Bilateral Foot Necrosis Caused by Hepatitis C Virus–Induced Mixed Type II Cryoglobulinemia


A 52-year-old woman was admitted for increasing severe pain in her feet during the previous month. Her symptoms began 2 years earlier when she noticed skin discoloration and occasional blisters in her feet that became worse before admission. Her medical history included dyslipidemia and hepatitis C virus (HCV) infection incompletely treated 4 years earlier. On physical examination, she had livedo reticularis (Figure A) with purple skin discoloration and blisters on the dorsum of the feet. In addition, severe distal necrosis of the toes with diminished pedal pulses was seen (Figure B). Significant laboratory results included positive serum mixed cryoglobulin type II titer, elevated rheumatoid factor (127 IU/mL), low C3 and C4 levels, and an HCV RNA viral load of 153,000 IU/mL. Skin biopsy of lower extremities confirmed leukocytoclastic vasculitis (Figure C). An arterial ultrasound of lower extremities showed mild-to-moderate plaques bilaterally with no significant stenosis. Angiographic studies showed aneurysms in the abdominal aorta and right common femoral artery. Clinical and laboratory findings were attributed to mixed cryoglobulinemia. The patient underwent bilateral amputation of lower extremities and treatment with pulse steroids.

Cryoglobulinemia can be detected in 36%–55% of patients infected with HCV, but only 3% develop vasculitic manifestations.1, 2 The most common clinical manifestations are cutaneous vasculitis, arthritis, peripheral neuropathy, and glomerulonephritis.2 Cutaneous vasculitis in mixed type II cryoglobulinemia is characterized by an orthostatic purpura in lower extremities caused by venous stasis and a nonspecific leukocytoclastic vasculitis with infiltration of skin, vessel walls, and microvascular thrombosis3; typically the presentation is not livedo or skin necrosis.4 The bilateral nature of the necrosis with insignificant arterial stenosis in this patient suggests diffuse systemic medium and small vessel disease. Endothelial dysfunction, atherosclerotic plaques, and vascular infiltration by immunocomplexes could cause this rapid presentation of bilateral foot necrosis.

The virologic response to antiviral therapy in HCV patients is not affected by the concurrent presentation of mixed cryoglobulinemia, and small studies show an improvement of cutaneous symptoms.3, 5, 6 Symptomatic response can be as high as 80% in patients receiving antiviral therapy, even when not associated with serologic response.7 However, the clinical remission is mostly limited to mild-to-moderate disease activity, and it is doubtful if it will improve symptoms in cases like ours with severe manifestations.



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