Patients present with palpable purpura in dependent areas, typically in the bilateral lower legs. Other clinical presentations include vesicles, papules, nodules, crusted ulcers, and, less commonly, livedo reticularis or annular lesions.^5,6 Extracutaneous manifestations are seen in about 20% of cases, and include arthralgias, myositis, low-grade fever, and malaise.

There is no discernible etiologic agent in approximately 40% of cases. The commonest known etiologic factors include drugs, infections, food or food additives, collagen-vascular diseases, and malignancies. Paraneoplastic (lymphoproliferative-, myeloproliferative-, or carcinoma-induced) vasculitis represents less than 5% of all cases of cutaneous vasculitis.⁷ Most paraneoplastic cases are the result of a paraproteinemia secondary to a lymphoproliferative disorder, typically cryoglobulins. In a study of vasculitis associated with hematologic malignancies, 22% of the patients with either lymphoma or leukemia developed cutaneous vasculitis before (26%), concomitantly (39%), or after (35%) the diagnosis of cancer. In 61% of these cases, malignancy was the suspected cause, whereas in the remainder, infections, medication, and mixed cryoglobulinemia were the suspected triggers.⁸

Hematologic dyscrasias associated with LCV include angioimmunoblastic T-cell lymphoma,⁹ diffuse large B-cell lymphoma,¹⁰ myelodysplastic syndromes,¹¹ mycosis fungoides,¹² hairy cell leukemia,¹³ acute myeloid leukemia,¹⁴ chronic lymphocytic leukemia,¹⁵ and multiple myeloma.^14,16,17 Medication-induced LCV has been reported with bortezomib,¹⁸ etoposide,¹⁹ interferon-α²⁰ sorafenib,²¹ and sunitinib²². Patients with type II cryoglobulinemia also present with LCV (usually associated with autoimmune disorders, hepatitis C virus [HCV] infection, and hematologic malignancies).

The histopathologic features of LCV vary with the age of the lesion (Fig. 60-1).²³ For best histologic findings, biopsy should be taken from lesions of 18 to 24 hours duration.⁴ The affected vessels in LCV are the small venules (postcapillary venules), and sometimes the small arterioles. The histopathology reveals infiltration of the vessel walls by neutrophils, which often show cellular disruption with nuclear fragmentation (“leukocytoclasis”). The vessel walls are thickened by edema and fibrinous exudate. Swollen endothelial cells and thrombosis can sometimes be present. The dermis reveals variable edema and extravasation of red blood cells (RBCs).²⁴ Other inflammatory cells such as eosinophils can also be present, and are more common in drug-induced LCV.²⁵ As the lesions evolve in time, vessel wall changes become less prominent, and neutrophils are replaced by lymphocytes and histiocytes. Sometimes, dermal edema evolves into a subepidermal vesicle. Direct immunofluorescence²⁶ shows variable deposits of fibrinogen, C3, IgM, and IgG within the vessel wall, typically in acute lesions (6 to 24 hours).^1,4

Henoch–Schönlein purpura (HSP) is a subtype of superficial dermal LCV characterized by IgA deposits in inflamed postcapillary venules.^27,28 Besides vasculitis, HSP patients present with arthralgias, abdominal pain, and renal involvement. More than 90% of HSP cases occur in pediatric patients (<10 years old). The clinical signs in childhood HSP resolve within few weeks, whereas in adults the symptoms endure longer with the potential for permanent kidney damage. While most HSP cases are precipitated by upper respiratory infection, the etiology of HSP is unknown. A minority of adult cases is associated with hematologic malignancies including myelodysplastic syndrome, follicular lymphoma, and diffuse large B-cell lymphoma, among others.^29,30,31,32

Wegener granulomatosis (WG), recently renamed as granulomatosis with poliangiitis, presents with superficial and deep LCV.⁸ Cases of WG can occur in association with solid tumors as well as lymphomas, leukemias, and myelodysplastic syndromes.^33,34,35,36 The incidence of cancers is also increased after therapy for WG.³⁴ Eosinophilic vasculitis is a recently described entity characterized by a predominantly eosinophilic-rich infiltrate producing a necrotizing vasculitis.^37,38 It presents as pruritic, erythematous, and purpuric papules and plaques. Association with connective tissue disorders,⁸ HIV,³⁹ and hypereosinophilic syndrome⁴⁰ had been described.

Urticarial vasculitis (UV) is a form of lymphocytic LCV with urticarial-like clinical findings that last for more than 48 hours. Besides the typical wheals, and angioedema, there is variable purpura. Rarely, hematologic conditions can be associated with UV, including IgA myeloma,⁴¹ IgM disease (Schnitzler syndrome, discussed separately), Castleman disease,⁴² and polycythemia vera.⁴³ It has also been shown in association with IV-Ig and methotrexate administration.

EED occurs in patients with connective tissue disorders,^44,45,46,47 infection, acquired immune deficiency,^48,49,50,51 and hematologic abnormalities, often with an IgA gammopathy.^{52,53,54,55,56} Other associations include lymphomas,⁵⁷ myelodysplastic syndromes,^58,59 and cryoglobulinemia.⁶⁰ Albeit of unknown clinical and pathologic significance, IgA class of antineutrophil cytoplasmic antibodies (IgA ANCA) have been detected in most EED patients.^61,62