Cutaneous Vasculitis Authors: Lorinda Chung, M.D. and David Fiorentino1, M.D., Ph.D. Creation date: March 2005 Scientific editor: Prof Loïc Guillevin 1Department of Dermatology, Division of Rheumatology and Immunology, Stanford University School of Medicine, 900 Blake Wilbur Drive W0074, Stanford, CA. USA. [email protected] Abstract Keywords Definition Classification / Etiology Approach to the Patient Treatment Future Directions References Abstract Cutaneous vasculitis is a histopathologic entity characterized by neutrophilic transmural inflammation of the blood vessel wall associated with fibrinoid necrosis, termed leukocytoclastic vasculitis (LCV). Clinical manifestations of cutaneous vasculitis occur when small and/or medium vessels are involved. Small vessel vasculitis can present as palpable purpura, urticaria, pustules, vesicles, petechiae, or erythema multiforme-like lesions. Signs of medium vessel vasculitis include livedo reticularis, ulcers, subcutaneous nodules, and digital necrosis. The frequency of vasculitis with skin involvement is unknown. Vasculitis can involve any organ system in the body, ranging from skin-limited to systemic disease. Although vasculitis is idiopathic in 50% of cases, common associations include infections, inflammatory diseases, drugs, and malignancy. The management of cutaneous vasculitis is based on four sequential steps: confirming the diagnosis with a skin biopsy, evaluating for systemic disease, determining the cause or association, and treating based on the severity of disease. Keywords Cutaneous vasculitis, leukocytoclastic vasculitis Definition Vasculitis is inflammation of the blood vessel Classification / Etiology wall that leads to various clinical manifestations The classification schemes for the vasculitides depending on which organ systems are involved. are based on several criteria, including the size Cutaneous vasculitis is a histopathologic entity of the vessel involved, clinical and characterized by neutrophilic transmural histopathologic features, and etiology. Large inflammation of the vessel wall associated with vessels include the aorta and large arteries and fibrinoid necrosis, termed leukocytoclastic veins; medium-sized vessels include the medium vasculitis (LCV). Other histologic findings that and small-sized arteries and veins; and small may be seen include extravasated erythrocytes, vessels refer to the arterioles, venules, and granulocytic debris (leukocytoclasis), capillaries. granulomatous or lymphocytic inflammation, and The American College of Rheumatology (ACR) deposition of immunoreactants in the vessel criteria of 1990 includes clinical, historical, and wall. Vasculitis has a wide spectrum of severity, histologic data to classify the vasculitides (Table ranging from skin-limited disease to life- 1) (1). In 1994, the Chapel Hill Consensus threatening systemic involvement. Recognizing Conference (CHCC) defined 10 types of the symptoms and signs implicating systemic vasculitis based primarily on histopathologic involvement is of paramount importance in the criteria (Table 2) (2). Although together these evaluation of patients with cutaneous vasculitis. classification schemes include most forms of cutaneous vasculitis, they were developed as Chung L and Fiorentino D Cutaneous vasculitis. Orphanet encyclopedia, March 2005. 1 http://www.orpha.net/data/patho/GB/uk-cutaneous-vasculitis.pdf research tools to define vasculitic syndromes (EED), a rare condition affecting the extensor and not as diagnostic criteria for the clinician. surface of the extremities, can show evidence of A clinically useful classification scheme for SVV with LCV on biopsy (11). cutaneous vasculitis could be based on etiology, differentiating between primary (idiopathic) and Clinical Manifestations secondary disease. Approximately 50% of The cutaneous findings of vasculitis depend cases are idiopathic, while infection (15-20%), upon which vessels are primarily involved. SVV inflammatory diseases (15-20%), drugs (10- most frequently presents as palpable purpura 15%), and malignancy (<5%) are the (Figure 3) but can also manifest as urticaria, predominant secondary causes of cutaneous pustules, vesicles, petechiae, or erythema vasculitis (Figure 1) (3-5). Multiple infectious multiforme-like lesions. Cutaneous signs in MVV agents including viruses (hepatitis B and C, include livedo reticularis, ulcers, subcutaneous HIV), bacteria, parasites, and fungi can be nodules, and digital necrosis (Figure 4). associated with vasculitis (6). Various inflammatory diseases such as rheumatoid Predominantly Small Vessel Vasculitides arthritis (RA), systemic lupus erythematosus (SLE), Sjogren’s syndrome (SS), and Cutaneous Small Vessel Vasculitis (CSVV) inflammatory bowel disease (IBD), can