Medium and large vessel vasculitis

Abstracts

As vasculites são constituídas por um grande grupo de síndromes caracterizadas por inflamação e necrose da parede dos vasos sangüíneos, resultando em estreitamento ou oclusão do lúmen. A distribuição dos vasos envolvidos varia consideravelmente e serve de base para a classificação das síndromes vasculíticas: grandes vasos (arterite de Takayasu, arterite temporal); pequenos e médios vasos (poliarterite nodosa, síndrome de Churg-Strauss, granulomatose de Wegener, vasculites nas doenças reumáticas); e pequenos vasos (vasculite de hipersensibilidade, púrpura de Henoch-Schonlein, poliangeíte microscópica, crioglobulinemia). Este artigo revisa as vasculites dos médios e grandes vasos e opções terapêuticas atuais; além de oferecer orientação sobre abordagem diagnóstica e tratamento dos pacientes com suspeita de vasculite cutânea.

Anticorpos anticitoplasma de neutrófilos; Arterite de células gigantes; Arterite de Takayasu; Doenças reumáticas; Granulomatose de Wegener; Poliarterite nodosa; Púrpura; Síndrome de Churg-Strauss; Vasculite; Vasculite alérgica cutânea

REVIEW ARTICLE

Medium and large vessel vasculitis

Hebert Roberto Clivati Brandt^I; Marcelo Arnone^II; Neusa Yuriko Sakai Valente^III; Mirian Nacagami Sotto^IV; Paulo Ricardo Criado^V

^IPreceptor Physician, Department of Dermatology, Medical School, University of Sao Paulo (FMUSP) - Sao Paulo (SP), Brazil

^IIDermatologist, Master in Sciences, Area of concentration Dermatology, FMUSP, Assistant of the Division of Clinical Dermatology, Medical School, University of Sao Paulo (FMUSP) - Sao Paulo (SP), Brazil

^IIIPh.D., Professor, Dermatologist and researcher of Laboratory of Medical Investigation, LIM 53, Medical School, University of Sao Paulo (FMUSP) - Sao Paulo (SP), Brazil

^IVAssociated Professor, Department of Dermatology, Medical School, University of Sao Paulo and Pathologist of Laboratory Histopathology, Division of Clinical Dermatology, Medical School, University of Sao Paulo (FMUSP) - Sao Paulo (SP), Brazil

^VDermatologist, Ph.D. in Sciences, area of concentration Dermatology at FMUSP, Assistant of Division of Clinical Dermatology and researcher of Laboratory of Medical Investigation, LIM 53, Hospital das Clinicas, Medical School, University of Sao Paulo (FMUSP) - Sao Paulo, Responsible for vasculitis outpatient unit (HC-FMUSP) - Sao Paulo (SP), Brazil

^{Mailing Address}

ABSTRACT

Vasculitis comprises a broad group of syndromes characterized by inflammation and necrosis on the walls of blood vessels, resulting in narrowing or occlusion of the lumen. The distribution of involved blood vessel varies considerably and serves as the basis for one classification of vasculitic syndromes: large vessels (Takayasu arteritis, giant cell arteritis); medium and small muscular arteries (polyarteritis nodosa, Churg-Strauss syndrome, Wegener's granulomatosis, vasculitis in rheumatic diseases); and small vessels ("hypersensitivity" vasculitis, Henoch-Schonlein purpura, microscopic polyangiitis, cryoglobulinemia). This article reviews medium and large vessel vasculitis and current treatment options; it also presents a comprehensive approach to diagnosing and treating patients with suspected cutaneous vasculitis.

Keywords:Antibodies, Antineutrophil Cytoplasmic; Takayasu's Arteritis; Rheumatic Diseases; Wegener Granulomatosis; Polyarteritis Nodosa; Purpura; Churg-Strauss Syndrome; Vasculitis; Vasculitis, Allergic Cutaneous

INTRODUÇÃO

Small vessel vasculitis, especially small vessel cutaneous vasculitis, is the most common type of vasculitis presented to dermatologists. However, palpable purpura may be presented within a spectrum of clinical manifestations of medium vessel vasculitis, which are more frequently directed to others specialists, such as rheumatologists, pneumologists and nephrologists, owing to their multi-systemic affection. In a recent Continuing Medical Education article at Brazilian Annals of Dermatology, we have reviewed small vessel vasculitis. The present review article is focused on medium and large vessel vasculitis.

