1. 
   

   When should a diagnosis of vasculitis be considered?

   
   
2. 
   

   How is a diagnosis of vasculitis made or excluded?

   
   
3. 
   

   What are the appropriate strategies for triage, consultation, and follow-up for vasculitis?

   
   
4. 
   

   What treatment and staging for vasculitis should be initiated in the hospital?

   
   
5. 
   

   In a patient with established vasculitis, how should new symptoms of illness be evaluated?

The diagnosis of vasculitis is considered far more often than these diseases are actually seen—appropriately, since these rare diseases have diverse presentations, are dangerous and often rapidly progressive, yet are treatable. All vasculitides feature inflammation of the walls of blood vessels, with symptoms and findings attributable to the size(s) and locations of the involved vessels. Vessel size, epidemiology, and/or a constellation of typical clinical features have proved useful for classifying the vasculitides, with key points summarized in (Table 264-1).

The classification of vasculitis remains imprecise with more than one system in use. “Primary” systemic vasculitides are further sorted by the sizes of the predominant arteries involved, leading to sets of small, medium, and large vessel vasculitides. There are also several “secondary” forms of vasculitis associated with infections, drug exposure, or another form of systemic disease such as systemic lupus erythematosis or rheumatoid arthritis.

All of the primary, idiopathic vasculitides are rare diseases, each categorized as an “orphan” disease in the United States (prevalence of < 200,000 persons). However, as a group, and especially among patients with initially unexplained systemic disease who are ill enough to be hospitalized, vasculitis is common enough that hospitalists will likely encounter cases.

The pathophysiology of the primary vasculitides is poorly understood. They are all considered immune mediated, based on histologic and serologic studies and by analogy to the many cases of vasculitis that have occurred secondary to infections or drug exposure. Since no pathogens have been found, the primary vasculitides are suspected to be autoimmune, with the humoral and cellular branches of the adaptive immune system involved to different degrees in different diseases.

Notes on Individual Forms of Vasculitis

It is impractical to describe each of the vasculitides in detail in a single chapter, but short summaries of most of the vasculitides are provided as reference points for the subsequent discussion.

Giant Cell Arteritis

Giant cell arteritis (GCA) only affects adults over the age of 50, and incidence markedly increases with age, to about 1:2000 per year among Caucasians of Northern European descent by age 80. Headache is the most common symptom (80%), with scalp tenderness, jaw claudication, constitutional symptoms, and polymyalgia rheumatica (pain and stiffness in the shoulders, hips, and/or neck) each seen in 40% to 70% of patients. The presentation of GCA is often insidious and diagnosed during outpatient care, but sometimes is acute and leads to hospitalization. GCA has also been reported to be an important cause (about 10%) of fever of unknown origin in the elderly, and since the aorta and its major branches are involved in more than 15% of cases, GCA is also an important consideration in cases of claudication, loss of pulse, and asymmetric blood pressure measurements in the elderly. (See the section on laboratory testing [acute phase reactants], imaging [angiography, ultrasound], and biopsy [temporal artery]).

Takayasu Arteritis

Takayasu arteritis is a rare disease (prevalence < 1:100,000), usually presenting in young adults, and 90% of patients are female. Patients often present with claudication, dizziness, abnormal blood pressure readings, and/or bruits. Diagnosis is confirmed by angiography. The types of presentation more likely to lead to hospitalization (eg, symptoms of coronary artery disease or cerebrovascular disease) carry a broad differential diagnosis, so suspicion for or against Takayasu may initially be gained by checking pulses and blood pressures and listening for bruits. (See the section on laboratory testing [acute phase reactants] and imaging [angiography, ultrasound]).

Granulomatosis with Polyangiitis (Wegener’s) and Microscopic Polyangiitis

Granulomatosis with polyangiitis (Wegener’s) (GPA) and microscopic polyangittis (MPA)—grouped by some authors as antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV)—are small-vessel vasculitides that together affect ˜1:20,000 persons. AAV is high in the differential diagnosis of patients presenting with pulmonary hemorrhage, acute renal disease, or acute peripheral neuropathy, and is also an important consideration in patients with palpable purpura, inflammatory eye disease (scleritis or episcleritis), acute sensorineural hearing loss, cutaneous ulcers, or digital ischemia. Renal disease in AAV often leads to elevated creatinine and urinary RBC casts but in the early stages patients may only have microscopic hematuria and modest proteinuria. GPA usually (70–80%) also features granulomatous inflammation of the upper airway, with nasal discharge and crusting, epistaxis, facial pain, and/or hearing loss, and the presence of these symptoms often facilitates the diagnosis of GPA. GPA is an important consideration in cases of subglottic stenosis, orbital mass with proptosis, or pulmonary nodule(s). However, many patients with AAV present only with nonspecific symptoms of malaise, myalgias, and arthralgias. The role of testing for ANCA in diagnosing AAV is discussed in detail below. (See section on laboratory testing [autoimmune serologies, acute phase reactants, tests of renal function], imaging [chest imaging, sinus imaging], and biopsy [skin, nasal cavity and sinuses, kidney, lung, peripheral nerve and muscle]).

Churg-Strauss Syndrome

Churg-Strauss syndrome (CSS) is worth considering in a patient who is ill with what might be vasculitis, has a history of asthma (often severe or poorly controlled), and has eosinophilia. The presentations of CSS most likely to lead to hospitalization are asthma exacerbation, pulmonary infiltrates, or acute peripheral neuropathy, but constitutional symptoms, nasal polyps, rash, and arthralgias are also common. Myocarditis, gastrointestinal ischemia, stroke, renal involvement (similar to AAV), and eye inflammation are less common but important presentations. Positive tests for ANCA may be present in 30% of patients and some consider CSS part of the spectrum of ANCA-associated vasculitis. (See section on laboratory testing [autoimmune serologies, acute phase reactants, tests of renal function, complete blood count], imaging [chest imaging, sinus imaging], and biopsy [skin, nasal cavity, and sinuses, kidney, lung, peripheral nerve and muscle]).