present CSVV is a diagnosis of exclusion used to with associated cutaneous vasculitis. These describe a SVV confined only to the skin. New patients typically have severe symptoms related medications or infectious agents are frequently to their underlying inflammatory disease and associated with the onset of CSVV. The typical have increased morbidity and mortality (7-10). clinical presentation is the development of a Several drugs, including penicillins, single crop of lesions that resolves sulfonamides, thiazides, and oral contraceptives, spontaneously within several weeks or a few as well as chemicals (insecticides, petroleum) months (14). The lesions may present as and foodstuff allergens (milk products, gluten) purpura, papules, vesicles or urticaria, and tend have been associated with cutaneous vasculitis to occur in dependent areas, in areas of trauma, (11). The diagnosis of drug-induced vasculitis is or under tight-fitting clothing (15). A chronic, a diagnosis of exclusion and is based on the recurrent form of CSVV can occur in up to 10% temporal relationship between exposure to the of patients (16). offending agent and the development of disease. Lastly, cutaneous vasculitis may be associated Urticarial Vasculitis (UV) with malignancy, typically a paraproteinemia or Approximately 5-10% of patients who present lymphoproliferative disorder, and abates with with chronic urticaria have UV (17, 18). treatment of the underlying cancer (12, 13). Features that differentiate UV from chronic Because multiple causes may contribute to the urticaria include the duration of lesions for development of cutaneous vasculitis, a greater than 24 hours, symptoms of burning classification scheme based on the diseased rather than itching, and the presence of purpura vessel size is perhaps most useful to the and hyperpigmentation from lesions that have clinician. Dermatologic signs of vasculitis are resolved (19). Most cases of UV are idiopathic, present only when small and medium-sized but frequent associations include connective vessels are involved. Therefore the diseases tissue diseases (SS, SLE), serum sickness, can be divided into those with predominantly infections (HCV), malignancy, or physical small vessel involvement, predominantly exposures (cold, UV light) (17). UV can be medium vessel involvement, both small and divided into two subsets, those with normal medium vessel involvement and other diseases complement levels (NUV) and those with low that can show cutaneous LCV as a secondary complement levels (hypocomplementemic finding (Figure 2). The predominantly small urticarial vasculitis (HUV)). The latter type is vessel vasculitides (SVV) include cutaneous associated with a higher risk of systemic disease small vessel vasculitis (CSVV), urticarial such as arthritis, obstructive airways disease, or vasculitis (UV), and Henoch-Schonlein purpura gastrointestinal symptoms (17, 20). (HSP). Polyarteritis nodosa (PAN) is the only Hypocomplementemic urticarial vasculitis cutaneous vasculitis involving predominantly syndrome (HUVS) is a rare form of UV medium-sized vessels (MVV). Vasculitis characterized by the presence of anti-C1q associated with cryoglobulinemia, connective antibodies, with clinical features similar to SLE, tissue diseases (CTD), and anti-neutrophil such as glomerulonephritis and pleuritis (21). cytoplasmic antibodies (ANCA) involve small and medium-sized vessels. Neutrophilic Henoch-Schonlein Purpura (HSP) dermatoses including Behcet’s disease and HSP typically presents in children (especially pyoderma gangrenosum, and other skin boys aged 4 to 8 years) and is characterized by diseases such as erythema elevatum diutinum palpable purpura affecting the lower extremities Chung L and Fiorentino D Cutaneous vasculitis. Orphanet encyclopedia, March 2005. 2 http://www.orpha.net/data/patho/GB/uk-cutaneous-vasculitis.pdf and buttocks, arthritis, nephritis, and colicky abdominal pain (22). The disease often Small and Medium Vessel Vasculitides presents acutely following an upper respiratory tract infection (23). Histologically HSP is Cryoglobulinemic Vasculitis (CV) characterized by the presence of IgA immune Cryoglobulins are cold-precipitable deposits in and around small vessels on direct immunoglobulins that can be divided into three immunofluorescence (DIF) (2). HSP is usually subtypes. Type I consists of monoclonal IgM self-limited, but chronic renal disease can occur and is always associated with a hematologic in 20-30% of patients with an increased disorder. Type I cryoglobulins lead to vessel incidence in adults compared to children (24). obstruction and can result in Raynaud’s phenomenon or acrocyanosis of the limbs (34). Predominantly Medium Vessel Vasculitides Types II and III, termed mixed cryoglobulins,