U.S. flag

An official website of the United States government

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-.

Cover of StatPearls

StatPearls [Internet].

Show details

Erythema Elevatum Diutinum

; .

Author Information and Affiliations

Last Update: September 5, 2022.

Continuing Education Activity

Erythema elevatum diutinum is a rare, chronic dermatosis characterized by red–violet to red–brown papules, plaques, and nodules that favor extensor surfaces. Lesions often are asymptomatic, though some patients may experience pain or a burning sensation. Non-cutaneous symptoms include constitutional symptoms such as arthralgia and fever. Although erythema elevatum diutinum is benign, it can occur in association with infections, hematologic abnormalities, autoimmune diseases, or other conditions. Spontaneous resolution commonly occurs after 5 to 10 years. This activity describes the pathophysiology, evaluation, and management of erythema elevatum diutinum and stresses the role of the interprofessional team in the care of affected patients.


  • Identify the etiology of erythema elevatum diutinum.
  • Describe the presentation of a patient with erythema elevatum diutinum.
  • Outline the management options available for erythema elevatum diutinum.
  • Explain interprofessional team strategies for improving care coordination and communication to advance the evaluation and management of erythema elevatum diutinum and improve outcomes.
Access free multiple choice questions on this topic.


Erythema elevatum diutinum (EED) is a rare, chronic dermatosis that is characterized by red–violet to red–brown papules, plaques, and nodules that favor the extensor surfaces. Lesions often are asymptomatic, though patients may experience pain or a burning sensation. Extracutaneous symptoms include arthralgia, fever, or other constitutional symptoms. The condition is benign in nature but may be associated with infections, hematologic abnormalities, autoimmune diseases, or other conditions. Spontaneous resolution often occurs after 5 to 10 years.[1][2]


The cause of EED is not well understood, but it is thought to be secondary to immune complex deposition in dermal blood vessels, which results in complement fixation and subsequent inflammation. The findings appreciated on examination of the skin may be seen due to deposition of immune complexes in small vessels, which leads to activation of complement, the influx of neutrophils, and the emission of destructive enzymes. Antineutrophil cytoplasmic antibodies may be pathogenic in EED. Furthermore, the initiation of EED may occur via activation of cytokines (interleukin-8), which causes selective recruitment of leukocytes to blood vessels. This leads to repetitive damage to the vessels and ultimately develops into fibrosis. [3][2][1]


EED is rare, with descriptions of only several hundred cases in the literature. The disease can develop at any age but is more common in the fourth and sixth decades. An earlier onset occurs more often in the setting of HIV infection. The male-to-female ratio is approximately equal, and no racial predilection has been observed. [1]


Although the etiology of EED is unknown, circulating immune complexes, with repeated deposition, associated inflammation, and partial healing are thought to represent the underlying pathogenesis. Immune complex deposition results in complement activation, neutrophilic infiltration, and the release of destructive enzymes. This results in fibrin deposition in and around small dermal vessels during the later stages of the disease.[3]

EED has been described in association with a number of systemic diseases. It is frequently found with hematologic disorders, such as IgA monoclonal gammopathy, myelodysplasia, myeloproliferative disorders, paraproteinemia, and hairy cell leukemia. Infections from group B streptococci, HIV, syphilis, and viral hepatitis are commonly associated with EED as well as autoimmune conditions, such as celiac disease, Crohn disease, systemic lupus erythematosus and rheumatoid arthritis. In the study performed by Katz et al., two of five patients with EED demonstrated a prevalence of recurrent bacterial infections that were usually Streptococcal in nature. They also demonstrated increased C1q binding in three of five patients, a finding suggestive of the presence of circulating immune complexes. [4][1][5]


Histologically, EED is characterized by early changes of a leukocytoclastic vasculitis with a polymorphonuclear cell infiltrate and deposition of fibrin in the superficial and mid dermis. Polymorphonuclear cells, macrophages, histiocytes, and eosinophils may surround the blood vessels. These infiltrates may accumulate between collagen bundles. A papillary edema also may be seen in early lesions as a reflection of clinical pseudo vesiculation.[4][6]

