Elsevier

Autoimmunity Reviews

Volume 12, Issue 4, February 2013, Pages 467-476
Autoimmunity Reviews

Review
Skin involvement in cutaneous and systemic vasculitis

https://doi.org/10.1016/j.autrev.2012.08.005Get rights and content

Abstract

Cutaneous vasculitides are a heterogeneous group of inflammatory disorders affecting skin blood vessels. They may be triggered by several factors, such as infection or drug, or may be related to underlying disease, notably connective tissue or malignancies. However, vasculitis occurs without any demonstrable triggering agents in a relevant number of patients. On the other hand, vasculitic skin lesions may manifest as a component of vasculitis affecting also internal organs; in someone of these patients, skin involvement occurs initially as the sole sign of disease, leading to consider cutaneous vasculitis a diagnosis of exclusion. In this review, we have focused on the most common variants of cutaneous vasculitis, including cutaneous small vessel vasculitis and urticarial vasculitis as well as Henoch–Schönlein purpura, a systemic form in which however skin involvement often predominates. We have also argued on livedoid vasculopathy, a cutaneous entity which, although nonfrankly vasculitic in origin, is frequently associated with connective tissue disease. Finally, we have analyzed the variety of cutaneous manifestations that may develop during the course of the main systemic vasculitides, such as Wegener's granulomatosis, Churg–Strauss syndrome and polyarteritis nodosa.

Introduction

Cutaneous vasculitis is defined as a pathological process characterized by inflammation of the skin blood vessel wall; the disease process causes an alteration of the blood flow, ischemia, and damage to the neighboring tissue [1]. Although any type of vessel can be affected, the skin veins, particularly post-capillary venules, are more often involved than arteries and capillaries. In fact, post-capillary venules are mainly affected in cutaneous small vessel vasculitis (CSVV), also known with the histologic term of leukocytoclastic vasculitis, which is the most common form of vasculitis in dermatology [2]. Cutaneous vasculitides may be triggered by various antigenic agents, such as infection or drug, or may be related to an underlying disease, such as connective tissue, inflammatory bowel, myelodysplastic or other malignancies. However, it is important to note that many vasculitides occur without any demonstrable triggering agents, leading to consider the vasculitic process as “idiopathic”. On the other hand, vasculitic skin lesions may manifest as a component of vasculitis affecting also internal organs, cutaneous involvement being sometimes the initial sign of disease.

The classification of vasculitides has been a confusing and debate-provoking topic over the last half century. Despite numerous attempts, the development of a clinically relevant and easy-to use classification system that incorporates clinical features, vessel site, histopathological and laboratory findings, and possible etiologic factors, is a goal that has not yet been fully achieved. Thus, we will adopt a recently proposed working classification for vasculitides [3] which is useful for the scope of the present review (Table 1). Here, we will focus on the most frequent clinical variants of cutaneous vasculitis such as CSVV and urticarial vasculitis (UV) as well as the variety of cutaneous manifestations that may be observed in the course of the main systemic vasculitides such as polyarteritis nodosa (PAN), Wegener's granulomatosis (WG) and Churg–Strauss syndrome (CSS). Henoch–Schönlein purpura (HSP) will be argued among the cutaneous vasculitides based on that skin involvement is often predominant [1], [4], [5]. Unique forms of cutaneous vasculitis of specific interest for dermatologists, such as erythema elevatum diutinum, granuloma faciale or nodular vasculitis, will not be discussed.

Livedoid vasculopathy (LV), a cutaneous disorder which, albeit nontruly vasculitic in origin, is frequently associated with antiphospholipid antibody syndrome and/or connective tissue diseases [6], [7], will be discussed because may be of interest not only for dermatologists but also for immunologists and general readers.

Section snippets

Definition

Affecting mainly cutaneous post-capillary venules, cutaneous small vessel vasculitis (CSVV) is the most common type of vasculitis in dermatology. The cutaneous picture of CSVV is typically polymorphous and may include in particular palpable purpura, ulcers and urticarial lesions mainly involving the legs, while its extracutaneous manifestations are by definition relatively uncommon. It affects both children and adults, and is seen more commonly in women [8], [9], [10].

Etiologic factors

The main etiologic factors

Definition

Polyarteritis nodosa is a rare, severe necrotizing vasculitis of small- and medium-sized arteries affecting multiple organ systems. The disease has a segmental distribution and localizes chiefly in bifurcations and branchings of arteries [2]. Cutaneous manifestations of systemic PAN should be distinguished from those proper to the benign form confined to the skin [1].

Cutaneous features

Skin involvement can be found in about half of the patients with systemic PAN. The most common skin lesions are palpable purpura

Take-home messages

  • Cutaneous vasculitis is a heterogeneous group of inflammatory disorders affecting skin blood vessels, particularly post-capillary venules.

  • Cutaneous small vessel vasculitis (CSVV), also known as leukocytoclastic vasculitis, is the most common entity within this group.

  • Many triggering factors may be identified in cutaneous vasculitis, but it is idiopathic in a relevant number of cases.

  • The cutaneous picture of CSVV is polymorphous, including purpura, urticarial lesions and ulcers, while its

References (116)

  • E. Witort-Serraglini et al.

    Endothelial injury in vasculitides

    Clin Dermatol

    (1999)
  • C. Comacchi et al.

    Gamma/delta T lymphocytes and infection: pathogenesis of leukocytoclastic cutaneous necrotizing vasculitis

    Clin Dermatol

    (1999)
  • A.M. Schilder

    Wegener's granulomatosis vasculitis and granuloma

    Autoimmun Rev

    (2010)
  • P.L. Meroni et al.

