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Erythema elevatum diutinum

Authors
Felipe Bochnia Cerci, MD
Joseph Jorizzo, MD
Section Editor
Jeffrey Callen, MD, FACP, FAAD
Deputy Editor
Abena O Ofori, MD

INTRODUCTION

Erythema elevatum diutinum (EED) is a chronic form of leukocytoclastic vasculitis consisting of violaceous, red-brown, or yellowish papules, plaques, or nodules that favor the extensor surfaces (picture 1A-D) [1,2]. EED may occur in association with infections, hematologic abnormalities, autoimmune diseases, or other conditions. Oral dapsone is the primary mode of treatment.

The clinical features, diagnosis, and management of EED will be reviewed here. Other manifestations of cutaneous leukocytoclastic vasculitis are reviewed separately. (See "Evaluation of adults with cutaneous lesions of vasculitis".)

EPIDEMIOLOGY

EED is a rare disease that most frequently affects young and middle-aged adults between the ages of 30 and 60 years. There is no known sex or racial predilection [3].

PATHOGENESIS

The pathogenesis of EED is not well understood. EED appears to be a form of immune complex-mediated vasculitis. The cutaneous findings may result from the deposition of immune complexes in small blood vessels in the skin, leading to complement activation, neutrophilic infiltration, and the release of destructive enzymes [4]. In support of this theory, direct immunofluorescence studies reveal perivascular deposition of complement, IgG, IgM, IgA, and fibrin in EED [5].

In addition, the findings of an in vitro study suggest that activation of cytokines such as interleukin-8 contributes to selective recruitment of leukocytes to affected skin [6]. Antineutrophil cytoplasmic antibodies (ANCA) may also play a role in the pathogenesis of EED [7].

              