Over time, the infiltrate contains more histiocytes and granulation tissue, and spindle cell proliferation may be seen. Extracellular cholesterol deposits may be observed in the fibrotic tissue. The fibrosis of late lesions is most likely a result of chronic dermal injury of leukocytoclastic vasculitis. Direct immunofluorescence may reveal changes consistent with vasculitis, such as fibrin deposits, intravascularly and perivascularly, complement, and immunoglobulins (IgG, IgA, IgM). [7][5][8]

History and Physical

On exam, lesions of EED present as red–brown, yellowish, or violaceous papules, plaques, or nodules. They typically are symmetrically distributed and favor acral and periarticular sites, specifically the extensor surfaces of the elbows, knees, ankles, hands, and fingers. Additional sites of involvement include the face, retro-auricular area, axillae, buttocks, and genitalia. The trunk is usually spared. The lesions usually feel firm and are mobile over the underlying tissue, except typically on the palms and the soles. [9][10]

Initially, the lesions are erythematous and soft but with time become red–brown or violaceous in color and firm to palpation secondary to fibrosis. Over the course of the disease process, the lesions can change in color as well as an increase in size and quantity. [2][11]

Typically, the lesions are asymptomatic, but there have been reports of patients who experienced pruritus and burning or tingling sensations, especially early in the disease course. EED in the setting of HIV infection is characterized by nodular lesions, used palmoplantar, that progress to form bulky masses. Arthralgias may develop in underlying joints, but extracutaneous involvement is extremely rare. The exception includes ocular abnormalities such as scleritis, uveitis, autoimmune keratolysis, and peripheral keratitis. [2][12]

The disease is chronic and has a relapsing and remitting course. The majority of cases resolve spontaneously over a period of 5 to 10 years, but the disease can last up to 40 years. EED lesions do not typically leave scars but can resolve with areas of hyperpigmentation or hypopigmentation. No mortality due to EED has been reported. [3][13]


A skin biopsy is the most useful study for the diagnosis of EED. Electron microscopy is not a necessary diagnostic tool but would show changes and features of leukocytoclastic vasculitis. The erythrocyte sedimentation rate in patients with EED is often elevated. Antineutrophil cytoplasmic antibodies of IgA class may be helpful as a marker of disease, and Immunoelectrophoresis can also be used to identify possible gammopathies.[14][5]

Treatment / Management

Treatment of EED is difficult because the disorder follows a chronic and recurrent course.

Dapsone, a sulfonamide antibiotic that impairs neutrophil chemotaxis and function, is the most effective treatment agent, but relapse is common upon discontinuation. It is also ineffective in nodular lesions, due to the fibrosis of the lesions. Other therapies include NSAIDs, niacinamide, tetracyclines, chloroquine, colchicine, and plasmapheresis. Topical and intralesional corticosteroids may be helpful for mild cases, but systemic corticosteroids are rarely indicated.[14]

Antimicrobials, such as tetracyclines, are thought to alter neutrophil chemotaxis and phagocytosis, suppressing neutrophil chemotaxis and random migration in vivo. Niacinamide, an in vitro specific inhibitor of cyclic AMP, acts as a transfer factor needed for the suppression of antigen-induced lymphocyte transformation. It is relatively non-toxic and can be used in the treatment of neutrophil-driven disorders, with fewer side effects than dapsone. Local surgical excision can be beneficial for localized fibrotic nodules of EED. Regardless of treatment, the recurrence rate of EED is high if the underlying triggering factors are not controlled.[3][2][1]

Differential Diagnosis

  • Acute febrile neutrophilic dermatosis
  • Dermatofibroma
  • Erythema multiforme
  • Granuloma annulare
  • Granuloma faciale
  • Multicentric reticulohistiocytosis
  • Pyoderma gangrenosum
  • Xanthomas

Enhancing Healthcare Team Outcomes

 EED is a skin disorder that is best managed by an interprofessional team that includes nurses and pharmacists. The diagnosis usually required a biopsy. However, treatment of EED is not adequate once it is established. The triggers or the primary cause must be treated; with all treatment recurrences are common. It often takes years for the skin disorder to resolve.

