systemic vasculitis: a clinical approach geordie lawry md chief, rheumatology uc irvine medicine hs...

Systemic Vasculitis: a clinical approach

Geordie Lawry MDChief, Rheumatology

UC IRVINE

Medicine HS Noon Conference: October 2015

Objectives 1

• List the 4 clinical features which should prompt you to CONSIDER A DIAGNOSIS of systemic vasculitis

• List the “Big 5” essential questions in patients with SUSPECTED GIANT CELL ARTERITIS

• Describe what is meant by PULMONARY RENAL SYNDROME

Objectives 2

• List at least 3 ORGANS / SITES commonly involved in:

CRYOGLOBULINEMIC VASCULITISGRANULOMATOUS POLYANGIITIS (GPA)MICROSCOPIC POLYANGIITIS (MPA)CLASSIC POLYARTERITIS NODOSAGIANT CELL ARTERITIS

Objectives 3

• List at least 2 ANCA VASCULITIS SYNDROMES, associated ANCA pattern / target antigens

• List at least 2 vasculitides which are NOT ASSOCIATED WITH ANCA

• List at least 3 or more conditions that can MIMIC THE CLINICAL FEATURES OF VASCULITIS

VASCULITIS: Talk Outline• Introduction and Definitions• Approach to vasculitis • Specific Disorders:

– Giant Cell Arteritis– Granulomatous polyangiitis (Wegener’s) – Microscopic Polyangiitis – Polyarteritis Nodosa– Cryoglobulinemia

• Take Home

VASCULITIS: principles 1

group of clinical syndromes characterized by inflammation of blood vessels

Normal Artery Artery: WBC inflammation in wall

VASCULITIS: principles 2

systemic diseases that can affect many different organ systems

can be difficult to diagnose: challenging clinical picture even for experienced clinicians

can be life-threatening

VASCULITIS: classification

www.wegenersgranulomatosis.net/imageRJN.JPG

General Approach to Vasculitis

Throw up your hands….


Slap at it ….

When should vasculitis be suspected? 1

• MULTISYSTEM inflammatory disease

• Significant CONSTITUTIONAL SYMPTOMS

• RAPIDLY PROGRESSIVE organ dysfunction

• HIGH ESRSEVERE anemiaPLATELETS > 500K

When should vasculitis be suspected? 2

CLINICAL FEATURES PARTICULARLYSUGGESTIVE of small vessel inflammation:

•SKIN: palpable purpura *

•LUNGS: pulmonary infiltrates / hemoptysis

•KIDNEY: active urinary sediment

•NEURO: foot drop **

What is the approach to a patient suspected of

having vasculitis?

WHAT IS YOUR APPROACH TO ANY COMPLEX MEDICAL

PROBLEM?


Gather your equipment….Find the target….Take aim…..NAIL IT !

COMPLEX MEDICAL PROBLEMS 1

HISTORY: PATIENT’S STORY

get careful CHRONOLOGY

…….PROBLEMS

PHYSICAL EXAM: BODY’S STORY

thoughtful, thorough

……..MORE PROBLEMS

LABORATORY: BEHIND-THE-SCENES STORY

Basic CBC, CHEMS, LFTs, UA/micro, CXR

……..MORE PROBLEMS

.


Develop a strategy: PROBLEM LIST

CREATE PROBLEM LIST

……… LIST EVERYTHING [split don’t lump]

PRIORITIZE PROBLEM LIST

……… WHAT’S THE BIG GORILLA(S) HERE?

“WORK” the PROBLEM LIST


“WORK” the PROBLEM LIST

• Think of 3 explanations for each problem Create a differential diagnosis

• What are the major organs involved?

• Do they inter-relate?Do the patient’s, body’s and the behind-the-scenes stories fit together in some way?


SYSTEMIC VASCULITIS ?

• Are there additional tests which could help confirm this suspicion?

• Serologic tests

• Imaging studies

• Tissue biopsy

VASCULITIS: additional testing 1

Serologic tests

•ANCA

•Hepatitis B surface antigen

•Hepatitis C, C3 & C4

•HIV

•ANA

•ACA, “lupus” anticoag panel


Imaging studies

•Sinus CT scan

•Chest CT scan

•Mesenteric angiogram


Tissue biopsy

•Temporal artery

•Sural nerve

•Muscle

•Lung

•Renal

Common Clinical Manifestations

• Systemic– Fever, sweats,

weight loss

• Skin– Palpable Purpura

• Neurologic– Mononeuritis Multiplex

• Musculoskeletal– Arthralgia / arthritis– Muscle pain /

claudication

• Respiratory– Sinusitis / Epistaxis– Pulmonary infiltrates

• Gastrointestinal– Abdominal Pain– Bloody stools

• Renal– Glomerulonephritis– Hypertension

CUTANEOUS

Palpable Purpura

Livedo Reticularis

Splinter Hemorrhages

NEUROLOGIC

• Mononeuritis multiplex: check for FOOT DROP

Sural nerve biopsy showing vasculitis

RESPIRATORY: upper

• Sinusitis• Or……

www.conseils-orl.com/.../sommaire_epistaxis.htm

RESPIRATORY: lower

• Pulmonary infiltrates• Nodules• Cavities

GENITOURINARY

• Glomerulonephritis• Hypertension• Hematuria• RBC casts

• Testicular pain(especially PAN)

