Chapter 11- Vasculitis Flashcards

Question

In many cases of immune complex vasculitis, it is not clear whether the antigen-antibody complexes form elsewhere and then deposit in a particular vascular bed, or if they form in situ from the seeding of antigen in a vessel wall followed by antibody binding ( Chapter 6 ). Moreover, in many cases of presumed immune complex vasculitis, antigen-antibody deposits are scarce . Either the immune complexes have been largely cleared at the time that the tissue diagnosis is made, or else other mechanisms may apply in such “**pauci-immune” cases**

Answer 1

Many patients with vasculitis **have circulating antibodies** that **react with neutrophil cytoplasmic antigens**, so-called antineutrophil cytoplasmic antibodies (ANCAs) . ANCAs are a **heterogeneous group of autoantibodies directed against constituents** (mainly enzymes) of neutrophil primary granules, monocyte lysosomes, and endothelial cells.

Answer 2

**intracellular distribution,** * either **cytoplasmic (c-ANCA)** or * **perinuclear (p-ANCA)** ****.

Answer 3

* **Anti-myeloperoxidase (MPO-ANCA**): * **Anti-proteinase-3 (PR3-ANCA)**

Answer 4

MPO is a **lysosomal granule** constituent **normally involved in generating oxygen free radicals** ( Chapter 2 ). MPO-ANCAs can be induced by a variety of therapeutic agents, in particular propylthiouracil. These have been called p-ANCA.

Answer 5

MPO-ANCAs can be induced by a **variety of therapeutic agents,** in particular **propylthiouracil.** These have been called p-ANCA.

Answer 6

Anti-proteinase-3 (PR3-ANCA): PR3 is also a **neutrophil azurophilic granule constituent.** That it **shares homology** wit**h numerous microbial** peptides may explain how **PR3-ANCAs develop**. [66] These have been called c-ANCA.

Answer 7

**Wegener granulomatosis**

Answer 8

* **microscopic polyangiitis** and **Churg-Strauss syndrome** (see below);

Answer 9

ANCAs serve as useful diagnostic markers for the ANCA-associated vasculitides, and their titers may reflect the degree of inflammatory activity. **ANCA titers also rise with recurrent disease** and are therefore **useful in clinical managemen**t. The **close association between ANCA titer**s and **disease activity** suggests a pathogenic role. Although the precise mechanisms are unknown, **ANCA can directly activate neutrophil**s and may **thereby stimulate neutrophils to release reactive oxygen species**and**proteolytic enzymes;** within the vasculature, this also leads to **endothelial cell-neutrophil interactions and subsequent endothelial cell damage**. [67]

Answer 10

antigenic targets of ANCAs are primarily intracellular but there is now abundant evidence that ANCA antigens (in particular PR3) are either constitutively present at low levels on the plasma membrane or are translocated to the cell surface in activated and apoptotic neutrophils

Answer 11

* D**rugs or cross-reactive microbial antigens** induce ANCAs; alternatively, neutrophil surface expression or release of PR3 and MPO (e.g., in the setting of infections) incites * **ANCA formation in a susceptible host.** * **Subsequent infection, endotoxin exposure, or other inflammatory stimuli** elicit cytokines such as TNF that cause surface expression of PR3 and MPO on neutrophils and other cell types. * **ANCAs react with these cytokine-activated cells** and either cause direct injury (e.g., to endothelial cells) or induce further activation (e.g., in neutrophils). * **ANCA-activated neutrophil**s degranulate and also cause injury by releasing reactive oxygen species, engendering endothelial cell toxicity and other indirect tissue injury.

Answer 12

Kawasaki disease

Answer 13

* most common form of vasculitis **among elderly individuals** in the United States and Europe. * It is a **chronic**, typically **granulomatous inflammation** of **large to small-sized arteries** that * affects principally the arteries in the head—**especially the temporal arteries**—**but also the vertebral and ophthalmic arteries**. [71]

Answer 14

**temporal arteries**—but **also the vertebral and ophthalmic arteries.** [71]

Answer 15

can lead to **permanent blindness**; **consequently, giant-cell arteritis is a medical emergency requiring prompt recognition and treatment**

Answer 16

. Lesions also occur in other arteries, including the **aorta (giant-cell aortitis)**

Answer 17

**remains elusive,** although **most evidence supports** an **initial T cell–mediated immune response** against an unknown, p**ossibly vessel wall, antigen.** ``` Proinflammatory cytokines (in **particular TNF)**, and **anti–endothelial cell humoral immune responses also probably contribute.**[72] ``` ``` An immune etiology is supported by the **characteristic granulomatous reaction**, a**correlation with certain HLA class II haplotypes**, and a**therapeutic response to steroids.** ``` The extraordinary predilection for a single vascular site (temporal artery) remains unexplained.