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Literature review current through: Nov 2016. | This topic last updated: Thu May 28 00:00:00 GMT 2015.
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References
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  1. Yiannias JA, el-Azhary RA, Gibson LE. Erythema elevatum diutinum: a clinical and histopathologic study of 13 patients. J Am Acad Dermatol 1992; 26:38.
  2. Mraz JP, Newcomer VD. Erythema elevatum diutinum. Presentation of a case and evaluation of laboratory and immunological status. Arch Dermatol 1967; 96:235.
  3. High WA, Hoang MP, Stevens K, Cockerell CJ. Late-stage nodular erythema elevatum diutinum. J Am Acad Dermatol 2003; 49:764.
  4. Shinkai K, Fox LP. Cutaneous vasculitis. In: Dermatology, 3rd ed, Bolognia JL, Jorizzo JL, Schaffer J. (Eds), Elsevier Limited, 2012. Vol 1, p.385.
  5. Shimizu S, Nakamura Y, Togawa Y, et al. Erythema elevatum diutinum with primary Sjögren syndrome associated with IgA antineutrophil cytoplasmic antibody. Br J Dermatol 2008; 159:733.
  6. Grabbe J, Haas N, Möller A, Henz BM. Erythema elevatum diutinum--evidence for disease-dependent leucocyte alterations and response to dapsone. Br J Dermatol 2000; 143:415.
  7. Ayoub N, Charuel JL, Diemert MC, et al. Antineutrophil cytoplasmic antibodies of IgA class in neutrophilic dermatoses with emphasis on erythema elevatum diutinum. Arch Dermatol 2004; 140:931.
  8. Di Giacomo TB, Marinho RT, Nico MM. Erythema elevatum diutinum presenting with a giant annular pattern. Int J Dermatol 2009; 48:290.
  9. da Cunha Bang F, Weismann K, Ralfkiaer E, et al. Erythema elevatum diutinum and pre-AIDS. Acta Derm Venereol 1986; 66:272.
  10. Dronda F, González-López A, Lecona M, Barros C. Erythema elevatum diutinum in human immunodeficiency virus-infected patients--report of a case and review of the literature. Clin Exp Dermatol 1996; 21:222.
  11. Muratori S, Carrera C, Gorani A, Alessi E. Erythema elevatum diutinum and HIV infection: a report of five cases. Br J Dermatol 1999; 141:335.
  12. Momen SE, Jorizzo J, Al-Niaimi F. Erythema elevatum diutinum: a review of presentation and treatment. J Eur Acad Dermatol Venereol 2014; 28:1594.
  13. Barzegar M, Davatchi CC, Akhyani M, et al. An atypical presentation of erythema elevatum diutinum involving palms and soles. Int J Dermatol 2009; 48:73.
  14. Tomasini C, Seia Z, Dapavo P, et al. Infantile erythema elevatum diutinum: report of a vesiculo-bullous case. Eur J Dermatol 2006; 16:683.
  15. Gibson LE, el-Azhary RA. Erythema elevatum diutinum. Clin Dermatol 2000; 18:295.
  16. Aldave AJ, Shih JL, Jovkar S, McLeod SD. Peripheral keratitis associated with erythema elevatum diutinum. Am J Ophthalmol 2003; 135:389.
  17. Mitamura Y, Fujiwara O, Miyanishi K, et al. Nodular scleritis and panuveitis with erythema elevatum diutinum. Am J Ophthalmol 2004; 137:368.
  18. Lekhanont K, Patarakittam T, Mantachote K, et al. Progressive keratolysis with pseudopterygium associated with erythema elevatum diutinum. Ophthalmology 2011; 118:927.
  19. Smitha P, Sathish P, Mohan K, et al. A case of extensive erosive and bullous erythema elevatum diutinum in a patient diagnosed with human immunodeficiency virus (HIV). Int J Dermatol 2011; 50:989.
  20. Prabhu S, Shenoi SD, Kishanpuria PS, Pai SB. Erythema elevatum diutinum associated with scleritis. Indian Dermatol Online J 2011; 2:28.
  21. Rover PA, Bittencourt C, Discacciati MP, et al. Erythema elevatum diutinum as a first clinical manifestation for diagnosing HIV infection: case history. Sao Paulo Med J 2005; 123:201.
  22. Martín JI, Dronda F, Chaves F. Erythema elevatum diutinum, a clinical entity to be considered in patients infected with HIV-1. Clin Exp Dermatol 2001; 26:725.
  23. Fakheri A, Gupta SM, White SM, et al. Erythema elevatum diutinum in a patient with human immunodeficiency virus. Cutis 2001; 68:41.
