Approach to Systemic Vasculitis Stephen R. K oller, M D William M. Edw ards, M D Richmond, Virginia Systemic vasculitis is a confusing subject which has been difficult to accumulation of inflammatory cells is classify and understand. Improvements in therapy increase the sometimes seen in the early or later importance of early diagnosis. This paper reviews the clinical and stages of vasculitis, but because such histopathology, by itself, is so non­ pathological differences of the systemic vasculitides, and a working specific, its presence is not considered approach to the differential diagnosis of vasculitis is formulated evidence of systemic necrotizing vas­ based on the size of the vessel involved. Vessel size and histo- culitis. pathology determine to what group of diseases a particular syndrome belongs, thereby allowing subclassification and a more rational approach to management. System of Classification There are two characteristics that may help the clinician differentiate one vasculitic syndrome from the Systemic vasculitis is a confusing classification, although quite helpful, many others. These are vessel size and and controversial subject. Its com­ is not entirely adequate because it is the cellular response to injury. plexity is attested to by the more than based on syndrome identification and one dozen syndromes it encompasses. does not emphasize the histopatho­ Size These syndromes differ not only logic changes within the vessels and There are four groups of arteries pathologically, but also in their clinical the signs and symptoms directly due which can arbitrarily be envisioned. settings and therapeutic responses. The to circulatory compromise secondary These are: development of relatively beneficial to those changes. It is the purpose of 1. Large arteries — the large elastic therapeutic regimens has heightened this paper to present a pathophysi­ arteries and their branches the need for early diagnosis. The most ologic approach to the differential 2. Medium arteries — vessels which are widely used classification devised by diagnosis of the systemic vasculitides. visible to the naked eye; these are Zeek1,2 and modified by Braverman3 This paper limits discussion to muscular and supply organs defines several syndromes by clinical those syndromes characterized by a and pathologic criteria (Figure 1). This necrotizing vasculitis, that is, where 3. Small arteries there are inflammatory cells within the a. microscopic arteries — vessels wall of the vessel during the acute 100 to 500 microns in diameter stage of the illness and/or necrosis of b. arterioles — vessels whose thick­ part or all of the vessel wall. This ness is approximately equal to From the Division of immunology and the size of the lumen; they are Connective Tissue Diseases, Department of necrotic material when stained with Medicine, Medical College of Virginia, hematoxylin and eosin takes on the less than 100 microns in outside Health Sciences Division, Virginia Com­ pinkish, homogeneous appearance of diameter monwealth University, Richmond, Virginia. 4. Capillaries — vessels with no media Requests for reprints should be addressed fibrin, hence the term “fibrinoid to Dr. Stephen R. Koller, Kenner Army Hospital, Fort Lee, Va 23801. necrosis.” A simple perivascular Despite some overlap, one or two t h e JO URNAL OF FAM ILY PRACTICE, VOL. 3, NO. 4, 1976 3 6 9 vessel groups may predominate in a Symptoms and signs of large artery cerebral ischemia or any of the myriad particular syndrome and the symp­ occlusion stem from a compromise in of syndromes that may follow occlu­ toms and signs that ensue can help the the circulation to areas directly sion of the cerebral vasculature. clinician distinguish among the vascu- supplied by the occluded vessel. Symptoms and signs of medium litic syndromes. Although veins and Involvement of the carotid or sub­ artery occlusion are extremely vari­ venules are often involved in many of clavian artery can induce a change in able. Involvement of cutaneous vessels the vasculitides, the clinical features of the pulse pressure or blood pressure. can cause ulcerations and gangrene the disease are most often due to Involvement of the vessels of the lower Raynaud’s phenomenon may occur arterial involvement. Therefore, or upper extremities may give inter­ There may be end-organ involvement venous involvement, as such, is mittent claudication. Similarly, there in the central nervous system, kidney ignored. may be symptoms of transitory pancreas, liver, lung, and heart, giving signs and symptoms of vascular insuf­ ficiency and clinical patterns related to disease in these organs. Visual dis­ turbances are noted when the ophthal­ NECROTIZING ANGIITIS mic artery is involved, and there may be headaches as well as tenderness