Erythema Elevatum Diutinum



Erythema elevatum diutinum (EED) is a rare type of leukocytoclastic vasculitis characterized by red, purple, brown, or yellow papules, plaques, or nodules. These lesions are usually distributed on the extensor surfaces of the body.[1] Erythema elevatum diutinum was first described in 1888 by Hutchinson[2] and in 1889 by Bury.[3] However, the name erythema elevatum diutinum was first used by Radcliff-Crocker and Williams[4] who found similarities between the cases of Hutchinson and Bury and their own. No clinical examination difference is apparent between the Hutchinson type and the Bury type of erythema elevatum diutinum. The difference lies in the patient population and possibly the cause of onset.


The pathophysiology of erythema elevatum diutinum is not well understood. According to Gibson and Su,[5] the lesions are thought to be caused by the deposition of immune complexes in small blood vessels. This induces an inflammatory cascade, which damages the vessels. This repetitive damage causes fibrosis and the appearance of cholesterol crystals and myelin figures in the vessels. Direct immunofluorescence shows deposits of complement as well as immunoglobulin G (IgG), immunoglobulin (IgM), immunoglobulin A (IgA),[6] and fibrin around the damaged vessels. The findings from Grabbe et al[7] support the idea that the initiation of erythema elevatum diutinum may occur via activation of cytokines such as interleukin 8, which causes selective recruitment of leukocytes to tissue sites.[8]


The cause of erythema elevatum diutinum (EED) has not yet been definitively established.

Disorders that have been associated with erythema elevatum diutinum include recurrent bacterial infections (especially streptococcal), viral infections (including hepatitis B or HIV),[9] rheumatologic disease (in the Bury type), lupus erythematosus, and B-cell lymphoma.[10, 11, 12, 13]

In recent years, several reports, including the 2 largest clinical studies completed on erythema elevatum diutinum, have suggested hematologic disease as the most common factor associated with erythema elevatum diutinum.

Monoclonal gammopathies, especially IgA monoclonal gammopathy, have been found in a significant number of patients in several studies.

Erythema elevatum diutinum has also been reported after the administration of erythropoietin.[14]



Erythema elevatum diutinum is a rare disease. Although first described in 1888, the largest study of erythema elevatum diutinum was published in 1992 and included 13 patients.[15]


No racial predilection is reported for erythema elevatum diutinum.


Erythema elevatum diutinum is found in both males and females. The Hutchinson type of erythema elevatum diutinum is predominant in men. The Bury type of erythema elevatum diutinum is found in women with a history of rheumatologic disease.


Erythema elevatum diutinum can occur at any age. However, erythema elevatum diutinum is mostly an adult disease that occurs from the third to sixth decade of life. Men with erythema elevatum diutinum are usually older (Hutchinson type), and women are usually younger (Bury type).


Erythema elevatum diutinum is a chronic disease that usually evolves over a 5- to 10-year period, at which point it may resolve. Erythema elevatum diutinum lesions tend to not leave scars, but areas of hyperpigmentation or hypopigmentation can be visible.

No mortality due to erythema elevatum diutinum has been reported. Erythema elevatum diutinum lesions can be completely asymptomatic, but they may be cosmetically disturbing. In other cases, the lesions can be associated with pain, itching, and/or a burning sensation. The most common systemic symptom is joint pain.

Dapsone and other therapies can be successful in limiting the progression of the disease.


Patients with erythema elevatum diutinum (EED) usually present with persistent, firm lesions on the extensor surfaces of their skin, especially over the joints. These lesions are most often nodules and round or oval plaques (see image below). However, on rare occasions, blisters and ulcers may also appear.

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Nodular lesions on the knees of a patient with erythema elevatum diutinum.

The color of the lesions progresses over time from yellow or pinkish to red, purple, or brown. In addition to the color changes, patients may describe the lesions as increasing in number and size over time. They may also note that the lesions enlarge during the day and return to their previous size overnight.[16]

The lesions can be completely asymptomatic, painful, or cause a sensation of burning or itching. These symptoms can be exacerbated by cold.

The general health of the patient may be otherwise excellent, although a history of arthralgia is found relatively often with erythema elevatum diutinum.

Physical Examination

Upon physical examination, erythema elevatum diutinum lesions are generally found symmetrically on the extensor surfaces of the skin, especially over the joints.[17]

Clinical studies show a preference for the extensor surfaces of the hands, the wrists, the elbows, the ankles, the Achilles tendons, the fingers, and the toes (see image below).

