1. Vasculitis Means inflammation of the blood vessel wall.
May affect arteries, veins and capillaries.
What causes the inflammation?
Immunologic hypersensitivity reactions:
Type II : complement dependent
Type III: immune complex mediated**
Type IV : cell mediated
Direct invasion by micro-organisms
Inflammation can occur in different types of blood vessels, e.g. elastic and muscular arteries, arterioles, capillaries and venules.

2. Etiopathogenesis Immunologic mechanisms
Immune complexe deposition
Responsible for most cases***
Deposition of immune complex 
Activation of complement 
Release of C5a
C5a  chemotactic for neutrophil
Neutrophils  damage endothelium and vessel wall  fibrinoid necrosis.
Endothelial damage  thrombosis 
Ischemic damage to tissue involved.
Example of IC mediated Vasculitis = Henoch-Schonlein purpura
C5a : neutrophil chemotaxis and also increases vessel permeability.
Neutrophils  damage vessel wall (release elastase, collagenase, free radicals)

3. Etiopathogenesis Immunologic mechanisms
Type IV hypersensitivity: delayed type of hypersensitivity reaction
implicated in some types of vasculitis due to presence of granulomas.
Example: Temporal arteritis
Direct Invasion:
by all classes of microbial pathogens
Rickettsiae
Meningococcus
Fungus
IN some type of vasculitis we see presence of granulomas in the involved blood vessels.
This proves that type IV hypersensitivity plays a role.

4. Laboratory testing in vasculitis
Antineutrophil cytoplasmic antibodies (ANCA)
Erythrocyte sedimentation rate (ESR)
A high ESR in conjunction with specific findings such as tender temporal artery can be highly suggestive of giant cell arteritis.

5. Antineutrophil cytoplasmic antibodies (ANCAs)
Are seen in some types of vasculitis esp small vessel vasculitis
Are circulating ab reactive with neutrophil cytoplasmic ag = ANCA.
The ANCAs activate neutrophils
Cause release of enzymes and free radicals resulting in vessel damage.
ANCA titers correlate with disease activity.
Detected by immunofluorescence
Even though ANCAs seem to be present in some types of vasculitis, their exact role in the pathogenesis is not clearly understood.

6. Two types of ANCAs Cytoplasmic (c-ANCAs):
Ab directed against proteinase 3 in cytoplasmic granules.
Cytoplasmic staining pattern
Example: Wegener’s granulomatosis.
Perinuclear (p-ANCAs):
Ab directed against myeloperoxidase.
Perinuclear pattern of staining
Example: Churg-Strauss syndrome, PAN.
In many patients with Vasculitis there are circulating ab reactive with neutrophil cytoplasmic ag.
These factors in serum are k/a ANCA.
The ANCAs activate neutrophils
two types of ANCAs
cytoplasmic (c-ANCAs):
antibodies are directed against proteinase 3 in cytoplasmic granules (e.g. Wegener’s granulomatosis)
perinuclear (p-ANCAs) :
antibodies are directed against myeloperoxidase
example : microscopic polyangitis, Churg – Strauss syndrome.
ANCAs are not 100% sensitive. Can be found in other conditions apart from vasculitis.
cANCA disease association: Wegener's granulomatosis
pANCA disease association: Churg-Strauss syndrome (MPO) Polyarteritis nodosa (MPO)

7. Classification of Vasculitis : based on vessel size
Large vessel Vasculitis:
Giant cell arteritis *
Takayasu’s arteritis *
Medium vessel Vasculitis
Polyarteritis nodosa (PAN)*
Kawasaki’s disease*
Thromboangitis obliterans (TAO)*
Small vessel Vasculitis
Hypersensitivity vasculitis
Henoch Schonlein purpura*
Churg Strauss syndrome
Wegener granulomatosis *
Large vessel vasculitis:
usually involves aorta and its larger branches to extremities and head and neck.
Medium sized vessel vasculitis:
involves arteries of the viscera and their branches
Small vessel vasculitis (most are due to immune complex deposition = type III hypersensitivity reaction)
involves arterioles, venules and capillaries