Answer 18

Involved arterial segments develop ***nodular intimal thickening (***with**occasional thromboses**) that **reduces the lumenal diameter**. Classic lesions **exhibit medial granulomatous inflammation that leads to elastic lamina fragmentation;** there is **an infiltrate of T cells (CD4+\> CD8+)** and **macrophages**. Multinucleated giant cells are found in upwards of 75% of adequately biopsied specimens ( Fig. 11-23 ). Occasionally, granulomas and giant cells are rare or absent, and lesions show only a nonspecific panarteritis composed predominantly of lymphocytes and macrophages. Inflammatory lesions are not continuous along the vessel, and long segments of relatively normal artery may be interposed. The healed stage is marked by medial scarring and intimal thickening, typically with residual elastic tissue fragmentation.

Answer 19

FIGURE 11-23 Giant-cell (temporal) arteritis. * A, H&E stain of section of temporal artery showing giant cells at the degenerated internal elastic lamina in active arteritis (arrow). * B, Elastic tissue stain demonstrating focal destruction of internal elastic lamina (arrow) and * intimal thickening (IT) characteristic of long-standing or healed arteritis. * 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).

Answer 20

* **vague and constitutional** * —fever, fatigue, weight loss—or include facial pain or headache that is most intense along the course of the superficial temporal artery, which can be painful to palpation. * Ocular symptoms (associated with involvement of the ophthalmic artery) appear abruptly in about 50% of patients; these range from diplopia to complete vision loss.

Answer 21

* Diagnosis depends on biopsy and * histologic confirmation. However, because giant-cell arteritis is extremely segmental, adequate **biopsy requires at least a 2- to 3-cm length of artery**; **even then, a negative biopsy result does not exclude the diagnosis.**

Answer 22

Treatment with **corticosteroid**s is generally effective, with **anti-TNF therapy** showing **promise in refractory cases.**

Answer 23

This is a **granulomatous vasculitis** of **medium and larger arteries** characterized principally by **ocular disturbances a**nd **marked weakening of the pulses in the upper extremities (hence, its other name, pulseless disease**).

Answer 24

characterized principally by **ocular disturbances** and **marked weakening of the pulses in the upper extremities** (hence, its other name, **pulseless disease).**

Answer 25

**pulseless disease** ocular disturbances and marked weakening of the pulses in the upper extremities

Answer 26

**transmural fibrous thickening of the aorta**—particularly the **aortic arch and great vessels**—and **severe luminal narrowing of the major branch vessels** ( Fig. 11-24 ).

Answer 27

**Aortic lesions share many attributes with giant-cell aortitis, including clinical features and histology;**indeed, the**distinction is typically made only on the basis of the age of the patien**t. Thos**e over 50 years of age are designated as having giant-cell aortitis**, while **those under 50** have **Takayasu aortitis**. [64] Though traditionally associated with the Japanese population and a subset of HLA haplotypes, Takayasu aortitis has a global distribution. The cause and pathogenesis are unknown, although immune mechanisms are suspected

Answer 28

FIGURE 11-24 Takayasu 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 (arrows).

Answer 29

aortic arch In a third of patients it also affects the remainder of the aorta and its branches. The **pulmonary artery is involved in half of cases; coronary and renal arteries may be similarly affected**.

Answer 30

There is **irregular thickening** of the vessel wall with **intimal hyperplasia;** when the aortic arch is involved the **great vessel lumens can be markedly narrowed or even obliterated** ( Fig. 11-24A and B ).

Answer 31

There is **irregular thickening of the vessel** wall with **intimal hyperplasia;** when the **aortic arch is involved the great vessel lumens can be markedly narrowed or even obliterated** ( Fig. 11-24A and B ). Such narrowing explains the weakness of the peripheral pulses.