View Image

Plaques and papular lesions on the wrists and the dorsum of the hands and the digits of a patient with erythema elevatum diutinum.

The buttocks, the face, and the ears as well as the palms, the soles, the legs, the forearms, and the genitals may be involved[18] ; however, the trunk is usually spared.

The lesions usually feel firm and are freely movable over the underlying tissue, except when on the palms and the soles.[18]

Their surface is generally smooth and sometimes slightly scaly.

Crusting and/or bleeding, although uncommon, have been noted.

Several studies have shown an association of erythema elevatum diutinum with ocular abnormalities, including nodular scleritis, panuveitis, autoimmune keratolysis, and peripheral keratitis.[19, 20] Therefore, attention should be given to ocular symptoms and eye examination findings.

Laboratory Studies

Electron microscopy is not routinely necessary for erythema elevatum diutinum (EED) but should show changes consistent with leukocytoclastic vasculitis.

Direct immunofluorescence study results show changes consistent with vasculitis, including deposits of complement, immunoglobulins (IgG, IgA, IgM), and fibrin intravascularly and perivascularly.

Immunoelectrophoresis (IEP) can be used to identify possible gammopathies. Yiannias et al advocate routine IEP testing for patients with erythema elevatum diutinum. The use of this technique is supported by the growing number of studies showing that monoclonal gammopathies might play a causal role in erythema elevatum diutinum.

A positive reaction to skin testing with streptokinase and streptodornase at 4 and 24 hours has been reported to help determine a causative association with bacterial infection.

The erythrocyte sedimentation rate in patients with erythema elevatum diutinum is often elevated.

Antineutrophil cytoplasmic antibodies of IgA class may become a helpful paraclinical marker of disease.[21]


A skin biopsy is the most useful study for the diagnosis of erythema elevatum diutinum. The histologic findings are discussed below.

Histologic Findings

Erythema elevatum diutinum (EED) is a type of necrotizing vasculitis. No specific histologic finding can be used to differentiate erythema elevatum diutinum from other leukocytoclastic diseases. However, the simultaneous presence of several histologic findings can help distinguish erythema elevatum diutinum from other diseases.

Early lesions show vasculitis in the small vessels of the upper and mid dermis. Furthermore, a perivascular infiltrate consisting of mainly polymorphonuclear neutrophils; nuclear dust; and, to a lesser extent, macrophages, lymphocytes, and eosinophils is present throughout the dermis. The infiltrate may accumulate between collagen bundles. In addition, fibrinoid degeneration, first described as toxic hyaline deposits by Weidman and Besancon,[22] can be detected perivascularly. The epidermis can be affected by the changes in the dermis; edema, acanthosis, and even necrosis can be observed. See image below.

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Fibrinoid changes in dermal blood vessels with polymorphonuclear neutrophil infiltration.

Granulation tissue and fibrosis in the dermis characterize older lesions. Toxic hyaline is less apparent, but extracellular cholesterol deposits may be observed in the fibrotic tissue.[23] This was termed extracellular cholesterosis (EC) and was thought at first to have a different etiology than erythema elevatum diutinum. Today, EC is known to be a manifestation of erythema elevatum diutinum. Furthermore, the use of the term extracellular cholesterosis tends to be limited since it is now believed that the main lipid deposits are intracellular and that they are formed of cholesterol esters produced by damaged tissue.

Medical Care

Dapsone (diaminodiphenylsulfone) revolutionized the treatment of patients with erythema elevatum diutinum (EED). Several studies and clinical experience have shown a good response to dapsone, therefore making it the treatment of choice.[24] The dosage depends on each patient. Sulfones have a suppressive effect on erythema elevatum diutinum, as shown by the recurrence of erythema elevatum diutinum after drug withdrawal. Systemic steroids generally have not been found to be effective.

Sulfapyridine has had similar effects as dapsone.

In one study, niacinamide was found to be helpful in suppressing erythema elevatum diutinum.[25]

Intermittent plasma exchange (PLEX) was shown to control IgA paraproteinemia associated with erythema elevatum diutinum.[26] The IgA levels responded to PLEX treatment, followed by consolidative doses of cyclophosphamide. This treatment might be promising for the control of severe erythema elevatum diutinum that is not controlled by dapsone.

