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Home , Systemic vasculitis

Emília Inoue Safo, Luís Eduardo Coelho Andrade

Systemic : a difficult diagnosis

othingtriggers a,ninternist's diagnostic interests virtually impossible to achieve one classification with more than a potential case of systemic vasculitis. universal acceptance.6 NThe ubiquitous nature of the target tissue, the In the Division of the Universidade variations in the rate and severity of disease progression, Federal de São Paulo (UNIFESP), we use Lie's and its ability to mimic other diseases mandate an intense classification 6 due to its practicality, although we have and focused approach to diagnosis and treatment. Blood implemented some minor modifications (Table I). Lie's vessels have limited ways of responding to injury: classification is based on the predominant size of the blood increased vascular permeability, weakening of vessel wall vessels involved and allows for overlap among major with resultant formation or hemorrhage or both, vasculitic syndromes. and intimaI proliferation and thrombosis which can result Several mechanisms of vascular damage have been in obstruction and ischemia. I proposed, including pathogenic immune complex Vasculitis is a heterogeneous group of disorders deposition, antiendothelial cell antibody-mediated vessel characterized by inflammation, often with necrosis and damage, injuries related to antibodies against lysosomal occlusion of blood vessels. These disorders may be enzymes (ANCA), cellular immune response and generalized or localized, primary (Le., the essential formation, vessel damage mediated directly by disorder affecting blood vessels) or secondary (associated infectious agents, and tumor-cell-mediated vessel damage. with a variety of different underlyng diseases). The clinicaI Although the role of each one of these mechanisms is spectrum of vasculitis represents one of the most variable in any given vasculitis syndrome, in "generalthe interesting and perplexing group of diseases in internaI lesion is ultimately caused by immune complex deposition, medicine.2 complement system activation, and inflammatory response. Since the first classification of vasculitis by Zeek in The involved antigens include autoantigens (nuclear or 1952,3 many other classification systems have been cytoplasmatic antigens), infectious antigens ( B proposed,4-7 but the lack of pathognomonic clinicaI and or C virus), tumoral antigens, drugs, and others not yet laboratory features, uniform histopathological expression, identified.8 and unknown or incompletely understood etiology and The role of adhesion molecules like ICAM-l and pathogenesis for the majority of the disorders make it VCAM-l, and inflammatory cytokines such as IL-l, IL-6 and TNF-alfa appear to be important in the pathogenesis of vascular damage in vasculitic syndromes. The Address for correspondence: expression of these factors in endothelial cells in response Emília Inoue Sato to a given initial stimulus (unknown in the majority of Rua Botucatu, 740 ~Vila Clementino São Paulo/SP - Brasil - 04023-062 cases), may be important in the modulation of the

SATO, E.1. & ANDRADE, L.E.C. - Systemic vasculitis: a difficult diagnosis São Paulo Medicai JournallRPM 115(3): 1418-1421, 1997 1419

neuropathy are observed. Systemic complaints are labia 1 Classifications of vasculitis. Lie 6 Modified - infrequent, except when due to associated diseases UNIFESP Primary vasculitis (secondary vasculitis syndromes). Laboratory tests are not specific, but may be helpful to diagnose secondary Vasculitis of large-sized blood vessel vasculitis such as those associated with autoimmune Giant cell (temporal) arteritis rheumatic diseases. In all cases of vasculitis affecting Takayasu arteritis mainly small vessels, it is important to look for cryoglobulins; when positive, it is necessary to investigate Vasculitis of medium- and small-sized blood vessel if it is associated with infections such as B or C hepatitis Churg-Strauss syndrome virus, neoplasm or autoimmune rheumatic diseases. Many Wegener's granulomatosis different diseases may present vasculitis affecting arterioles, capillaries and venules, thus requiring several laboratory tests for an exact diagnosis. Vasculitis affecting predominantly small-sized blood Small- and medium-size artery involvement is vessels characterized by cutaneous ulceration, distaI gangrene, mononeuritis multiplex, hypertension, coronary Henoch-Schonlein Syndrome insufficiency, /arthritis, central nervous system Essential cryoglobulinemic vasculitis involvement, and constitutional symptoms such as weight Cutaneous leukocytoclastic angiitis loss, fever and weakness. Polyarteritis nodosa is the most Miscellaneous conditions representative of this group of vasculitis. The presence of Buerger's disease and should bring to mind the Cogan Syndrome possibility of Churg-Strauss disease, and the involvement Behçet disease of the upper airways with destructive lesions and pulmonary and/or renal involvement may suggest Secondary vasculitis Wegener's disease. The presence of antineutrophil Infection-related vasculitis antibody with cytoplasmic fluorescence pattern (cANCA) Vasculitis secondary to connective tissue disease supports the diagnosis of Wegener's disease, while the Drug-hypersensitivity-related vasculitis presence of antineutrophil antibody with perinuclear Malignancy-related vasculitis fluorescence-pattem (pANCA) is more frequently found Hypocomplementemic Post-organ-transplant vasculitis in microscopic polyangitis, but is nonspecific and may be found with less frequency in other diseases such as

