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MEDIUM AND LARGE VESSEL VASCULITIS

General aspects, diagnosis, and investigations

The typical medium- and large-vessel vasculitides of dermatologic importance are polyarteritis nodosa, Wegener granulomatosis, and Churg–Strauss disease. In each of these, there may also be small-vessel disease. Lymphomatoid granulomatosis is a rare disorder in which there is necrotizing vasculitis of large vessels, but this has a poor prognosis, as it may progress to frank lymphoma; it is discussed in Chapter 33. Other large-vessel vasculitis rarely presents to dermatologists, but occasionally forehead or scalp ulceration due to temporal arteritis may be seen initially in dermatology departments.

Nodular lesions occur in medium- and large-vessel vasculitis of numerous types (Fig.14.42) due to the presence of necrotizing lesions; for example, they are a feature of cutaneous polyarteritis nodosa and of the granulomatous lesions of Wegener granulomatosis. In such cases, they usually occur with other vasculitis features, such as livedo or small-vessel palpable purpura. They also occur in panniculitis (Ch.22) and erythema induratum (Ch.11). However, the term nodular vasculitis is generally unhelpful, as it is descriptive rather than identifying a cause.

Figure 14.42 Nodular vasculitis. These lesions had a distribution suggestive of erythema nodosum, and close-up morphology suggestive of Sweet disease. Nodular vasculitis is best approached as a descriptive term rather than a diagnosis.

Antineutrophil cytoplasm antibodies

Antineutrophil cytoplasm antibodies are primarily of relevance in large-vessel vasculitis, although they also occur in other disorders. The main patterns are as follows.

Figure 14.43 Fingertip necrosis in a patient with glomerulonephritis and positive proteinase-3 c-ANCA serology.

Polyarteritis nodosa

Polyarteritis nodosa (PAN) is a spectrum of disease affecting small- to medium-sized vessels, causing a leukocytoclastic vasculitis with segmental infarction of the vessel walls (Figs 14.44 and 14.45). Neutrophilia, positive rheumatoid factor, elevated ESR, hypergammaglobulinemia, and positive hepatitis B serology are all common features. Three patterns are now felt to occur, but clinical overlap between the patterns can cause diagnostic problems.

Figure 14.44 Polyarteritis nodosa, showing a pattern of patchy ‘broken’ livedo on the lower leg.

Figure 14.4 5Polyarteritis nodosa, lesions on the hands: (a) scattered necrotic papules, and (b) splinter hemorrhages in several fingers. Although trauma is the most common cause of splinter hemorrhages, lesions affecting several digits in individuals who are not performing manual tasks are very suggestive of a systemic cause.

Microscopic PAN

This disorder typically presents as glomerulonephritis; one-third of patients have pulmonary involvement, which may present with alveolar hemorrhage. The skin is involved in one-third of patients, usually with palpable purpura or ulceration of the legs. Peripheral neuropathy, pericarditis, and ocular involvement may occur. ANCA is positive in 90% of patients, approximately equally divided between p-ANCA and c-ANCA.

Cutaneous PAN

This affects predominantly small arterioles, and causes tender nodules, livedo, and ulceration. Fever, myalgia or arthralgia, and neuropathy all occur fairly frequently, but severe systemic disease is not a feature. Digital gangrene can occur.

Classic PAN

This disease occurs predominantly in men. Some cases appear to be triggered by infections such as hepatitis B or streptococcal disease; it may occur due to drugs such as amphetamines, and some cases are associated with hairy cell leukemia. It affects small- and medium-sized arteries, and small-vessel vasculitis is not a feature. Skin involvement is therefore uncommon in classic PAN, and is usually either palpable aneurysms or acral ulceration and necrosis. Oral lesions include papules, nodules, and ulcers. More typical features are fever, myalgia, arthralgia, hypertension, and neuritis, which may be of mononeuritis multiplex type. Renal or hepatic arterial aneurysms are demonstrated in two-thirds of patients, and mesenteric arterial aneurysms in one-third. However, visceral microaneurysms can occur in other vasculitides (such as Behçet syndrome) and in bacterial endocarditis, hereditary hemorrhagic telangiectasia, and emboli from atrial myxoma. ANCA is positive in only about 30% of patients with classic PAN, p-ANCA more commonly than c-ANCA.

Differential diagnosis

This is wide when all presenting features are considered. In the skin, the differential is from other causes of livedo, vascular occlusion, and vasculitis, as already discussed.

