**8. Viral causes of vasculitis**

Patients may present with evidence of elevated acutephase reactants, fever, malaise, myalgia,

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

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

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

Treponema pallidum and borrelia burgdorferi are also rare causes of infectious vasculitis

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

Mycobacterial or fungal pulmonary infections may mimic Wegener's granulomatosis or

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

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

*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,*

Churg-Strauss vasculitis in eliciting a granulomatous reaction in vessels [73].

may be associated with post-streptococcal infection, distinct from endocarditis [66, 67].

arthralgia, Osler's nodes, Janeway lesions, and septic infarcts [49,50].

depends on the clinical setting [51-57].

146 Updates in the Diagnosis and Treatment of Vasculitis

[71].

pneumonia.

central nervous system

presentation in the western United States.

ultimately multisystem failure if untreated. [69, 70].

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 idiopathic vasculitis.

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 the Wa idiotype [27,28].

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 involved as well, especially in the kidneys.

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 immune response to occur. Viral replication increases HBsAg load, and is temporally associated with jaundice [32]. The immune complexes eventually no longer form in antigen excess, and the serum sickness-like illness resolves. HBV has also been associated with largevessel polyarteritis nodosa-like illness [33]. Onset is early in the course of chronic HBV hepatitis.

Ziegler et al demonstrated the presence of vasculitis in infected falcons by the West Nile virus. West Nile virus (WNV) is a zoonotic flavivirus that is transmitted by blood-suckling mosqui‐ toes with birds serving as the primary vertebrate reservoir hosts (enzootic cycle). Some bird species like ravens, raptors and jays are highly susceptible and develop deadly encephalitis while others are infected subclinically only. Pathological findings in infected birds consistently included splenomegaly, non-suppurative myocarditis, meningoencephalitis and vasculitis. By immunohistochemistry WNV-antigens were demonstrated intralesionally. These results impressively illustrate the devastating and possibly deadly effects of WNV infection in falcons, independent of the genetic lineage and dose of the challenge virus used. Due to the relatively high virus load and long duration of viremia falcons may also be considered competent WNV amplifying hosts, and thus may play a role in the transmission cycle of this zoonotic virus.

Infectious Causes of Vasculitis http://dx.doi.org/10.5772/55189 149

Rare cases of vasculitis have similarly been reported following rubella virus, adenovirus, echovirus, coxsackievirus, parainfluenza virus, herpes simplex viruses, and hepatitis A virus

*Toxocara canis* presented in an adolescent as palpable purpura with additional features suggesting Henoch-Schönlein purpura [149]. *Cysticercus* has caused vasculitis and arachnoi‐ ditis as it infects the central nervous system [150] *Angiostrongylus* nematodes apparently caused a Wegener's granulomatosis-like pulmonary angiitis [151]. Loa loa, a filarial parasite,

[1] Zeek, P. M. Periarteritis nodosa: a critical review. Am J Clin Pathol(1952). , 22, 777-90.

[2] Hunder, G. G. Vasculitis: diagnosis and therapy. Am J Med(1996). suppl. A):, 37-45.

posal of an international conference. Arthritis Rheum(1994). , 37, 187-92.

[3] Jennette, J. C, Falk, R, Andrassy, K, et al. Nomenclature of systemic vasculitis. Pro‐

infections [23, 138-148].

**Author details**

Jacques Choucair

**References**

**9. Parasitic causes of vasculitis**

presented with cutaneous leukocytoclastic vasculitis

Hotel Dieu de France hospital, Beirut, Lebanon

Immune complexes containing HBsAg, HBsAb, and complement are found in the vessel wall [34]. The determinants of small vessel versus larger vessel disease in the two syndromes of HBV infection are unknown.

Human immunodeficiency virus (HIV) patients may present with a variety of vasculitides. However, it is difficult to specifically attribute the various vasculitides seen to HIV because of frequent co-infections with other agents that may cause vasculitis in the absence of HIV infection.

Human T lymphotropic virus l infection may cause retinal, cutaneous, or central nervous system vasculitis [35-38].

The herpesviruses (cytomegalovirus, varicella-zoster, herpes simplex viruses 1 and 2, and herpes hominis) may be associated with retinal vasculitis in immunocompromised patients [39-45]. Varicella-zoster may also cause a diffuse central nervous system small arterial granulomatous vasculitis, or a small- and/or large-artery vasculopathy [46-48, 117]. Herpes simplex viruses 1 and 2 have been associated with cutaneous vasculitis and necrotizing arteritis of small and medium vessels [118-120]. Epstein-Barr virus has been suggested as a cause of both small- and large-vessel disease in a number of cases and short series [121-126]. However, the ability to demonstrate causality in many instances is made all the more difficult by the latency of herpesvirus infection.

Varicella zoster virus and CMV have been as well implicated in the etiopathogenesis of various vasculitides via numerous and overlapping mechanisms including direct microbial invasion of endothelial cells, immune complex mediated vessel wall damage and stimulation of autoreactive B and/or T cells through molecular mimicry and superantigens [71].

Vasculitis following varicella-herpes zoster infection occasionally develops in the form of a central neurological deficiency (locomotor deficiency with or without aphasia around one month after an ophthalmologic herpes zoster) or involving the retina or, more rarely, the skin or the kidneys. Vasculitis associated with cytomegaloviral infection,predominantly observed in immunodepressed patients, is diffuse and basically involving the digestive tube, notably the colon, the central nervous system and the skin [127].

Parvovirus B19 has been suggested as the causative agent of Wegener's granulomatosis and polyarteritis nodosa in a number of cases and short series [128-133]. However, the issue of latency and the failure to eliminate B19 from pooled blood products provides a cautionary note when considering causality [134-137]. Rare cases of vasculitis have similarly been reported following rubella virus, adenovirus, echovirus, coxsackievirus, parainfluenza virus, herpes simplex viruses, and hepatitis A virus infections [23, 138-148].

Ziegler et al demonstrated the presence of vasculitis in infected falcons by the West Nile virus. West Nile virus (WNV) is a zoonotic flavivirus that is transmitted by blood-suckling mosqui‐ toes with birds serving as the primary vertebrate reservoir hosts (enzootic cycle). Some bird species like ravens, raptors and jays are highly susceptible and develop deadly encephalitis while others are infected subclinically only. Pathological findings in infected birds consistently included splenomegaly, non-suppurative myocarditis, meningoencephalitis and vasculitis. By immunohistochemistry WNV-antigens were demonstrated intralesionally. These results impressively illustrate the devastating and possibly deadly effects of WNV infection in falcons, independent of the genetic lineage and dose of the challenge virus used. Due to the relatively high virus load and long duration of viremia falcons may also be considered competent WNV amplifying hosts, and thus may play a role in the transmission cycle of this zoonotic virus.

Rare cases of vasculitis have similarly been reported following rubella virus, adenovirus, echovirus, coxsackievirus, parainfluenza virus, herpes simplex viruses, and hepatitis A virus infections [23, 138-148].