  24. Sanz-Trelles A, Ayala-Carbonero A, Ojeda-Martos A. Erythema elevatum diutinum in an HIV+ hemophilic patient. Am J Dermatopathol 1999; 21:587.
  25. Suárez J, Miguélez M, Villalba R. Nodular erythema elevatum diutinum in an HIV-1 infected woman: response to dapsone and antiretroviral therapy. Br J Dermatol 1998; 138:717.
  26. Soni BP, Williford PM, White WL. Erythematous nodules in a patient infected with the human immunodeficiency virus. Erythema elevatum diutinum (EED). Arch Dermatol 1998; 134:232.
  27. LeBoit PE, Cockerell CJ. Nodular lesions of erythema elevatum diutinum in patients infected with the human immunodeficiency virus. J Am Acad Dermatol 1993; 28:919.
  28. Cream JJ, Levene GM, Calnan CD. Erythema elevatum diutinum: an unusual reaction to streptococcal antigen and response to dapsone. Br J Dermatol 1971; 84:393.
  29. Kim H. Erythema elevatum diutinum in an HIV-positive patient. J Drugs Dermatol 2003; 2:411.
  30. Requena L, Sánchez Yus E, Martín L, et al. Erythema elevatum diutinum in a patient with acquired immunodeficiency syndrome. Another clinical simulator of Kaposi's sarcoma. Arch Dermatol 1991; 127:1819.
  31. Chow RK, Benny WB, Coupe RL, et al. Erythema elevatum diutinum associated with IgA paraproteinemia successfully controlled with intermittent plasma exchange. Arch Dermatol 1996; 132:1360.
  32. Wayte JA, Rogers S, Powell FC. Pyoderma gangrenosum, erythema elevatum diutinum and IgA monoclonal gammopathy. Australas J Dermatol 1995; 36:21.
  33. Katz SI, Gallin JI, Hertz KC, et al. Erythema elevatum diutinum: skin and systemic manifestations, immunologic studies, and successful treatment with dapsone. Medicine (Baltimore) 1977; 56:443.
  34. Delaporte E, Alfandari S, Fenaux P, et al. Erythema elevatum diutinum and chronic lymphocytic leukemia. Clin Exp Dermatol 1994; 19:188.
  35. Futei Y, Konohana I. A case of erythema elevatum diutinum associated with B-cell lymphoma: a rare distribution involving palms, soles and nails. Br J Dermatol 2000; 142:116.
  36. Walker KD, Badame AJ. Erythema elevatum diutinum in a patient with Crohn's disease. J Am Acad Dermatol 1990; 22:948.
  37. Buahene K, Hudson M, Mowat A, et al. Erythema elevatum diutinum--an unusual association with ulcerative colitis. Clin Exp Dermatol 1991; 16:204.
  38. Nakajima H, Ikeda M, Yamamoto Y, Kodama H. Erythema elevatum diutinum complicated by rheumatoid arthritis. J Dermatol 1999; 26:452.
  39. Collier PM, Neill SM, Branfoot AC, Staughton RC. Erythema elevatum diutinum--a solitary lesion in a patient with rheumatoid arthritis. Clin Exp Dermatol 1990; 15:394.
  40. Grupper C, Edelson Y. [Erythema elevatum diutinum associated with rheumatoid polyarthritis]. Bull Soc Fr Dermatol Syphiligr 1969; 76:759.
  41. Rodriguez-Serna M, Fortea JM, Perez A, et al. Erythema elevatum diutinum associated with celiac disease: response to a gluten-free diet. Pediatr Dermatol 1993; 10:125.
  42. Tasanen K, Raudasoja R, Kallioinen M, Ranki A. Erythema elevatum diutinum in association with coeliac disease. Br J Dermatol 1997; 136:624.
  43. Kwon JL, Sigal AC, Bossenbroek NM. Erythema elevatum diutinum in association with celiac disease. Int J Dermatol 2009; 48:787.
  44. Delgado J, Gómez-Cerezo J, Sigüenza M, et al. Relapsing polychondritis and erythema elevatum diutinum: an unusual association refractory to dapsone. J Rheumatol 2001; 28:634.
  45. Bernard P, Bedane C, Delrous JL, et al. Erythema elevatum diutinum in a patient with relapsing polychondritis. J Am Acad Dermatol 1992; 26:312.
  46. Hancox JG, Wallace CA, Sangueza OP, Graham GF. Erythema elevatum diutinum associated with lupus panniculitis in a patient with discoid lesions of chronic cutaneous lupus erythematosus. J Am Acad Dermatol 2004; 50:652.
  47. Woody CM, Lane JE, Davis LS. Erythema elevatum diutinum in the setting of connective tissue disease and chronic bacterial infection. J Clin Rheumatol 2005; 11:98.
