Abstract
Vasculitis includes a heterogeneous group of conditions characterized by blood vessel inflammation and necrosis. The clinical manifestations depend on the localization and size of the involved vessel. Most patients with cutaneous vasculitis (CV) are included in the category of small-vessel vasculitis. Palpable purpura is the typical manifestation of vasculitis involving the skin. Urticarial lesions or cutaneous nodules may occur in the context of vasculitis. CV is often idiopathic. Drugs and infections are the most common underlying etiologies in adults with vasculitis involving the skin. IgA vasculitis, which typically involves the skin, is the most common type of systemic vasculitis in children. CV may also be observed in patients with antineutrophil cytoplasmic antibody-associated vasculitis that typically involves small vessels, in the setting of immune complex small-vessel vasculitis or associated with other systemic diseases. Skin biopsy is the gold standard test for the diagnosis of CV. When the vasculitic involvement of the skin is a manifestation of a systemic vasculitis or a connective tissue disease, therapy should be individualized and focused on the management of the systemic disease.
Keywords
Cutaneous vasculitis, Nodules, Palpable purpura, Small- and medium-sized blood vessels, Urticarial lesions
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Vasculitic processes may be idiopathic or associated with infections, drugs, malignancies, or connective tissue diseases.
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Drugs and infections are the most common underlying etiologies in adults with cutaneous vasculitis (CV).
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IgA vasculitis (Henoch-Schönlein purpura) is the most frequent vasculitic condition associated with CV in children.
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Clinical manifestations depend on the localization and size of the involved vessel.
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Although the Chapel Hill Consensus Conference has established nomenclature that might be useful for the classification of vasculitis, there exists controversy on the definitions and manifestations of cutaneous disease in this classification system.
Introduction
The term vasculitis refers to a wide spectrum of diseases characterized by blood vessel inflammation and necrosis. Vasculitic processes may be associated with infections, drugs, malignancies, or connective tissue diseases (CTDs). In the absence of an underlying disease we refer to them as primary or idiopathic systemic vasculitides. These conditions exhibit a wide spectrum of manifestations depending on the localization and size of the involved vessels, and often have overlapping clinical and pathologic manifestations. When skin vessels are affected we talk about cutaneous vasculitis (CV). CV may be a process confined exclusively to the skin, or a manifestation of a more widespread entity associated with a variable grade of visceral involvement.
Nomenclature and Classification Criteria
Classification of vasculitis has been a challenging problem for decades. A widely accepted set of diagnostic criteria for the vasculitides has never been established. To fill this void classification criteria were developed to create homogeneous cohorts for clinical research. There are two classification schemes that have been proposed. One developed in 1990 by the American College of Rheumatology (ACR) and one developed by a consensus conference of multiple specialists held in Chapel Hill, North Carolina, known as the Chapel Hill Consensus Conference (CHCC). The CHCC classification was initially published in 1994 and a 2012 revision was published in January 2013 ( Table 4-1 ). Dermatologists were not involved in the development of any of these classifications systems and thus there are some entities seen on the skin that are not included and there are some nuances regarding cutaneous involvement that might be seen differently by the dermatologic community. The CHCC deals with and tries to define noninfectious vasculitides.
| Primary Vasculitis |
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| Secondary Vasculitis |
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In view of different classification and definition schemes, vasculitis of the skin has been referred to over time by using a number of terms, namely, hypersensitivity vasculitis, leukocytoclastic angiitis, and more recently single-organ cutaneous small-vessel vasculitis (SoCSVV). SoCSVV refers to a vasculitis confined to the skin with no features suggesting a limited expression of a systemic vasculitis.
Nevertheless, three major groups of systemic vasculitides could be identified in all classification schemes: large-vessel vasculitis (giant cell arteritis and Takayasu), medium-sized vessel vasculitis (polyarteritis nodosa [PAN] and Kawasaki), and small-sized vessel vasculitis. Within this latter group we can identify disorders associated with antineutrophil cytoplasmic antibody (ANCA), disorders associated with immune complex deposition, and Henoch-Schönlein purpura characterized by IgA dominant immune deposits, among others.