8. Clinical manifestations of vasculitis
Clinical picture depends on the size and extent of the vessel involvement.
Large vessel Vasculitis:
Presents with loss of pulse or
Stroke
Medium vessel Vasculitis
Presents with infarction or aneurysm
Small vessel Vasculitis
Presents with Palpable purpura*
General features:
Fever, weight loss, malaise, myalgias
Loss of pulse : in upper extremity due to involvement of subclavian artery. Vasculitis  narrowing of lumen decreased blood flow loss of pulse
Stroke: due to involvement of internal carotid artery
Infarction and aneurysms: due to involvement of medium size arteries like the coronary, the renal, the popliteal. Patients may present with myocardial infarction (coronary), renal infarction ( renal artery) and infarction of lower limb (popliteal artery).
Inflammation in the vesel wall may damage it and lead to formation of aneurysm e.g. coronary artery aneurysm seen in Kawasaki Disease.
Purpura : are small areas of hemorrhage in the skin. They are larger than petechiae.
Purpura could be seen in different clinical settings.
Example: Thrombocytopenia, vessel wall instability (vit C deficiency) and small vessel vasculitis.
Purpura due to thrombocytopenia or vessel instability is not palpable, because acute inflammation is not involved.*********
Small vessel vasculitis causes palpable Purpura because the vessel wall is damaged and blood extravastes plus the vessel wall is inflamed (“tumor” of inflammation)

9. Patient: temporal arteritis Note the prominent temporal artery
Patient: temporal arteritis
Note the prominent temporal artery. A biopsy of the artery reveals multinucleated giant cells (granulomatous vasculitis, see arrow)
What do you see??

10. Patient Profile # 1 Old female patient presents with
Headache in the temporal region
Pain in the jaw while chewing
Muscle aches and pains
Develops problems with vision.
On examination:
Has nodular and palpable temporal artery.
Labs:
elevated ESR
Biopsy: ( temporal artery)
granulomatous inflammation with giant cells
Diagnosis:
Giant cell (temporal) arteritis

11. Large vessel vasculitis Giant cell (temporal) arteritis
Is the most common vasculitis**.
Occurs in women > 50 years (Female > male)
Vessel involvement::
Typically involves temporal artery and extra-cranial branches of external carotid.
Involvement of ophthalmic branch of external carotid  blindness.
Etiopathogenesis:
Type IV hypersensitivity mediated reaction causing granulomatous inflammation.
Remember: the age of onset of giant cell arteritis is usually 70 years. Its rare before 50 years. Therfore the age at onset helps it differentiate this condition from other vasculitis that may involve similar vessels such as Takayasu arteritis which occurs in much younger people.
Giant cell arteritis
It may rarely involve the aortic arch = giant cell aortitis.

12. Giant cell arteritis: Pathology
Affected vessel are cordlike and show nodular thickening.
Microscopy:
Focal Granulomatous inflammation of temporal artery
Fragmented internal elastic lamina
Giant cells.

13. C, Examination of the temporal artery of a patient with giant-cell arteritis shows a thickened, nodular, and tender segment of a vessel on the surface of head (arrow).

14. Temporal (giant cell) arteritis
A, H&E stain of section of temporal artery showing giant cells at the degenerated internal elastic membrane in active arteritis (arrow).
B, Elastic tissue stain demonstrating focal destruction of internal elastic membrane (arrow) and intimal thickening (IT) characteristic of long-standing or healed arteritis.
Giant cell arteritis involves an abnormal inflammatory attack on elasic tissue in the walls of some arteries, commonly the temporal artery and other branches of the external carotid circulation. The elastic tissue is not easily degraded and stimulates the formation of multinucleate giant cells as part of the granulomatous chronic inflammatory process.

15. Giant cell (temporal) arteritis
Clinical features:
Fever, fatigue, weight loss
Temporal headache* (MC symptom), facial pain.
Painful, palpably enlarged and tender temporal artery*
Generalized muscular aching and stiffness (shoulders and hip)
Temporary / permanent blindness*
Signs and symptoms: explanation
unilateral headache along the course of temporal artery (MC symptom).
temporary / permanent blindness due to involvement of ophthalmic artery
Jaw claudication

16. Giant cell (temporal) arteritis
Investigations:
ESR: screening test of choice ; markedly elevated.
Temporal artery biopsy : definitive diagnosis (positive in only 60% cases)
Treatment:
Corticosteroids (to prevent blindness)
Temporal artery biopsy is not positive in all cases as the inflammatory process in not continuous but skips areas. Therfore if biopsy is obtained from the part of the artery which is not involved, positive findings would then be missing.
Treatment: is imediate institution of Corticosteroid therapy to prevent blindness

17. What do you see? X-ray study: Takayasu's arteritis
The arrows point to numerous areas of constriction in the subclavian arteries.
The patient most likely had weak to absent pulses in both upper extremities.

