**7. Bacterial causes of vasculitis**

Intracranial mycotic aneurysms (ICMAs) complicate about 2% to 3% of infective endocarditis (IE) cases, although as many as 15% to 29% of patients with IE have neurologic symptoms [24-26]. Of all intracerebral aneurysms, only 2% to 6% have an infectious etiology. Signs and symptoms of mycotic aneurysms may be misleading during the early stages, resulting in misdiagnosis and delays in treatment [27]. Early diagnosis of ICMA is the cornerstone of

Mycotic aneurysms can be divided into 4 types: [1] *embolic*, secondary to bacterial endocarditis (*embolomycotic aneurysms*); [2] *extravascular*, secondary to extension of contiguous infection from a septic focus neighboring an artery; [3] *cryptogenic* or primary bacteremic; and [4] direct contamination following arterial wall trauma, which may be postprocedural [28]. Aneurysms can occur in the cerebral circulation, usually at points of vessel bifurcation, or in the systemic

In IE-associated mycotic aneurysms, septic emboli are released from infected cardiac vegeta‐ tions. These tiny septic emboli occlude the vasa vasorum or entire arterial lumen, which leads to damage to the muscular layer of the vessel. ICMA tend to occur in the more distal portions of the middle cerebral artery, near the surface of the brain, involving the secondary and tertiary branches. In contrast, berry aneurysms occur at proximal branch points in or near the circle of Willis [26]. The outcome depends upon the anatomical location of the embolus, the causative bacteria and associated virulence of the organism, underlying host defenses, and appropriate antibiotic therapy. Mycotic aneurysms can decrease, increase, remain the same in size, or even

Patients with bacterial intracranial aneurysms have variable neurological symptoms, and early symptoms of infection may be subtle. In ICMA, patients may have symptoms ranging from nonspecific, general complaints, including fever or headache, to neurological deficits or catastrophic intracranial hemorrhage. Laboratory results are typically suggestive of an underlying inflammatory process and may include leukocytosis, elevated erythrocyte sedimentation rate and/or C-reactive protein concentration, and anemia. Blood cultures are

Computed tomographic angiography, magnetic resonance angiography (MRA), and catheter angiography are used to study the size, location, and morphology of intracranial aneur‐ ysms. Aneurysms 5 mm in diameter or larger can be detected by CTA and MRA. Smaller aneurysms are detected less reliably or detected in retrospect after comparison with cerebral angiography.[31-33]. Cerebral angiography is the gold standard and is often used in preoperative assessment and in determining prognosis[34]; however, it is not routinely recommended due to risk of complications associated with it. The size of the aneurysm during therapy can be safely and accurately monitored using CTA and MRA. In our patient,

Treatment of ICMA is controversial, in that the appropriate patients for surgical intervention, need for follow-up imaging, and most efficacious treatment are not well delineated in the medical literature. The appropriate treatment always involves medical and sometimes surgical therapies [35]. Moreover, there is no single uniformly accepted approach to the treatment of

effective treatment.

144 Updates in the Diagnosis and Treatment of Vasculitis

circulation [29].

disappear during treatment for endocarditis [30].

almost universally positive for microbial growth.

CTA was selected as the diagnostic tool.

Bacterial seeding of vessels may lead to necrosis through direct bacterial action. Vessels may be seeded intraluminally at sites of endothelial injury or flow turbulence. Seeding of vasa vasora may cause destruction of vessels from the outside in. An injury of a large vessel by this mechanism is classically termed a "mycotic aneurysm."

Contiguous spread from an infected site to a vessel may occur. Vessels may also be seeded from within the lumen, as in subacute bacterial endocarditis in which septic emboli embed within the wall of smaller vessels, causing a "mycotic" process via a luminal route. Immune response to bacteria or to bacterial components may also lead to vasculitis, usually by immunecomplex–mediated mechanisms[24].

In subacute bacterial endocarditis, direct spread via septic emboli and immune complex injury may occur.

Patients may present with evidence of elevated acutephase reactants, fever, malaise, myalgia, arthralgia, Osler's nodes, Janeway lesions, and septic infarcts [49,50].

*Nocardia, Aspergillus, Mucor, Curvularia, Pseudallescheria, Fusarium, Morganella, Metarrhizium,*

Infectious Causes of Vasculitis http://dx.doi.org/10.5772/55189 147

Before AIDS, syphilis was the infectious agent known as the "great imposter," presenting as large- or medium size vessel disease (aortitis or coronary arteries) or as the small-vessel rash of secondary lues. Aortic aneurysms were insidious in clinical presentation. *Treponema pallidum* spirochetes were rarely detected in fibrosed and scarred vessels [100-102]. At least briefly, *Borrelia burgdorferi,* the causative agent of Lyme disease, was known as an "imposter." Vasculitic changes may be seen in the central nervous system, retina, and temporal arteries

Our knowledge of viral pathogenesis has exploded in the last quarter of the twentieth century, accelerated in large part by epidemics of "emerging" viral diseases. Hepatitis C virus, discovered in 1989, has worldwide prevalence [25]. The10- to 20-year latent period before hepatic or rheumatic manifestations of disease explains the increasing number of cases of hepatitis C virus–mediated vasculitis currently being seen in the United States following the epidemic of new infections in the 1980s [26]. Prior to the discovery and characterization of hepatitis C virus in the late 1980s, the triad of arthritis, palpable purpura, and type II cryoglo‐ bulinemia was given the sobriquet "essential mixed cryoglobulinemia" and considered an