Surgical Care

Surgical excision of the lesions is sometimes performed to provide symptomatic relief if medical therapy is not effective.[27]


A strict gluten-free diet was shown to help achieve full healing of a patient with celiac disease for whom dapsone therapy was not completely effective.[28]

Medication Summary

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Dapsone (Avlosulfon)

Clinical Context:  Dapsone is the drug of choice. It is bactericidal and bacteriostatic against mycobacteria; its mechanism of action is similar to that of sulfonamides, where competitive antagonists of PABA prevent the formation of folic acid, inhibiting bacterial growth.

The dose depends on the patient. The optimal dose should be determined by the physician. Dapsone is available for oral intake in 25- and 100-mg scored tablets. It is not considered to have an effect on the growth and development of the child.

Class Summary

These agents have been demonstrated to effectively suppress the manifestations of erythema elevatum diutinum.

Niacin (Vitamin B-3)

Clinical Context:  A 1980 study showed niacinamide to be helpful in suppressing clinical manifestations of erythema elevatum diutinum. It has also been used for the management of many disorders, including livedoid vasculitis and leprosy. The presumed mechanism of action is as an anti-inflammatory agent and as a vasodilator. It is mainly used for the treatment and prevention of pellagra and niacin or tryptophan deficiency. It is available for oral intake in 50-, 100-, and 500-mg tablets.

Class Summary

These agents may suppress erythema elevatum diutinum. They are essential for normal DNA synthesis and are used in tissue respiration, lipid metabolism, and glycogenolysis.


Firas G Hougeir, MD, Staff Dermatologist, Private Practice, Georgia

Disclosure: Nothing to disclose.


James A Yiannias, MD, Associate Professor of Dermatology, Associate Dean, Mayo School of Graduate Medical Education, Mayo Foundation for Medical Education and Research; Vice Chair, Medical Division, Department of Dermatology, Mayo Clinic Scottsdale

Disclosure: Nothing to disclose.

Specialty Editors

Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Disclosure: Nothing to disclose.

Christen M Mowad, MD, Professor, Department of Dermatology, Geisinger Medical Center

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD, Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

Disclosure: Received income in an amount equal to or greater than $250 from: Elsevier; WebMD.

Additional Contributors

Carrie L Kovarik, MD, Assistant Professor of Dermatology, Dermatopathology, and Infectious Diseases, University of Pennsylvania School of Medicine

Disclosure: Nothing to disclose.