www.bio.davidson.edu/.../Cresgn.jpg

MUSCULOSKELETAL

• Polyarthralgias - common• Polyarthritis - less common

• Myalgias - common• Myositis - biopsy may demonstrate

vasculitis in muscle

GASTROINTESTINAL

• Mesenteric ischemia– pain 30 minutes after eating– bloody diarrhea– bowel perforation

• hepatitis• pancreatitis• cholecystitis

library.med.utah.edu/WebPath/COW/COW125.html

OCULAR

http://www.uveitis.org/images/sarcoid6.jpg

Retinal Vasculitis

http://webmedia.unmc.edu/eye/iritis.jpg

Iritis

Scleritis

eyelearn.med.utoronto.ca/.../RedEye/10Sclera.htm

Common Laboratory Findings

INFLAMMATION:

Elevated ESR (can be > 100)

Elevated CRP

Leukocytosis

Thrombocytosis

Anemia

Low Albumin

VASCULITIS MIMICS

• INFECTIOUS DISEASES– Endocarditis– HIV

• DRUGS– Cocaine– Methamphetamine

• CHOLESTEROL EMBOLI• ANTIPHOSPHOLIPID ANTIBODY

SYNDROME

Questions?

• In the ACR diagnostic criteria for Giant Cell Arteritis (Temporal Arteritis), a patient needs to be greater than what age?A. > 40 years

B. > 50 years

C. > 60 years

D. > 70 years

E. > 80 years

Questions?

• In the ACR diagnostic criteria for Giant Cell Arteritis (Temporal Arteritis), a patient needs to be greater than what age?A. > 40 years

B. > 50 years

C. > 60 years

D. > 70 years

E. > 80 years

-Almost all are > 60

-Average age is 70

Specific Entities


Arthritis Rheum. 1990;33:1122.

Giant Cell ArteritisACR Criteria (3 of 5)

• Age > 50• New onset headache• ESR (Westergren) 50 • Abnormal artery biopsy

(mononuclear cell infiltrate, granulomatous inflammation, usually multinucleated giant cells)

• Temporal artery abnormality (tender or decreased pulse)

Giant Cell Arteritis(Other clinical manifestations)

• Visual loss, jaw/tongue claudication, scalp tenderness

• Fever, weight loss• PMR symptoms (proximal muscle pain)• 10% with large vessel involvement (e.g.

subclavian artery)• Blindness (ischemic optic neuropathy) is

major complication to avoid

GCA:Biopsy

• Temporal artery biopsy– large specimen (4-6 cm)– multiple sections evaluated

• Infiltration of vessel wall with WBC

• Granulomata, Giant Cells• Necrotic material

GCA: Therapy

• Corticosteroids mainstay of therapy (~1 mg/kg)– Calcium and vitamin D– Consider bisphosphonates

• Try to prevent visual loss with therapy:– Treat, then biopsy!

Questions?

• The confirmatory antibody for a positive C-ANCA in a patient suspected of having Wegener’s Granulomatosus is:A. Topoisomerase

B. Histidine tRNA synthetase

C. Smith

D. Proteinase-3

E. Myeloperoxidase

Questions?

• The confirmatory antibody for a positive C-ANCA in a patient suspected of having Wegener’s Granulomatosus is:A. Topoisomerase

B. Histidine tRNA synthetase

C. Smith (Sm)

D. Proteinase-3

E. Myeloperoxidase C is the 3rd letter of the alphabet:

Pr-3 C-ANCA

Granulomatous Polyangiitis(GPA) … formerly Wegener’s

• Necrotizing vasculitis that affects the small vessels of the respiratory tract and renal system: PULMONARY-RENAL SYNDROME

• Age ~ 40s: M > F 2:1

Arthritis Rheum 1990;33:1101.