18. Patient profile # 2 Middle aged Asian woman presents with:
Visual disturbances
Marked decrease in blood pressure in upper extremity and
Absent radial, ulnar and carotid pulses.
Angiography shows:
Marked narrowing of aortic arch vessels
Biopsy:
Granulamatous inflammation with giant cells
Diagnosis:
Takayasu’s arteritis (pulseless disease)

19. Takayasu’s arteritis (pulseless disease)
Is an inflammatory disease of vessels affecting
the aorta and its major branches
Seen in Asian women <50 years old.
Vessel involvement:
Typically involves the aorta* and the aortic arch vessles* (carotids, subclavian).
Can also involve: pulmonary, renal, coronary
Etiopathogenesis:
Type IV hypersensitivity reaction causing granulomatous inflammation (granulomatous vasculitis)
Difference from Giant cell arteritis:
age; <50 yrs.old (majority are under 30 years)
location; aortic arch & main branches

20. Takayasu’s arteritis Takayasu’s arteritis.
A, Aortic arch angiogram showing narrowing of brachiocephalic, carotid, and subclavian arteries (arrows).
B, Gross photograph of two cross-sections of the right carotid artery taken at autopsy of the patient shown in A, demonstrating marked intimal thickening with minimal residual lumen.
C, Histologic view of active Takayasu aortitis, illustrating destruction of the arterial media by mononuclear inflammation with giant cells.

21. Takayasu’s arteritis (pulseless disease)
Pathology:
Thickening of vessels ( aorta & branches) with narrow ( stenosis) lumen 
decreased blood flow
Microscopic
Similar to/indistinguishable from Giant Cell Arteritis

22. Takayasu’s arteritis (pulseless disease)
Clinical:
Dizziness,syncope.
Absent upper extremity pulse (pulseless disease)**
Blood pressure discrepancy* between extremitis : low in upper and higher in lower
Visual disturbances
Diagnosis:
angiography
Early disease responds to corticosteroids but late disease requires surgical correction

23. Patient profile # 3
Young male IV drug abuser with history of Hepatitis (HBV) presents with
Hypertension, abdominal pain, melena, muscle aches and pains and skin nodulations.
Biopsy of skin nodules:
Segmental transmural inflammation of blood vessels with fibrinoid necrosis.
Labs:
HBsAg +ve
pANCA +ve
Diagnosis:
Polyarteritis nodosa (PAN)
Hypertension  renal artery narrowing
Abdominal pain and melena  infarction of bowel due to involvement of superior mesentric artery ( supplies the bowel)
Muscle aches and pains  due to ischemia secondary to vessel narrowing
Skin nodulations due to focal aneurysm formation (nodosa)
Polyarteritis nodosa = involves multiple vessels (medium sized) and is associated with segmental transmural inflammation of vessel wall  weakening of vessel wall focally  dilatation (aneurysm)  responsible for nodules in skin

24. Polyarteritis nodosa (PAN)
A systemic disease.
Vessel involvement:
Affects medium sized & small muscular arteries*.
Typically involves vessels of
Kidney, heart, liver, GIT and skin
Spares the lung**
Etiology:
Mediated by type III hypersensitivity ( ag-ab complex deposition).
Associations:
strong association with HBV antigenemia
hypersensitivity to drugs (IV amphetamines).
Pathogenesis:
immunecomplex deposition (e.g. HBsAg / anti- HBsAg)
*But not of arterioles, capillaries and venules
* sometimes can also involve larger arteries
PAN was considered to be a rare disease until 1940, when there was a striking increase in its incidence. Increase was due to
Widespread use of antisera to bacteria, and toxins produced in animals and with use of sulfonamides.
The diagnosis is made by biopsy of the affected arterial segment.