1 - Predominantly medium vessels

They affect skin vessels that are 50 to 100µm in diameter in the dermo-hypodermal junction.

1. Polyarteritis nodosa

Polyarteritis nodosa may have systemic and cutaneous manifestations. It is divided into classical polyarteritis nodosa and cutaneous polyarteritis nodosa

1.1a . Classical polyarteritis nodosa

Classical polyarteritis nodosa (PAN) is a multi-systemic disease that may cause great morbidity. Skin lesions occur in only 20 to 50% of the patients, and palpable purpura is the most common manifestations. Cutaneous lesions suggestive of large vessel involvement are manifested as large or "sharp"skin ulcers and digital gangrene ^1-4.

The characteristics of classical polyarteritis nodosa are multi-systemic disease, normally affecting more men, of any age, whose main symptoms are fever, malaise, weight loss, and arthralgia. Vasculitis determines symptoms and signs such as muscle fatigue, abdominal pain, multiple mononeuritis, arterial hypertension, orchitis (more common when associated with HBV infection), congestive heart failure. It has hepatitis B virus as common cause in 5% to 7%, plus there are multiple dilations in medium vessels in the kidneys, liver and other internal organs. These dilations are not pathognomonic, present also in other diseases. Cutaneous manifestations are observed in 20% to 50% of the cases, especially palpable purpura, and there may be also livedo reticularis, large ulcers, subcutaneous nodules and, more rarely, digital infarction ^12,4-6.

1.1b. Cutaneous polyarteritis nodosa

Cutaneous PAN present lesions which are dermal or subcutaneous nodules at onset, especially located on the lower portion of the legs, close to malleolar region, which may go up to the thighs and buttocks and sometimes to the hands and feet (Figure 1). These nodules may get ulcerated (Figure 2) and when they regress, they leave behind livedoid pigmentation such as "starry powder"(Figure 1) or ivory starry scars such as white atrophy.

In children, there is digital gangrene. Peripheral neuropathy affects 20% of the patients, usually multiple mononeuritis. In some patients, we can observe only extensive racemose livedo and peripheral neuropathy (Figure 3). Cutaneous PAN is associated with streptococcus infection (specially in children), parvovirus B19, HIV, hepatitis B virus, tuberculosis, in addition to inflammatory intestinal disease and inferior vena cava thrombosis. According to the study of some series, there are five factors associated with greater mortality of patients: creatinine > 1.58 mg/dl; proteinuria > 1g/day, gastrointestinal tract affection; affection of central nervous system, and cardiomyopathy. The authors observed 5-year survival of patients according to the presence of the manifestations listed above and they detected the following figures: no factor (88%), one factor present (74%), two or more factors present (54%) 1,2,4-6.

It is observed that the biopsy material shows necrotizing and obliterative inflammatory arteritis, affecting many small and medium vessels, with focal panniculitis. There may be aneurysms. Arterial branches are the most affected one, causing luminal thrombosis and obliteration, with distal ischemia and necrosis (Figure 4).

2 - Medium and small vessels

Medium and small vessel vasculitis may present as follows:

2.1. Associated with ANCA ("pauciimmune")

In addition to etiopathogenic factors involved in cutaneous small vessel vasculitis, which also apply to medium and large vessel necrotizing vasculitis, currently the involvement of superantigen has been demonstrated in the group of vasculitis. Superantigens (SAgs) are peptides capable of inducing many immune processes and they play an important role in maintaining the inflammatory status. SAgs bind to the proteins which are not normally processed by antigen presenting cells and class II MHC molecules located in the non-polymorphic regions. These regions are different from the binding sites of immunologically processed binding antigens. Thus, SAgs may interact with large number of T lymphocytes that do not need to present an antigen-specific T cell receptor. Most SAgs are molecules of microbial origin. Studies have shown that in Wegener's granulomatosis, Kawasaki syndrome, Takayasu arteritis, microscopic polyangeitis, and giant cell arteritis, S. aureus SAgs and less frequently, S. pyogenes SAgs, either they may maintain the process of vasculitis in non-colonized patients, or they have nasal form of these bacteria ^7-10. ANCA is present in 5% of the normal population. In IFI, there are 3 standards of ANCA ^{9, 10}: cytoplasmatic (c-ANCA), perinuclear (p-ANCA) and atypical pattern (a-ANCA).

