On April 16, warfarin was discontinued, and anticoagulation was maintained with subcutaneous unfractionated heparin until anisindione was made available to the patient. The skin lesions improved within 5 days of discontinuing warfarin. Twelve days later, she developed proteinuria and hematuria while on unfractionated heparin. The results of a urinalysis revealed few bacteria and white blood cells, but no nitrites. Her antifactor Xa level and activated partial thromboplastin time at 6 hours postdose were 0.67 IU/mL and 54.9 seconds (ratio 1.82), respectively. The heparin dose was reduced secondary to hematuria.
On May 7, anisindione was initiated, and the patient's skin lesions resolved by May 28. However, proteinuria and hematuria persisted despite the change to anisindione therapy. Two months later, anisindione also was discontinued because of the concern of possible worsening of nephropathy with continued anisindione.16 Self-injection with subcutaneous enoxaparin was recommended, but the patient refused. Proteinuria and hematuria persisted along with an increase in serum creatinine levels. Results of a renal ultrasound on May 29 revealed a right superior pole focal pyelonephritis. The patient continued to refuse treatment with low molecular weight heparin therapy and was lost to follow-up in July 1997. Although the patient was not actively followed by the cardiac/anticoagulation clinic, a more recent review of her hospital chart indicated that in August 1998, she returned to the medical center for a cystic pelvic mass. A hospital note also indicated that while in Ecuador in July 1998, the patient was restarted on warfarin therapy. Another follow-up note from December 1998 was unremarkable for any recurrence of cutaneous manifestations due to warfarin.
Comment
LV is an inflammatory disease involving the small vessels that usually presents as nonthrombocytopenic palpable purpura. Cutaneous lesions typically begin as asymptomatic localized hemorrhages that become palpable as blood leaks out of the vessels. Other cutaneous manifestations that may be encountered with LV include vesicles, nodules, hemorrhagic bullae, and superficial infarctions. The eruptions may be asymptomatic or associated with itching, burning, or edema. Although lesions are commonly seen on the lower extremities, they may occur elsewhere, including areas under local pressure, such as the back in bedridden patients.17
It is reported that about half of the cases of LV have associated systemic effects that may involve the kidney; gastrointestinal tract; or pulmonary, cardiovascular, or central nervous systems (in addition to the cutaneous lesions).17 Signs and symptoms may include general malaise, myalgia, arthralgia, abdominal pain, nausea, proteinuria, hematuria, and fever. In cases with severe systemic involvement, mortality has been reported.17
The differential diagnosis of LV encompasses a wide spectrum of diseases, including Henoch-Schönlein purpura, CVDs, and cryoglobulinemic vasculitis. LV-associated Henoch-Schönlein purpura presents as palpable purpura in the lower extremities and buttocks. The condition commonly manifests in children, especially in young boys. Henoch-Schönlein purpura usually follows an upper respiratory tract infection and is characterized by a tetrad of findings: palpable purpura, arthralgias or arthritis, abdominal symptoms, and renal failure.18 The cutaneous lesions usually disappear in 10 to 14 days, though dapsone appears to be effective in clearing the cutaneous eruption and in shortening the duration of the disease.19 Intravenous immunoglobulin therapy also has demonstrated some benefits.20 The disease is self-limiting and generally has excellent prognosis in children. Characteristic histopathology features IgA deposition and neutrophilic predominance.1
LV-associated CVDs account for 15% to 20% of patients with vasculitis18 and usually affect multiple organs. These CVDs include systemic lupus erythematous, rheumatoid arthritis, Sjögren syndrome, and Wegener granulomatosis.1 Unlike drug-induced LV, which primarily targets small vessels, LV-associated CVD involves both small and medium vessels with multiple patterns of vascular injury.1 LV-associated CVD is mediated by a type-2 immune mechanism in contrast to drug-induced LV, which is essentially a type-3 response. Depending on the particular CVD, the histopathology highlights different features: pauci-inflammatory, lymphocytic, neutrophilic, or granulomatous.1 For LV associated with CVD, the goal is to treat the underlying condition.
Cryoglobulinemic vasculitis presents as lower extremity purpura precipitated by cold, prolonged standing, trauma, infection, or drug reaction.1 A common cause of cryoglobulinemia is HCV, which accounts for approximately 80% to 90% of cases.18,21-23 However, the overall incidence of LV induced by cryoglobulinemia is only 3%.23 The hallmark of cryoglobulinemia is the presence of cryoprecipitates, which are composed of a mixture of monoclonal and polyclonal immunoglobulins. Neutrophilic and/or lymphocytic infiltrates with mural necrosis and thrombosis of vascular plexus are seen in the dermis.18 In addition to cryoglobulin production, HCV also induces autoantibody production.21-23 HBV reacts by a similar mechanism. Unlike HCV, HBV is associated with polyarteritis nodosa.24 Interestingly, the histopathology of hepatitis B and C is distinguished from that of other vasculitis in that there is deposition of IgM and fibrinogen but absence of IgA deposition.