25. Small to medium sized muscular arteries
IMMUNECOMPLEX DEPOSITION
Activation of complement system
Acute inflammation
Damage to vessel wall
neutrophil infiltration
fibrinoid necrosis
Thrombosis
Aneurysms
Infarction in involved organs
Nodules

26. fibrinoid necrosis Neutrophils
Polyarteritis nodosa. The intense inflammatory cell infiltrate in the arterial wall and surrounding connective tissue is associated with fibrinoid necrosis and disruption of the vessel wall.
fibrinoid necrosis

27. Segmental fibrinoid necrosis
A, Polyarteritis nodosa.
In polyarteritis nodosa ,there is segmental fibrinoid necrosis and thrombotic occlusion of the lumen of this small artery.
Note that part of the vessel wall at the upper right (arrow) is uninvolved.
Vascular lesions
involve only part of the vessel (segmental necrotizing vasculitis) . Induce
thrombosis, causing distal ischemic injury
Wekening of arterial wall  aneurysms.
Micro: transmural inflammation, fibrinoid necrosis.
Lesions present in different stages of development
acute lesions: characterized by arterial fibrinoid necrosis with associated neutrophilic infiltrate
healing lesions: show fibroblast proliferation
healed lesions : show marked fibrotic thickening of the artery.
Segmental fibrinoid necrosis

28. PAN Pathology: Transmural inflammation (involving all layers).
Lesion in the vessel wall may
involve entire circumference or part of it
Fibrinoid necrosis
Consequences:
development of
Thrombosis  infarction
Weakening of vessel wall Aneurysms (kidney, heart and GI tract)
Also associated with

29. PAN: Clinical features
More common in young to middle aged men
Signs and symptoms: due to ischemic damage.
Target organs:
Kidneys : Vasculitis/infarction  hypertension , hematuria, albuminuria.
GI tract: Bowel infarction  abdominal pain, melena.
Skin: Ischemic ulcers and nodules.
Coronary arteries: aneurysms, MI
Systemic manifestation: fever, malaise and weight loss.
Cause of death: Renal failure MC COD
Lung : Not commonly involved in classic PAN
MC COD = most common cause of death

30. PAN Laboratory findings: HbsAg positive in 30% of cases
Hematuria with RBC cast
Diagnosis:
arteriography or biopsy of palpable nodulations in the skin or organ involved .
Treatment:
Untreated cases: almost fatal
Good response to immunosuppressive therapy.
Untreated cases: almost fatal
Good response to immunosuppressive therapy.
corticosteroids and cyclophophamide

31. Churg-Strauss Syndrome (Allergic granulomatous angitis)
Is a systemic vasculitis that occurs in persons with asthma*.
A variant of PAN.
Involves small* & medium vessels of
upper/lower respiratory tract*
heart, spleen, peripheral nerves, skin , kidney.
Pathology:
Inflammation of vessel wall (eosinophils)
Fibrinoid necrosis
Thrombosis and infarction
Corticosteroids are successful in treating these patients

32. Churg-Strauss Syndrome (Allergic granulomatous angitis)
Features very similar to PAN but patients with CSS have:
History of atopy
Bronchial asthma, allergic rhinitis and
peripheral blood eosinophilia.
Microscopy:
Similar to PAN
Labs:
peripheral eosinophilia , high serum IgE,
p-ANCA*

33. Patient profile # 4 A 4 year old Japanese child presents with
Fever, redness of eyes and oral cavity
Swollen hands and feet
Rash over the trunk and extremities
Peeling of skin and
Cervical lymphadenopathy.
Labs:
ECG changes consistent with myocardial ischemia
Diagnosis:
Kawasaki Disease (mucocutaneous lymphnode syndrome)

34. Kawasaki’s disease Is also known as mucocutaneous lymphnode syndrome.
Is an acute self limited febrile illness of infants and children (< 5 yrs).
Is endemic in Japan , Hawaii
One of the manifestations is vasculitis (coronary artery).
In other words:
KD is a childhood vasculitis that mainly targets coronary arteries.
Coronary artery involvement:
can lead to coronary thrombosis or aneurysm formation and its rupture.
Afflicts children <5 years old
Pathology:
Transmural inflammation of vessels with neutrophils and mild fibrinoid necrosis.