Patients normally express only one pattern, either c-ANCA or p-ANCA. If they are concomitantly expressed it is suggestive of drug-induced vasculitis. p-ANCA is the least specific, more frequently present in microscopic polyangeitis, Churg-Strauss syndrome, idiopathic growing necrotizing glomerulonephritis, and drug-induced vasculitis. c-ANCA is the most frequent and specific in Wegener’s granulomatosis ^2,4,6.

Small vessel vasculitis associated with ANCA (SVV-ANCA) present symptoms combined with the different types of vasculitis associated with them. Pulmonary hemorrhage and growing necrotizing glomerulonephritis may be associated, forming a "pulmonary-renal syndrome". Small vessel vasculitis associated with ANCA is predominantly pauciimmune, given that direct immunofluorescence does not show or reveals only scarce evidence of immunocomplex deposits on the walls and around the vessels. ANCA should be investigated considering the suspicion of SVV-ANCA in the following clinical situations ^2,4,6,11: presence of pulmonary hemorrhage, glomerulonephritis, long course of otitis or sinusitis, presence of mass or retro-orbital tumor (suspicion of Wegener's granulomatosis), or any systemic vasculitis that affects multiple organs.

2.1.1. Microscopic Polyangeitis

Microscopic polyangeitis is a necrotizing vasculitis, with few or no immune deposits, affecting small vessels. There may be presence of necrotizing arteritis involving small and medium vessels. Necrotizing glomerulonephritis is very common (79%-90%) and pulmonary capillarities is frequent (25%-50%), with hemorrhages in 12% to 29% of the patients 12, 13. In microscopic polyangeitis there are systemic symptoms such as fever, myalgia, weight loss and arthralgia. Palpable purpura is manifested in 46% of the patients at the time the disease is presented and about 90% of the patients have positive ANCA in serum ^3,4,6,11.

We can observe in Chart 1 the differences between nodous polyarteritis and microscopic polyangeitis.

2.1.2. Wegener’s Granulomatosis

It is rare multisystemic disease comprising necrotizing granulomatous vasculitis. The upper respiratory tract and the kidneys are the primary sites of affection. It happens on the 4th or 5th decades of life, there is no gender preference and Caucasian subjects are the most affected one 2-4.

Fatigue, malaise, myalgia, arthralgia, anorexia and weight loss are frequent. Pulmonary disease is common (50-85%) and it is manifested by chronic dry cough, moderate and severe hemoptysis, and respiratory failure; approximately 1/3 of the patients are asymptomatic ^14,15. There may be acute diffuse pneumonitis as well as associated alveolar hemorrhage ^{15, 16}. Affection of upper respiratory tract occurs as chronic sinusitis (50-80%). More rarely, there is septal perforation and saddle nose. Chronic oral ulcers may be painful ^15-17. Involvement of the ear may be shown by auditory canal obstruction (otitis) and conductive or sensorineural hearing loss. Inflammation may compress the 7th cranial nerve (peripheral facial palsy). Wegener’s granulomatosis (WG) may affect any organ such as skin, eyes, trachea, central nervous system, heart, breasts, prostate, gastrointestinal tract, vulva and cervix ^{3, 4}.

Cutaneous manifestations are present in 45% of the cases and they are polymorphous; there may be palpable purpura, nodules, necrotic ulcerations, vesicles, pustules and pyoderma gangrenosum lesions. Skin lesions rarely predominate over the clinical manifestations ^17-19.

WG is a clinical-pathologic entity, reason why clinical manifestations should be complemented by histologic findings of necrotizing granulomatous vasculitis in all affected organs, especially in the lung tissue. Granulomatous vasculitis in renal tissue is very rare ^3,4,19.

Histopathological exam is characterized by nodular infiltrates, such as abscesses, with great build-up of polymorphonuclear cells surrounded by lymphocytes, plasmocytes, histiocytes in palisade, fibroblasts and giant cells ¹⁹.