Answer 32

range from **adventitial mononuclear infiltrates** with **perivascular cuffing of the vasa vasorum**, to **intense mononuclear inflammation in the media**, to **granulomatous inflammation, replete with giant cells and patchy medial necrosis.** The histologic appearance ( Fig. 11-24C ) is indistinguishable from that of giant-cell (temporal) arteritis. As the disease progresses, **collagenous scarring, with admixed chronic inflammatory infiltrates,** occurs in **all three layers of the vessel wall.**Occasionally,**aortic root involvement causes aortic insufficiency.**

Answer 33

**Initial symptoms** are **usually nonspecific,** including **fatigue, weight loss, and fever** . With progression, **vascular symptoms appear and dominate the clinical picture,** including **reduced blood pressure and weaker pulses in the upper extremities**;**ocular disturbances, including visual defects, retinal hemorrhages, and total blindness; and neurologic deficits** . Involvement of the **more distal aorta** may **lead to claudication** of the **legs; pulmonary artery involvement may cause pulmonary hypertension**. Narrowing of the coronary ostia may lead to **myocardial infarction,** and involvement of the renal arteries leads to systemic hypertension in roughly half of patients. The course of the disease is variable. In some there is rapid progression, while others enter a quiescent stage at 1 to 2 years, permitting long-term survival, albeit sometimes with visual or neurologic deficits.

Answer 34

Involvement of the **more distal aorta**

Answer 35

Polyarteritis nodosa (PAN) is a **systemic vasculitis of *small or medium-sized muscular arteries* (*but not arterioles, capillaries, or venules*),**typically**involving renal and visceral vessels but sparing the pulmonary circulation**. There is **no association with ANCA**s, but about **30% of patients with PAN have chronic hepatitis B**with**HBsAg-HbsAb complexes in affected vessel**s, indicating an immune complex–mediated etiology (see Chapter 6 ) in that subset. Nevertheless, the cause remains unknown in the majority of cases; there may be etiologic and important clinical distinctions between classic idiopathic PAN, the cutaneous forms of PAN, and the PAN associated with chronic hepatitis. [73,] [74] Polyarteritis nodosa (PAN) is a systemic vasculitis of small or medium-sized muscular arteries (but not arterioles, capillaries, or venules), typically involving renal and visceral vessels but sparing the pulmonary circulation. There is no association with ANCAs, but about 30% of patients with PAN have chronic hepatitis B with HBsAg-HbsAb complexes in affected vessels, indicating an immune complex–mediated etiology (see Chapter 6 ) in that subset. Nevertheless, the cause remains unknown in the majority of cases; there may be etiologic and important clinical distinctions between classic idiopathic PAN, the cutaneous forms of PAN, and the PAN associated with chronic hepatitis. [73,] [74] Clinical manifestations result from ischemia and infarction of affected tissues and organs. "But disease" ***but not arterioles, capillaries, or venules\*** **sparing the pulmonary circulation**.

Answer 36

**segmental transmural necrotizing** inflammation of **small to medium-sized arteries.**

Answer 37

Vessels of the **kidneys, heart, liver, and gastrointestinal tract**are involved in descending order of frequency. Lesions usually affect **only part of the vessel circumference** and show a **predilection for branch points.** The ***inflammatory process weakens*** the arterial wall and can **lead to aneurysms or even rupture.** Impaired perfusion resulting in ulcerations, infarcts, ischemic atrophy, or hemorrhages in the distribution of affected vessels may be the first sign of disease

Answer 38

**Impaired perfusion resulting in ulcerations, infarcts, ischemic atrophy, or hemorrhages in the distribution of affected vessels** may be the first sign of disease

Answer 39

* *transmural inflammation** of the **arterial wall** with a **mixed infiltrate of neutrophils,** **eosinophils, and mononuclear cells,** frequently accompanied by * *fibrinoid necrosis (** Fig. 11-25 ). **Luminal thrombosis can occur.**

Answer 40

Later, the **acute inflammatory infiltrate is replaced by fibrous****(occasionally nodular)** thickening of the vessel wall that can extend into the adventitia. C**haracteristically, all stages of activity (from early to late) coexist in different vessels**or**even within the same vessel,** suggesting ongoing and recurrent insults.

Answer 41

FIGURE 11-25 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.

Answer 42

Though **typically a disease of young adults,** PAN can **also occur in pediatric and geriatric populations.** **PAN**kahalatang edad!