35. Coronary artery aneurysms
Kawasaki disease.
The heart of a child who died from Kawasaki disease shows conspicuous coronary artery aneurysms

36. Clinical features : Kawasaki’s disease
Oral Erythema
Conjunctivitis
Palmer Erythema

37. Clinical features : Kawasaki’s disease
Rash
Desquamation
Edema: feet and arms

38. Erythematous rash of trunk and extremities with desquamation of skin.
Clinical findings:
High fever
Erythematous rash of trunk and extremities with desquamation of skin.
Mucosal inflammation : cracked lips, oral erythema
Erythema, swelling of hands and feet.
Localized lymphadenopathy (cervical adenopathy)
MCC of an acute MI in children******
Lab:
Neutrophilic leukocytosis
Thrombocytosis : characteristic finding
High ESR
abnormal ECG (e.g. acute MI)*****
Treatment:
Aspirin reduces the long term sequelae.
Intravenous gamma globulin
Steroids contraindicated  increase risk for coronay aneurysms and rupture
(corticosteroids decreases healing and fibrosis and can lead to higher risk of aneurysm and rupture)
Diagnosis requires presence of 5 of 6 criteria
Fever
Conjunctivitis
Oral involvement
Rash
Cervical lymphdenopathy
+/- Edema, erythema or desquamation

39. Patient profile # 5
A young smoker male patient from Israel presents with C/O
Pain in the foot
Which is severe and present even at rest
On examination:
Presence of ulcers and blackish areas over the fingers and toes.
Some missing digits.
Biopsy from lower limb vessel:
Acute inflammation of vessel wall with Obliteration of vessel lumen by a thrombus.
Diagnosis: Thromboangitis Obliterans (Buerger’s Disease)

40. Also known as Thromboangitis Obliterans.
Buerger’s Disease
Also known as Thromboangitis Obliterans.
Is a peripheral vascular disease of smokers.
Pathology:
Earliest change: Acute inflammation involving the small to medium sized arteries in the extremities (tibial, popliteal & radial arteries).
Inflammation of vessel  thrombus formation  obliterates lumen  ischemia  gangrene of extremity.
Inflammation also extends to adjacent veins and nerves.
Involvement of entire neurovascular compartment.
(greater frequency in Jewish males)

41. E, Thromboangiitis obliterans (Buerger disease).
In a typical case of Buerger disease (E), the lumen is occluded by a thrombus containing two abscesses (arrow).
The vessel wall is infiltrated with leukocytes.

42. Buerger’s Disease
Top left picture: Patient: thromboangiitis obliterans (Buerger’s disease)
Note the blackened digits (coagulation necrosis).
Autoamputation of the digits is likely to occur in this patient.
young to middle aged adults.
Close association with history of cigarette smoking.
Unknown products in tobacco smoke: produce direct damage to endothelium.
The etiologic role of smoking in Buerger disease is underscored by the fact that cessation of smoking may lead to remission, and resumption of smoking to exacerbation.
Yet, how tobacco smoke produces Buerger disease is obscure.

43. Buerger’s Disease Clinical findings:
Young-middle age, male, heavy smoker*
Israel*, Japan, India.
Symptoms start between 25 to 40 years
Early manifestation:
Intermittent Claudication in feet or hands
Cramping pain in muscles after exercise, relieved by rest
Late manifestation:
Painful ulcerations of digits
Gangrene of the digits often requiring amputation.
Claudication : limping
Pain is due to ischemia secondary to narrowing of vessel lumen because of vasculitis

44. Buerger’s Disease Diagnosis: biopsy Rx:
early stages of vasculitis frequently cease on discontinuation of smoking.

45. Small vessel vasculitis

46. Small vessel vasculitis Hypersensitivity (leukocytoclastic) vasculitis
Refers to a group of immune complex mediated vasculitides.
Characterized by:
Acute inflammation of small blood vessels
Manifesting as palpable purpura***.
Organs involved:
Usually skin ( other organs less commonly affected).
Difference from PAN:
in leukocytoclastic vasculitis , vessels involved are smaller, all lesions tend to be of the same age, necrotizing glomerulonephritis and involvement of pulmonary capillaries is common.
Purpura due to platelet abnormalities or non immunologic weakness of small blood vessels is not palpable.

