Resident Corner

An Approach to Vasculitis and Vasculopathy

Amanda Pickert, MD

asculitis and vasculopathy may arise from (ie, hospitalization if not already addressed). Ideally a primary or secondary cause, which often the workup should be tailored to the clinical situation Vmakes the workup and diagnosis challenging. and the diagnosis. Generally I order several specific Vasculitis occurs when inflammation in the blood tests at the initial visit to look for diagnoses such vessel wall leads to its destruction and vasculopathy as connective-tissue disease or infection. Frequently when a thrombus forms in the arterial lumen and taking a good patient history will guide you on what compromises blood flow. The difference is subtle but to order. However, when I am uncertain, gauging the important to distinguish since there are divergent severity and level of care needed should be the first diagnoses and treatments for vasculitis and vascu- step. Organ involvement usually results in morbidity lopathy. The hallmark clinical feature of vasculitis is and mortality and requires aggressive intervention palpable purpura, which also can be a manifestation and treatment. After assessing the patient’s level of of vasculopathy. Similarly theCUTIS emergence of livedo illness, determining whether the outbreak is vasculitis reticularis is more consistent with vasculopathy but or vasculopathy is crucial. Unless there is compelling also may be seen with either entity. This overlap is evidence for vasculopathy, I tend to assume patients important to keep in mind. Herein I will give a brief have a vasculitis and consider adding in the workup overview of how I approach vasculitis and vasculopa- for vasculopathy as appropriate. thy. For starting residents, having an uncomplicated methodology will allow you to work quickly and Vasculitis Versus Vasculopathy thoroughlyDo through the possible Not causes of vasculitis Laboratories Copy to evaluate inherited vasculopathies are and vasculopathy. expensive. Nevertheless, as already stated, when sus- pecting vasculitis, vasculopathy is always in the dif- The Workup ferential diagnosis and vice versa. If livedo reticularis When vasculitis or vasculopathy is suspected, I is present, I usually consider performing a workup for perform a skin biopsy to confirm the diagnosis and vasculopathy. Retiform purpura is the netlike pattern immediately pursue an evaluation to survey for other of livedo reticularis with purpura and is rather specific organ involvement. A thorough review of the organ for vessel occlusion. If retiform purpura is present, I systems with the patient can be useful. Even when the favor vasculopathy over vasculitis. A skin biopsy usu- exact cause may be unknown, severity can be quickly ally can differentiate between vasculitis and vascu- evaluated with a nonspecific workup including a lopathy; if the patient shows no symptoms of illness, complete blood cell count, comprehensive metabolic it can be helpful to wait for the results of the skin panel, urinalysis, erythrocyte sedimentation rate assay, biopsy. The vasculopathy differential diagnoses can and chest radiograph. I can then make an incisive be divided into sick patients and nonsick patients. decision about care escalation and how to proceed If the patient is sick, diagnoses such as disseminated intravascular coagulation, purpura fulminans, throm- botic thrombocytopenic purpura, heparin-induced skin necrosis, and cholesterol emboli should be considered. If the patient is not acutely sick, I con- sider type 1 cryoglobulinemia or myeloproliferative From Mayo Clinic Arizona, Scottsdale. disease, cryofibrinogenemia, antiphospholipid anti- The author reports no conflict of interest. body syndrome, and the inherited mutations causing