Epidemiology
In Norwich, UK, the reported annual incidence of biopsy-proven CV in a population 16 years of age and older was 38.6 per million. In northwestern Spain, in a population 21 years of age and older it was 55.2 per million. In Olmsted County, Minnesota, USA, the incidence rate was 45 per million considering all age groups.
In reports from the United States, Malaysia, and Kuwait, men and women were affected almost equally. In series reported from the United Kingdom and Singapore, females outnumbered males in a ratio of approximately 2:1. In contrast, in series reported from northwestern Spain and Australia males outnumbered females in a ratio of approximately 2:1.
In series of adult patients reported from Spain and Kuwait, CV as an idiopathic process limited to the skin accounted for 32% and 36.8% of cases, respectively. In these series, CV was a manifestation of a primary systemic vasculitis (PSV), other than hypersensitivity vasculitis, in 22% of patients from Spain and 12.2% from Kuwait. In both series, Henoch-Schönlein purpura was the commonest underlying PSV, accounting for 15% and 8.8% of cases, respectively.
Among the patients with secondary CV, CTDs were the most frequently reported conditions in Spanish series (30%). This percentage was lower in series from Malaysia (16.5%), Belgium (15.8%), Kuwait (12.1%), and Australia (8.6%). Rheumatoid arthritis constituted the most common CTD associated with CV.
Taken on the whole, drugs and infections are the most common underlying etiologies. In most series Gram-positive cocci ( Streptococcus and Staphylococcus ) and Neisseria species were the most common bacteria implicated. However, Gram-negative bacteria, anaerobes, mycobacteria, and Brucella have also been implicated in the development of CV. In series reported from Australia and Malaysia, infection accounted for 25.8% and 20.2% of cases, respectively. In Kuwait and Spain these percentages were lower (14% and 11%, respectively). Drugs have been reported as the causative agent in 8.7% to 28.2% of patients with CV. Among the drugs, antibiotics and nonsteroidal anti-inflammatory drugs were the most commonly implicated.
Malignancy associated with CV is uncommon. Reported frequencies from Kuwaiti, Australian, Malaysian, and Spanish series were 1.7%, 2.2%, 2.4%, and 4%, respectively. Hematologic disorders are the most common group of neoplasms associated with CV.
CV may affect all age groups. Noteworthy, the clinical spectrum is broader in adults. Blanco et al. (1998) retrospectively reviewed 303 consecutive patients with CV: 172 adults and 131 children (≤20 years). Fourteen children were classified as having hypersensitivity vasculitis (10.7%), and 116 as having Henoch-Schönlein purpura (88.5%), representing the most frequent vasculitic condition associated with CV in this age group. Therefore, almost 100% of children with CV had one of these two conditions.
Clinical Manifestations
General Concepts
Cutaneous lesions seen in CV are correlated with the size of the affected vessel. Small-sized blood vessels generally include capillaries, post-capillary venules, and nonmuscular arterioles (diameter <50 μm). These are mainly localized within the superficial papillary dermis. The pattern of skin involvement when cutaneous small vessels are affected is usually a maculopapular rash followed by palpable purpura ( Fig. 4-1 ), resulting from extravasation of erythrocytes through damaged blood vessel walls into the dermis. These lesions, in contrast to simple purpura, do not blanch when pressure is applied to the skin. Other skin lesions such as nonpalpable macules and patches, urticaria, bullous lesions, vesicles, pustules, splinter hemorrhages, and ulcerations may also be seen ( Fig. 4-2 ). Moreover, a combination of different lesions is common. Because of increased hydrostatic pressure, skin lesions are commonest on the legs and buttocks. Medium-sized blood vessels (diameter between 50 and 150 μm) have muscular walls and are located principally in the deep reticular dermis, near the junction of the dermis and subcutaneous tissues. Vasculitis involving cutaneous medium-sized blood vessels manifests as subcutaneous nodules, ulcers, livedo reticularis, digital infarctions, and papulonecrotic lesions ( Figs 4-3 and 4-4 ). Larger vessels are not found within the skin. CV may also be the presenting manifestation of an overlap of small and medium-sized blood vessel involvement. Furthermore, other conditions like pigmented purpuric eruptions, severe thrombocytopenic purpura, or scurvy may mimic CV. This is why a skin biopsy is always required to confirm the presence of vasculitis.
