Ahmed Yehia Ismaeel

Ass. Lecturer

Bani-Sweif

Nephrologists

&

Vasculitis

BLOOD VESSELS

Pathology in blood vessels

Congenital Anomalies

Arteriosclerosis

HTN

Vasculitides ( inflammations)

Aneurysms & Dissections

Veins & Lymphatics

Tumors

What is Vasculitis?

Inflammation of blood vessels

occlusion aneurysm

ischemia hemorrhage

WHICH BLOOD VESSELS

ARE AFFECTED?

ANY BLOOD VESSEL CAN BE AFFECTED:

ARTERIES

ATERIOLES

CAPILLARIES

VENULES

VEINS

CAN DAMAGE VIRTUALLY ANY ORGAN OR

TISSUE.

Vasculitis classification

According to:

Size of Vessels involved

Site of involvement

Characteristic Features

CLASSIFICATION OF

VASCULITIS1990- American College of Rheumatology

(ACR) Classification Criteria

1994- Chapel Hill Consensus Conference (CHCC)

European Medicines Agency developed a stepwise algorithm for vasculitis in 2007

CHCC definitions were revised in 2012

•ANCA testing not

included

•PAN and MPA put

togather

•Size of blood vessel (tissue

Bx)

•PAN and MPA seperated

•ANCA suggested

•AAV- WG, CSS, MPA

•ACR

•Lanham crietria for

CSS

•ANCA

•CHCC defination

Large vessels are the aorta and its major branches

and the analogous veins.

Medium vessels are the main visceral arteries and

veins and their initial branches

Small vessels are intraparenchymal arteries,

arterioles, capillaries, venules, and veins

Case

A-57-year old male was admitted to

nephrology unit because of renal dysfunction

and severe anemia. One month before

admission, he was in a relatively good health.

Physical examination on admission revealed

BP 140/100, temperature: 37.3ºC and apical

systolic murmur was found.

Caspian J Intern Med 2012; 3(3): 496-499

Early laboratory examination revealed

s.creatinine: 2.8 mg/dl, BUN: 94 mg/dl,

urinalysis; 2+ proteinuria / hematuria,

WBC: 8700/µl, hemoglobin: 7.3 g/dl,

ESR: 110 mm/h, CRP:+ve

24 hours urine :800 mg/day proteinuria.

Negative results for hepatitis B and hepatitis

C infections.

S. complement C3: 53 mg/dl (90-180),

C4: 15 mg/dl (10-40), CH50: <50 (70-150U)

Anti-GBM antibody: 5.8 U/ml (< 15)

PR3-ANCA: 45 U/ml (<0.4),

MPO- ANCA: 0.1 U/ml (<3.1U/ml),

Rheumatoid factor (RF): 2+ positive,

(ANA):1+ positive,

(anti-dsDNA) and anti-cardiolipine antibodies : -

ve.

Ultrasound :increased renal parenchymal

echogenicity, RT kidney size :112mm & LT :

Renal biopsy revealed focal and segmental

glomerular necrosis with an increase in

mesangial matrix, capillary lumen narrowing

and closure without hypercellularity.

An immunofluorescent study showed IgG, IgM,

and C3 deposit in the mesangial regions.

What is the first line of

treatment?

Renal biopsy was performed and with the

suspicion of renal limited ANCA associated

(RPGN),

methylprednisolone pulse therapy, 500 mg

daily for two consecutive days was started.

3 days after receiving steroid therapy the

patient’s general condition worsened and

started chilling with high grade fever.

Blood culture was performed and empiric

antibiotic therapy with 3rd generation

cephalosporin and vancomycin were started.

Echocardiography: multiple large vegetations

on the aortic valve, severe aortic

regurgitation with pseudoaneurysm

formation with systolic bulging.

TEE confirmed the findings.

The patient became afebrile after the start of IV

antibiotic therapy with ceftriaxone, gentamicin and vancomycin. His fever dropped within 72 hours, then he underwent cardiac surgery and aortic valve replacement.

After 2 months, the patient’s general condition improved dramatically and his serum creatininelevel was1.7 mg/dl hemoglobin reached 12 mg/dl.

The results of PR3-ANCA, RF and ANA negative and C3 serum level level returned to normal.

Message from the case

Sub-acute bacterial endocarditis

(SBE) can rarely manifest with

features of SVV.

It is usually attributed to

microembolism and the effects

of circulating immune

complexes on the vascular

endothelium.

The differentiation

The differentiation between SBE induced

vasculitis and primary SVV can be difficult

sometimes especially if the heart murmur is

absent.

The minor criteria for SBE including fever,

GN and purpura are similar to the manifestations

of primary AAV.

Osler's nodes, Janeway lesions and splinter

hemorrhages typical for SBE may mimic

cutaneous vasculitis .

