eMedicine Specialties > Dermatology > Diseases of the Vessels

Erythema Elevatum Diutinum: Differential Diagnoses & Workup

Author: Firas G Hougeir, MD, Staff Physician, Department of Dermatology, Mayo Clinic Scottsdale
Coauthor(s): 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
Contributor Information and Disclosures

Updated: Jun 30, 2009

Differential Diagnoses

Acute Febrile Neutrophilic Dermatosis
Pyoderma Gangrenosum
Dermatofibroma
Xanthomas
Erythema Multiforme
Granuloma Annulare
Granuloma Faciale

Other Problems to Be Considered

Multicentric reticulohistiocytosis

Workup

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.19

Procedures

  • 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,20 can be detected perivascularly. The epidermis can be affected by the changes in the dermis; edema, acanthosis, and even necrosis can be observed.


Fibrinoid changes in dermal blood vessels with po...

Fibrinoid changes in dermal blood vessels with polymorphonuclear neutrophil infiltration.

[ CLOSE WINDOW ]
Fibrinoid changes in dermal blood vessels with po...

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.21 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.

More on Erythema Elevatum Diutinum

Overview: Erythema Elevatum Diutinum
Differential Diagnoses & Workup: Erythema Elevatum Diutinum
Treatment & Medication: Erythema Elevatum Diutinum
Follow-up: Erythema Elevatum Diutinum
Multimedia: Erythema Elevatum Diutinum
References
Further Reading
[ CLOSE WINDOW ]

References

  1. Hutchinson J. On two remarkable cases of symmetrical purple congestion of the skin in patches, with induration. Br J Dermatol. 1880;1:10.

  2. 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.

  3. Radcliffe-Crocker H, Williams C. Erythema elevatum diutinum. Br J Dermatol. 1894;6:1-9.

  4. Gibson LE, Su WP. Cutaneous vasculitis. Rheum Dis Clin North Am. May 1990;16(2):309-24. [Medline].

  5. 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. Sep 2008;159(3):733-5. [Medline].

  6. Grabbe J, Haas N, Moller A, Henz BM. Erythema elevatum diutinum--evidence for disease-dependent leucocyte alterations and response to dapsone. Br J Dermatol. Aug 2000;143(2):415-20. [Medline].

  7. Farley-Loftus R, Dadlani C, Wang N, et al. Erythema elevatum diutinum. Dermatol Online J. Oct 15 2008;14(10):13. [Medline].

  8. Yiannias JA, el-Azhary RA, Gibson LE. Erythema elevatum diutinum: a clinical and histopathologic study of 13 patients. J Am Acad Dermatol. Jan 1992;26(1):38-44. [Medline].

  9. 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. Jan 2008;27(1):105-6. [Medline].

  10. Di Giacomo TB, Marinho RT, Nico MM. Erythema elevatum diutinum presenting with a giant annular pattern. Int J Dermatol. Mar 2009;48(3):290-2. [Medline].

  11. 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. Jan 2009;48(1):73-5. [Medline].

  12. Aldave AJ, Shih JL, Jovkar S, McLeod SD. Peripheral keratitis associated with erythema elevatum diutinum. Am J Ophthalmol. Mar 2003;135(3):389-90. [Medline].

  13. 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. Apr 2001;20(3):329-32. [Medline].

  14. 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. Jan 2000;142(1):116-9. [Medline].

  15. 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. Apr 2004;50(4):652-3. [Medline].

  16. Mitamura Y, Fujiwara O, Miyanishi K, Sato H, Saga K, Ohtsuka K. Nodular scleritis and panuveitis with erythema elevatum diutinum. Am J Ophthalmol. Feb 2004;137(2):368-70. [Medline].

  17. 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. Jan 2009;63(1):151-3. [Medline].

  18. 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. [Medline].

  19. 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. Aug 2004;140(8):931-6. [Medline].

