Serologic screening of asymptomatic patients with SSc has shown a low frequency of ANCA-positivity (10%C13%)4, but her markedly positive p-ANCA and MPO strongly suggested a true inflammatory digital vasculitis rather than the bland SSc vasculopathy. ANCA-associated vasculitis (AAV) in the setting of SSc often presents with high ESR and CRP10. were normal. There was bilateral edema, cyanosis, and severe tenderness of distal extremities, without synovitis. There was diffuse superficial, livedo-like purpura on her thighs, frank necrosis of the suggestions of all her toes and 4 fingers, but no ulcerative lesions (Figures 1A, 1B). Her upper arms, thighs, and trunk were spared from lesions or pain. Open in a separate window Physique 1 A. Scattered necrotic Cortisone acetate bullae and blisters around the dorsum of the feet are visible, with necrotic suggestions of the toes. Aggressive progression of necrosis experienced occurred within 10 days of the onset of blisters, and within 2 days Cortisone acetate of the patient noticing ischemia around the suggestions of her toes. B. Necrotic fingertips, palmar aspect. Initial blood examination results included erythrocyte sedimentation rate (ESR) 96 mm/h, leukocytosis (white blood cells 10.25 em /em l, 79% polymorphonuclear), ANA titer 1:640, Scl-70 6.0 (normal 1.0), immunofluorescent perinuclear ANCA (p-ANCA) 1:640, myeloperoxidase (MPO) 89 U (normal 21 U), and rheumatoid factor 157 IU/ml (normal 25 IU/ml). Assessments for hepatitis, cryoglobulins, antiphospholipids, and antibodies to SSA/SSB and centromere were unfavorable. Renal function, C3/C4, and urinalysis were normal. Bilateral lesser extremity computed tomography (CT) angiogram with runoff failed to reveal inflammatory vasculitis, but vessels distal to the dorsalis pedis could not be visualized. A high resolution chest CT scan showed increased reticulations in the left lung with septal thickening, suggestive of early subpleural ZAK honeycombing. Pulmonary function screening demonstrated forced vital capacity 88% of predicted and DLCO 21% of predicted. There was no evidence of pulmonary hypertension by echocardiogram. Skin (punch) biopsy of the right shin showed small-vessel vasculitis with fibrinoid necrosis in the vessel wall, leukocytoclasia, and eosinophilia (Physique 2). Open in a separate window Physique 2 Skin biopsy of the right shin: fibrinoid necrosis can be seen around the blood vessel wall (thin white arrow); an infiltrate of neutrophils, neutrophilic debris, and scattered eosinophils can also be seen (solid white arrow). After admission, treatment with intravenous (IV) heparin, narcotics, and methylprednisolone at 1 g daily for 3 days was started. IV cyclophosphamide (1 g) was given. IV epoprostenol was titrated up to 8 ng/kg/min for 6 Cortisone acetate days. Oral vasodilators included sildenafil Cortisone acetate 20 mg tid and nifedipine 10 mg tid. Vascular surgery discussion advised against any surgical intervention. After discharge, she received 40 hyperbaric oxygen treatments for her gangrenous digits, IV cyclophosphamide 1 g monthly for 6 months, and oral sildenafil 20 mg tid. Mycophenolate mofetil was then substituted and titrated to 2. 5 g orally daily. Over 24 months, all of the 14 necrotizing digits underwent autoamputation. She resumed full-time work as an accountant. Her p-ANCA test remains positive with high anti-MPO titers (76C130 U/ml). Even though vasculopathy of SSc is usually characterized as a noninflammatory, concentric obliterative process, true inflammatory vasculitis has rarely been reported in the pre-ANCA era1,2. More recent reports have explained syndromes felt to be related to ANCA-positivity, including rapidly progressive glomerulonephritis3,4, pulmonary hemorrhage, severe scleroderma5, and necrotizing vasculitis6. Less strong associations include seizures7, leukocytoclastic vasculitis8, and interstitial lung disease9. Only a few reports have explained ANCA-associated digital necrosis3. Our individual presented with acute necrosis of 14 digits, resulting in total or partial autoamputation. She experienced no known vasculitic internal organ involvement or background of Sj?grens syndrome or antiphospholipid antibody syndrome. Serologic screening of asymptomatic patients with SSc has shown a low frequency of ANCA-positivity (10%C13%)4, but her markedly positive p-ANCA and MPO strongly suggested a true inflammatory digital vasculitis rather than the bland SSc vasculopathy. ANCA-associated vasculitis (AAV) in the setting of SSc often presents with high ESR and CRP10. Either p- or c-ANCA (with/without MPO) may be positive. Higher ANCA titers often correlate with.