Secondary Vasculitis

, David G. I. Scott² and Chetan Mukhtyar²

(1)

Department of Rheumatology, Ipswich Hospital NHS Trust, Ipswich, UK

(2)

Department of Rheumatology, Norfolk and Norwich University Hospital, Norwich, UK

16.1 Introduction

Vasculitis often occurs as a primary event (de novo), but can occur on the background of a number of other diseases; in particular, it is associated with certain infections, drugs, and connective tissue diseases such as rheumatoid arthritis and SLE. It can also occur in association with some malignancies.

16.2 Definition

Secondary vasculitis describes systemic vasculitis occurring on the background of other diseases or known infections/or associated with drug treatment.

16.3 Epidemiology

There is little data on the incidence of secondary vasculitis. Systemic vasculitis complicating rheumatoid arthritis has become much less frequent over the last two decades [1], but there is little evidence of any major change in association with other trigger factors.

16.4 Etiology

Some drugs originally associated with vasculitis, particularly hydralazine and penicillamine, are now used much less frequently. There are, however, reports of EGPA associated with leukotriene inhibitors and the commonest cause of ANCA-associated vasculitis secondary to drug treatment is propylthiouracil.

16.5 Infection and Vasculitis

The association between infection and vasculitis has been recognized for many years and a number of different organisms identified (see Table 16.1).

Table 16.1

Infection and vasculitis

Vessel involved		Infection
Large arteries	Bacterial	Staphylococcus, Salmonella, mycobacteria, Streptococcus
	Spirochaetal	Treponema pallidum
	Fungal	coccidioidomycosis
Medium arteries	Bacterial	Group A Streptoccus, mycobacteria
Medium arteries	Viral	HBV, HCV, HIV, parvovirus B19
Small vessels and medium arteries	Bacterial	Streptococcus
	Viral	HBV, HCV, HIV, CMV
	Bacterial	Staphylococcus, Salmonella, mycobacteria, Streptococcus, Yersinia, Neisseria, Rickettsiae
Small vessel (leukocytoclastic)	Viral	HIV, CMV, herpes zoster, parvovirus B19, HBV, HCV

Adapted from Somer and Finegold [2]

CMV cytomegalovirus’, HBV hepatitis B virus, HCV hepatitis C virus, HIV human immunodeficiency virus

The most widely publicized association is between hepatitis B (HBV) and polyarteritis nodosa. This association was first described over 40 years ago and the highest reported incidence of PAN was 77 per million in an area endemic for HBV infection. In France, falling HBV infection rate has correlated with a significant decrease in HBV-associated PAN [3]. In our population in Norwich we find this to be very rare. The common clinical features are very similar to classic PAN with mononeuritis multiplex (83.5 %), GI involvement (57 %), renal tract (38 %), skin (31 %), and hypertension (31 %) [3]. HBV-associated PAN usually develops within 12 months of infection and hepatitis is often quite mild. Angiography will show typical microaneurysms and/or stenosis in the celiac axis and renal blood vessels. ANCA are not associated with HBV vasculitis.

Treatment for HBV-associated vasculitis is with a combination of antiviral agents, together with plasma exchange (see Table 16.2).

Table 16.2

Major viruses associated with vasculitis and their treatment

Virus	Type of vasculitis	Standard therapy
HBV	PAN	Short CS, PE, Lamivudine
HCV	Cryoglobulinemic vasculitis	Short CS, IFNx, and ribavirin ± PE
HIV	PAN large/medium/small vessel vasculitis Cerebral vasculitis	Short CS with ARV ± PE
Parvovirus	PAN	CS
B19	“HSP”-like	CS and/or Mg
Varicella zoster	Retinitis meningoencephalomyelitis	Aciclovir ± CS
CMV	Retinitis Colitis PAN	Valganciclovir, ganciclovir or foscarnet

Adapted from Pagnoux et al. [4]

ARV anti-retroviral drugs, CMV cytomegalovirus, CS glucococorticoid, HBV hepatitis B virus, HCV hepatitis C virus. HIV human immunodeficiency virus, HSP Henoch–Schönlein purpura (now called IgA vasculitis), PAN polyarteritis nodosa, PE plasma exchange

Hepatitis C is also associated with vasculitis, but almost always with cryoglobulinemia and cryoglobulinemic vasculitis (see Chap. 14). Other viruses associated with vasculitis are as shown in Table 16.2.

Direct invasion of blood vessel wall by pyogenic organisms (most often staphylococcus and streptococcus) can also cause vasculitis. It is often associated with a predisposing condition such as diabetes mellitus and may occur at a site of previous damage by atheroma or surgery.

Large artery involvement is rare, but when it occurs, the usual process is by the formation of mycotic aneurysms. This is most commonly associated with streptococcus pneumonii and salmonella, although often in association with underlying/predisposing conditions such as diabetes or intravenous drug use.

There are descriptions of vasculitis also associated with mycobacteria, spirochetes (Treponema pallidum associated with aortitis), and rickettsia, usually presenting with an extensive maculopapular rash in patients with rocky mountain spotted fever and also fungal infections – mainly associated with immunocompromised patients involving both CNS and large arteries (mycotic aneurysm formation).