associated with higher mortality

Investigations
• Laboratory investigations are usually non‐specific
• Biopsy
• visceral angiography

MANAGEMENT
First line
• Nsaids
• Salicylates
• Corticosteroids
• Methotrexate
• Dipyridamole
• Sulfapyridine
• Pentoxifylline and dapsone
Second line
• hepatitis B‐associated PAN
high‐dose corticosteroids
for 2 weeks, followed by
antiviral treatment and
plasma exchange
• combination of
cyclophosphamide and
corticosteroids
Chronic leg ulcers resistant to treatment with high‐dose corticosteroids
have been successfully treated with granulocyte–macrophage
colony‐stimulating factor (GM‐CSF)

2.Kawasaki disease
• arteritis associated with the mucocutaneous lymph node
syndrome.
• affecting medium and small arteries.
• Coronary arteries are often involved (aorta and large arteries)
• usually occurs in infants and young children.

• in infants and children less than 5 years of age
• Benign febrile illness associated with mucocutaneous
inflammation and lymphadenopathy, until the
demonstration of coronary arteritis
• commonest cause of acquired heart disease in children

• annual incidence per 100 000 children aged
under 5 years
Incidence and
prevalence
• always occurs in children under 5 yrs
Age
• Mild male predilection
sex
• coronary vessel aneurysms and myocardial
infarction
Associated
diseases
EPIDEMIOLOGY

PATHOPHYSIOLOGY
• It is an intense inflammatory
response to an unidentified
infectious agent
• in genetically susceptible hosts.
PATHOLOGY
• Initially, there is medial edema
associated with neutrophilic
infiltration
• The inflammatory processes results:
– in the breakdown of internal and
external elastic laminae
– resulting in aneurysms and thrombosis.
• The inflammatory processes heal with
scarring
• resultant stenosis of the affected blood
vessel

GENETICS
• ITPKC (inositol‐1,4,5‐trisphosphate 3‐kinase C) gene on
chromosome 19q13.2
• significantly associated with a susceptibility to Kawasaki
disease and coronary artery aneurysms

CLINICAL
FEATURES
Presentation
• Patients present with at least 5 days of fever,
irritability, vomiting, anorexia, cough, diarrhea,
runny nose, weakness and abdominal and joint
pain.
• The fever is typically spiking and unresponsive to
paracetamol.
• There is acral and perianal erythema and acral
oedema
• bilateral conjuncitivitis with anterior uveitis,
• fissured lips and a strawberry tongue
• cervical lymphadenopathy, typically a single large
cervical node.
History
initial stage:
febrile stage lasting up to 2
weeks.
second phase:
lasting 4–6 weeks
increase risk of death from
coronary aneurysms.
Convalescent phase:
lasting up to 3 months
Chronic phase: risk of late
aneurysm rupture even in
adult life.

Scarlet fever
(strawberry tongue)
systemic‐onset juvenile
idiopathic arthritis
erythema multiforme

CLASSIFICATION OF SEVERITY
• Harada score has been used in some countries as an
indication for intravenous immunoglobulin therapy
4 of following 7 criteria are needed:
(i) white blood count >12 000/mm
(ii) platelet count <35 × 10 4 /mm
(iii) CRP >3
(iv) haematocrit <35%
(v) albumin <3.5 g/dL
(vi) age <12 months
(vii) male sex

• There may be hepatic, renal and gastrointestinal
dysfunction,myocarditis and pericarditis

• Deaths may occur due to
– myocarditis
– dysrhythmias
– pericarditis
– rupture of aneurysms
– occlusion of coronary arteries
• increased risk of atherosclerosis due to endothelial cell
dysfunction
• Coronary aneurysms are demonstrated in around 20% of
patients (and in 90% of those who die)
• some will regress (potentially with stenosis) but giant
aneurysms (>80 mm) may require bypass surgery.

Cont.
• Clinical factors that predict a higher risk of coronary artery
arteritic lesions or aneurysms, or that predict a poor
response to treatment are:
– include age below 1 year
– low serum albumin
– low haemoglobin
– high CRP
– abnormal liver function
– duration of fever before treatment.
– Peripheral blood eosinophilia (>4%) after treatment is also associated with
treatment resistance.

Cont.
• Early intravenous immunoglobulin (IVIg)
reduces the coronary aneurysm risk from around 25% to
less than 5%.
• Delaying IVIg beyond day 10 of fever increases the risk of
death, particularly in boys under 1 year old.

INVESTIGATIONS
• There are no diagnostic tests and Kawasaki disease
remains a clinical diagnosis

MANAGEMENT
First line:
• IV immunoglobulin and aspirin should be given early.
• Aspirin 100 mg/kg/day is given initially until the fever has
settled
• then reduced to 3–5 mg/kg/day for 6–8 weeks (in those
with no cardiac abnormality, but longer in those with coronary
aneurysms. )
• All children should receive IVIg, usually given as a single
dose of 2 g/kg over 12 h

MANAGEMENT
Second line
• For children who remain febrile 36 h after the first dose of
IVIg,
• a further dose of 2 g/kg can be given.
• Patients who are unresponsive to IVIg can be treated
with high‐dose prednisolone 2 mg/kg/day, which should
be tapered after normalization of the CRP

1.GIANT CELL ARTERITIS
• Giant cell arteritis (GCA) is an arteritis, often granulomatous
• Usually affecting the aorta and/or its major branches, with a
predilection for the branches of the carotid and vertebral arteries.
• Often involves the temporal artery.
• Often associated with polymyalgia rheumatica

• Disease of the elderly.
• Often associated with polymyalgia rheumatica,
• Which presents with headaches and tender palpable
arteries, usually the temporal artery.
• It can rarely cause cutaneous infarction, so presenting to
dermatologists