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hypercoagulability (eg, proteins C and S, antithrom- into 3 types and usually is caused by an underly- bin III, and factor V Leiden mutation). ing disorder but can be idiopathic. Type 1 is always associated with a lymphoproliferative disorder, such Classifying Vasculitis as Waldenström macroglobulinemia, which is a There is no formal classification system for vasculitis. vasculopathy and not a vasculitis. Types 2 and 3 Historically, vasculitides have been classified by the are associated with connective-tissue disorders or size of the vessel involvement. As a rule of thumb, the infections (ie, hepatitis B, hepatitis C, cytomegalo- risk for organ involvement beyond the skin increases virus, Epstein-Barr virus, human immunodeficiency with the size of the involved blood vessels. Palpable virus). The difference between type 2 and type 3 purpura emerges when there is vasculitis in the post- cryoglobulinemia is the causative immunoglobulin: capillary venules and skin ulceration occurs when the monoclonal (type 2) or polyclonal (type 3). Similar arterioles or small arteries become involved. Gan- to HSP, skin involvement is common and can be grene as well as gastrointestinal, renal, pulmonary, associated with arthritis, Raynaud phenomenon, or or neurologic symptoms can occur with capillary to glomerulonephritis. Urticarial vasculitis usually is medium-sized artery involvement. Involvement of caused by underlying disorders, such as connective- the kidneys or lungs is common with purely capil- tissue disorders. I consider urticarial vasculitis to be lary involvement. a diagnosis of exclusion that takes into account the When evaluating vasculitis, I rule out secondary clinical presentation. causes first because management can differ and the Medium Vessel Vasculitis—Vasculitides involving conditions often are self-limited. Infection can be a medium-sized vessels include polyarteritis nodosa, secondary cause of vasculitis and administration of Wegener granulomatosis, Churg-Strauss syndrome, immunosuppressive therapy can have catastrophic and microscopic polyangiitis. Contained within consequences. Considerations would include this group are antineutrophil cytoplasmic antibody group A streptococci, mycoplasma, tuberculosis, (ANCA)–associated vasculitides. Because medium- hepatitis C or B, and others. Other secondary causes sized vessels are involved, several organ systems can of vasculitis include drug reactions; malignancy; and be affected. If a patient presents with lung involve- connective-tissue disorders, CUTIS most commonly sys- ment, I generally jump to this group of vasculitides. temic lupus erythematosus and rheumatoid arthritis. Palpable purpura with livedo reticularis also is a The term hypersensitivity vasculitis is often used to common presentation in medium vessel vasculitis. refer to secondary causes of vasculitis. A hypersen- Polyarteritis nodosa can appear similar to erythema sitivity vasculitis primarily affects the postcapillary nodosum but with ulcerations; erythema nodosum venules of the skin. However, if hypersensitivity never ulcerates. Polyarteritis nodosa can involve vasculitis is serious, it also may affect the joints, gas- any organ system but generally not the lungs. trointestinalDo tract, and kidneys. Not After ruling out the The developmentCopy of the mononeuritis multiplex is secondary causes of vasculitis, I will consider the size unique to polyarteritis nodosa. Mononeuritis mul- of the involved vessels based on the patient’s history, tiplex occurs when at least 2 separate peripheral present symptoms, physical examination, and simple nerves (sensory or motor) exhibit damage. Poly- laboratory evaluation. However, receiving the test arteritis nodosa is not cytoplasmic or perinuclear results of some laboratory evaluations may take ANCA positive. Granulomatous involvement of time. Skin ulceration and organ involvement speaks the upper respiratory tract (ie, sinusitis) is unique to to larger vessel pathology. The patient’s age also Wegener granulomatosis. Wegener granulomatosis should be considered as well as the organ systems is nearly always cytoplasmic ANCA positive with that have been affected. antibody to proteinase 3. Churg-Strauss syndrome– Small Vessel Vasculitis—Henoch-Schönlein purpura associated vasculitis can be related to allergic rhini- (HSP), cryoglobulinemia, and urticarial vasculitis are tis, asthma, and eosinophilia. Both Churg-Strauss small artery vasculitides. Henoch-Schönlein purpura syndrome–associated vasculitis and microscopic generally is seen in the pediatric population follow- polyangiitis can have perinuclear ANCA positivity ing an upper respiratory tract infection. Classically, with antibody to antimyeloperoxidase. Microscopic HSP presents with palpable purpura on the buttocks polyangiitis may present with both lung and kid- and lower extremities. Generally it is self-limited and ney involvement. requires no treatment. However, the risk for arthri- Large Vessel Vasculitis—Large vessel vasculitis tis, glomerulonephritis, and gastrointestinal ischemia includes temporal arteritis and Takayasu arteritis. from intussusception can be a concern. Cryoglobulins Neither one typically presents with skin findings are immunoglobulins that reversibly precipitate with such as palpable purpura; therefore, they are not exposure to the cold. Cryoglobulinemia is divided discussed here.

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Summary especially with the ANCA-associated vasculitides. My approach to vasculitis and vasculopathy includes: (3) If vasculitis, rule out the secondary causes (ie, in- (1) Determine the level of care the patient needs. If I fection, drug reactions, malignancy, connective-tissue am not sure, I will order a basic laboratory evaluation disorders) first. (4) Determine the size of the vessel while I decide on the more specific laboratory tests to involvement and the organ systems involved, which order and of course do a skin biopsy. (2) Determine if will narrow down the differential diagnosis. Although the eruption represents vasculitis or vasculopathy. The no one approach works for everyone, I find this presence of livedo reticularis or retiform purpura points method to be simple and keeps you organized when toward vasculopathy, but keep in mind the overlap, tackling the workup of vasculitis and vasculopathy.

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