Clinically, there is the classical triad - respiratory tract necrotizing granuloma, cutaneous necrotizing vasculitis and

glomerulonephritis, which guides the diagnosis, but these affections are not necessarily observed simultaneously ^2-4. In general, laboratory findings are not specific, revealing systemic inflammatory disease ^{14, 20}.

Clinical and histopathological criteria are proposed by the American College of Rheumatology, and they may be used as guidelines in diagnosing the disease ².

Davies, in 1982, and Van der Woude, in 1985, demonstrated the presence of antineutrophil cytoplasmatic antibodies (ANCA) in the serum of Wegener's granulomatosis patients ^21-23. These antibodies are serology markers of the disease and have 99.3% specificity. Those that have cytoplasmatic pattern (c-ANCA) are directed against proteinase-3 (PR-3), which is serine-protease with molecular weight of 29kD, distributed in azurophyl granules of human neutrophil lysosomes. Antibodies with perinuclear pattern (p-ANCA) are directed against myeloperoxidase (MPO), catepsin G, lactoferrin, elastase and against other non-identified antigens ^3,4,21-23.

Proteinase-3 cloning enabled definition of large grade homology with myeloblastin, upon comparing its molecular sequence, which suggested a common codifying gene ^{22, 23}.

Considering genetic aspects, there is association between ANCA expression and patients with Wegener's granulomatosis and class II genes of main histocompatibility complex, in such a way that frequency of HLA-DQw7 in Caucasians is significantly increased from 53% against 27% in controls, with relative risks of 2.9%.

Apparently, haplotype DQw7 associated with DR2 makes ANCA be persistently positive ^{3, 4}.

Differential diagnosis should be made with classical polyarteritis nodosa, vasculitis caused by hypersensitivity, Goodpasture syndrome, Churg-Strauss allergic vasculitis, necrotizing sarcoid granulomatosis, and lymphomatoid granulomatosis ^3-5. Treatment in these patients should be early defined and be based on corticosteroids and immunosuppressants, specifically cyclophosphamide, to avoid fatal course of the disease given that without treatment, 90% of the patients die within 2 years, owing to uremia or respiratory failure ^3,4,18,24,25.

2.1.3. Churg-Strauss Syndrome

It is a granulomatous eosinophil-rich inflammation involving the respirator tract and necrotizing small and medium vessel vasculitis associated with asthma and eosinophilia ²⁶. It is a middle-age disease that affects both genders ^{1, 27}. The triggering factors of Churg-Strauss syndrome (CSS) are: vaccination, desensitization procedures, use of leukotriene inhibitors (still controversial), and sudden interruption of corticosteroid use ²⁸.

The disease normally starts with respiratory manifestations such as asthma or rhinitis ^{3, 4}. These manifestations may come first or sometimes simultaneously to vasculitis. Lungs are normally affected, with diffuse or nodular infiltrate, without tendency to cavitation and they may progress in episodes ²⁸. Clinical presentation is asthma, no previous history of atopia, associated with rhinitis and sinusitis ²⁹. Peripheral neuropathy is expressed as multiplex mononeuritis, occurring in 60% of the cases ^30,31. Digestive tract is affected in 60% of the cases, with abdominal pains, perforation and intestinal obstruction and mesenteric vasculitis with diarrhea and digestive hemorrhage. There may be myocarditis, pericarditis and coronary disease, and heart lesions are the cause of death in 40% of the patients ^32-34.

Cutaneous manifestations occur in about 50% of the cases: palpable purpura in 48% of the cases, subcutaneous nodules in 30%, macular-papular eruption in 25%, and urticariform eruptions in 25% of the patients ²⁹.

Prognosis of CSS is better than that of PAN or WG ^{4, 30, 32}

CSS has three different progression stages: 1st stage - allergic rhinitis, nasal polyposis and asthma, persisting for years or decades; 2nd stage - eosinophilic pneumonia, gastroenteritis and peripheral eosinophilia, with frequent recurrences; and 3rd stage - systemic vasculitis with granulomatous inflammation, occurring up to 30 years after initial manifestations, on average 3 years after it ³⁰.

Laboratory findings of CSS reveal affections similar to those observed in WG. However, in CSS there is predominant eosinophilia (> 10%/ml) and positive ANCA in 60% to 70% of the patients, with p-ANCA pattern ^{20, 28}.

