Although the presenting manifestations of vasculitis are protean, they can be grouped into five categories of clinical clues (Table 29–3). The first general clue is that most forms of systemic vasculitis begin with constitutional symptoms (such as malaise, fever, sweats, fatigue, decreased appetite, and weight loss). These nonspecific symptoms, in the absence of more specific signs, usually effectively camouflage the vasculitic nature of the patient’s illness. A second clue is that most forms of vasculitis unfold subacutely over weeks or months. In contrast to many patients with acute infections, patients with vasculitis usually cannot pinpoint the hour or the day that their illness began. More typically, patients with vasculitis struggle to define the month or the season in which their nonspecific symptoms accumulated sufficiently to become memorable. A corollary of the subacute course typical of vasculitis is that the initial diagnosis of vasculitis is rarely made (correctly) in the intensive care unit. Although pulmonary hemorrhage, bowel infarction, or other devastating complications of vasculitis frequently result in a patient being admitted to the intensive care unit, these catastrophic events usually develop late, weeks or months after other clinical clues have suggested or established the patient’s diagnosis.
The tendency of most forms of vasculitis to produce striking signs of inflammation constitutes a third general clue. Manifestations of inflammation can include fever, arthritis, rash, pericarditis, anemia of chronic disease, or a markedly elevated erythrocyte sedimentation rate. Pain is a fourth common feature of the vasculitides and can originate from many different sources, such as arthritis; myalgia; or infarction of a digit, nerve, bowel, or testicle. The fifth general clinical clue is that vasculitis tends to cause multisystem disease. The skin, joints, nervous system, kidneys, lung, and gastrointestinal tract are especially favorite targets of many different forms of vasculitis. Although specific forms of vasculitis can defy generalization, most vasculitides start with constitutional symptoms that evolve over weeks and months to a painful disorder marked by signs of inflammation and multiorgan injury.
The signs and symptoms of specific forms of vasculitis are detailed in the individual chapters. The signs and symptoms common to many forms of systemic vasculitis are found in Table 29–4.
Table 29–4. Organ- or Tissue-Specific Manifestations of Vasculitis. ||Download (.pdf)
Table 29–4. Organ- or Tissue-Specific Manifestations of Vasculitis.
|Organ or Tissue||Manifestation|
|Skin||Livedo reticularis, palpable purpura, nodules, ulcers, gangrene|
|Peripheral nervous system||Mononeuritis multiplex, polyneuropathy|
|Central nervous system||Stroke, seizure, encephalopathy|
|Kidney||Hypertension, proteinuria, hematuria, renal failure|
|Heart||Myocardial infarction, cardiomyopathy, pericarditis, arrhythmia|
|Lung||Cough, chest pain, hemoptysis, breathlessness|
|Gastrointestinal tract||Pain, bleeding, perforation|
|Genitals||Testicular infarction, ovarian mass|
In general, the skin and the peripheral nervous system signs are especially useful because they often develop early in the course of the disease and because they can be detected at the bedside. The onset of small-vessel vasculitis (eg, hepatitis C–associated vasculitis) is often heralded by palpable purpura, usually on the lower extremities, whereas medium-vessel diseases (eg, polyarteritis nodosa) more commonly produce nodules, ulcers, or digital gangrene.
