Erythema elevatum diutinum

Erythema elevatum diutinum (EED) is a distinctive form of chronic cutaneous vasculitis. Described over 100 years ago, the early descriptions are still an excellent source for information regarding the symptoms and signs of this unusual disease. Early writings separated EED into the Bury type, occurring in young women with a history of rheumatic disease, as well as the Hutchinson type, occurring in elderly men. The disease now is considered one entity regardless of the underlying cause.1–4 Most often, EED presents as persistent, symmetrical, firm, tender, red to reddish brown or purple papules and nodules that then may coalesce to form larger nodules or plaques. The extensor aspects of the extremities are the preferred location for skin lesions, although truncal and retroauricular lesions have also been described. These lesions are usually located near joints such as the fingers, hands, elbows, ankles, and knees, although palmar and plantar lesions are also seen (Fig 1). At times the lesions may resemble vesicles, hemorrhagic nodules, ulcerations, or other vascular processes. Partial resolution may give a yellowish or brown hue to the lesions, resembling xanthomata (Fig 2).5,6 Recent reports of HIV-associated EED emphasize nodular lesions as well as palmar/plantar involvement.7–13 Although asymptomatic in some cases, the onset of new lesions may be associated with pruritus or a burning or stinging sensation in the skin. Established lesions may be tender to the touch. Patients may have arthralgias as well as fever and other systemic symptoms. As a general rule, EED is seen more often in patients in the fourth through the six decade and with a slight male predominance. Cases associated with HIV infection more often have onset at an earlier age. The cause of EED is unknown, but it is presumed to be related to vascular immune complex deposition. The classic papers cite streptococcal infection and/or rheumatoid disease as possible causes for immune-complex formation; however, EED may also be associated with several autoimmune disorders including seropositive rheumatoid arthritis, ulcerative colitis, Crohn’s disease, relapsing polychondritis, pyoderma gangrenosum, type I diabetes mellitus, and gluten-sensitive enteropathy. Associated infections have included bacterial, viral, tuberculous, hepatitis, as well as syphilis.14–23 Several case reports over the past decade have detailed the association of EED with HIV infection.7–13 Many of these HIV patients are also infected with hepatitis B, C, or cytomegalovirus (CMV) in addition to other opportunistic organisms. The histopathologic changes in EED have been thoroughly reviewed.10,24–27 Early lesions begin with leukocytoclastic vasculitis (LCV) with a wedge-shaped polymorphonuclear cell infiltrate and fibrin deposition in the superficial and mid-dermis. Polymorphonuclear cells, leukocytoclastic debris and macrophages as well as histiocytes and, rarely, eosinophils may surround the blood vessels in early stages (Figs 3 and 4). Early on, papillary edema may be present to such a degree as to correlate clinically with pseudovesiculation. Superficial resemblance to Sweet’s syndrome may be seen, although the latter by definition must lack significant leukocytoclasis and/or vasculitis. As the process continues, histiocytes make up a larger proportion of the infiltrate, and one may see phagocytosed leukocytoclastic debris. Later lesions demonstrate a combination of granulation response or healing skin together with a proliferation of dermal spindle cells with or without multinucleate giant cells (Fig 5). At this stage the histopathology may resemble sclerosing hemangioma, various types of fibrous histiocytoma or, in the extreme, dermatofibrosarcoma protuberans. Ongoing vessel damage is documented by the presence of dilated blood vessels with hypertrophic endothelial cells projecting into the lumen, simulating a granulation response.28 At times this response can be confused with Kaposi’s sarcoma or bacillary angiomatosis.29 The latter two possibilities become more problematic in the cases associated with HIV infection. Xanthomatized histiocytes may be seen in more chronic lesions (Fig 6). Several studies30–32 have documented that the lipid is actually intracellular as opposed to the older nomenclature, which refers to EED as extracellular cholesterolosis. Recent reviews of the histopathologic changes in EED have documented the presence of spindle cells comprised of histiocytes, fibroblasts, and myofibroblasts, with positive staining with markers such as Mac387, CD34, and focal, alpha-smooth muscle actin (aFrom the Department of Dermatology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA. Address correspondence to Lawrence E. Gibson, MD, Mayo Clinic, 200 First St., Rochester, MN 55905, USA.