2015 mangement of Systemic Vasculitis.ppt

rheumatology

1. Systemic Vasculitis:
a clinical approach
Geordie Lawry MD
Chief, Rheumatology
UC IRVINE
Medicine HS Noon Conference: October 2015

2. 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

3. Objectives 2
•List at least 3 ORGANS / SITES commonly
involved in:
CRYOGLOBULINEMIC VASCULITIS
GRANULOMATOUS POLYANGIITIS (GPA)
MICROSCOPIC POLYANGIITIS (MPA)
CLASSIC POLYARTERITIS NODOSA
GIANT CELL ARTERITIS

4. Objectives 3
•List at least 2 ANCA VASCULITIS
SYNDROMES, associated ANCA
pattern / target antigens
•List at least 2 vasculitideswhich are
NOT ASSOCIATED WITH ANCA
•List at least 3 or more conditions
that can MIMIC THE CLINICAL
FEATURES OF VASCULITIS

5. VASCULITIS: Talk Outline
•Introduction and Definitions
•Approach to vasculitis
•Specific Disorders:
–Giant Cell Arteritis
–Granulomatous polyangiitis(Wegener’s)
–Microscopic Polyangiitis
–PolyarteritisNodosa
–Cryoglobulinemia
•Take Home

6. VASCULITIS: principles 1
group of clinical syndromes
characterized by inflammation
of blood vessels
Normal Artery
Artery: WBC
inflammation in wall

7. 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

8. VASCULITIS: classification
www.wegenersgranulomatosis.net/imageRJN.JPG

9. General Approach to
Vasculitis
Throw up your hands….

10. General Approach to
Vasculitis
Slap at it ….

11. When should vasculitis be
suspected? 1
•MULTISYSTEM inflammatory disease
•Significant CONSTITUTIONAL
SYMPTOMS
•RAPIDLY PROGRESSIVE organ
dysfunction
•HIGH ESR
SEVERE anemia
PLATELETS > 500K

12. When should vasculitis be
suspected? 2
CLINICAL FEATURES PARTICULARLY
SUGGESTIVE of small vessel
inflammation:
•SKIN: palpable purpura *
•LUNGS: pulmonary infiltrates /
hemoptysis
•KIDNEY: active urinary sediment
•NEURO: foot drop **

13. What is the approach to
a patient suspected of
having vasculitis?
WHAT IS YOUR
APPROACH TO ANY
COMPLEX MEDICAL
PROBLEM?

14. General Approach to
Vasculitis
Gather your equipment….
Find the target….
Take aim…..
NAIL IT !

15. 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

16. COMPLEX MEDICAL PROBLEMS 2
Develop a strategy: PROBLEM LIST
CREATEPROBLEM LIST
……… LIST EVERYTHING [split don’t lump]
PRIORITIZEPROBLEM LIST
……… WHAT’S THE BIG GORILLA(S) HERE?
“WORK” the PROBLEM LIST

17. COMPLEX MEDICAL PROBLEMS 3
“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?

18. COMPLEX MEDICAL PROBLEMS 4
SYSTEMIC VASCULITIS ?
•Are there additional tests which could
help confirm this suspicion?
•Serologic tests
•Imaging studies
•Tissue biopsy

19. VASCULITIS: additional testing 1
Serologic tests
•ANCA
•Hepatitis B surface antigen
•Hepatitis C, C3 & C4
•HIV
•ANA
•ACA, “lupus” anticoagpanel

20. VASCULITIS: additional testing 2
Imaging studies
•Sinus CT scan
•Chest CT scan
•Mesenteric
angiogram

21. VASCULITIS: additional testing 3
Tissue biopsy
•Temporal artery
•Sural nerve
•Muscle
•Lung
•Renal

22. 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

23. CUTANEOUS
Palpable Purpura

24. Livedo Reticularis

25. Splinter Hemorrhages

26. NEUROLOGIC
•Mononeuritis multiplex:
check for FOOT DROP
Sural nerve biopsy showing vasculitis

27. RESPIRATORY: upper
•Sinusitis
•Or……
www.conseils-orl.com/.../sommaire_epistaxis.htm

28. RESPIRATORY: lower
•Pulmonary infiltrates
•Nodules
•Cavities

29. GENITOURINARY
•Glomerulonephritis
•Hypertension
•Hematuria
•RBC casts
•Testicular pain
(especially PAN)
www.bio.davidson.edu/.../Cresgn.jpg

30. MUSCULOSKELETAL
•Polyarthralgias -common
•Polyarthritis -less common
•Myalgias -common
•Myositis -biopsy may demonstrate
vasculitis in muscle

31. GASTROINTESTINAL
•Mesenteric ischemia
–pain 30 minutes after eating
–bloody diarrhea
–bowel perforation
•hepatitis
•pancreatitis
•cholecystitis
library.med.utah.edu/WebPath/COW/COW125.html