polyarteritis nodosa and systemic . 9 When the involvement is predominantly of large- sized arteries, the main clinicaI features are limb immunological response at the target to the vascular (mostly upper limb), hypertension, component leading to vascular damage.8 neurological symptoms (headache, syncope, stroke, ClinicaI manifestations are polymorphic and depend dizziness, vision complaints, transient ischemic attacks) on the size of the involved vessels, and the localization and cardiac involvement. A decreased or absent pulse in young patients reguires arteriography to investigate the and extension of the vascular injury. The polymorphism possible diagnosis ofTakayasu's arteritis. Elderly patients of clinicaI features frequently brings these patients to a complaining of severe headache should be considered for host of different medicaI specialists. Thus, these patients the diagnosis of temporal arteritis, whiching requires a may be seen by neurologists, cardiologists, nephrologists, biopsy of the affected temporal artery. Laboratory tests vascular surgeons, rheumatologists etc., making the study are not specific, and in the majority of cases, acute phase of vasculitis of great interest to alI physicians independent reactants are raised. of the speciality. Patient histolosy and clinicaI examination are The most frequent type of vasculitis affects extremely important in cases of systemic vasculitis, predominantly arterioles, capillaries, and venules, and the bringing immediate and valuable information, such as corresponding clinicalfeatures are mainly skin lesions such whether the vasculitis is primary or secondary, the size of as vascular , vesicles or sometimes urticarial vessels predominantly affected, and a possible diagnosis lesions. Less frequently, arthritis, glomerulonephritis, hypothesis. The confirmation of vasculitis occurs through abdominal pain, intestinal bleeding and peripheral the histopathological study of the affected organ andlor

SATO, E.1. & ANDRADE, L.E.C. - Systemic vasculitis: a difficult diagnosis São Paulo Medicai JournallRPM 115(3): 1418-1421,1997 1420

by arteriography. However, determining the exact cause vasculitis, corticosteroid is the treatment of choice, and of vasculitis or the precise classification requires a battery only in nonresponsive cases or in the presence of important of laboratory tests in accordance with the suspected side effects of corticosteroid therapy should diagnosis. In some cases, it is not possible to come up immunosupressive drugs be administered. Unlike in with the exact classification of the vasculitis despite all vasculitis affecting medium-size vessels, in cases of laboratory, histologic and arteriographic examinations. Takayasu arteritisl3 and temporal arteritis,14 the At the Multiprofessional Vasculitis Clinic at immunossupressive drug most used is methotrexate in low UNEFESP, comprised of rheumatologists, vascular doses, once a week. The efficacy of intravenous surgeons, and physical therapistis, we studied 69 consecutive immunoglobulin (IVIg) is established only for Kawasaki's patients with systemic vasculitis: 49 (71 percent) females disease to prevent development of coronary artery and 20 males, 47 (68 percent) white,with ages ranging of9 .15 IVIg,16 and monoclonal antibodies targeted to 82 years, and with an avarage disease duration of 62 to T cells 17 are alternatives to conventional months. The most frequent diagnoses were Takayasu's immunosupressive drugs for the management of systemic arteritis in 13 (19 percent), Buerger's disease in 11 cases vasculitis, but have been used in only a few cases and (16 percent), poliarteritis nodosa in 7 (10 percent), and need to be more extensively studied. Plasmapheresis cutaneous leucocytoclastic vasculitis in 4. Despite intense proved useful in cases of -related polyarteritis and expensive investigation, 15 patients (22 percent) nodosa,18 but its excessive cost renders it seldom used in remained without defined diagnose, being classified as Brazil.

