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Laboratory evaluation included a urinalysis and 24-hour urine collection, results of which showed proteinuria and gross hematuria. The prothrombin-proconvertin test value was 24%. Laboratory test results for a complete blood count, erythrocyte sedimentation rate, C3, C4, antistreptolysin O titer, rheumatoid factor, HBV, and HCV were negative or within reference range. However, the patient's cryoglobulin level was elevated (7%), and the results of a skin lesion biopsy during this admission was interpreted as LV.
On September 18, one day after the patient's admission, warfarin was discontinued, and anticoagulation was begun with subcutaneous unfractionated heparin. By September 29, the skin lesions had improved, and warfarin treatment was restarted to "challenge" the patient; on October 3, the patient was discharged on his previous maintenance dose of warfarin, digoxin, insulin, and subcutaneous unfractionated heparin until the prothrombin-proconvertin test value was in the therapeutic range.
On October 26, 23 days after warfarin was restarted, new petechial lesions were again observed over both lower extremities (Figure 1C); the patient was readmitted to the hospital. The results of several laboratory tests, including multiple blood cultures, C3, C4, antistreptolysin O titer, rheumatoid factor, hepatitis B surface antigen, antinuclear antibodies, and purified protein derivative, were either negative or within reference range. The results of a urinalysis revealed proteinuria and hematuria. The results of a second skin lesion biopsy during this admission confirmed LV; immunofluorescence was positive for immunoglobulin A (IgA), IgG, IgM, C3, and fibrinogen deposits.
During this admission, warfarin was discontinued, and intravenous unfractionated heparin was reinstituted. The cutaneous lesions resolved within 4 days (Figure 1D). Long-term anisindione therapy was begun with no appearance of new lesions during the subsequent 5 years.
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Patient 3
The third patient was a 39-year-old Hispanic woman with a medical history of rheumatic heart disease, severe tricuspid and mitral regurgitation post–mitral valve replacement with a St. Jude Medical® mechanical heart valve and tricuspid valve commissurotomy, congestive heart failure, atrial fibrillation, and a hysterectomy. In January 1999, she was admitted to the hospital for heart failure and pruritic plaques on both lower extremities (Figure 2A). According to the patient, the plaques had begun appearing intermittently since 1997. She also described symptoms of swelling, erythema, palpable purpura, and tenderness from her knees to her feet.
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The patient denied exposure to new drugs, new laundry detergent, insect bites, and poison ivy or oak. She was afebrile. Chemistry panel, hematologic profile, liver function, rheumatoid factor, antinuclear antibody, hepatitis B surface antigen, antibodies to hepatitis B core antigen, and anti-HCV test results were negative or within reference range. However, proteinuria and hematuria were present on urinalysis. The erythrocyte sedimentation rate was found to be elevated. Her international normalized ratio was 2.59.
The results of a skin lesion biopsy confirmed LV. On the patient's discharge from the hospital, captopril was added to her therapeutic regimen. During several follow-up appointments at the anticoagulation clinic, the skin lesions were found to have persisted with no improvement. Subsequently, a decision was made to discontinue warfarin and attempt a trial with anisindione. There were no further alterations to the patient's medications. During the next several months, while maintaining the patient's international normalized ratio goal with anisindione, the lesions gradually improved and resolved. She was subsequently followed through October 1999 with no further development of skin lesions (Figure 2B).
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Patient 4
The fourth patient was a 48-year-old Hispanic woman with a history of rheumatic heart disease, post–mitral valve replacement with a St. Jude Medical mechanical heart valve, atrial fibrillation, hypothyroidism, and anaphylaxis to radio-contrast dye.
In April 1997, the patient was admitted to the hospital with a 6-day history of a nonpruritic maculopapular rash on her legs, feet, and chest. She was afebrile and denied joint pains or symptoms of nausea or vomiting. Her medications included warfarin, digoxin, and levothyroxine, all of which she had been taking since April 1994. There were no recent changes in the patient's medications. The results of a urinalysis taken on admission were negative for blood, protein, and bacteria. The results of tests for platelet counts, C3, C4, rheumatoid factor, HBV, HCV, antinuclear antibody, thyroid function, and serum creatinine were all negative or within reference range. Her prothrombin time and activated partial thromboplastin time were 16.9 and 28.0 seconds, respectively. The patient's erythrocyte sedimentation rate and cryoglobulin level were elevated. Her white blood count of 11,500 cells/mm3 and neutrophil count of 84% were slightly elevated. LV was suspected; however, the patient was discharged home with a prescription of diphenhydramine as needed for pruritus, in addition to her previous medications.