Histopathological analysis of CSS is characterized by eosinophilic infiltrate of the tissue, extravascular granulomas of cutaneous tissue and internal organs, and necrotizing vasculitis affecting arteries and veins. CSS granuloma contains necrotic polymorphonuclear leukocytes, eosinophils, marked fibrinoid and collagen fibers degeneration, and proliferation of granulation tissue.

2.2. Drug-induced vasculitis associated with ANCA

There is strong evidence of the occurrence of vasculitis associated with use of hydralazine, propylthiouracil and similar drugs, minocycline, penicillamine, allopurinol or sulphasalazine 3. Other related drugs are methimazole, phenytoin, thiazide, cefotaxime and retinoids ^{28 35}.

Common dermatological lesions in this group are acral purpuric plaques and nodules (face, breasts, extremities and ears) and digital gangrene (Figure 5). Clinical pathology analysis reveals leukocytoclastic vasculitis in superficial and profound dermis with Direct Immunofluorescence (DIF) without specific fluorescence. There is normally association with necrotizing glomerulonephritis and pulmonary hemorrhage ^{36- 38}. Hydralazine-induced vasculitis associated with ANCA is frequently misdiagnosed as drug-induced lupus. It is differentiated from lupus by presenting renal affection. There may be anti-histone antibodies and anti-double helix DNA.

There is no association with slow acetylating phenotype and there is no serositis ^{37, 38}.

Minocycline-induced vasculitis associated with ANCA presents livedo reticularis and/or subcutaneous nodules in the extremities associated with fever and arthralgia. Most patients present positive p-ANCA or anti-myeloperoxidase antibodies. Patients normally have no anti-histone antibodies 39. Minocycline is known for inducing immune reactions such as serum-similar disease, drug-induced lupus, autoimmune hepatitis, eosinophilic pneumonia, and vasculitis. Most cases of minocycline-induced vasculitis occur after 2 years of use, especially in patients treating acne. This association should be considered especially in young women with vasculitis that have used the drug and have autoimmune clinical manifestations ^{35, 40, 43}.

Vasculitis caused by propylthiouracil (PTU) hypersensitivity represents a type of vasculitis, leukocytoclastic type, of superficial and deep vessels. It may occur with anti-thyroid drugs that are chemically related with PTU. Manifestations vary from fever and arthralgia to pulmonary-renal syndrome. This type of vasculitis is associated with articular pain, fever, malaise, weight loss, nephritis, hepatitis, pericarditis, which are part of the lupus-like reactions induced by PTU. These findings may take place with purpuric and necrotic lesions on the skin, especially acral lesions and on the ear pinna, in addition to necrotic ulcers on the oral cavity and oropharynx. After discontinuation of PTU there is clinical resolution of hypersensitivity vasculitis, followed by normalization of laboratory findings ^36-38.

In general, clinical manifestations of small vessel vasculitis associated with ANCA are: constitutional, such as fever, weight loss, anorexia, malaise; musculoskeletal, such as myalgia, arthralgia, skin, palpable purpura, urticaria; renal, such as proteinuria, hematuria, renal failure, necrotizing glomerulonephritis; respiratory: dyspnea, cough, hemoptysis, pulmonary infiltrate, interstitial pulmonary disease, pulmonary hemorrhage; involving the nervous system, such as, peripheral neuropathy, especially mononeuritis; gastrointestinal, such as blood in feces, increase in liver enzymes, diarrhea, nausea, vomiting, and abdominal pain.

3 - Vasculitis associated with autoimmune and connective tissue diseases

Vasculitis may be associated with autoimmune and collagen diseases, such as in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjögren syndrome, CREST syndrome (calcinosis, Raynaud, esophageal involvement, sclerodactylia, telangiectasia) and progressive systemic sclerodermia.

Vasculitis is an uncommon manifestation, but a significant one for autoimmune diseases. It is more frequently observed in RA, SLE, systemic sclerodermia, and Sjögren syndrome ⁴⁴.

Rheumatoid vasculitis (RV) affects 5% to 15% of the patients with rheumatoid arthritis. RV affects only middle-aged patients with RA who are smokers, have had the disease for a long time, and have high levels of rheumatoid factor. Skin and nerves are the most frequently affected tissues, causing peripheral gangrene and multiple mononeuritis ^45-51.