47. Hypersensitivity (leukocytoclastic) vasculitis
May be precipitated by
Exogenous antigens
Drugs
E.g. aspirin/penicillin/thiazide diuretics
Infectious organisms
E.g. strep/staph infections,TB,viral diseases
Foods
Chronic diseases
E.g. SLE, RA etc.

48. Hypersensitivity (leukocytoclastic) vasculitis
Pathology:
acute inflammation of small blood vessels (arterioles, capillaries, venules)
Neutrophilic infiltrate in vessel wall.
Leukocytoclastic refers to nuclear debris from disintegrating neutrophils
The neutrophils undergo karyorrhexis.
Erythrocyte extravasation

49. B, Leukocytoclastic vasculitis.
In leukocytoclastic vasculitis (B), shown here from a skin biopsy, there is fragmentation of neutrophils in and around blood vessel walls.

50. Cutaneous necrotizing vasculitis.
Palpable purpuric tender papules on the legs of a 25-year-old woman. The condition resolved after therapy for streptococcal pharyngitis.
B. The vessel is surrounded by pink fibrin and neutrophils, many of which have disintegrated (leukocytoclasis).
Extravasated red blood cells (arrows) and inflammation give the classic clinical appearance of “palpable purpura.”

51. Hypersensitivity (leukocytoclastic) vasculitis
C/F:
The disease typically presents as palpable purpura* involving the skin principally of lower extremities.
May also involve other organs
Lungs hemoptysis
GIT abdominal pain
Kidneys  hematuria and
Musculoskeletal system  arthralgia
brain, heart
Lesions of hypersensitivity vasculitis:
are 2 to 4 mm purpuric papules which are red, palpable lesions that do not blanch under pressure (palpable purpura)
multiple lesions appear in crops on the lower extremity.

52. Hypersensitivity (leukocytoclastic) vasculitis
Diagnosis:
Skin biopsy is often diagnostic.
Treatment:
removal of offending agent

53. Patient profile # 6
A 14 year old child with history of URT infection develops:
Polyarthritis
Colicky abdominal pain
Hematuria with RBC casts
Palpable purpura localized to lower limbs and buttocks.
Lab:
Neutrophilic leukocytosis
Deposition of IgA-C3 immune complex : in skin and renal lesions

54. Henoch Schonlein purpura (HSP)
A variant of hypersensitivity vasculitis.
Seen in children** (MC vasculitis in children) , rare in adults.
Etiopathogenesis:
Usually occurs following an upper respiratory infection*.
Caused by deposition of IgA-C3 immune complexes in vessel wall.
Vessels involved:
Arterioles, capillaries and venules of
Skin, GIT,Kidney,musculoskeletal system.
Immune vasculitis mostly occurring in children following an upper respiratory infection.
Renal involvement is similar to IgA nephropathy.

55. Henoch Schonlein purpura (HSP): Patient has multiple palpable purpuric lesions in the lower limbs and buttock area.

56. Henoch Schonlein purpura (HSP)
Clinically characterized by:
Palpable purpura over extensor aspects of arms and legs.
commonly limited to lower extremities/ buttocks.
Involvement of
GIT  colicky abdominal pain, melena
Musculoskeletal system  Arthralgia (non migratory), and myalgias
Kidneys  hematuria due to focal proliferative GN.
Lung  rare

57. Henoch Schonlein purpura (HSP)
Lab:
Neutrophilic leukocytosis
Deposition of IgA-C3 immune complexes : in skin and renal lesions
Rx: steroids

58. Wegener Granulomatosis (WG)
Is characterized by:
Necrotizing granulomatous inflammation of URT and LRT and
Granulomatous vasculitis of the same areas plus kidneys.
Therefore patients have:
Lesions of the nose, sinuses and lungs* (upper & lower respiratory tract) and
Kidney*
Highly associated with c-ANCA**
Necrotizing granulomas and vasculitis in upper respiratory tract (nasopharynx, sinuses, trachea) lower respiratory tract (pulmonary vessels) give rise to respiratory tract signs and symptoms ; kidneys (crescentric glomerulonephritis)
Other organs are less commonly involved.
Etiopathogenesis:
Type II, III, and IV hypersensitivity reactions all contribute to the development of WG.