over ---------------------- J I I the temporal artery when it is in­ GIANT CELL ALLERGIC WEGENER'S ARTERITIS GRANULOMATOSIS AND VARIANTS volved. It is important to note that angiography may be helpful in diag­ nosing medium vessel arteritis because of the aneurysms and occlusive POLYARTERITIS HYPERSENSITIVITY ANGIITIS changes visualized.4 NODOSA (LEUCOCYTOCLASTIC ANGIITIS) Small artery involvement may also take many forms. Livedo reticularis is due partially to reflex capillary dilation secondary to arteriolar insufficiency.5 HYPERSENSITIVITY HENOCH- ANGIITIS (ZEEK) SCHONLEIN Small artery occlusions may occur in PURPURA the kidney, brain, and skin as well as other organs. Involvement of the vasa 1-3 nervorum causes mononeuritis multi­ Figure 1. Currently accepted classification of necrotizing angiitis plex.6 Nodules may be a consequence of small artery disease.7 Table 1 Arteritic Syndromes HISTOPATHOLOGY VESSEL SIZE Large Vessel Syndromes Medium Vessel Syndromes Small Vessel Syndromes Involving Involving Involving (Large arteries, (Medium arteries, (Small arteries, medium arteries) small arteries) capillaries) Granulomatous Giant cell arteritis Allergic angiitis Wegener's granulomatosis temporal arteritis of cranial arteritis Churg and Strauss Takayasu's arteritis Non-gra nulomatous Polyarteritis nodosa Hypersensitivity angiitis (Acute or chronic Rheumatoid arteritis Henoch-Schonlein purpura inflammation Polyarteritis with Serum sickness depending on a. Hepatitis associated Childhood dermatomyositis stage of disease) antigen Subacute bacterial endocarditis b. Methamphetamine Systemic lupus erythematosus Cryoglobulinemia 3 7 0 THE JO URN AL OF FAM ILY PRACTICE, VOL. 3, NO. 4, 1976 Finally, capillary disease has its exclude the diagnosis of giant cell bifurcation, fibrinoid necrosis, and oWn distinct features. Petechiae are arteritis. Therefore, Anderson and various stages of healing of the vessels the hallmark of capillaritis and are Bayles suggest that the diagnosis be are characteristic histological lesions. m0St easily seen in the skin, but may made clinically. They reserve a Vascular thrombosis and aneurysm also be found in other organs including temporal artery biopsy for those formation contribute to the clinical bowel, kidney, brain, and joints. patients with known origin or when picture. Fever, abdominal pain, hyper­ the diagnosis is clouded by psycho- tension, neuritis, and musculoskeletal o genic features. However, others feel complaints occur frequency. Approxi­ that a positive biopsy should be mately 80 percent of patients with obtained before committing a patient polyarteritis nodosa will ultimately to any potentially dangerous therapy. have renal involvement. The diagnosis Histopathology Although the polymyalgia rheumatica- is suggested by the multisystem signs The second consideration is histo- giant cell arteritis syndrome is self- and symptoms and is confirmed by the pathology. There are two basic types limiting, lasting one to two years, the biopsy of involved organs or by deep of involvement: (1) Granulomatous, end result may be a severe vascular muscle biopsy. Some investigators, as and (2) Non-granulomatous. catastrophe. Takayasu’s arteritis, a mentioned previously, have found There are some syndromes which syndrome of large vessel granu­ angiography to be of great value in have granulomas and/or giant cells in lomatous arteritis with giant cells, is detecting aneurysms of the medium- the pathologic specimen regardless of found predominantly in young sized branches of the renal, cerebral, when a biopsy is taken. Other syn­ women. Signs and symptoms may and celiac arteries.4,11 About ten dromes are not ordinarily associated resemble those of polymyalgia rheu­ percent of patients with polyarteritis with granulomas. Instead, in the acute matica. In addition, arterial obstruc­ nodosa will have a benign cutaneous stage, polymorphonuclear leukocytes tion may be so severe that pulses may variant manifested by a chronic or are found in the vasculitis lesion. As be quite decreased or absent. Obstruc­ recurrent course and a variable healing takes place, a mononuclear tive lesions have been treated success­ response to corticosteroids, but with a (chronic) reaction occurs. Keeping in fully by arterial grafts. Corticosteroids favorable ultimate outcome.12 These mind that there is overlap and using have provided an effective means of patients have a syndrome charac­ the vessel size and histopathology as a preventing thrombotic disasters and, if terized by subcutaneous nodules, foundation, a partial classification of initiated early in the course of the livedo reticularis, and myalgias. the arteritic syndromes can be formu­ disease, produce a dramatic remission A polyarteritis-like syndrome has lated (Table