Antiglomerular-Basement-Membrane Disease

In contrast to AAV, symptoms of antiglomerular-basement-membrane (GBM) disease are limited to the kidneys and/or lungs (if both = Goodpasture syndrome), with rapidly progressive glomerulonephritis and/or pulmonary hemorrhage as manifestations. A blood test for anti-GBM antibodies is diagnostic, as is kidney biopsy. Testing for anti-GBM antibodies should be obtained rapidly for any patient for whom anti-GBM disease is possible, since the disease can lead to irreversible kidney damage or death from pulmonary hemorrhage. (See section on laboratory testing [autoimmune serologies, tests of renal function], and imaging [chest imaging], biopsy [kidney, lung]).

Polyarteritis Nodosa

The most common features of polyarteritis nodosa (PAN) are livedo reticularis (a lacy pattern of cutaneous blood vessels on extremities that is more commonly due to benign conditions rather than vasculitis), painful cutaneous nodules or ulcers, hypertension, abdominal pain, myalgias, peripheral neuropathy, testicular pain, and digital ischemia. There is a strong association between hepatitis B virus infection and PAN; the incidence of PAN has markedly declined in countries with high rates of hepatitis B vaccination. PAN is probably the most challenging type of vasculitis to diagnose, because (1) it is particularly rare (in regions where the hepatitis B virus infection is also rare), (2) it features the most nonspecific array of symptoms and findings among the vasculitides, and (3) there are no helpful diagnostic blood tests analogous to ANCA, cryoglobulins, or eosinophil count. Biopsy or angiography is usually required for the diagnosis of PAN. For all of these reasons, PAN is contemplated much more often than it is diagnosed. (See section on laboratory testing [acute phase reactants, tests of renal function, selected testing for infectious diseases], imaging [angiography], and biopsy [skin, kidney, peripheral nerve and muscle, other organs]).

BehçET Disease

The manifestations of Behçet disease (BD) that may lead to hospitalization are extraordinarily diverse: visual loss or a red and painful eye, deep vein thrombosis (including dural sinus thrombosis or Budd-Chiari syndrome), colitis resembling inflammatory bowel disease, meningoencephalitis, or pulmonary artery rupture leading to massive hemorrhage. Considering the diagnosis of BD in these settings requires recognition of the various milder but more common features of BD that may be concurrently present or reported by the patient, including recurrent oral ulcers (required for diagnosis), genital ulcers, erythema nodosum, acneiform skin lesions, inflammatory arthritis, and superficial thrombophlebitis. The diagnosis or exclusion of BD is always made on clinical grounds since there are no specific blood tests or biopsy features of the disease.

Primary Vasculitis of the Central Nervous System

This rare disease is limited to the central nervous system (CNS) and presents with symptoms of encephalopathy, multiple small strokes, and often headache. Angiography may be normal since the disease affects small vessels. Furthermore, angiography cannot easily distinguish vasculitis from atherosclerosis or from cerebral vasospasm (which usually presents with a severe headache of sudden onset). Thus, diagnosis of CNS vasculitis is ideally made by brain biopsy. (See section on imaging [angiography], and biopsy [brain]).

Cryoglobulinemic Vasculitis

Cryoglobulinemia encompasses a variety of clinical syndromes associated with circulating immune complexes that precipitate at cold temperatures. The majority of cases of cryoglobulinemia are associated with chronic hepatitis C virus infection, with plasma cell malignancies and systemic rheumatic diseases accounting for most other cases. Cryoglobulinemia associated with chronic hepatitis C virus infection or systemic rheumatic disease causes a small-vessel vasculitis that typically involves skin (palpable purpura and/or ulcers), commonly involves peripheral nerves or kidneys (glomerulonephritis), and less commonly involves a wide range of internal organs. (See section on laboratory testing [tests of renal function, paraproteins, selected testing for infectious diseases], and biopsy [skin, kidney, peripheral nerve and muscle]).

Henoch-Schönlein Purpura

Henoch-Schönlein purpura (HSP) is much more common among children than adults. It is usually self-limited and presents with palpable purpura, often in association with inflammatory arthritis and abdominal pain. A minority of patients has severe renal involvement, and the presence or absence of significant proteinuria or elevated creatinine is often used to determine whether to treat with immunosuppressive agents; however, the usefulness of such treatment has not been established. (See section on laboratory testing [tests of renal function] and biopsy [skin, kidney]).

Kawasaki Disease

Kawasaki disease (KD) is almost exclusively a disease of young children, and it is not rare in its characteristic age group (incidence 1:10,000 in the U.S.). The syndrome classically includes fever persisting for at least five days, erythematous rash with desquamation in the hands and feet, conjunctivitis, oral mucosal inflammation, and lymphadenopathy. However, many patients present without all of these features and, since a consequence of untreated KD is life-threatening coronary artery aneurysms, the diagnosis is considered in almost any young child with a fever lasting five days.

Vasculitis Associated with Other Autoimmune Diseases

Systemic lupus, rheumatoid arthritis, Sjögren syndrome, and inflammatory bowel disease have all been associated with vasculitis, mostly involving small vessels (palpable purpura, ulcers, neuropathy), but occasionally medium-sized vessels (analogous to PAN). Inflammatory bowel disease, relapsing polychondritis, and Cogan syndrome are each rarely associated with large-vessel vasculitis similar to Takayasu arteritis. (See section on laboratory testing [autoimmune serologies and tests of renal function]).