  20. Weidman FD, Besancon JH. Erythema elevatum diutinum: role of streptococci, and relationship to other rheumatic dermatoses. Arch Dermatol Syphilol. 1929;20:593.

  21. Wolff HH, Maciejewski W, Scherer R. [Erythema elevatum diutinum. I. Electron microscopy of a case with extracellular cholesterosis (author's transl)]. Arch Dermatol Res. Feb 15 1978;261(1):7-16. [Medline].

  22. 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). Sep 1977;56(5):443-55. [Medline].

  23. Kohler IK, Lorincz AL. Erythema elevatum diutinum treated with niacinamide and tetracycline. Arch Dermatol. Jun 1980;116(6):693-5. [Medline].

  24. 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. Nov 1996;132(11):1360-4. [Medline].

  25. Tasanen K, Raudasoja R, Kallioinen M, Ranki A. Erythema elevatum diutinum in association with coeliac disease. Br J Dermatol. Apr 1997;136(4):624-7. [Medline].

  26. Devillierre M, Verola O, Rybojad M, et al. [Pseudoneoplastic lesion of erythema elevatum diutinum]. Ann Dermatol Venereol. Aug-Sep 2008;135(8-9):575-9. [Medline].

  27. Haber H. Erythema elevatum diutinum. Br J Dermatol. Apr 1955;67(4):121-45. [Medline].

  28. Habif TP. Clinical Dermatology. 3rd ed. St. Louis, Mo: Mosby-Year Book; 1996:589-96.

  29. Hines HL. Erythema elevatum diutinum. Dermatol Int. Apr-Jun 1968;7(2):70-4. [Medline].

  30. Laymon CW. Erythema elevatum diutinum. A type of allergic vasulitis. Arch Dermatol. Jan 1962;85:22-8. [Medline].

  31. McEvoy GK, ed. AHFS Drug Information, 1999. Bethesda, Md: American Society of Health-System Pharmacists; 1999:731-5, 3182-4.

  32. Mraz JP, Newcomer VD. Erythema elevatum diutinum. Presentation of a case and evaluation of laboratory and immunological status. Arch Dermatol. Sep 1967;96(3):235-46. [Medline].

  33. Wilkinson SM, English JS, Smith NP, Wilson-Jones E, Winkelmann RK. Erythema elevatum diutinum: a clinicopathological study. Clin Exp Dermatol. Mar 1992;17(2):87-93. [Medline].

[ CLOSE WINDOW ]

Further Reading

Clinical guideline

Dermatologic manifestations.
New York State Department of Health - State/Local Government Agency [U.S.]. 2004. 15 pages. NGC:003931

Related eMedicine topics

 Leukocytoclastic Vasculitis

Polychondritis

Acute Febrile Neutrophilic Dermatosis

Hypersensitivity Vasculitis

Neutrophilic Eccrine Hidradenitis

[ CLOSE WINDOW ]

Keywords

erythema elevatum diutinum, extracellular cholesterosis, EED, leukocytoclastic vasculitis

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Firas G Hougeir, MD, Staff Physician, Department of Dermatology, Mayo Clinic Scottsdale
Firas G Hougeir, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

Coauthor(s)

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
James A Yiannias, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

Medical Editor

Carrie L Kovarik, MD, Assistant Professor of Dermatology, Dermatopathology, and Infectious Diseases, University of Pennsylvania School of Medicine
Carrie L Kovarik, MD is a member of the following medical societies: Alpha Omega Alpha
Disclosure: Nothing to disclose.

Pharmacy Editor

Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University School of Medicine; Consulting Staff, Mountain View Dermatology, PA
Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Christen M Mowad, MD, Associate Professor, Department of Dermatology, Geisinger Medical Center
Christen M Mowad, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, and Phi Beta Kappa
Disclosure: Nothing to disclose.

CME Editor

Catherine M Quirk, MD, Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania
Catherine M Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

RELATED EMEDICINE ARTICLES
 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.