Treatment of PAN

Classic systemic PAN has a poor prognosis due to renal disease, hypertension, and bowel infarction. Renal and lung involvement may be severe in microscopic PAN. In both of these, treatment is with systemic steroids, cyclophosphamide, or azathioprine, along with treatment of effects such as hypertension, and treatment of underlying diseases (such as interferon for hepatitis). Cutaneous PAN is often chronic, and symptoms occur due to tender nodules, myalgia or arthralgia, and neuropathy. Steroids and NSAIDs are useful in some patients.

Wegener granulomatosis

Etiology and pathogenesis

Wegener granulomatosis is a triad of respiratory tract granulomas, renal granulomas, and vasculitis of small to medium arteries and veins, which may affect various organs. The etiology is unknown, although infectious foci may be important in the lung. It follows a variable course, the prognosis being determined mainly by renal involvement, although some patients have no demonstrable renal disease.

Clinical features

The initial presentation is often with nasal symptoms of discomfort and bleeding, which may cause cartilage destruction and collapse of the nasal bridge. In the skin, the initial lesions may be a small-vessel leukocytoclastic vasculitis, which is purpuric but without any granulomatous component, or may resemble PAN; the features therefore range from a small-vessel vasculitis to nodules and ulcers (Figs 14.46 and 14.47). Other features include pyrexia, malaise, otitis media, neuropathies, and vasculitis of other organs. ANCA, usually c-ANCA, is positive in over 90% with active systemic Wegener granulomatosis, and the positivity usually decreases with clinical improvement. Biopsies of skin, kidney, and other organs may be required to confirm the type of vasculitis, although renal biopsy usually demonstrates glomerulonephritis rather than granulomatous vasculitis, and investigations of organ damage are as for other vasculitides. Neutrophilia, anemia, positive ANA and rheumatoid factor, and elevated C-reactive protein and ESR are all common.

Figure 14.46 Vasculitis due to Wegener granulomatosis. (a) Necrotic lesions due to small-vessel vasculitis of skin; (b) more nodular lesions, suggesting a medium or large vessel vasculitis process.

Figure 14.47 Wegener granulomatosis. There is a marked depression of the nasal bridge due to preceding inflammation.

Differential diagnosis

Wegener granulomatosis often presents with nasal rather than cutaneous symptoms. However, it may cause a small-vessel vasculitis of skin (and is therefore part of the differential of CSVV), or may cause non-specific cutaneous ulceration that may suggest a primary skin infection, or pyoderma gangrenosum (see later).

Treatment

The disorder is usually treated with systemic corticosteroids and immunosuppressive agents, typically cyclophosphamide. Nasal spray steroids may be useful, and intralesional steroids for skin nodules. Long-term co-trimoxazole reduces morbidity and mortality, even in the absence of overt chest infections.

Churg–Strauss syndrome

Etiology and pathogenesis

This disorder, also termed allergic granulomatosis, is a multisystem vasculitis of small- to medium-sized vessels, with asthma and eosinophilia of uncertain etiology.

Clinical

Skin lesions occur in about 50% of patients (Figs 14.48 and 14.49), and may be the presenting feature in about 10% of these (usually a purpuric vasculitis). The skin lesions that occur include a leukocytoclastic vasculitis (which may be ulcerated, necrotic, bullous, or resemble erythema multiforme), necrotizing granulomas, livedo reticularis, and nodules due to panniculitis. Systemic features include asthma, allergic rhinitis, peripheral neuropathy (may be mononeuritis multiplex), arthralgia or myalgia, cardiac failure, hypertension, pericarditis, and abdominal pain. There is marked eosinophilia, often elevated IgE, and often positive ANCA (usually p-ANCA).

Figure 14.48Churg–Strauss syndrome, with ulceration on the side of a finger.

Figure 14.49 Churg–Strauss syndrome. This patient, with asthma and peripheral eosinophilia, developed infiltrated papules and plaques on the trunk.

Differential diagnosis

The skin lesions may mimic any cause of vasculitis or livedo, although they are often relatively subtle or non-specific. Lesions around the elbows are rather suggestive of Churg–Strauss syndrome. The most important differential diagnosis is that of the asthma component, or of associated systemic vasculitis (such as mononeuritis multiplex). An important issue in differential diagnosis is the apparent provocation of Churg–Strauss syndrome with use of leukotriene antagonists. Whether this is correct is uncertain; it is more likely that such cases were actually those that presented with milder asthma symptoms and were not initially recognized.

Treatment

There is typically a good response to oral steroids, but other immunosuppressive agents may be required (azathioprine, chlorambucil, and cyclophosphamide).

White/Cox: Diseases of the Skin, 2ed.(c) 2006, Elsevier Inc. All rights reserved.