Unusual Presentation of Erythema Elevatum Diutinum With Underlying Hepatitis B Infection
Erythema elevatum diutinum (EED) is a rare, chronic, cutaneous small vessel vasculitis of unclear pathogenesis. Classically, lesions present as symmetric red to purple plaques, papules, and nodules overlying joints. First-line therapy is dapsone. We present a case of EED with widespread lesions involving the hands, extensor arms and legs, and trunk. Multiple biopsies showed concentric intradermal perivascular inflammation with dermal fibrosis and leukocytoclastic vasculitis (LCV) suggesting EED in various stages of evolution. An extensive workup was positive for underlying hepatitis B infection. Our case represents the clinicopathologic spectrum that EED can present and emphasizes the importance of searching for an underlying etiology.
Practice Points
- Erythema elevatum diutinum (EED) often is associated with an underlying infectious process, including hepatitis B and hepatitis C, or a hematologic or autoimmune condition.
- If EED is suspected clinically, it may be beneficial to perform multiple biopsies from lesions at different stages of evolution to establish the diagnosis.
- First-line therapy includes treatment of any underlying condition and dapsone.
Comment
Overview of EED
Erythema elevatum diutinum represents a rare form of chronic cutaneous small vessel vasculitis. Originally described by Hutchinson7 and Bury8 as symmetric purpuric nodules of the skin, it was later named by Crocker and Williams9 in 1894. The disease classically presents as firm, fixed, red-brown to violaceous papules, plaques, and nodules affecting the extensor upper or lower extremities.1 Lesions are most commonly found symmetrically overlying joints of the hands, feet, elbows, and knees, as well as the Achilles tendon and buttocks.3 Less common locations include the palms and soles, face,10,11 trunk,12 and periauricular region.1 Although they are typically asymptomatic, sensations such as burning, stinging, and pruritus have been noted.1 Our patient was unique because in addition to typical lesions of EED, he presented with crusted papules on the flanks and violaceous papules of the lower legs and periumbilicus.
Etiology
Originally associated with Streptococcus as isolated from EED lesions,3,13 additional infectious etiologies include viral hepatitis,4-6 human herpesvirus 6,14 and rarely HIV.1,15 Hepatitis B and C are well known to be associated with EED, with only rare reports in patients with concomitant HIV infection. Erythema elevatum diutinum also has been described in relationship to myeloproliferative disorders and hematologic malignancies such as IgA myeloma,16 non-Hodgkin lymphoma,17 chronic lymphocytic leukemia,18 and hypergammaglobulinemia.19 In a study of 13 patients with EED, 4 had associated underlying IgA monoclonal gammopathy.2 Autoimmune conditions such as rheumatoid arthritis,20 ulcerative colitis,21 relapsing polychondritis,22 and systemic lupus erythematosus23 also have been implicated.
Pathogenesis
Although the precise pathogenesis of EED remains unknown, it has been suggested that a complement cascade initiated by immune-complex deposition in postcapillary venules induces an LCV.24,25 Chronic antigenic exposure or high antibody levels26 in the face of infections, autoimmune disease, or malignancy may incite this immune-complex reaction. Skin lesions seen in association with hepatitis reflect circulating immune-complex deposition in vessel walls causing destruction. It has been postulated that the duration of immune complexemia may be sufficient to account for the differences in the type of vascular injury seen in acute versus chronic infection.27
Histopathology
Erythema elevatum diutinum may present on a histopathologic spectrum of LCV, as manifested in our patient. Early lesions show predominantly polymorphonuclear cells with nuclear dust pattern in a wedge-shaped infiltrate with fibrin deposition in the superficial and mid dermis.2,3 Later lesions show vasculitis in addition to dermal aggregates of lymphocytes, neutrophils, fibrosis, and areas of granulation tissue. The fibrosis may be dense and comprised of fibroblasts and myofibroblasts.28 Newly formed vessels within the granulation tissue have been postulated to be more susceptible to immune-complex deposition, thus potentiating the process.1,29
Management
Spontaneous resolution of EED may occur, albeit after a prolonged and recurrent course of up to 5 to 10 years.30 Treatment of the underlying cause, when identified, remains paramount. First-line therapy includes dapsone, shown to be effective in reducing lesion size to complete resolution in 80% of the 47 cases reviewed by Momen et al.31 Dapsone monotherapy tends to be less effective in treating nodular lesions associated with HIV-positivity, likely due to the extensive fibrosis.4,31 Combination therapy with dapsone and a sulfonamide,32 niacinamide and tetracycline,33 colchicine,34 or surgical excision35 may be necessary in more resistant cases.
Conclusion
Our case exemplifies the clinical histologic spectrum that EED can present. The constellation of clinical findings was histologically confirmed to be manifestations of the disease in various stages of evolution. When typical lesions of EED present along with cutaneous findings in less common locations, performing multiple biopsies can be helpful. The clinician should retain a high index of suspicion for an underlying etiology and perform a complete workup for infection, malignancy, or autoimmune disease.