Granulomatous Polyangiitis (GPA)ACR Criteria (3 of 5)

• Nasal or oral inflammation (oral ulcers or bloody nasal drainage)

• Abnormal chest radiograph (nodules, fixed infiltrates, cavities)

• Urinary sediment (> 5 RBC/ hpf or casts)

• Abnormal Biopsy: showing vasculitis

• Proteinase-3 antibodies

Granulomatous Polyangiitis(GPA) : Respiratory Involvement

• Sinusitis– Nasal septal ulceration

• Pneumonitis– few symptoms until late– usually no mediastinal

lymphadenopathy– nodules that can

cavitate

Granulomatous Polyangiitis(GPA) : Renal Involvement

• 85% of patients• Focal/segmental

necrotizing glomerulonephritis

• Usually progressive

www.bio.davidson.edu/.../Cresgn.jpg

Granulomatous Polyangiitis(GPA) : ANCA

• AntiNeutrophil Cytoplasmic Antibody– C (cytoplasmic staining) ANCA– Proteinase 3 (C is the 3rd letter)

• Pulmonary-renal disease– sensitivity of 95%– specificity of 95%

• Limited disease…– lower sensitivity and specificity

Granulomatous Polyangiitis (GPA): Tissue Biopsy

• Yield of biopsy– Lung

• Open – highest yield • Bronchoscopy - lower yield

– Sinus - 40% yield– Renal

• Vasculitis rarely seen• Focal proliferative GN is the typical finding

Granulomatous Polyangiitis(GPA) : Rx

• Prior to cyclophosphamide, 80-90% mortality• With cyclophosphamide, 5-10% mortality• Concern about long-term toxicity of PO

cyclophosphamide (bladder especially)• IV CYTOXAN no significant bladder risk• Rituximab: very effective for induction &

maintenance• Azathioprine for maintenance

Microscopic Polyangiitis (MPA)

• Systemic vasculitis with predominant small vessel involvement

• Separate disease from PAN (Initially thought to

be a variant of PAN)

• Usually RPGN and sometimes with pulmonary hemorrhage

• More common than PAN (both are rare)

MPA: Clinical Manifestations

• Renal manifestations 79%• Weight loss 73%• Skin involvement 62%• Mononeuritis multiplex 58% • Fever 55%• Arthralgias/Myalgias 50%• Pulmonary involvement 25%

MPA: ANCA

• P (perinuclear) ANCA• Myeloperoxidase antibodies• Sensitivity/Specificity

unclear

MPA: Epidemiology & Rx

• Ave. age 57• Males > Females (slightly)

• Cyclophosphamide decreases mortality• IV CYTOXAN no significant bladder risk• Rituximab: very effective for induction &

maintenance• Azathioprine for maintenance

Polyarteritis Nodosa

• Necrotizing vasculitis of medium & small arteries• Age ~ 40s; M > F• Constitutional symptoms are common

– fever 50%– weight loss 50%

• Vasculitis can be variable in distribution making diagnosis difficult

Arthritis Rheum. 1990;33:1088

Polyarteritis Nodosa ACR Criteria (3 of 10)

• Wt loss > 4 kg• Livedo reticularis• Testicular pain• Myalgias, weakness or

leg tenderness• Mononeuropathy or

polyneuropathy

• Diastolic BP > 90 BUN or Creatinine• Hepatitis B virus • Arteriographic

abnormality• Biopsy of small or

medium artery containing PAN

Classic PAN: Manifestations

• Mononeuritis multiplex 50%• Renal involvement: 60% (renal arteries, interlobular arteries)

– Hypertension (more common)– Glomerulonephritis (uncommon)

• Abdominal involvement 45%• Arthralgias/Myalgias/Myositis64%• Testicular pain 25%• Pulmonary involvement rare

Polyarteritis Nodosa

• Association with Hepatitis B (surface antigen)

• Classic PAN is NOT associated with ANCA

ANCA

Cryoglobulinemia 1

• Paradigm of small vessel vasculitis• Association with hepatitis C infection• Damage is immune complex-mediated• Cryoprecipitate Hepatitis C Ag – Ab• Complement fixing: C4 consumption

C4 levels VERY low

Cryoglobulinemia 2

Cryoglobulinemia 3

PATTERN OF ORGAN INVOLVEMENT:•constitutional•Cutaneous•articular•vascular• neurologic

Cryoglobulinemia 4

PATTERN OF LABORATORY FINDINGS:•rheumatoid factor •complement C4 ↓ ↓ ↓• cryoglobulin (cryocrit)

TREATMENT:•Antiviral therapy …. clearance of hep C virus!

VASCULITIS: classification


VASCULITIS OF SMALL >> MEDIUM-SIZED VESSELS:

•drug-induced small vessel vasculitis (hypersensitivity vasculitis), •Henoch-Schönlein purpura (IgA vasculitis), •ANCA-associated vasculitis (granulomatosis with polyangiitis [Wegener’s], microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis [Churg Strauss syndrome]), •infection-related vasculitis (bacterial endocarditis, poststreptococcal vasculitis and glomerulonephritis) plus hepatitis C-related cryoglobulinemia)

• vasculitis associated with CTD (SLE, RA, Sjögren's)

VASCULITIS OF MEDIUM-SIZED VESSELS: • classic polyarteritis nodosa (PAN)

VASCULITIS OF LARGE VESSELS: • Giant cell arteritis• Takayasu arteritis

MIMICS OF VASCULITIS:• infectious, thrombotic, and embolic disorders

systemic vasculitis: a clinical approach geordie lawry md chief, rheumatology uc irvine medicine hs...

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