Non-infectious endocarditis sometimes is a part

of a clinical spectrum of systemic vasculitis.

The D.D. is much more difficult when a culture-

negative SBE has positive laboratory test results for

ANCA.

Misdiagnosis of SBE as AAV and an inappropriate

immunosuppressive therapy can have

catastrophic consequences.

AKI can complicate the course of SBE as :

1. infection induced interstitial nephritis,

2. acute tubular necrosis,

3. glomerulonephritis and

4. antibiotic related interstitial nephritis.

Clues for secondary

vasculistis??

Double ANCA positivity.

Low levels of serum complement.

Multiple antibody positivities: e.g.RF, ANA,

cryoglobulins and anticardiolipin antibodies.

The patients with primary ANCA associated

vasculitis have higher rate of nasal and sinus

involvement.

The biopsy

The common denominator in all types of RPGN is severe glomerular injury

SUMMARY OF CLASSIFICATION

It has weak or no demonstrable immunoglobulin / complement deposition,

RAPIDLY PROGRESSIVE

GLOMERULONEPHRITIS

Type III

RPGN

IMMUNOFLUORESCENCE

Abstract

Objective: Chronic infections tend to induce the production of ANCA.Infective

endocarditis (IE) has been reported to exhibit positive ANCA tests and to mimic ANCA-

associated vasculitis, which may lead to a misdiagnosis and inappropriate treatment.

The aim of this study was to clarify whether there is any difference in the clinical features

between ANCA-positive IE and ANCA-negative IE.

Methods: A retrospective study was carried out on 39 IE patients whose (PR3)-ANCA

and (MPO)-ANCA levels were measured. After dividing the patients into ANCA-positive

and ANCA-negative IE, we compared their clinical features.

Results: we compared 13 ANCA-positive IE patients with 26 ANCA-negative IE

patients. All 13 ANCA-positive IE patients were PR3-ANCA positive. The prevalence of

lower limb edema, LDH level and positive blood cultures rate were higher in ANCA-

positive IE group, but there was no significant difference in other clinical features.

Conclusion: if a patient presents with fever, arthralgia, skin rash and

is ANCA-positive, appropriate steps should be taken to

exclude infection (especially IE) before confirming the diagnosis

of ANCA-associated vasculitis and embarking on long-term

immunosuppressive therapy.Ying C-M, Yao D-T, Ding H-H, Yang C-D (2014) Infective Endocarditis with Antineutrophil Cytoplasmic Antibody: Report of 13 Cases and Literature

Review. PLoS ONE 9(2): e89777. doi:10.1371/journal.pone.0089777

Hepatitis B virus

PAN

Hepatitis C virus

Cryoglobulinemic vasculitis

A case from Bani-Sweif (our

department)

A 28 year old male patient, complaining of shortness of

breath for 3 months duration.

**3 months prior to admission:

Dyspnea on moderate exertion progressing to dyspnea at rest with orthopnea and P.N.D.

**2 months later:

Periorbital puffiness, associated with bilateral lower limb swelling & abdominal distension.

Throughout illness: constitutional manifestations, recurrent epistaxis & occipital headache .

On Examination

• Radial Pulse: 88/min, regular, of big pulse

• Blood Pressure:

(230/140 mmHg) • Respiratory Rate: 30/min.

Investigations

Laboratory work up:Na: 139 mEq/L.K: 4.5 mEq/L.Blood urea: 65 250 mg/ dL. Serum creatinine: 1.9 6.8 mg/dLCRP: +ve (48 mg/L). ESR: 45 mm / 1st hour.Serum albumin: 3.4 gm %. Total proteins: 6.4 gm %.Urine analysis: Granular casts (++) & albuminuria (++). 24-hours urine collection for albumin: 465 mg / day. CBC: Normocytic&normochromic anemia.Lipogram: Normal

Viral markers: -HBs Ag: -ve HBc Ab: - ve-HCV Ab: -ve-HIV Ab: -ve

Abdominal Ultrasound:

-Rt. kidney is small in size (7.5 x 2.5 cm) with grade II echogenic parenchyma.

Colour duplex of both renal arteries:

Rt. renal artery is attenuated distally .

DTPA Scintigraphy (split renal function):

17% residual contribution of Rt kidney.

Next step?

Is it fibromuscular

dysplasia?

Is it atherosclerotic?

So, MRA of the aorta & its main branches:

Stenosed Lt. subclavian and Lt common carotid arteries.

• Angiography of the aorta & its main branches:

-Attenuated Rt. renal artery.

-Aortic arch shows normal origin and caliber of both the innominate and Lt. common & carotid arteries.

-The origin of the Lt. subclavian artery is obliterated.

-The Lt. subclavian fills from the vertebral artery.

