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.

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)

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.

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.

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.

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)

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

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)

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??

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

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.

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.

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).

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.

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

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

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.

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)

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

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.

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

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

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

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.

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

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

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

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

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

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

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

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*

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)

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.

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

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

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

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

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)

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)

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.

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.

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

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

Small vessel vasculitis

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.

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.

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

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

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.”

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.

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

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

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.

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

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

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

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.

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

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

Clinical features Persons most commonly affected by WG are middle aged 40-50 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.

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

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)