SMALL VESSEL VASCULITIS A CLINICAL REVIEW

1. Systemic Vasculitis:
a clinical approach
Dr Raheel Ahmed
Resident Nephrology
Weekly CPC: September 2018

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

3. VASCULITIS: principles 1
• Vasculitis- Inflammation of blood vessels
characterised by leucocytic infiltration of the
vessel walls
• Different patterns of vessels’ involvement
in different entities
• Vessel lumen compromised ischemia of the
corresponding organ

4. Artery: WBC inflammation in wall
Normal Vessel Wall

5. VASCULITIS: principles 2
systemic diseases that can affect many different organ systems
For example, involvement of
•glomerular capillaries causes nephritis;
•alveolar capillaries, pulmonary hemorrhage;
•dermal venules, purpura;
•upper respiratory tract mucosal venules, rhinitis and sinusitis;
•abdominal visceral arteries, abdominal pain; and
•epineural arteries, mononeuritis multiplex.
can be difficult to diagnose: challenging clinical
picture even for experienced clinicians..
can be life-threatening

6. Small-Vessel Vasculitis is necrotizing vasculitis that predominantly affects
vessels including capillaries, venules, and arterioles; however, arteries, especially
small arteries, also may be involved.The most common renal target for small-vessel
vasculitis is glomerular capillaries.
Medium-Vessel Vasculitis is necrotizing arteritis that predominantly affects
major visceral arteries. In the kidneys, the interlobar arteries and arcuate arteries
are affected most frequently, although any arteries from the main renal artery to the
smallest interlobular arteries may be affected.
Large-Vessel Vasculitis is chronic granulomatous arteritis that predominantly
affects the aorta and its major branches more often than other forms of
vasculitis.When there is renal involvement, the ostia of the renal arteries and the main
renal arteries are most often affected. The most common clinical renal manifestation is
renovascular hypertension.

8. Pathology
The acute vascular lesion of the pauci-immune small-vessel vasculitides is segmental fibrinoid
necrosis, often accompanied by leukocyte infiltration and leukocytoclasia (leukocyte
fragmentation).
The earliest vasculitic lesions have infiltrating neutrophils that are quickly replaced by
predominantly mononuclear leukocytes.
The acute necrotizing lesions evolve into sclerotic lesions and may be complicated by
thrombosis
Necrotizing arteritis of interlobular artery in
patient
with ANCA-associated small-vessel vasculitis.
There is segmental
fibrinoid necrosis with adjacent perivascular
leukocyte infiltration

9. Pathology …
Early mild lesions have segmental fibrinoid necrosis with or
without an adjacent small crescent.
Non-necrotic segments within segmentally injured glomeruli) and
glomeruli without necrosis typically have slight or no histologic
abnormalities.
Segmental glomerular necrosis and
crescent formation
in patient with ANCA-associated small-
vessel vasculitis. The
fibrinoid material is red.
The uninvolved segments appear normal.

10. Pathology……Severe acute lesions may
have essentially global necrosis with
large circumferential crescents
Global glomerular necrosis and
circumferential crescent
formation in a glomerulus from patient
with ANCA-associated small-vessel
vasculitis.

11. Pathology……In addition to GN, patients with AAV also may
have renal arteritis, most often affecting interlobular arteries
and medullary angiitis affecting the vasa recta.
The medullary angiitis may be severe enough to cause papillary
necrosis, although this is a rare complication.
Medullary leukocytoclastic angiitis
involving vasa recta in a patient with
granulomatosis with polyangiitis

13. Histopathologic classification for AAV GN
Sclerotic class (50% globally sclerotic glomeruli),
Focal class (50% normal glomeruli),
Crescentic class (50% of glomeruli with cellular crescents),
Mixed class if none of these features predominated.
Renal survival at 5 years was
 93% for the focal class,
76% for crescentic class,
61% for mixed class, and
 50% for sclerotic class.
Validation studies are
underway to better understand
the utility of this classification.

