Cutaneous Manifestations of ANCA-Associated Small Vessels Vasculitis

Abstract

Skin lesions are frequent manifestations of underlying systemic conditions, including systemic autoimmune vasculitis. In particular, anti-neutrophil cytoplasmic antibodies (ANCA) are associated with distinct forms of vasculitis characterized by inflammatory cell infiltration of the walls of small and medium-sized vessels leading to vascular destruction and tissue necrosis. ANCA-associated vasculitis is rare and systemic diseases, which can be classified based on different distribution of vascular inflammation and presence or absence of granulomatosis and asthma. Despite their diversities, ANCA-associated vasculitis, namely microscopic polyangiitis, granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis, can all display a broad variety of cutaneous manifestations, which can appear during the course of the disease or even as first sign at the time of onset. Different skin manifestations might coexist in the same patient and occur in different occasions during the course of the vasculitis. Thus, a deep knowledge of the spectrum of skin lesions as part of ANCA-associated vasculitis is mandatory for a correct diagnostic process, whenever cutaneous vasculitis is suspected. Due to this broad variety of manifestations, the diagnosis of skin involvement in ANCA-associated vasculitis is very challenging and it must be supported by a detailed medical history, accurate physical examination, specific histopathological analysis of skin biopsy and the presence of ANCA serology. In this review, we focus on the cutaneous manifestations that can develop in the context of ANCA-associated vasculitis, detailing the clinical features, the histopathological aspects as well as the direct immunofluorescence studies for each of the three conditions. Moreover, we acknowledged the differential diagnoses that must be ruled out in the diagnostic process and the main therapeutic approaches available for treatment of ANCA-associated vasculitis.

Vasculitis

“…Long-term out-comes are generally good, and relapse was noted in 26-28% of patients in remission [58]. The overall 5-year and 10-year survival rates were 88.9% and 78.6%, respectively [48]. ANCApositive patients more frequently had a "vasculitic" phenotype, ENT involvement, peripheral neuropathy, and/or renal involvement, whereas the ANCA-negative patients would have an eosinophilic "tissue" phenotype -more frequently cardiomyopathy [56].…”

“…Necrotizing glomerulonephritis and pulmonary capillaritis are common symptoms. It is associated with P-ANCA due to antibodies against MPO in 50-75% of cases [48]. Although environmental factors such as silica exposure have been implicated, the etiology of MPA remains unknown.…”

“…MPA is a systemic vasculitis that can affect multiple organs; however, it can be restricted to only the kidneys. Renal involvement often as rapidly progressive glomerulonephritis is invariably seen in all patients [48]. Renal symptoms seen in 80-100% of patients can range from an asymptomatic urinary sediment to end-stage renal disease necessitating dialysis.…”

“…Glomerulonephritis is the only symptoms in some cases. Pulmonary involvement can be seen in 25-55% with diffuse alveolar hemorrhage resulting in hemoptysis, dyspnea, cough, and pleuritic chest pain as the classic presentation [48]. Cutaneous involvement as palpable purpura, livedo reticularis, nodules, urticarial lesions, and skin ulcers on bilateral extremities can be seen in 30-60% of patients.…”

“…EGPA is considered a systemic disease; however, limited expressions of EGPA confined to the upper or lower respiratory tract may occur. ANCA with a perinuclear immunofluorescence staining pattern is positive in only about 40-60% of patients [48]. Those with ANCA were more likely to have definitive features or surrogates of small-vessel vasculitis, purpura, peripheral neuropathy, myalgia, arthralgia, and glomerulonephritis [54], whereas those without ANCA developed myocarditis, lung infiltrates, and gastrointestinal symptoms frequently.…”