In Sjögren syndrome, cutaneous vasculitis may be manifested in 20% of the patients as palpable purpura (Figure 6), ecchymosis and urticaria. We can also find the presence of Raynaud phenomenon and erythematous nodules on the thighs ⁵³. In systemic sclerodermia or in patients with CREST, skin small vessels are primarily affected causing ulcerations and scars on the tip of the fingers and toes ⁵⁴.

4 - Neutrophilic dermatosis with associated vascular disorders

Neutrophilic dermatoses (ND) are a heterogeneous group of diseases unified by histopathological findings in common: large neutrophilic non-infectious dermal inflammatory infiltrate. Extracutaneous manifestations and systemic diseases may frequently be associated with ND. Overlapping of these entities can also be observed. Historically, these diseases have been classified based on presence of vasculitis in cutaneous lesions ^{6, 55} (i) no associated vasculitis (1. Sweet syndrome; 2. Pyoderma gangrenosum; 3. Rheumatoid neutrophilic dermatitis; 4 .Arthritis-dermatitis syndrome associated with intestinal inflammatory disease); (ii) with associated vasculitis (Behçet disease); 2. Erythema elevatum diutinum; 3. Facial granuloma.

It is difficult to define whether vascular insult is a primary pathogenic mechanism, that is, a damage mediated by immunocomplexes (primary vasculitis), or whether it is a secondary occurrence or an epiphenomenon (secondary vasculitis). The presence of immunocomplexes inside the vascular wall observed by DIF is indicative diagnosis of vasculitis primarily mediated by immunocomplexes or leukocytarian vasculitis of small vessels. However, in the absence of these DIF findings, it is not possible to completely exclude vasculitis as a primary process ^5,6,55.

4.1. Chronic fibrosing vasculitis on the skin

This group comprises two forms of cutaneous vasculitis that are characteristically resolved with fibrosing cutaneous reaction: erythema elevatum diutinum and facial granuloma ^56-59.

4.1.1. Erythema elevatum diutinum

It affects more women and the anatomical pathological substrate of leukocytoclastic vasculitis. It may be associated with hematological abnormalities, especially monoclonal gammopathy by IgA. It has also been associated with HIV, HHV-6, myeloid leukemia, myelodysplasia, chronic infections, intestinal inflammatory disease or after liver transplantation. It seems to be related with infectious stimuli, especially streptococcus, because the disease is exacerbated after streptococcus infections and even after using streptokinase thrombolic agent. Many patients have associated intestinal inflammatory disease and there is report of the progression of multiple myeloma type IgA ^58,60-64.

Skin lesions may occur as papules, papulous plaques or non-purpuric nodules, of chronic course, erythematous or sometimes brownish. They preferably occur on the extensive surface of extremities (Figure 7A), on the skin over the hand and knee joints, which is highly characteristic distribution. It may also be associated with the buttocks and over the calcaneal tendon. Face and pinna may be involved, normally sparing the trunk and mucosas. The surface is normally smooth, and there may be mild scaling over the lesions. There may be lesions with purpura, blisters, hemorrhagic crust, ulceration, especially edematous lesions. On the course of the disease, the lesions may disappear spontaneously, leaving behind atrophic areas with hyper or hypopigmentation. About 40% of the patients have associated arthralgia. The course is chronic, sometimes there is involution. Cold weather seems to aggravate the disease ^58,60-64.

Histopathological analysis of acute lesions shows leukocytoclastic vasculitis, including eosinophils on the upper and medium dermis. In chronic lesions, there is fibrosis, capillary proliferation, and macrophages, plasmocytes and lymphocytes infiltrate. Intra and extra-cellular cholesterol deposits may be present in old lesions (Figure 7B, C, D).

There is good therapeutic response to dapsone and sulphapyridine. There is reference to suppressant effects of nyacinamide in disease activity. The localized forms may be treated with intralesional corticosteroid or high-potency topical agents ^57-58.

4.1.2. Facial Granuloma

It is an uncommon affection characterized by onset of brownish-purpuric lesions on the face. They are papular or nodous plaques, normally located on the regions of the face, nose or mouth. The surface is smooth, and it may lead to accentuation of follicular ostia. Other regions than the face are rarely affected (Figure 8 A and B). There is a variant that affects the nasal mucosa, named eosinophilic angiocentric fibrosis, which rarely coexists with facial skin lesions. It affects primarily adults ^65-68.