Diagnosis?

Diagnosis

TAKAYASU

ARTERITIS

(The occlusive

thromboaortopathy or

pulseless disease)

Clues not to be missed

From history : Marked constitutional

symptoms.

From investigations : ++ acute phase reactants

Abdominal Ultrasound:

-Rt. kidney is small in size (7.5 x 2.5 cm) with grade II echogenic parenchyma.

Colour duplex of both renal arteries:

Rt. renal artery is attenuated distally

The most important & easiest

clue

which is usually missed:•Radial Pulse: 88/min, regular, of big pulse volume on the Rt side but absent on the Lt side, all other peripheral pulses were felt with no radio-femoral delay.

•Blood Pressure:Rt. arm (230/140 mmHg) Lt. arm (150/100 mmHg).

AHA recommendations

The AHA recommends that at least two readings be taken, with a one-minute interval between them, and the average of the measurements recorded. The firstreading in a series is usually the highest. Additional readings should be taken if the difference between the first two is greater than 5 mm Hg

At the first visit, blood pressure should be measured in both arms, which may be useful for identifying coarctation of the aorta and upper-extremity arterial obstruction. If there is a consistent difference in measurement between the arms, the highest pressure should be recorded. In children, the right arm is always preferable for consistency and comparison with reference tables.

Am Fam Physician. 2005 Oct 1;72(7):1391-1398.

European Society of Hypertension

recommendations

The recommendation is that bilateralmeasurement should be made on

first consultation and, if reproducible

differences greater than 20 mmHg for

systolic or 10 mmHg for diastolic pressure

are present on consecutive readings, the

patient should be referred to a

cardiovascular centre for further evaluation

with simultaneous bilateral measurement

and the exclusion of arterial disease .Journal of Hypertension 2003, 21:821–848

Diagnostic pathway

1.Suspect

2.Investigate:

systematic,

serology,

biopsy

3.Exclude mimics

and identify

drivers

Step one: When to suspect

vasculitis?

Step two: The diagnostic strategy

Having considered the possibility of primary vasculitis we suggest you try to answer the following questions in

succession:

Is this a condition that could mimic the presentation of vasculitis?

Is this a secondary vasculitis?

How do I confirm the diagnosis of vasculitis and what is the extent of the disease?

What specific type of vasculitis is this?

1.When to suspect vasculitis?

1.Constitutional features:fatigue,

weight loss, night sweats and low grade fever (the B-symptoms), weakness & anorexia.

2.Musculoskeletal :

Myalgias , arthralgia & arthritis.

3.Skin:

Palpable purpura , digital infarction , punched out ulcers & livido reticularis.

4.Multisystem involvement(according to the type of vasculitis)

When to suspect vasculitis

Presence of following findings alone or in combination or other bizarre systemic manifestations should raise the suspicion of vasculitis - – Occlusive arterial disease or hypertension in young adults.

– Unexplained fever, weight loss.

– Unexplained proteinuria with or without casts.

– Splinter haemorrhages in nails

– cutaneous lesions - palpable purpura, erythema, subcutaneous nodules or urticaria.

– Sudden retinal vascular disease without hypertension or diabetes.

2.Rule out vasculitis mimickers (they cause vessel

occlusion without true inflammation):

1.Cholesterol embolization.

2.antiphospholipid syndrome.

3.infective endocarditis embolism.

4.chronic egotism.

5.atrial myxoma with emboli

•Persistent headache with sudden visual impairment (monocular blindness) in elderly.

•J aw claudication

•Sudden appearance of peripheral neuropathy - wrist drop, foot drop.

•C erebrovascular/cardiovascular events in young.

•Unexplained finding of pulmonary nodular/cavitatory lesions.

Mimicks of vasculitis

Mimicks of vasculitis

Challenging mimickers of

primary systemic vasculitisThe need to distinguish true primary systemic vasculitis from its

multiple potential mimickers is one of the most challenging diagnostic conundrums in clinical medicine. This article reviews 9 challenging vasculitis mimickers:1. fibromuscular dysplasia, 2. calciphylaxis, 3. segmental arterial mediolysis,

4. antiphospholipid syndrome,

5. hypereosinophilic syndrome,

6. lymphomatoid granulomatosis,

7. malignant atrophic papulosis,

8. livedoid vasculopathy, and

9. immunoglobulin G4-related disease.

Rheum Dis Clin North Am. 2015;41(1):141-60,

In particular, infections deserve careful attention, as they are major mimics of vasculitis and would be

aggravated by medication aimed to suppress vascular inflammation. Infective endocarditis should always be

considered. It is known to mimic vasculitis. Although the endocardium is the primary site of infection, it often

results in multisystem manifestations, involving several organs. Bacteraemia and peripheral embolic events

are common. Circulating immune complexes may lead to immune responses most often affecting the skin, the

kidney and the central nervous system.