32. OCULAR
http://www.uveitis.org/images/sa
rcoid6.jpg
Retinal Vasculitis
http://webmedia.unmc.edu/eye/iritis.jpg
Iritis
Scleritis
eyelearn.med.utoronto.ca/.../RedE
ye/10Sclera.htm

33. Common Laboratory Findings
INFLAMMATION:
Elevated ESR (can be > 100)
Elevated CRP
Leukocytosis
Thrombocytosis
Anemia
Low Albumin

34. VASCULITIS MIMICS
•INFECTIOUS DISEASES
–Endocarditis
–HIV
•DRUGS
–Cocaine
–Methamphetamine
•CHOLESTEROL EMBOLI
•ANTIPHOSPHOLIPID ANTIBODY
SYNDROME

35. 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

36. 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

37. Specific Entities
www.wegenersgranulomatosis.net/imageRJN.JPG

38. Arthritis Rheum. 1990;33:1122.
Giant Cell Arteritis
ACR 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)

39. 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

40. GCA:Biopsy
•Temporal artery biopsy
–large specimen (4-6 cm)
–multiple sections evaluated
•Infiltration of vessel wall with
WBC
•Granulomata, Giant Cells
•Necrotic material

41. 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!

42. 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

43. Questions?
•The confirmatory antibody for a positive C-
ANCAin 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 3
rd
letter
of the alphabet:
Pr-3 C-ANCA

44. 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

45. 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 orcasts)
•Abnormal Biopsy: showing vasculitis
•Proteinase-3 antibodies

46. Granulomatous Polyangiitis
(GPA) : Respiratory Involvement
•Sinusitis
–Nasal septal ulceration
•Pneumonitis
–few symptoms until late
–usually no mediastinal
lymphadenopathy
–nodules that can
cavitate

47. Granulomatous Polyangiitis
(GPA) : Renal Involvement
•85% of patients
•Focal/segmental
necrotizing
glomerulonephritis
•Usually progressive
www.bio.davidson.edu/.../Cresgn.jpg

48. Granulomatous Polyangiitis
(GPA) : ANCA
•AntiNeutrophil Cytoplasmic Antibody
–C (cytoplasmic staining)ANCA
–Proteinase 3(Cis the 3
rd
letter)
•Pulmonary-renal disease
–sensitivity of 95%
–specificity of 95%
•Limited disease…
–lower sensitivity and specificity

49. 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

50. 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

51. 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)

52. MPA: Clinical Manifestations
•Renal manifestations 79%
•Weight loss 73%
•Skin involvement 62%
•Mononeuritis multiplex 58%
•Fever 55%
•Arthralgias/Myalgias 50%
•Pulmonary involvement 25%

53. MPA: ANCA
•P(perinuclear)ANCA
•Myeloperoxidase antibodies
•Sensitivity/Specificity
unclear

54. 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

55. Polyarteritis Nodosa
•Necrotizing vasculitis of medium & small arteries
•Age ~ 40s; M > F
•Constitutional symptoms are common
–fever 50%
–weight loss50%
•Vasculitis can be variable in distribution making
diagnosis difficult

56. 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

57. 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

58. Polyarteritis Nodosa
•Association with
Hepatitis B (surface
antigen)
•Classic PAN
is NOT associated with
ANCA
ANCA

59. Cryoglobulinemia 1
•Paradigm of small vessel vasculitis
•Association with hepatitis C infection
•Damage is immune complex-mediated
•CryoprecipitateHepatitis C Ag –Ab
•Complement fixing: C4 consumption
C4 levels VERY low

60. Cryoglobulinemia 2

61. Cryoglobulinemia 3
PATTERN OF ORGAN INVOLVEMENT :
•constitutional
•Cutaneous
•articular
•vascular
•neurologic

62. Cryoglobulinemia 4
PATTERN OF LABORATORY FINDINGS :
•rheumatoid factor
•complement C4 ↓ ↓ ↓
•cryoglobulin(cryocrit)
TREATMENT:
•Antiviral therapy …. clearance of hepC virus!

63. VASCULITIS: classification
www.wegenersgranulomatosis.net/imageRJN.JPG

64. VASCULITIS OF SMALL >> MEDIUM -SIZED
VESSELS:
•drug-induced small vessel vasculitis
(hypersensitivity vasculitis),
•Henoch-Schönleinpurpura (IgA vasculitis),
•ANCA-associated vasculitis
(granulomatosis with polyangiitis[Wegener’s],
microscopic polyangiitis, eosinophilic granulomatosis
with polyangiitis[ChurgStrauss syndrome]),
•infection-related vasculitis
(bacterial endocarditis, poststreptococcalvasculitis
and glomerulonephritis) plus hepatitis C-related
cryoglobulinemia)

65. •vasculitis associated with CTD
(SLE, RA, Sjögren's)
VASCULITIS OF MEDIUM-SIZED VESSELS:
•classic polyarteritisnodosa(PAN)
VASCULITIS OF LARGE VESSELS :
•Giant cell arteritis
•Takayasuarteritis
MIMICS OF VASCULITIS:
•infectious, thrombotic, and embolic disorders