Availability of diagnostic testing for hepatitis C virus demonstrated that almost all of these cases were associated with hepatitis C virus infection. Immune response to the virus elicits a response to the Fc portion of immunoglobulin with the majority of elicited antibody having

Immune complexes of anti–Fc Wa idiotypic antibody and pre-existing antibody, and virus have the peculiar physical property of precipitating out of solution in the cold ("cryoglobu‐ lins"). Presumably, Wa idiotype recognizes a cross-reactive epitope found on hepatitis C virus and immunoglobulin. Extremities and skin are sufficiently cold so as to explain a predilection for small-vessel leukocytoclastic vasculitis of the skin; gravity enhances vascular injury in dependent distal vessels, giving rise to palpable purpura predominantly in the lower extrem‐ ities. More severe cases may manifest visceral organ involvement including membranoproli‐ ferative glomerulonephritis and bowel involvement. Small- and mediumsized arteries may be

Hepatitis B virus (HBV) infection provides the classic example of virally mediated immune complex disease. A lymphocytic venulitis or neutrophilic vasculitis of small vessels with leukocytoclasticorfibrinoidchangespresentstypicallyasan"urticaria-arthritissyndrome."[29]. Immune complexes of hepatitis B virus surface antigen (HBsAg) and antibodies to hepati‐ tis B virus surface antigen (HBsAb) circulate in the blood and are found deposited in vessels in association with complement [30, 31]. The long latency period of HBV allows time for an

*Xanthomonas, Klebsiella, E coli,* and *Aeromonas* infections.[87-99].

[103-116].

**8. Viral causes of vasculitis**

idiopathic vasculitis.

the Wa idiotype [27,28].

involved as well, especially in the kidneys.

Staphylococcus and streptococcus infections are common causes. Gram-negative organisms, other gram-positive cocci, fungi, and parasites may be causative as well, and their occurrence depends on the clinical setting [51-57].

Mycotic aneurysms resulting from septic emboli are common with staphylococcus, streptococ‐ cus, and *Salmonella* species [58-60]. Patients with subacute infections may develop cryoglobu‐ lins[61-63].Bacteremiamaypresentasleukocytoclasticvasculitis[64,65].Small-vesselvasculitis may be associated with post-streptococcal infection, distinct from endocarditis [66, 67].

The *Rickettsiae* are a group of obligate intracellular bacteria with tropism for vascular endo‐ thelium [68]. Infection results in widespread microvascular leak, local thrombosis, and ultimately multisystem failure if untreated. [69, 70].

Treponema pallidum and borrelia burgdorferi are also rare causes of infectious vasculitis [71].

In the lung, necrosis of vessels may occur from septic emboli or from contiguous spread in primary pneumonias. In the latter setting, *Pseudomonas aeruginosa* and *Legionella pneumophila* often cause direct necrosis via contiguous spread [72]. The presentation, however, is that of pneumonia.

Mycobacterial or fungal pulmonary infections may mimic Wegener's granulomatosis or Churg-Strauss vasculitis in eliciting a granulomatous reaction in vessels [73].

Spread of *Mycobacterium tuberculosis* to the aorta may be seen as a cause of tuberculous aortitis, coronary arteritis, and mycotic aneurysm [74-76]. *Aspergillus aeruginosa, Aspergillus fumiga‐ tus,* and *Mucor* may be characterized by direct vessel invasion and necrosis [59, 77, 78] *Coccidioides immitis* meningitis may be associated with vasculitis that can be confused with central nervous system

Angeitis [79, 80]. *Coccidioides immitis* may also present as an immune-complex–mediated disease with erythema nodosum, periarthritis predominantly of the ankles, and bihilar lymphadenopathy [81, 82]. This presentation is often confused with Löfgren's syndrome of sarcoidosis. While sarcoidosis as a cause of Löfgren's syndrome is more prevalent in eastern United States populations, *Coccidioides* immitis is a more likely cause of a Löfgren's-like presentation in the western United States.

*Neisseria* species may be associated with small-vessel vasculitis. In *Neisseria gonorrhea* infection, cutaneous papules vesiculate, then becomes necrotic [83]. In *N meningitides* infections, vasculitis may manifest in the skin and gastrointestinal tract with the endothelium showing necrosis and thrombosis [84-86]. In immunocompromised hosts, *Pseudomonas aeruginosa* and other gram-negative organisms can present as a large 1- to 5-cm macular erythema that develops central necrosis and peripheral edema and induration—a condition termed "ecthyma gangrenosum." Vessel thrombosis results from direct bacterial invasion of the vessels. Similar lesions may be seen in immunocompromised patients with disseminated *Pseudomonas,* *Nocardia, Aspergillus, Mucor, Curvularia, Pseudallescheria, Fusarium, Morganella, Metarrhizium, Xanthomonas, Klebsiella, E coli,* and *Aeromonas* infections.[87-99].

Before AIDS, syphilis was the infectious agent known as the "great imposter," presenting as large- or medium size vessel disease (aortitis or coronary arteries) or as the small-vessel rash of secondary lues. Aortic aneurysms were insidious in clinical presentation. *Treponema pallidum* spirochetes were rarely detected in fibrosed and scarred vessels [100-102]. At least briefly, *Borrelia burgdorferi,* the causative agent of Lyme disease, was known as an "imposter." Vasculitic changes may be seen in the central nervous system, retina, and temporal arteries [103-116].
