Key points

Introduction

Small vessel vasculitis of the skin, which classically and most commonly presents as palpable purpura on the lower extremities, has been referred to interchangeably using a number of terms, each of which carries a slightly different shade of meaning. These include “cutaneous leukocytoclastic vasculitis,” or simply “leukocytoclastic vasculitis,” “hypersensitivity vasculitis,” “cutaneous leukocytoclastic angiitis,” and “cutaneous small vessel vasculitis,” the term for skin-limited small vessel vasculitis favored in the recently revised 2012 Chapel Hill Consensus Criteria.

Regardless of the terminology used, it is important to note that the clinical presentation of small vasculitis in the skin must be considered initially a symptom rather than an entity in and of itself. In other words, when diagnosing skin-limited vasculitis, one must first rule out potential systemic manifestations (such as joint, kidney, or gastrointestinal involvement), underlying causes, and disease associations that affect management and prognosis. In addition, patients may start with skin-limited disease and develop systemic manifestations over time, necessitating careful follow-up. One specific subset of small vessel vasculitis of the skin deserves special mention; immunoglobulin (Ig)A vasculitis (otherwise known as Henoch–Schonlein purpura) is an IgA-mediated syndrome characterized by cutaneous, gastrointestinal, joint, and/or kidney involvement. Though the initial presentation of this condition can be indistinguishable from non–IgA-mediated small vessel skin vasculitis, its management and prognosis is different. Overall, however, small vessel vasculitis of the skin is most often acute and self-limited, and its prognosis is favorable, particularly when internal involvement is absent.

Introduction

Small vessel vasculitis of the skin, which classically and most commonly presents as palpable purpura on the lower extremities, has been referred to interchangeably using a number of terms, each of which carries a slightly different shade of meaning. These include “cutaneous leukocytoclastic vasculitis,” or simply “leukocytoclastic vasculitis,” “hypersensitivity vasculitis,” “cutaneous leukocytoclastic angiitis,” and “cutaneous small vessel vasculitis,” the term for skin-limited small vessel vasculitis favored in the recently revised 2012 Chapel Hill Consensus Criteria.

Regardless of the terminology used, it is important to note that the clinical presentation of small vasculitis in the skin must be considered initially a symptom rather than an entity in and of itself. In other words, when diagnosing skin-limited vasculitis, one must first rule out potential systemic manifestations (such as joint, kidney, or gastrointestinal involvement), underlying causes, and disease associations that affect management and prognosis. In addition, patients may start with skin-limited disease and develop systemic manifestations over time, necessitating careful follow-up. One specific subset of small vessel vasculitis of the skin deserves special mention; immunoglobulin (Ig)A vasculitis (otherwise known as Henoch–Schonlein purpura) is an IgA-mediated syndrome characterized by cutaneous, gastrointestinal, joint, and/or kidney involvement. Though the initial presentation of this condition can be indistinguishable from non–IgA-mediated small vessel skin vasculitis, its management and prognosis is different. Overall, however, small vessel vasculitis of the skin is most often acute and self-limited, and its prognosis is favorable, particularly when internal involvement is absent.

Epidemiology

Small vessel vasculitis of the skin affects both sexes equally and patients of all ages. Studies from Spain have reported an annual incidence of 30 cases of hypersensitivity vasculitis per million adults per year. By contrast, IgA vasculitis has an incidence of 14 cases per million adults per year. A recent, population-based study in Minnesota found the incidence of cutaneous leukocytoclastic vasculitis (including IgA vasculitis as well as other types of small vessel vasculitis) to be almost identical, at 45 cases per million. In children, by contrast, IgA vasculitis is much more common than non-IgA small vessel vasculitis of the skin. The presence of an associated underlying systemic vasculitis, connective tissue disease, or malignancy is much more common in adults than in children.

Pathophysiology

Small vessel vasculitis of the skin is mediated by immune complex deposition in affected vessels. Circulating antigens due to medications, infections, connective tissue disease, or neoplasia are bound by antibodies, forming immune complexes that become lodged and trapped within small vessels, whether in the superficial dermis, most frequently in dependent areas, the joints, the gastrointestinal tract, or the glomeruli. These complexes, in turn, activate complement and induce an inflammatory response that leads to vessel destruction and extravasation of red blood cells. In the case of palpable purpura in the skin, this small vessel involvement accounts for the (usually) small size of the lesions; the complement cascade and subsequent inflammation account for the palpability and symptomatology of the lesions (which often burn); and the red blood cell extravasation results in nonblanching purpura ( Fig. 1 ).