    Antiphospholipid antibodies and the endothelium

    Rheum Dis Clin North Am

    (2001)
  • A. Radice et al.

    Anti-neutrophil cytoplasmic autoantibodies: methodological aspects and clinical significance in systemic vasculitis

    Autoimmun Rev

    (2013)
  • M.F. Fredenberg et al.

    Sulfone therapy in the treatment of leukocytoclastic vasculitis. Report of three cases

    J Am Acad Dermatol

    (1987)
  • I.W. Uthman et al.

    Response of deep cutaneous vasculitis to infliximab

    J Am Acad Dermatol

    (2005)
  • A.K. Black

    Urticarial vasculitis

    Clin Dermatol

    (1999)
  • N.P. Sanchez et al.

    The clinical and histopathologic spectrums of urticarial vasculitis: study of forty cases

    J Am Acad Dermatol

    (1982)
  • D.R. Mehregan et al.

    Urticarial vasculitis: a histopathologic and clinical review of 72 cases

    J Am Acad Dermatol

    (1992)
  • M.D. Davis et al.

    Clinicopathologic correlation of hypocomplementemic and normocomplementemic urticarial vasculitis

    J Am Acad Dermatol

    (1998)
  • J.S. Lee et al.

    Prolonged urticaria with purpura: the spectrum of clinical and histopathologic features in a prospective series of 22 patients exhibiting the clinical features of urticarial vasculitis

    J Am Acad Dermatol

    (2007)
  • K.T. Calamia et al.

    Livedo (livedoid) vasculitis and the factor V Leiden mutation: additional evidence for abnormal coagulation

    J Am Acad Dermatol

    (2002)
  • F.T. Saulsbury

    Clinical update: Henoch–Schönlein purpura

    Lancet

    (2007)
  • Y.H. Yang et al.

    The immunobiology of Henoch–Schönlein purpura

    Autoimmun Rev

    (2008)
  • J. Levin et al.

    Skin disorders with arthritis

    Best Pract Res Clin Rheumatol

    (2006)
  • J.L. Jorizzo et al.

    Low-dose weekly methotrexate for unusual neutrophilic vascular reactions: cutaneous polyarteritis nodosa and Behçet's disease

    J Am Acad Dermatol

    (1991)
  • T. Kawakami et al.

    Use of warfarin therapy at a target international normalized ratio of 3.0 for cutaneous polyarteritis nodosa

    J Am Acad Dermatol

    (2010)
  • I. Decleva et al.

    Cutaneous manifestations in systemic vasculitis

    Clin Rev Allergy Immunol

    (1997)
  • J.C. Jennette et al.

    Nomenclature of systemic vasculitides. Proposal of an international consensus conference

    Arthritis Rheum

    (1994)
  • N.H. Cox et al.

    Vasculitis neutrophilic dermatoses and related disorders

  • A.V. Marzano et al.

    Widespread livedoid vasculopathy

    Acta Derm Venereol

    (2003)
  • S. Khenifer et al.

    Livedoid vasculitis associated with a double heterozygous factor V Leiden and prothrombin G20210A gene mutations

    Clin Exp Dermatol

    (2009)
  • J.C. Jennette et al.

    Small-vessel vasculitis

    N Engl J Med

    (1998)
  • J.A. Carlson et al.

    Cutaneous vasculitis update: small vessel neutrophilic vasculitis syndromes

    Am J Dermatopathol

    (2006)
  • K.R. Chen et al.

    Clinical approach to cutaneous vasculitis

    Am J Clin Dermatol

    (2008)
  • D.F. Fiorentino

    Cutaneous vasculitis

    J Am Acad Dermatol

    (2003)
  • S.M. ten Holder et al.

    Cutaneous and systemic manifestations of drug-induced vasculitis

    Ann Pharmacother

    (2002)
  • T. Lotti et al.

    Cutaneous small-vessel vasculitis

    J Am Acad Dermatol

    (1998)
  • M.S. Kluger

    Vascular endothelial cell adhesion and signaling during leukocyte recruitment

    Adv Dermatol

    (2004)
  • J.S. Lee et al.

    Lymphocytic thrombophilic arteritis: a newly described medium-sized vessel arteritis of the skin

    Arch Dermatol

    (2008)
  • P. Guilpain et al.

    Antiendothelial cells autoantibodies in vasculitis-associated systemic diseases

    Clin Rev Allergy Immunol

    (2008)
  • R. Blanco et al.

    Cutaneous vasculitis in children and adults. Associated diseases and etiologic factors in 303 patients

    Medicine

    (1998)
  • G. Sais et al.

    Prognostic factors in leukocytoclastic vasculitis: a clinicopathologic study of 160 patients

    Arch Dermatol

    (1998)
  • M.A. Gonzalez-Gay et al.

    Clinical approach to cutaneous vasculitis

    Curr Opin Rheumatol

    (2005)
  • Y.J. Tai et al.

    Retrospective analysis of adult patients with cutaneous leukocytoclastic vasculitis

    Australas J Dermatol

    (2006)
  • A.N. Crowson et al.

    Cutaneous vasculitis: a review

    J Cutan Pathol

    (2003)
  • D.J. Ioannidou et al.

    Cutaneous small vessel vasculitis: an entity with frequent renal involvement

    Arch Dermatol

    (2002)
  • J.A. Carlson

    The histological assessment of cutaneous vasculitis

    Histopathology

    (2010)
  • S. Bahrami et al.

    Tissue eosinophilia as an indicator of drug-induced cutaneous small-vessel vasculitis

    Arch Dermatol

    (2006)
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