<< Return to Coalescing purpuric plaques

Coalescing purpuric plaques

Noah S. Scheinfeld, MD, JD

November 10 2009

CASE #1

A 55-year-old woman presented with a three-week history of purpura on her shins. She had no cutaneous or systemic complaints. The patient's medical history was significant only for hypertension, which was controlled by atenolol. Physical examination found her to be otherwise healthy. Laboratory studies for antistreptolysin, hepatitis, and antinuclear antibodies (ANAs) were within normal limits. A stool guaiac test was normal. Biopsy showed inflammation of small blood vessels with “nuclear dust,” fragments of inflammatory cells.

CASE #2

A 35-year-old HIV-positive man presented with purple plaques on his back. His CD4 count was 210/µL. The lesions had developed several months earlier when his CD4 count was much lower. His medications included Combivir (lamivudine/zidovudine) and nelfinavir. A biopsy revealed increased spindle cells with vascular slits. Vascular structures demonstrated endothelial cells with extravasated erythrocytes and hemosiderin-laden macrophages. A guaiac test and abdominal and pulmonary CTs were normal.

What is the diagnosis?

Click "NEXT" for CASE #1 and "3" for CASE #2.

CASE #1: Leukocytoclastic vasculitis

The woman had idiopathic leukocytoclastic vasculitis (LCV), a clinicopathologic entity affecting the small vessels of the skin. It is also known as “hypersensitivity vasculitis,” “allergic vasculitis,” and “allergic angiitis.” This condition represents a type III, or immune complex-mediated, hypersensitivity reaction, in which immune complex lodges in capillaries. Neutrophils burst in response, leading to a vasculitis and extravasation of blood. It is typically characterized by round, 1- to 5-mm palpable or inflammatory purpura on the lower legs. The lesions coalesce to form plaques and may ulcerate.

LCV is often an acute self-limited condition, but chronic forms can occur. Involvement is typically limited to the skin, although cases have been seen in the kidneys, GI tract, and other organs. Morbidity and mortality are minimal if the condition involves only the skin. Some patients have no associated symptoms, while others complain of itching, burning, or pain.

Up to half of all cases are of unknown etiology. The most common causes of LCV are medication reactions (e.g., to beta-lactams), streptococcal infections, and hepatitis. Uncommon causes include collagen vascular disease, inflammatory bowel disease, Waldenström's macroglobulinemia, cryoglobulins, and HIV.

LCV can be confused with a number of conditions, including Henoch-Schönlein purpura, scurvy, purpuric drug reactions, benign pigmented purpura, other forms of vasculitis, and macular Kaposi's sarcoma. A complete history, including recent respiratory infections, IV drug use, hepatitis, transfusion, and travel, as well as symptoms or history of inflammatory bowel disease and collagen vascular diseases, is required in suspected cases. A review of symptoms should assess fever, arthralgia, arthritis, myalgia, abdominal pain, diarrhea, hematochezia, cough, hemoptysis, sinusitis, paresthesia, weakness, and hematuria.

Biopsy will reveal vascular and perivascular infiltration of polymorphonuclear leukocytes with nuclear dust. A hallmark of LCV is the presence of fibrinoid necrosis, a ring of fibrin obliterating the vessel walls.

Laboratory tests help determine the presence of systemic disease as well as identify any associated disorders. Requisite tests include complete blood count, erythrocyte sedimentation rate, blood chemistry, and urinalysis. If bowel symptoms are present, a stool guaiac test should be performed. Patients without an obvious cause of LCV should have ANA, antineutrophil cytoplasmic antibody, and rheumatoid factor determinations. Complement levels may be ordered for patients who have lupus erythematosus or urticarial vasculitis. Streptozyme or antistreptolysin-O titers, serum protein electrophoresis, cryoglobulins, and hepatitis C antibody are also helpful. Finally, HIV testing should be performed in patients who are at high risk of the virus.

A skin biopsy for direct immunofluorescence distinguishes LCV from forms of immunoglobulin A vasculitis, such as Henoch-Schönlein purpura. A chest x-ray is a helpful part of an LCV evaluation.

Isolated, idiopathic LCV usually resolves without treatment. If related to other conditions, treatment of these conditions can help the LCV to resolve. Prednisone (1-2 mg/kg), colchicine, or dapsone may be administered for patients with or without joint manifestations. Our patient decided to forgo therapy. Several months after presentation, her rash resolved without complication.

CASE #2: Kaposi's sarcoma

This patient had Kaposi's sarcoma (KS), a cancerlike condition caused by human herpesvirus 8. There are four forms of KS. Classic KS was first described more than a century ago. This form usually affects middle-aged and older American men of Mediterranean and Eastern European (Ashkenazi) Jewish lineage. It produces painful and often disfiguring leg tumors, but these are rarely life-threatening. Endemic KS primarily occurs in boys and men from east Africa and the Congo. Iatrogenic KS is typically found in transplant patients who take immunosuppressive drugs to prevent rejection. This form can be reversed once the medication is stopped. The final form of KS is HIV-associated, which is what our patient had.

One of the most visible signs of the disease, HIV-associated KS usually manifests as violaceous patches, papules, plaques, or nodules on the face and trunk. These may be preceded by chronic lymphedema. Early lesions often mimic insect bites. The nodules tend to enlarge into dome-shaped tumors. In advanced stages, lesions may be disseminated on the face, head, and trunk, often forming large plaques.

In some cases (10%-15%), lesions first appear on the oral mucosa, most frequently the palate. This can cause difficulties with swallowing or eating. Involvement of the pharynx can lead to respiratory distress.

Although rare, tumors can also occur on the GI tract, lungs, and lymph nodes. GI involvement is found in up to 80% of AIDS patients with KS, especially those with extensive cutaneous lesions. Symptoms can include nausea, ulceration, blockage, and bleeding. Pulmonary involvement may cause severe coughing, shortness of breath, and respiratory distress. Lymph node involvement may result in swelling of the face or extremities. Prognosis is poor with extracutaneous KS, and morbidity and mortality is often the result of bleeding in the affected organ systems.

The differential diagnosis for HIV-associated KS includes eruptive dermatofibromas, pyogenic granulomas, bacillary angiomatosis, lymphoma, leukemia, vasculitis, and arteriovenous malformations (pseudo-Kaposi's sarcoma). A diagnosis is often made on visual inspection. Lesions of KS are usually painless, with no pruritus or drainage. When pressed, they do not lose their color.

If KS is suspected, a definitive diagnosis can be made by biopsy. A proliferation of slitlike blood vessels with atypical endothelial cells is characteristic; increased numbers of plasma cells and hemosiderin deposits are also seen. If internal involvement is suspected, bronchoscopy, endoscopy, stool guaiac testing, and chest x-ray or abdominal CT may be required.

Highly active antiretroviral therapy (HAART) has been shown to be the most effective treatment for HIV-associated KS. In many patients, HAART can stop the growth of lesions or even clear them. It can also extend survival substantially. If lesions are few or in their early stages, they can be treated with cryotherapy or surgically excised. For more extensive disease,a variety of chemotherapeutic agents and radiation treatments may be therapeutic. Optimal treatment is to raise the patient's CD4 count, at which point the KS often resolves on its own.

Prior to our initial meeting, this patient's lesions had been treated with cryotherapy two times over two months. After each treatment, the lesions would clear. They eventually resolved completely.