   

Histopathological analysis reveals leukocytoclastic vasculitis, plasmocyte, lymphocyte histiocyte, neutrophil infiltrate and numerous eosinophils. DIF show deposits of IgA, IgG, IgM and C3 on vessel walls, suggesting the participation of immunocomplexes on the lesion genesis (Figure 8 C and D). ^66,68 Diagnosis is clinical and histopathological. The differential diagnosis is made with lymphomas, pseudolymphomas, sarcoidosis, syphilis, tumid lupus, Hansen's disease, granulomatous rosacea, and polymorphic eruption to light exposure. Extra-facial forms should be distinguished from erythema elevatum diutinum 56,65.

Management options are intralesional corticosteroid, sulphone, non-hormonal antiinflammatory drugs, and chofazimine. There are reports of good results with laser. Cryosurgery is also effective, with the disadvantages of residual scars 58,60-64.

4.2. Nodular Vasculitis

Nodular vasculitis (NV) affects primarily middle-aged women. Legs are predominantly affected, with nodular lesions, especially on the posterior-lateral regions. There may be lesions on the thighs and arms. There may be resolution of the lesions that do not suffer ulceration within two to six weeks, progressing with scar but little atrophy. Nodules appear in regular intervals during months to years. Histopathology may show cutaneous small vessel vasculitis and affection of subcutaneous cell tissue presented as panniculitis. Classically, the cases of nodular vasculitis that occur as tuberculide manifestations are named erythema induratum of Bazin. In such circumstances, many authors have isolated fragments of M. tuberculosis DNA by making tissue analysis of the lesions using the technique of Polymerase Chain Reaction (PCR) 7,8,69,70.

Other conditions that may be associated with cutaneous small vessel vasculitis are Sweet syndrome, pyoderma gangrenosum, Behcet disease, spider sting, Waldenström hypergammaglobulinemic purpura, and intestinal inflammatory diseases, which are not the scope of our review and may be found in the specific literature 69,71-73.

5 - Large Vessel Vasculitis

Large vessel vasculitides are represented by giant cell arteritis (temporal arteritis) and Takayasu arteritis.

5.1. Giant cell arteritis (temporal arteritis)

Involvement of medium and large arteries of the temporal region in a uni or bilateral fashion is the most common manifestation of giant cell arteritis. Elderly Caucasian women are the most affected subjects. Anemia, high ESR, fever, headache and rheumatic

polymyalgia are the most frequent manifestations. Classical skin lesion is ulceration of the scalp and thickness of temporal artery. If present, retina arteritis may lead to blindness. Histopathology analysis shows panarteritis of multinucleate giant cells 74-85. Criteria for diagnosis of giant cell arteritis are advocated by the American College of Rheumatology 2.

5.2. Takayasu arteritis

It is a chronic arteritis that affects the aorta and its main branches. Systemic manifestations may be extensive depending on the location and the severity of the vascular bed affected by the disease. The dermatological manifestations include palpable purpura, ulcers or gangrenous-like pyoderma lesions. Granulomatous arteritis with stenosis of artery and fibrosis are observed in the anatomical pathological analysis. The use of systemic corticosteroids and immunosuppressant agents is frequently necessary, as well as surgical intervention 86-90. Diagnosis criteria for Takayasu arteritis are those advocated by the American College of Rheumatology 1, 2.

FINAL CONSIDERATIONS

Medium and large vessel vasculitides are a challenge to diagnose and treat. Concepts, classifications and diagnostic techniques are in constant progression. It is important for dermatologists to get to know the many different presentations and clinical signs of vasculitides, trying to reduce morbidity and mortality by early detection and appropriate treatment, whose synopsis may be seen in Chart 2.

REFERENCES

How to cite this article: Brandt HRC, Arnone M, Valente NYS, Sotto MN, Criado PR. Vasculites dos médios e grandes vasos. An Bras Dermatol. 2009;84(1):55-67.

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Publication Dates

• Publication in this collection
  23 June 2009
• Date of issue
  Feb 2009

History

• Accepted
  26 Dec 2008
• Received
  20 June 2008