The most characteristic nervous system manifestation of vasculitis is mononeuritis multiplex, which is defined as a distinctive peripheral neuropathy in which named peripheral nerves are infarcted one at a time. The nerve infarctions result from vasculitis of the vessels of the vasa nervorum, causing ischemia of a nerve. Clinically, the two features that characterize this neuropathy are the asynchrony and asymmetry of the symptoms and findings. These features are best illustrated by comparing mononeuritis multiplex with other peripheral neuropathies. With most forms of nonspecific neuropathy, the patient experiences numbness and tingling in a symmetric, stocking or glove distribution; these symptoms develop so slowly that the patient cannot accurately date the onset of the neuropathy. Examination of these patients usually fails to identify the involvement of large, named nerves. In sharp contrast, the onset of mononeuritis multiplex is strikingly memorable: The patient often recalls the day that his or her foot drop or wrist drop began. The patient also often vividly recalls how the neuropathy progressed asynchronously so that each month or so a new area of the body (usually an extremity) became involved. On examination, the damage from mononeuritis multiplex can be mapped to individual, named nerves (eg, the peroneal, tibial, ulnar, radial, or median nerves). Almost all patients have sensory abnormalities and about half have weakness as well. Although mononeuritis multiplex is often bilateral, the lesions are usually asymmetric. The right hand may demonstrate a median nerve infarct while the left hand has an ulnar nerve lesion.
Mononeuritis multiplex produces such a characteristic clinical picture that usually it can be diagnosed at the bedside. Occasionally, identifying mononeuritis multiplex becomes difficult late in the course when the infarctions of so many nerves can coalesce to produce an unusually symmetric pattern of deficits. In most cases, the early history of sequential peripheral nerve lesions supports the diagnosis of vasculitic neuropathy. In some cases, proof of mononeuritis multiplex requires electrodiagnostic studies.
Mononeuritis multiplex is one of the physical findings in medicine of great differential diagnostic value. In the absence of diabetes or multiple compression injuries, mononeuritis multiplex usually means the patient has some form of vasculitis. Polyarteritis nodosa, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome), and granulomatosis with polyangiitis (formerly Wegener granulomatosis) are the forms of vasculitis most likely to cause mononeuritis multiplex.
Laboratory abnormalities accompany virtually every form of vasculitis (Table 29–5). Some abnormalities, such as anemia and an elevated erythrocyte sedimentation rate, are very nonspecific and can be seen with many other diseases. Other findings, such as red blood cell casts in the urine (indicating vasculitis of the glomeruli) or antineutrophil cytoplasmic antibodies (associated with granulomatosis with polyangiitis [formerly Wegener granulomatosis]), have much greater specificity.
Table 29–5. Common Laboratory Tests in Vasculitis. ||Download (.pdf)
Table 29–5. Common Laboratory Tests in Vasculitis.
|Test||Laboratory Finding and Associated Disease|
|Hematocrit||Low in many forms|
|Erythrocyte sedimentation rate||Usually high, especially in giant cell arteritis|
|Creatinine||Elevated by renal forms of vasculitis|
|Urinalysis||Often abnormal, red blood cell casts caused by vasculitis of the glomeruli|
|Liver function tests||Abnormal in hepatitis B- or C-associated polyarteritis|
|Serum cryoglobulins||Present in cryoglobulinemia|
|Complement levels||Low in SLE, cryoglobulinemia|
|Immunoelectrophoresis||Monoclonal gammopathies common in hepatitis C–related vasculitis|
|Antineutrophil cytoplasmic||Positive in granulomatosis with polyangiitis,a microscopic polyangiitis,|
The role of imaging studies depends greatly on the form of vasculitis suspected. Plain radiographs rarely provide important clues except in granulomatosis with polyangiitis (formerly Wegener granulomatosis), where views of the sinuses and chest may yield findings (albeit usually not specific ones). CT scans of the chest are more sensitive in granulomatosis with polyangiitis (formerly Wegener granulomatosis). Angiograms—performed conventionally with CT or with MR—are especially helpful in supporting or establishing the diagnosis of Takayasu arteritis, polyarteritis nodosa, and primary central nervous system vasculitis.
Biopsy of involved tissues is the most common method for establishing definitively the diagnosis of vasculitis. Skin, peripheral nerves, airways, arteries, kidney, and gut are the most commonly sampled tissues. In general, biopsies of symptomatic areas have a yield of about 66%, whereas biopsy of sites with no symptoms or findings have low yield. Special stains are sometimes required to reveal the degree of damage to particular arterial layers (such as the internal elastic lamina) or the extent of immune complex deposition.