Answer 43

The course may be a**cute, subacute, or chronic, a**nd is **frequently remitting and episodic,**with**long symptom-free intervals.**

Answer 44

Because the **vascular involvement is widely scattered,**the**clinical signs and symptoms of PAN may be varied, puzzling, and not always referable to a vascular source.**

Answer 45

The most common manifestations are **malaise, fever, and weight loss;** **hypertension, usually developing rapidly due to renal involvement; abdominal pain and melena (bloody stool**) due**to vascular lesions in the gastrointestinal tract**;**diffuse muscular aches and pains;** and peripheral neuritis. **Renal arterial involvement is often prominent and a major cause of death** . Untreated, the disease is fatal in most cases, either during an acute fulminant attack or following a protracted course

Answer 46

. However, therapy with **corticosteroids and cyclophosphamide**results in**remissions or cures in 90% of cases**

Answer 47

The **leading cause of acquired heart disease** in **children**, Kawasaki disease, is an **acute febrile,** **usually self-limited illness of infancy and childhood (80% are younger than 4 years)** associated with an a**rteritis affecting large to medium-sized,** and **even small, vessels**.

Answer 48

Its clinical significance **stems primarily from a predilection** for **coronary artery involvement;** such **coronary arteritis can cause aneurysms t**hat rupture or thrombose, resulting in**acute myocardial infarctions.** Originally described in Japan, the disease is now increasingly reported in the United States and other countries.

Answer 49

The etiology is uncertain, but the **vasculitis is thought to result from a delayed-type** **hypersensitivity reaction of T cells** to an as **yet uncharacterized antigen.** This **leads to cytokine production**and**macrophage activation,**and is**accompanied by polyclonal B-cell activation.** This **results in formation of autoantibodies** to **endothelial cells and smooth muscle cells,** which **precipitate the acute vasculitis.** It is currently speculated that a variety of infectious agents (most likely viral) can trigger the disease in genetically susceptible persons

Answer 50

As with polyarteritis nodosa, **lesions exhibit pronounced inflammation** affecting the **entire thickness of the vessel wall;** however, **fibrinoid necrosis is usually less prominent.** Although the acute vasculitis subsides spontaneously or in response to treatment, **aneurysm formation with thrombosis can supervene**. As with other causes of arteritis, healed lesions may have obstructive intimal thickening. Pathologic changes outside the cardiovascular system are rarely significant.

Answer 51

Kawasaki disease is also known as **mucocutaneous lymph node syndrome**, because it **presents with conjunctival and oral erythema and erosion, edema of the hands and feet, erythema of the palms and soles,**a**desquamative rash, and cervical lymph node enlargement**.

Answer 52

develop cardiovascular sequelae, ranging from **asymptomatic coronary arteritis, to coronary artery ectasia and aneurysm formation, to giant coronary artery aneurysms (7–8 mm) with rupture or thrombosis, myocardial infarction, and sudden death**.

Answer 53

With i**ntravenous immunoglobulin therapy and aspirin**, the **rate of coronary artery disease is reduced to about 4%**

Answer 54

This is a **necrotizing vasculitis** that **generally affects capillaries,** as well as **arterioles and venules of a size smaller than those involved in polyarteritis nodosa; rarely, larger arteries may be involved.** It is **also called hypersensitivity vasculitis or leukocytoclastic vasculitis**.

Answer 55

Unlike polyarteritis nodosa, **all lesions of microscopic polyangiitis tend to be of the same age in any given patient.** The skin, mucous membranes, lungs, brain, heart, gastrointestinal tract, kidneys, and muscle can all be involved; necrotizing glomerulonephritis (90% of patients) and pulmonary capillaritis are particularly common. Disseminated vascular lesions of hypersensitivity angiitis can also occur as a presentation of other disorders (e.g., **Henoch- Schönlein purpura, essential mixed cryoglobulinemia, and vasculitis associated with connective tissue disorders)**