  1. Sardiña LA, Jour G, Piliang MP, Bergfeld WF. Erythema elevatum diutinum a rare and poorly understood cutaneous vasculitis: A single institution experience. J Cutan Pathol. 2019 Feb. 46 (2):97-101. [View Abstract]
  2. Hutchinson J. On two remarkable cases of symmetrical purple congestion of the skin in patches, with induration. Br J Dermatol. 1880. 1:10.
  3. Bury JS. A case of erythema with remarkable nodular thickening and induration of the skin associated with intermittent albuminuria. Illus Med News. 1889. 3:145.
  4. Radcliffe-Crocker H, Williams C. Erythema elevatum diutinum. Br J Dermatol. 1894. 6:1-9.
  5. Gibson LE, Su WP. Cutaneous vasculitis. Rheum Dis Clin North Am. 1990 May. 16(2):309-24. [View Abstract]
  6. Shimizu S, Nakamura Y, Togawa Y, Kamada N, Kambe N, Matsue H. Erythema elevatum diutinum with primary Sjögren syndrome associated with IgA antineutrophil cytoplasmic antibody. Br J Dermatol. 2008 Sep. 159(3):733-5. [View Abstract]
  7. Grabbe J, Haas N, Moller A, Henz BM. Erythema elevatum diutinum--evidence for disease-dependent leucocyte alterations and response to dapsone. Br J Dermatol. 2000 Aug. 143(2):415-20. [View Abstract]
  8. Farley-Loftus R, Dadlani C, Wang N, et al. Erythema elevatum diutinum. Dermatol Online J. 2008 Oct 15. 14(10):13. [View Abstract]
  9. Rover PA, Bittencourt C, Discacciati MP, Zaniboni MC, Arruda LH, Cintra ML. Erythema elevatum diutinum as a first clinical manifestation for diagnosing HIV infection: case history. Sao Paulo Med J. 2005 Jul 7. 123(4):201-3. [View Abstract]
  10. 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 Jan. 142(1):116-9. [View Abstract]
  11. 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 Apr. 50(4):652-3. [View Abstract]
  12. Mitamura Y, Fujiwara O, Miyanishi K, Sato H, Saga K, Ohtsuka K. Nodular scleritis and panuveitis with erythema elevatum diutinum. Am J Ophthalmol. 2004 Feb. 137(2):368-70. [View Abstract]
  13. Liu TC, Chen IS, Lin TK, Lee JY, Kirn D, Tsao CJ. Erythema elevatum diutinum as a paraneoplastic syndrome in a patient with pulmonary lymphoepithelioma-like carcinoma. Lung Cancer. 2009 Jan. 63(1):151-3. [View Abstract]
  14. Gubinelli E, Cocuroccia B, Fazio M, Annessi G, Girolomoni G. Papular neutrophilic dermatosis and erythema elevatum diutinum following erythropoietin therapy in a patient with myelodysplastic syndrome. Acta Derm Venereol. 2003. 83(5):358-61. [View Abstract]
  15. 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. [View Abstract]
  16. Golmia A, Grinblat B, Finger E, Klieman C, Assir F, Scheinberg M. The development of erythema elevatum diutinum in a patient with juvenile idiopathic arthritis under treatment with abatacept. Clin Rheumatol. 2008 Jan. 27(1):105-6. [View Abstract]
  17. Di Giacomo TB, Marinho RT, Nico MM. Erythema elevatum diutinum presenting with a giant annular pattern. Int J Dermatol. 2009 Mar. 48(3):290-2. [View Abstract]
  18. Barzegar M, Davatchi CC, Akhyani M, Nikoo A, Daneshpazhooh M, Farsinejad K. An atypical presentation of erythema elevatum diutinum involving palms and soles. Int J Dermatol. 2009 Jan. 48(1):73-5. [View Abstract]
  19. Aldave AJ, Shih JL, Jovkar S, McLeod SD. Peripheral keratitis associated with erythema elevatum diutinum. Am J Ophthalmol. 2003 Mar. 135(3):389-90. [View Abstract]
  20. Casanova FH, Meirelles RL, Tojar M, Martins MC, Rigueiro MP, de Freitas D. Autoimmune keratolysis in a patient with leukocytoclastic vasculitis: unusual erythema elevatum diutinum with granulomatous pattern. Cornea. 2001 Apr. 20(3):329-32. [View Abstract]
  21. 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 Aug. 140(8):931-6. [View Abstract]
  22. Weidman FD, Besancon JH. Erythema elevatum diutinum: role of streptococci, and relationship to other rheumatic dermatoses. Arch Dermatol Syphilol. 1929. 20:593.
  23. Wolff HH, Maciejewski W, Scherer R. [Erythema elevatum diutinum. I. Electron microscopy of a case with extracellular cholesterosis (author's transl)]. Arch Dermatol Res. 1978 Feb 15. 261(1):7-16. [View Abstract]
  24. 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. [View Abstract]
  25. Kohler IK, Lorincz AL. Erythema elevatum diutinum treated with niacinamide and tetracycline. Arch Dermatol. 1980 Jun. 116(6):693-5. [View Abstract]
  26. 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. [View Abstract]
  27. Ahmad S, Delarosa M, Kleinman W, Ahmad R. Primary Surgical Treatment of Erythema Elevatum Diutinum. J Hand Surg Am. 2018 Sep 18. [View Abstract]
  28. Tasanen K, Raudasoja R, Kallioinen M, Ranki A. Erythema elevatum diutinum in association with coeliac disease. Br J Dermatol. 1997 Apr. 136(4):624-7. [View Abstract]

Nodular lesions on the knees of a patient with erythema elevatum diutinum.

Plaques and papular lesions on the wrists and the dorsum of the hands and the digits of a patient with erythema elevatum diutinum.

Fibrinoid changes in dermal blood vessels with polymorphonuclear neutrophil infiltration.

Plaques and papular lesions on the wrists and the dorsum of the hands and the digits of a patient with erythema elevatum diutinum.

Nodular lesions on the knees of a patient with erythema elevatum diutinum.

Fibrinoid changes in dermal blood vessels with polymorphonuclear neutrophil infiltration.