59. Wegener Granulomatosis
Pathology: two different types of lesions
Granulomatous Vasculitis
involving small vessels of URT and LRT and kidneys.
Necrotizing granulomatous lesions
in the above sites.
Granuloma formation with giant cells

60. Wegener Granulomatosis
C and D, Wegener granulomatosis.
In Wegener granulomatosis (C), there is inflammation (vasculitis) of a small artery along with adjacent granulomatous inflammation, in which epithelioid cells and giant cells (arrows) are seen.
D, Gross photo from the lung of a patient with fatal Wegener granulomatosis, demonstrating large nodular lesions.
Picture: Lower right: saddle nose deformity in a patient with WG due to destruction of nasal septum by granulomatous inflammation.
Congenital syphilis can also produce the saddle nose deformity. And so can lepromatous leprosy.
D/D of WG:
tubercular granulomas / fungal granulomas

61. Clinical features Persons most commonly affected by WG are
middle aged yrs (Peak incidence)
Male> females
Respiratory tract signs and symptoms dominate the clinical picture:
Upper respiratory tract (nasopharynx, sinuses, trachea)
Chronic Sinusitis, ulcers of nasopharyngeal mucosa.
Saddle nose deformity* : Nasal cartilage destroyed
Lower respiratory tract
Recurrent pneumonia with
Nodular lesions which undergo cavitation
Kidney: Crescentric glomerulonephritis  can cause renal failure.
The classical triad of WG:
Granulomas in upper and lower respiratory tracts ( sinuses, nasopharynx, lungs { Saddle nose deformity due to destruction of nasal septum caused by granuloma)
Granulomatous vasculitis of URT/LRT and other organs.
Renal disease (crescentric glomerulonephritis).
Renal involvement can cause hematuria and proteinurua
Other findings: Fever, myalgias, arthralgias, and skin rashes may also occur with WG.

62. bilateral nodular infiltrates or cavitary lesions. Diagnosis: biopsy
Lab:
c-ANCA* present in 90% of patients with active disease (good marker of disease activity)
Specific for WG
Chest radiograph:
bilateral nodular infiltrates or cavitary lesions.
Diagnosis:
biopsy
Treatment:
Cyclophosphamide
Danger of hemorrhagic cystitis and Transitional cell carcinoma
Steroids
Without treatment 80% die within 1 year
Lymphomatoid granulomatosis:
a rare granulomatous vasculitis (often involving lungs and other organs)
characterized by
infiltration by atypical lymphoid and plasmacytoid cells
may progress to non Hodgkins lymphoma
importance:
should be differentiated from WG

63. Infectious vasculitis
Fungal vasculitis: vessel invading fungi
Mucor, Aspergillus ,Candida.
Rocky Mountain spotted fever
Rickettsia rickettsiae
Disseminated meningococcemia:
Small vessel vasculitis  petechial hemorrhages
Infective endocarditis*
Roth’s spots in retina
Janeway’s lesions on hands (painless)
Osler’s nodes on hands (painful)
Glumerulonephritis
Fungal vasculitis: vessel invading fungi ( mnemonic = MAC)
Mucor, Aspergillus Candida,
Rocky Mountain spotted fever
Caused by Rickettsia rickettsiae
Transmitted by hard tick Dermacentor andersoni.
Organisms invade vessel endothelium and cause inflammation and rupture of weakened vessels
This produces classical petechial lesions that begin on the sole and palms and spread to trunk
Classic traid of rash, fever and history of tick bite
Disseminated meningococcemia:
Small vessel vasculitis  petechial hemorrhages
Disseminated gonococcemia
small vessel vasculitis located on the hands , feet and wrist
Viral vasculitis
HBV and HCV
Immune complex mediated
Infective endocarditis*
Immune complex vasculitis* . Thought to be responsible for:
Roth’s spots in retina
Janeway’s lesions on hands (painless)
Osler’s nodes on hands (painful) and
Glumerulonephritis
(Not due to organisms but due to formation of immune complexes)