Answer 56

``` In some cases, an **antibody response to antigens such as drugs (e.g., penicillin), proteins, or tumor proteins has been implicated;** this can **either result in immune complex deposition or may trigger secondary immune responses (e.g., the development of p-ANCAs)**that are**ultimately pathogenic.** ``` However, **most lesions are pauci-immun**e (devoid of immune complexes), and i**ncreasingly, MPO-ANCAs are causally im-plicated.** [68] Recruitment and activation of neutrophils within a particular vascular bed may be responsible for the disease manifestations.

Answer 57

Microscopic polyangiitis is characterized by **segmental fibrinoid necrosis** of the **media with focal transmural necrotizing lesions; *granulomatous inflammation is absent***. These **lesions morphologically resemble polyarteritis nodosa but typically spare medium-sized and larger arteries;**consequently, macroscopic infarcts are uncommon. In some areas (typically post-capillary venules), only infiltrating and fragmenting neutrophils are seen, giving rise to the term **leukocytoclastic vasculitis** ( Fig. 11-26A ). Although immunoglobulins and complement components can be demonstrated in early skin lesions, little or no immunoglobulin can be seen in most lesions (so-called pauci-immune injury). FIGURE

Answer 58

In some areas (typically post-capillary venules), **only infiltrating and fragmenting neutrophils are seen**, giving rise to the term **leukocytoclastic vasculitis** ( Fig. 11-26A ).

Answer 59

Although immunoglobulins and complement components can be demonstrated in early skin lesions**, little or no immunoglobulin can be see**n in most lesions (so-called pauci-immune injury). FIGURE

Answer 60

FIGURE 11-26 Representative forms of ANCA-associated small-vessel vasculitis. A, Leukocytoclastic vasculitis (microscopic polyangiitis) with fragmentation of neutrophils in and around blood vessel walls. B and C, Wegener granulomatosis. B, Vasculitis of a small artery with adjacent granulomatous inflammation including epithelioid cells and giant cells (arrows). C, Gross photo from the lung of a patient with fatal Wegener granulomatosis, demonstrating large nodular centrally cavitating lesions

Answer 61

Depending on the vascular bed involved, major clinical features include **hemoptysis; hematuria, and proteinuria**;**bowel pain or bleeding**;**muscle pain or weakness;**and**palpable cutaneous purpura**.

Answer 62

With the **exception of those who develop widespread renal or brain involvement**, **cyclophosphamide and steroid immunosuppression induces remission and markedly improves long-term survival**

Answer 63

Churg-Strauss syndrome (also **called allergic granulomatosis and angiitis)** is a **relatively rare (roughly one in a million people)**small-vessel**necrotizing vasculitis classically associated with asthma, allergic rhinitis, lung infiltrates, peripheral hypereosinophilia, and extravascular necrotizing granulomas**.

Answer 64

Vascular lesions can be histologically similar to **polyarteritis nodosa or microscopic polyangiitis**but are**also characteristically accompanied by granulomas and eosinophils**. [77] ANCAs (mostly MPO-ANCAs) are present in less than half the cases and raise the possibility that there are distinct subsets of patients with the syndrome. Nevertheless, when present, the ANCAs are probably responsible for the vascular manifestations of the disease.

Answer 65

``` Cutaneous involvement (palpable purpura), gastrointestinal tract bleeding, and renal disease (primarily as focal and segmental glomerulosclerosis) are the major associations. ``` Myocardial infiltrates of eosinophils and cytotoxicity caused by them are implicated in the cardiomyopathy seen in Churg-Strauss syndrome; the heart is involved in 60% of patients, and accounts for almost half of the deaths in the syndrome

Answer 66

Wegener granulomatosis is a necrotizing vasculitis characterized by a triad of: * Acute necrotizing granulomas of the upper respiratory tract (ear, nose, sinuses, throat) or the lower respiratory tract (lung) or both * • Necrotizing or granulomatous vasculitis affecting small to medium-sized vessels (e.g., capillaries, venules, arterioles, and arteries), **most prominent in the lungs and upper** airways but affecting other sites as well * Renal disease in the form of focal necrotizing, often crescentic, glomerulonephritis

Answer 67

respiratory tract. Conversely, a **widespread form of the disease can affect eyes, skin, and other organs,** notably **the heart;** clinically, this resembles polyarteritis nodosa except that there is also respiratory involvement.

Answer 68

that there is **also respiratory involvement.**

Answer 69

Wegener granulomatosis probably represents a **form of T cell–mediated hypersensitivity** **reaction,** possibly **to an inhaled infectious or other environmental agent;** such a pathogenesis is su**pported by the presence of granulomas and a dramatic response to immunosuppressive therapy**.

Answer 70

**PR3-ANCAs** are present in up to 95% of cases; they are a useful marker of disease activity and may participate in disease pathogenesis. After immunosuppressive treatment, a rising PR3-ANCA titer suggests a relapse; most patients in remission have a negative test or falling titers.

Answer 71

Upper respiratory tract lesions range from **inflammatory sinusitis with mucosal granulomas to ulcerative lesions of the nose, palate, or pharynx, rimmed by granulomas with geographic patterns of central necrosis and accompanying vasculiti**s ( Fig. 11- 26B ).