• Highest mean annual incidence,32.8/100
000 in southern Norway
Incidence and
prevalence
• over the age of 50
Age
• 2–3 times more common in women than
men
sex
• polymyalgia rheumatica
Associated
diseases
EPIDEMIOLOGY

PATHOPHYSIOLOGY
• an inflammatory response
• Local dendritic cells activates CD4
cells in the adventitia.
• Cytokine cascades involving Th1
and Th17 pathways dominate in
the early phase,
• followed by a chronic smouldering
arteritis led by chronic Th1
activation.
• Resulting is a stenosing arteritis.
PATHOLOGY
• Lesions can be found in all layers of the
affected branches of the aorta,
particularly the carotid branches.
– These show segmental and focal
pan‐arteritis
– polymorphic cell infiltrates along
with T cells, macrophages and
multinucleated giant cells
– intimal hyperplasia
– with a fragmented internal elastic
lamina

Giant cell arteritis at (a) lower and (b) higher magnifications. There
are obliterative vascular changes with a lymphocytic and multinucleated giant cell
reaction in the vessel wall
(a) (b)

CLINICAL
FEATURES
Presentation
• Headache may be localized to the area of the
affected artery, that is
– temporal with temporal arteritis and
– occipital with vertebrobasilar artery
• Sudden, permanent visual loss related to ocular
or orbital artery involvement may occur.
• Transient monocular loss of vision (amaurosis
fugax) may precede permanent loss.
• Vertebrobasilar artery involvement may cause
ataxia, vertigo or deafness.
• The temporal arteries may be tender, thickened
and pulseless.
• A bruit may be heard over affected arteries (e.g.
axillary).
History
Fever and weight loss
Polymyalgia rheumatica
(in about 50% of patients)
Headache
Facial pain
Vision loss
Deafness

Clinical variant
Isolated aortic inflammation without cranial artery
Differential diagnosis:
ANCA‐associated vasculitides
Cancer
• Permanent visual loss
• aortic aneurysms

• slight excess mortality over 2 years (standard mortality rate 1.52;
95% confidence interval 1.20–1.85)
• The excess mortality was greater in women and in those
aged ≤70 years

INVESTIGATIONS
1. Biopsy of an affected artery ,the biopsy should be performed within
1–2 weeks of commencing corticosteroid therapy
2. Colour Doppler ultrasound of the temporal and axillary
arteries,reveals intramural inflammatory change
3. Positron emission tomography with 18‐fluorodeoxyglucose is of
value to demonstrate aortitis
• The ESR or CRP are almost always elevated. A normochromic,normocytic anaemia,
thrombocytosis and raised alkaline phosphatase may all be present

MANAGEMENT
First line
• Corticosteroids, for example
prednisolone 40–60 mg
daily
• Treatment is usually for
about 2 years
Second line
• methotrexate,which can be
used in doses of 15–20
mg/week

2. TAKAYASU ARTERITIS
• Takayasu arteritis is often granulomatous
• Predominantly affects the aorta and/or its major branches.
• onset is usually in those younger than 50 years

• 0.5–2.5/million,more higher
in japan
Incidence and
prevalence
• below the age of 50
Age
• common in women than men
sex
• Common in asians
Associated
diseases
EPIDEMIOLOGY

PATHOLOGY
• The aorta and its branches are targeted and skip lesions can occur.
• During the acute phase, a pan‐arteritis is present.
• inflammatory infiltrate around the vasa vasorum,
• fibrosis
• vessel lumen may be narrowed
• secondary to the fibrosing stenotic lesions
• or by intraluminal thrombosis.
• In older patients atherosclerosis, and calcification

GENETICS
• IL‐12B on chromosome 5
• MLX on chromosome 17
• FCGR2A/FCGR3A on chromosome 1
• HLA‐B*52:01 are known associations

CLINICAL
FEATURES
Presentation
• Hypertension, pyrexia and pulseless disease are
common findings in children.
• Skin lesions
– erythema nodosum
– erythema induratum
– pyoderma
– Gangrenosum
– ulcerated subacute nodular lesions
– papulonecrotic eruptions
– papular erythematous lesions of the handsand
fingers
– facial lupus‐like rashes
– panniculitis
– Cutaneous necrotizing vasculitis
History
•Headache
•Malaise
• fever
Common in children
• Cutaneous lesions (1/3 of
patients)

Facial pyoderma gangrenosum
Associated with takayasu arteritis

• Renal artery stenosis
• Increased arterial stiffness
• Increased sensitivity of the carotid sinus reflex all contribute to the hypertension.
• Abdominal pain, bleeding or perforation may result.
• Involvement of the aortic arch and its branches can lead to the ’aortic arch syndrome’
with arm claudication, absent radial or brachial pulses (hence ’pulseless disease’) or
subclavian artery bruits.
• Aortic regurgitation
• Coronary artery ischaemia with angina or myocardial infarction
• Pulmonary hypertension, stroke, syncope and visual disturbances can occur

• Most patients with Takayasu arteritis will need vascular
surgery
• although restenosis is common
• The disease and its treatment both lead to an impairment
in quality of life

INVESTIGATIONS
• Gold standard test : Positron emission tomography using
18‐fl uorodeoxyglucose. However, due to the high radiation
dose
• magnetic resonance angiography could be used for
follow‐up monitoring.
• The ESR and CRP are usually elevated but this may be
modest

MANAGEMENT
First line
• Prednisolone 1 mg/kg/day
• azathioprine
Second line
• Cyclophosphamide
• infliximab
• tocilizumab

Cutaneous vasculitis by dr maria

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