nonspecified systemic vasculitis. 10 Evidently, most patients Cases not amenable to exact classification or diagnosis with manifestations restricted to the skin were attended in need to be treated according to the severity of each case. the Dermatology Clinic, and not referred to our service. Thus, patients with visceral involvement should be treated The treatment of systemic vasculities varies with high-dose corticosteroid and immunosupressive drugs. according to the different diagnoses, but to obtain quick Platelet antiaggregant or anticoagulant drugs may be useful control of inflammation, high-dose corticosteroid is used in cases in which there is a high risk of thrombosis in most cases. Immunosupressive drugs, especially complicating vasculitis, especially in cases affecting , need to be used in all cases ofWegener medium- or large-sized blood vessels. granulomatosis,11 microscopic polyangitis, and in cases We conclude that vasculitic syndromes are difficult of polyarteritis nodosa or nonspecific vasculitis with to diagnose, but when obtained, the exact diagnosis allows visceral involvement.12 In other vasculitis syndromes such better choice of treatment and knowledge of the prognosis as Takayasu' s arteritis, temporal arteritis or cutaneous for each specific case.

REFERENCES 7. Jennette JC, Falk RJ, Andrassy K, et aI. Nomenclature of systemic vasculitides: proposal of an intemational consensus conference. Arthritis Rheum 1994;37: 187-92. 1. MandeI BFR, Hoffman OS. Oifferentianting the vasculitis. 8. Sundy JS, Haynes BF. Pathogenic mechanisms of vessel Rheum Ois Clin North Am 1994;20(2):409-42. damage in vasculitis syndromes. Rheum Ois Clin North Am 2. Lie JT. Vasculitis, 1815 to 1991: Classification and Oiagnosis 1995;21(4):861-81. Specificity. J Rheumatology 1992;19(1):83-9. 9. Oross WL. Antineutrophil Cytoplasmic autoantibody testing in 3. Zeek PM. Periarteritis nodosa: A criticaI review. Am J Clin vasculitides. Rheum Ois Clin North Am 1995;21(4):987-1011. Pathol 1952;22:777-90. 10. Sato EI, Sallorenzo C, Hatta F et aI. Aspectos clínicos e 4. Oillian JN, Smiley JO. Cutaneous necrotizing vasculitis and laboratoriais das vasculites. Rev Bras Reumatologia (abstr) related disorders. Ann Allergy 1976; 37:328-39. 1996;36(5):321. 5. Fauci AS, Haynes BF, Katz P. The spectrum of vasculitis: 11. Hoffman OS, Kerr OS, Leavit RY, et aI. Wegener clinicaI, pathologic, immunologic, and therapeutic granulomatosis. An analysis of 158 patients. Ann Int Med considerations. Ann Intem Med 1978;89:660-76. 1992;116:48-98. 6. Lie JT. Nomenclature and classification of vasculitis: Plus 12. Lhote F, Ouillevin L. Polyarteritis nodosa, microscopic ca change, Plus c' est La meme chose. Arthritis Rheum polyangiitis and Churg-Strauss syndrome. Rheum Ois Clin 1994;37(2): 181-86. North Am 1995;21(4):911-47.

SATO, E.1. & ANDRADE, L.E.C. - Systemic vasculitis: a difficult diagnosis São Paulo Medicai Journal/RPM 115(3): 1418-1421,1997 1421

13. Kerr GS. Takayasu's arteritis. Rheum Dis Clin North Am 16. Richter C, Schnabel A, Csemok E, et aI. Treatment of ANCA- 1995;21( 4): 1041-58. associated systemic vasculitis with high-dose intravenous 14. Nordborg E, Nordborg C, Malmvall Bo-Erikl, Andersson R, immunoglobulin. Arthritis Rheum (abstr) 1994;37:(suppI9) S 353. Bengtsson, Bengt-Ake. . Rheum Dis Clin 17. Lockwood CM, Thiro S, Isaacs JD, et aI. Long-term remission North Am 1995;21(4): 1013-26. of intractable systemic vasculitis with mónoclonal antibody 15. Newburger JW, Takahashi M, Beiser AS, et aI. The treatment therapy. Lancet 1993;341:620-23. of Kawasaki syndrome with intravenous gamma globulin. N 18. Guillevin L, Lhote F, Cohen P, et aI. Polyarteritis nodosa Engl J Med 1986;315:341-345. related to hepatitis B virose Medicine 1995;74(5):238-53 .

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SATO, E.1. & ANDRADE, L.E.C. - Systemic vasculitis: a difficult diagnosis São Paulo Medicai JournallRPM 115(3): 1418-1421, 1997