Answer 72

The necrotizing granulomas are **surrounded by a zone of fibroblastic proliferation** with **giant cells and leukocyte infiltrate**, reminiscent of **mycobacterial or fungal infections**. Multiple granulomas can coalesce to produce radiographically visible nodules that can also cavitate; late-stage disease may be marked by extensive necrotizing granulomatous involvement of the parenchyma ( Fig. 11-26C ); alveolar hemorrhage may be prominent. Lesions may ultimately undergo progressive fibrosis and organization. A spectrum of **renal lesions may be seen (** Chapter 20 ). In early stages, glomeruli exhibit only focal necrosis with thrombosis of isolated glomerular capillary loops (focal and segmental necrotizing glomerulonephritis); there is minimal parietal cell proliferation in Bowman's capsule. More advanced glomerular lesions are characterized by diffuse necrosis and parietal cell proliferation to form crescents (crescentic glomerulonephritis).

Answer 73

**Males are affected more often than females**, at an **average age of about 40 years.**

Answer 74

Classic features include **persistent pneumoniti**s with **bilateral nodular and cavitary infiltrates (95%),** **chronic sinusitis (90%)**, **mucosal ulcerations of the nasopharynx (75%**), and **evidence of renal disease (80%).** Other features **include rashes, muscle pains, articular involvement,** mononeuritis or polyneuritis, and fever. Left untreated, the disease is usually rapidly fatal; 80% of patients die within 1 year..

Answer 75

Treatment with **steroids, cyclophosphamide,** and more recently **TNF-antagonists,** have turned Wegener granulomatosis into a chronic remitting and relapsing disease.

Answer 76

is a **distinctive disease that often leads to vascular insufficiency;** it is characterized by **segmental, thrombosing, acute and chronic inflammation of medium-sized and small arteries,** principally the **tibial and radial arterie**s, with **occasional secondary extension** into the veins and nerves of the extremities. Buerger disease is a **condition that occurs almost exclusively in heavy cigarette smokers**, usually **before the age of 35.** **"Masarap magyosi after kumain ng BURGER!**

Answer 77

The **strong relationship to cigarette smoking** is thought to be **due to direct endothelial cell toxicity by some component of tobacco,**or an**idiosyncratic immune response to the same agents.** Most patients have **hypersensitivity to intradermally injected tobacco extracts,** and their **vessels exhibit impaired endothelium-dependent vasodilation** when challenged with acetylcholine. Genetic influences are suggested by an **increased prevalence in certain ethnic groups (Israeli, Indian subcontinent, Japanese) and an association with certain HLA haplotypes**

Answer 78

Thromboangiitis obliterans is characterized by a **sharply segmental acute** and **chronic vasculitis of medium-sized and small arteries, predominantly of the extremities.** Microscopically, there is acute and chronic inflammation, accompanied by luminal thrombosis. Typically, the thrombus contains small microabscesses composed of neutrophils surrounded by granulomatous inflammation ( Fig. 11-27 ); the thrombus may eventually organize and recanalize. The inflammatory process extends into contiguous veins and nerves (rare with other forms ofvasculitis), and in time all three structures become encased in fibrous tissue.

Answer 79

FIGURE 11-27 Thromboangiitis obliterans (Buerger disease). The lumen is occluded by a thrombus containing abscesses (arrow), and the vessel wall is infiltrated with leukocytes

Answer 80

The **early manifestations are a superficial nodular** **phlebitis, cold sensitivity of the Raynaud type (see below) in the hands, and pain in the instep of the foot induced by exercise (so-called instep claudication).** In **contrast to the insufficiency caused by atherosclerosis,** in ***Buerger disease there tends to be severe pain, even at rest, related undoubtedly to the neural involvement.*** Chronic ulcerations of the toes, feet, or fingers may appear, which can be followed in time by frank gangrene. Abstinence from cigarette smoking in the early stages of the disease often brings dramatic relief from further attacks.

Answer 81

* rheumatoid arthritis, * SLE, cancer, * or systemic illnesses such as mixed cryoglobulinemia, * antiphospholipid antibody syndrome, and * Henoch-Schönlein purpura.

Answer 82

longstanding, severe rheumatoid arthritis and usually affects small and medium-sized arteries. I**t can lead to visceral infarction** and **sometimes causes a clinically significant aortitis.** Identifying the underlying pathology may be therapeutically important. For example, although classic immune complex lupus vasculitis and antiphospholipid antibody syndrome are morphologically similar, anti-inflammatory therapy is required in the former while anticoagulant therapy is indicated in the latter.

Answer 83

**direct invasion of infectious agents**, usually **bacteria or fungi, and in particular *Aspergillus and Mucor species.*** Vascular invasion can be part of a localized tissue infection (e.g., bacterial pneumonia or adjacent to abscesses), or—less commonly—it can arise from hematogenous seeding of bacteria during septicemia or embolization from sepsis of infective endocarditis.