Typical palpable purpura on the legs of a patient with cutaneous small vessel vasculitis after exposure to an antibiotic.

Etiology

About half of cases are idiopathic. The remainder are most often either drug induced or post infectious. Antibiotics, and β-lactams in particular, are common culprits, but almost any drug or drug additive can cause vasculitis. Among infectious causes, upper respiratory infections (such as β-hemolytic Streptococcus group A) and hepatitis C are commonly implicated; however, numerous infectious triggers have been described. Determining a specific cause can be difficult, particularly in the hospitalized setting, when many patients have both a history of recent infection and exposure to numerous medications.

Although palpable purpura is most often due to infection or a drug, it is important to remember that small vessel vasculitis can also be due to an underlying connective tissue disease such as systemic lupus erythematosus, Sjögren syndrome, rheumatoid arthritis, or dermatomyositis, and may, in fact, be the presenting sign of such disease. Vasculitis due to underlying connective tissue disease may be associated with more significant internal involvement. Cutaneous manifestations of small vessel vasculitis such as palpable purpura and urticarial lesions can also be a feature of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis with overlapping involvement of small and medium-sized cutaneous vessels. A small percentage of patients (<5%) may have an underlying hematologic or solid organ malignancy. Vasculitis tends to appear 7 to 10 days after exposure to a drug or infectious trigger and a mean of 6 months after the onset of an underlying medical condition. In practice, however, the range and timing of onset varies greatly.

Viral upper respiratory infection or streptococcal pharyngitis frequently precede the onset of IgA vasculitis by 1 to 2 weeks. Overall, about 40% of cases are attributable to an infectious cause, of which very many have been reported. Medication exposure may be to blame in around 20%. In adults, paraneoplastic IgA may be considered; 90% of such patients are male. As with small vessel cutaneous vasculitis as a whole, a significant fraction of cases have no identifiable cause.

Patients with cutaneous vasculitis that is not self-limited or that is refractory or recurrent may be more likely to have an underlying medical illness driving the vasculitis. In such instances, further workup may be required to elucidate the underlying cause. Conversely, recurrence of vasculitis after treatment may herald the relapse of a treated malignancy.

Clinical features

Physical Examination

Small vessel vasculitis in the skin classically presents with crops of purpuric, round, 1- to 3-mm papules that appear over 1 or 2 days on dependent areas, such as the lower legs (see Fig. 1 ). Areas of pressure or trauma, such as the sock lines or underneath sequential compression devices in the hospitalized patient, may be more heavily involved. Although such sites are preferred, lesions can appear anywhere, and for patients confined to bed, clear preference for dependent areas may be less apparent or altered, favoring sites like the back. In IgA vasculitis, palpable purpura above the waist may be a marker for renal vasculitis, but this is controversial. The number of lesions may vary from dozens to hundreds. New lesions can appear daily until treatment is initiated or a trigger withdrawn; they resolve over 2 to 3 weeks and slowly fade away, leaving behind postinflammatory hyperpigmentation.

In addition to typical palpable purpura, more subtle, nonpalpable petechial or purpuric lesions may also be present. Larger plaques or even ulcers may develop as purpuric papules coalesce ( Fig. 2 ). Vigorous reactions and subsequent ischemic necrosis result in vesicles, pustules, and small hemorrhagic bullae ( Fig. 3 ). Hivelike papules and plaques can mimic urticaria but may be the presenting sign of small vessel vasculitis. Unlike true urticaria, these lesions persist longer than 24 hours, burn rather than itch, and leave behind bruiselike, ecchymotic marks on resolution. Some of these patients are best classified as urticarial vasculitis, with either low or normal complement levels.

Coalescing necrotic purpuric plaques with ulceration in a patient with small vessel vasculitis due to underlying hematologic malignancy (chronic lymphocytic leukemia).

Hemorrhagic, necrotic bullae in an adult patient with immunoglobulin A vasculitis.

Absent are manifestations more typical of medium vessel vasculitis, such as subcutaneous nodules, livedo reticularis, retiform purpura, larger hemorrhagic bullae, and more significant ulceration and necrosis. The jagged or retiform shape of purpuric skin fed by medium-sized deep dermal or subcuticular vessels reflects the irregular branching and distribution of downstream small vessels. If such lesions are seen, suspicion for medium vessel vasculitis, namely cutaneous or systemic polyarteritis nodosa, or for ANCA-associated or cryoglobulinemic vasculitis, which can affect both small- and medium-sized cutaneous vessels and present with palpable purpura, should be high.