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

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

16. HISTORY: PATIENT’S STORY
Neither sensitive nor specific for the diagnosis of vasculitis such as fever, fatigue,
weight loss, and arthralgias
 A history of eye inflammation, particularly scleritis.
Persistent nasal crusting, epistaxis, or other upper airway disease.
The presence of acute foot drop or wrist drop may be due to a motor neuropathy
from an ischemic process.
Limb claudication, especially in the upper extremities or in a person at low risk for
atherosclerosis, is suggestive of a large arterial occlusion from Takayasu arteritis or
giant cell arteritis (GCA).
Unexplained hemoptysis raises concern for alveolar hemorrhage and AAV.
The combination of lung hemorrhage and renal insufficiency should immediately
raise concern for vasculitis

17. PHYSICAL EXAM: BODY’S STORY
Findings of a sensory and/or motor neuropathy ..classical mononeuritis
multiplex and peripheral symmetric or asymmetric polyneuropathy.
Palpable purpura –is a strong sign of cutaneous leukocytoclastic vasculitis
Absent, diminished, or tender pulses, bruits, or blood pressure
discrepancies.
A careful and full vascular examination is extremely helpful in identifying
signs of large-vessel vasculitis .
The vascular examination should include palpation for pulses in multiple
areas including, but not limited to, the radial, brachial, carotid, femoral,
popliteal, posterior tibial, and dorsalis pedis arteries.
Auscultation for bruits in the regions of the carotid, subclavian, renal, and
femoral arteries and the thoracic and abdominal aorta.

18. LABORATORY:
BEHIND-THE-SCENES STORY
Basic CBC, CHEMS, LFTs, UA/micro,
CXR
……..MORE PROBLEMS

19. SYSTEMIC VASCULITIS ?
• Are there additional tests which could help
confirm this suspicion?
• Serologic tests
• Imaging studies
• Tissue biopsy

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

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

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

23. 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
NB…Many patients with vasculitis trace the onset of their disease to a flu-like illness

24. CUTANEOUS
Non-blanching, palpable purpuric skin lesions

25. Livedo Reticularis

26. Splinter Hemorrhages

27. Vasculitis Lesions

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

29. RESPIRATORY: upper
Manifestations of upper respiratory tract disease include
• subglottic stenosis,
• sinusitis,
• rhinitis,
• nasal septal collapse, and
• otitis media.

30. Saddle Nose Deformity

31. Tracheal wall involvement in granulomatosis with polyangiitis
(Wegener's)

32. LOWERE RESPIRATORY: Nodules/Cavities

33. Pulmonary Infiltrates

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

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

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

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

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

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

40. 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

41. 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

42. 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)
Arthritis Rheum. 1990;33:1122.

43. Giant Cell Arteritis
• Visual loss, jaw/tongue claudication, scalp
tenderness
• Fever, weight loss
• PMR symptoms (proximal muscle pain)
• BLINDNESS-most serious complication
(ischemic optic neuropathy)
• 10% with large vessel involvement
(e.g. subclavian artery)

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

45. 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!

46. Pauci-immune Vasculitis
Pulmonary capillaritis PLUS Glomerulonephritis
Granulomas +Asthma Churg Strauss
Granulomas +NO asthma Wegener’s
NO granulomas, NO asthma Microscopic
Polyangiitis

47. 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

48. Questions?
• The confirmatory antigen 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

49. Granulomatous Polyangiitis (GPA) …
formerly Wegener’s
• Classical triad  URT + LRT + renal
• Necrotizing vasculitis that affects the small
vessels of the respiratory tract and renal
system: PULMONARY-RENAL SYNDROME
• Age ~ 40s: M > F 2:1

50. Granulomatous Polyangiitis (GPA)
ACR Criteria (3 of 5)
1.Nasal or oral inflammation (oral ulcers or bloody nasal drainage)
2.Abnormal chest radiograph (nodules, fixed infiltrates, cavities)
3.Urinary sediment (> 5 RBC/ hpf or casts)
4.Abnormal Biopsy: showing vasculitis
5.Proteinase-3 antibodies(PR-3)
Arthritis Rheum 1990;33:1101.

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

53. Granulomatous Polyangiitis (GPA) :
Renal Involvement
• 85% of patients
• Focal/segmental
necrotizing
glomerulonephritis
• Rapidly Progressive
Glomerulonephritis www.bio.davidson.edu/.../Cresgn.jpg

54. 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

56. 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

57. 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 due to less
cumulative dose
• Rituximab: very effective for induction &
maintenance
• Azathioprine for maintenance

58. 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)

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

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

62. 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

63. AAV & KDIGO
RECOMMENDATIONS

70. 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

71. 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
Arthritis Rheum. 1990;33:1088

73. Classic PAN: Manifestations
• Mononeuritis multiplex 50%
• Renal involvement: 60%
(renal arteries, interlobular arteries)
– Hypertension (more common)
– Glomerulonephritis (uncommon)
• Abdominal involvement 45%
• Arthralgias/Myalgias/Myositis 64%
• Testicular pain 25%
• Pulmonary involvement rare

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

75. Thank You