Differential diagnosis is not always simple.

EULAR on-line course on Rheumatic Diseases

Diagnostic strategies in rheumatology – In-depth discussion 1 – Module 1

©2007-2014 EULAR

Clinical and laboratory

similarities between infection

and vasculitis Clinical findings:

• B-symptoms (fatigue, weight-loss, fever)

• myalgia

• arthralgia

Laboratory findings:

• normocytic normochromic anaemia

• lymphocytosis

• thrombocytosis

• elevated ESR

• raised CRP

Laboratory work up for the evaluation of suspected

vasculitis and for determining systemic involvement:

-DIRECTED:

1.blood cultures.

2.Infection serologies

3.ANA, RF

4.Antiphosphlipid antibodies.

5.C3 / C4 / CH50

6.Cryoglobulins.

-Other diagnostic studies.

1.chest X-ray or CT scan

2.Sinus X-ray or CT scan.

3.Brain CT or MRI

4.EMG, NC studies.

5.ECHOcardiography

3.Exclude Secondary vasculitis

(Exclude underlying cause)

1. Infection related vasculitis ( HB&CV-IE)

2. Connective tissue diseases : RA ,SLE Sjögren's

syndrome, inflammatory myopathies

3. Inflammatory bowel disease.

4. Malignancy related vasculitis: Lymphom, leukemia,

myeloproliferative or myelodysplastic syndromes.

5. Drugs

• These lists pose an important practical problem: immediate onset of immunosuppressive treatment might be

• lifesaving in primary vasculitis – but it could be fatal for one of the other conditions.

• A structured diagnostic approach is indispensable.

EULAR on-line course on Rheumatic Diseases

Diagnostic strategies in rheumatology – In-depth discussion 1 – Module 1

©2007-2014 EULAR

4.Determine the size of the vessel

affected:

*Palpable purpura ,superficial ulceration ,

mononeuritis multiplex & RBCs casts in urine

small vessel vasculitis

* Cutaneous nodules , livido reticularis ,

papulonecrotic lesions & digital infarction

medium vessel vasculitis

*Pulse deficit or bruit large vessel vasculitis

*Organ failure is not specific for any size e.g AKI

(RPGN or acute renal infarction)

Clinical finding according to

vessel involvement

5.Determine the specific type of

vasculitis within the vessel size group:

e.g. GPA &MPA are pauci-immune.

(IgAv) HSP is characterized by IgA-dominant

immune complex deposition.

GPA classically involves upper airways,

lungs and kidneys.

Cogan’s syndrome involves eyes, inner

ears and large arteries (in 10 -15 % of

cases)

IgAv typically affect skin, joints, kidneys and

gut.

ORGAN

TROPISMS

The epidemiologic features features of

individual forms of systemic vasculitis vary

by

Behcet’s disease more common in countries

bordering the ancient Silk road …

Takayasu’s arteries is the most common

cause of renal artery stenosis in India…

Geographic location

is an important

considerations in

epidemiology of vasculitis.

80% of patients with Kawasaki’s disease are younger than 5 years of age.

Giant cell arteries never occurs in patients younger than 50years old.

HSP (IgAv) in children have self-limited courses.

In adult HSP has a higher likelihood of chronicityand poor renal outcome

Age

Buerger’s disease is the only form of vasculitis

with striking male predominance.

TA has great tendency to occur in female (9-1).

Gender

Forms of vasculitis associated with

inflammation

Giant – cell arteritis.

Takayasu’s arteritis.

Cogan’s syndrome.

GPA.

Primary angiitis of CNS.

EGPA.

Granulomutous

Eosenophilic infiltrate

Leukocytoclastic angiitis…

with fragmented neutrophils

infltration of the wall of cutaneous

vessels differes from MPA …

It does not involve internal organs

ANCA -ve

FAST FACTS

Vasculitides affect multiple organ systems

and have highly variable presentations often

without classic findings.

FAST FACTS

Conventional angiography,

Computed Tomographic Angiography

(CTA) Magnitic Resonance

Angiography (MRA) are useful

diagnostic modalities.

•New imaging modalities such as colour

Doppler ultrasound and positron-emission

tomography are providing insights into the

extent and pathogenesis of large vessel

vasculitis.

•But have not yet replaced temporal artery

biopsy and angiography as the gold standards

for diagnosis

FAST FACTS

The mainstay of treatment for most of systemic

vasculitides is corticosteroids ,,, additional

Immunosuppressives may be necessary

in severe diseases.

FAST FACTS

• Details on AAV

• Pitfalls in ANCA testing

• Guidelines & updates in management

Is our next topic in shaa ALLah