  48. Chan Y, Mok CC, Tang WY. Erythema elevatum diutinum in systemic lupus erythematosus. Rheumatol Int 2011; 31:259.
  49. Kavanagh GM, Colaco CB, Bradfield JW, Archer CB. Erythema elevatum diutinum associated with Wegener's granulomatosis and IgA paraproteinemia. J Am Acad Dermatol 1993; 28:846.
  50. Marie I, Courville P, Levesque H. Erythema elevatum diutinum associated with dermatomyositis. J Am Acad Dermatol 2011; 64:1000.
  51. Yilmaz F, Artaç M, Ciftçioglu MA, Yilmaz E. A case of erythema elevatum diutinum associated with breast carcinoma. Int J Dermatol 2005; 44:948.
  52. Aftab MN, Dee A, Helm TN. Erythema elevatum diutinum arising in the setting of dermatitis herpetiformis. Cutis 2006; 78:129.
  53. Kanitakis J, Cozzani E, Lyonnet S, Thivolet J. Ultrastructural study of chronic lesions of erythema elevatum diutinum: "extracellular cholesterosis" is a misnomer. J Am Acad Dermatol 1993; 29:363.
  54. Ben-Zvi GT, Bardsley V, Burrows NP. An atypical distribution of erythema elevatum diutinum. Clin Exp Dermatol 2014; 39:269.
  55. Lisi S, Mussi A, Muscardin L, Carducci M. A case of erythema elevatum diutinum associated with antiphospholipid antibodies. J Am Acad Dermatol 2003; 49:963.
  56. Ziemer M, Koehler MJ, Weyers W. Erythema elevatum diutinum - a chronic leukocytoclastic vasculitis microscopically indistinguishable from granuloma faciale? J Cutan Pathol 2011; 38:876.
  57. Manni E, Cervadoro E, Papineschi F. Case of erythema elevatum diutinum associated with IgA paraproteinemia successfully controlled with thalidomide and plasma exchange. Ther Apher Dial 2015; 19:195.
  58. Liu TC, Chen IS, Lin TK, et al. Erythema elevatum diutinum as a paraneoplastic syndrome in a patient with pulmonary lymphoepithelioma-like carcinoma. Lung Cancer 2009; 63:151.
  59. Caputo R, Alessi E. Unique aspects of a lesion of erythema elevatum diutinum. Am J Dermatopathol 1984; 6:465.
  60. Fort SL, Rodman OG. Erythema elevatum diutinum. Response to dapsone. Arch Dermatol 1977; 113:819.
  61. Elsner J, Kiehl P, Kapp A, Weiss J. [Erythema elevatum and diutinum in Crohn disease]. Hautarzt 1996; 47:701.
  62. Planagumà M, Puig L, Alomar A, et al. Pyoderma gangrenosum in association with erythema elevatum diutinum: report of two cases. Cutis 1992; 49:201.
  63. Vaiyavatjamai P, Wattanakrai P. Erythema elevatum diutinum associated with peripheral ulcerative keratitis. J Eur Acad Dermatol Venereol 2011; 25:741.
  64. Wilkinson SM, English JS, Smith NP, et al. Erythema elevatum diutinum: a clinicopathological study. Clin Exp Dermatol 1992; 17:87.
  65. Galeone M, Arunachalam M, Bassi A, et al. Erythema elevatum diutinum. QJM 2014; 107:227.
  66. Frieling GW, Williams NL, Lim SJ, Rosenthal SI. Novel use of topical dapsone 5% gel for erythema elevatum diutinum: safer and effective. J Drugs Dermatol 2013; 12:481.
  67. Kohler IK, Lorincz AL. Erythema elevatum diutinum treated with niacinamide and tetracycline. Arch Dermatol 1980; 116:693.
  68. Henriksson R, Hofer PA, Hörnqvist R. Erythema elevatum diutinum--a case successfully treated with colchicine. Clin Exp Dermatol 1989; 14:451.
  69. Chowdhury MM, Inaloz HS, Motley RJ, Knight AG. Erythema elevatum diutinum and IgA paraproteinaemia: 'a preclinical iceberg'. Int J Dermatol 2002; 41:368.
  70. Schumacher HR, Carroll E, Taylor F, et al. Erythema elevatum diutinum: cutaneous vasculitis, impaired clot lysis, and response to phenformin. J Rheumatol 1977; 4:103.
  71. Takahashi H, Fukami Y, Honma M, et al. Successful combination therapy with dapsone and cyclosporine for erythema elevatum diutinum with unusual appearance. J Dermatol 2012; 39:486.
  72. Zacaron LH, Gonçalves JC, Curty VM, et al. Clinical and surgical therapeutic approach in erithema elevatum diutinum--case report. An Bras Dermatol 2013; 88:15.
  73. Rinard JR, Mahabir RC, Greene JF, Grothaus P. Successful surgical treatment of advanced erythema elevatum diutinum. Can J Plast Surg 2010; 18:28.