Review Questions


Gibson LE, el-Azhary RA. Erythema elevatum diutinum. Clin Dermatol. 2000 May-Jun;18(3):295-9. [PubMed: 10856661]
Dowd PM, Munro DD. Erythema elevatum diutinum. J R Soc Med. 1983 Apr;76(4):310-3. [PMC free article: PMC1438960] [PubMed: 6601714]
Bansal R, Aron J, Rajnish I. Erythema Elevatum Diutinum. Am J Med Sci. 2017 Feb;353(2):189. [PubMed: 28183422]
Wahl CE, Bouldin MB, Gibson LE. Erythema elevatum diutinum: clinical, histopathologic, and immunohistochemical characteristics of six patients. Am J Dermatopathol. 2005 Oct;27(5):397-400. [PubMed: 16148408]
Chow RK, Benny WB, Coupe RL, Dodd WA, Ongley RC. Erythema elevatum diutinum associated with IgA paraproteinemia successfully controlled with intermittent plasma exchange. Arch Dermatol. 1996 Nov;132(11):1360-4. [PubMed: 8915315]
Wilkinson SM, English JS, Smith NP, Wilson-Jones E, Winkelmann RK. Erythema elevatum diutinum: a clinicopathological study. Clin Exp Dermatol. 1992 Mar;17(2):87-93. [PubMed: 1516248]
Yiannias JA, el-Azhary RA, Gibson LE. Erythema elevatum diutinum: a clinical and histopathologic study of 13 patients. J Am Acad Dermatol. 1992 Jan;26(1):38-44. [PubMed: 1732334]
Archimandritis AJ, Fertakis A, Alegakis G, Bartsokas S, Melissinos K. Erythema elevatum diutinum and IgA myeloma: an interesting association. Br Med J. 1977 Sep 03;2(6087):613-4. [PMC free article: PMC1631545] [PubMed: 902003]
Khan F, Chan CS, LeLeux TM, Diwan AH, Hsu S. JAAD Grand Rounds quiz. Adult with red-brown nodules and plaques. J Am Acad Dermatol. 2011 Aug;65(2):469-471. [PubMed: 21763595]
Mraz JP, Newcomer VD. Erythema elevatum diutinum. Presentation of a case and evaluation of laboratory and immunological status. Arch Dermatol. 1967 Sep;96(3):235-46. [PubMed: 4166920]
High WA, Hoang MP, Stevens K, Cockerell CJ. Late-stage nodular erythema elevatum diutinum. J Am Acad Dermatol. 2003 Oct;49(4):764-7. [PubMed: 14512939]
Jose SK, Marfatia YS. Erythema elevatum diutinum in acquired immune deficiency syndrome: Can it be an immune reconstitution inflammatory syndrome? Indian J Sex Transm Dis AIDS. 2016 Jan-Jun;37(1):81-4. [PMC free article: PMC4857691] [PubMed: 27190420]
Ramsey ML, Gibson B, Tschen JA, Wolf JE. Erythema elevatum diutinum. Cutis. 1984 Jul;34(1):41-3. [PubMed: 6467974]
Katz SI, Gallin JI, Hertz KC, Fauci AS, Lawley TJ. Erythema elevatum diutinum: skin and systemic manifestations, immunologic studies, and successful treatment with dapsone. Medicine (Baltimore). 1977 Sep;56(5):443-55. [PubMed: 142192]

Disclosure: Jessica Newburger declares no relevant financial relationships with ineligible companies.

Disclosure: George Schmieder declares no relevant financial relationships with ineligible companies.

Copyright © 2023, StatPearls Publishing LLC.

This book is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ), which permits others to distribute the work, provided that the article is not altered or used commercially. You are not required to obtain permission to distribute this article, provided that you credit the author and journal.

Bookshelf ID: NBK448069PMID: 28846276


  • PubReader
  • Print View
  • Cite this Page

Related information

  • PMC
    PubMed Central citations
  • PubMed
    Links to PubMed

Similar articles in PubMed

See reviews...See all...

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...