eMedicine Specialties > Dermatology > Diseases of the Vessels

Erythema Elevatum Diutinum: Treatment & Medication

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 3, 2010

Treatment

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.22 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.23
  • Intermittent plasma exchange (PLEX) was shown to control IgA paraproteinemia associated with erythema elevatum diutinum.24 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.

Diet

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.25

Medication

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

Sulfones

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


Dapsone (Avlosulfon)

DOC in patients with EED. Bactericidal and bacteriostatic against mycobacteria; mechanism of action is similar to that of sulfonamides where competitive antagonists of PABA prevent formation of folic acid, inhibiting bacterial growth.
Dose depends on patient. Optimal dose should be determined by physician. Available for oral intake in 25 mg and 100 mg scored tablets. Not considered to have an effect on growth and development of the child.

Adult

50-300 mg/d PO

Pediatric

Not established

Trimethoprim, probenecid, and folic acid antagonists (eg, pyrimethamine, MTX) may increase levels; activated charcoal, PABA, and rifampin may decrease levels; sulfonamides and hydroxychloroquine may increase hemolysis risk

Absolute: Documented hypersensitivity
Relative: G-6-PD deficiency (especially in African Americans, persons of Middle Eastern heritage, and Asians); significant cardiopulmonary disease; significant hematologic disease; sulfa allergy (cautious use in patients with sulfa allergy may be attempted; cross-reactivity is relatively rare and mild; do not use if previous reaction to sulfa was anaphylactic)

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Dose-related hemolytic anemia in all persons receiving dapsone to some degree; older RBCs more susceptible; most patients have 2g/dL drop in hemoglobin, with re-equilibration at 1g/dL below normal; reticulocyte count may be used to monitor bounce-back ability; patients with G-6-PD deficiency more affected
Dose-related methemoglobinemia may occur; degree of cyanosis not predictive of degree of methemoglobinemia; patients with significant cardiopulmonary disease or low baseline hemoglobin levels may not be able to tolerate low levels of methemoglobin; vitamin E 800 IU/d and cimetidine 400 mg tid shown to provide a small amount of protection from formation of methemoglobin or hemolysis
Agranulocytosis may occur (1 in 240-425), is idiosyncratic, and mechanism not known; has occurred as early as 3 wk; All cases developed within 12 wk; fever, pharyngitis, and sepsis reported, with mortality rate of 50%; if discovered promptly, recovery occurs in 7-14 d; granulocyte colony-stimulating factor may speed recovery
Distal motor neuropathy with some sensory involvement may occur; distal motor weakness of hands and legs and wasting of hand muscles; most patients recover completely with discontinuance but recovery can take 2 wk to 2 y; mechanism of neuropathy unknown
Permanent retinal damage reported with overdosage; thought to be due to hypoxia
Acute psychosis may occur but usually only in leprosy patients
GI upset minimized if taken with food; primary hepatocellular hepatitis, cholestatic hepatitis, hypoalbuminemia, gall bladder perforation, pancreatitis may occur
Dapsone hypersensitivity syndrome is mononucleosislike eruption with fever; skin eruption has ranged from maculopapular to TEN; hepatitis; peripheral eosinophilia; fatalities reported; treatment with steroids have been tried but due to its rarity, success unproven
Cutaneous hypersensitivity eruptions may include maculopapular, EM or TEN (rare); photosensitivity may occur; animal studies (not human) have shown slight increase in malignancies if taken for 2 y or longer

Vitamins

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


Niacinamide (Vitamin B-3)

A 1980 study showed niacinamide to be helpful in suppressing clinical manifestations of EED. Has also been used for management of many disorders, including livedoid vasculitis and leprosy. Presumed mechanism of action is as an anti-inflammatory agent and as a vasodilator. Mainly used for treatment and prevention of pellagra and niacin or tryptophan deficiency. Available for oral intake in 50-, 100-, and 500-mg tab.

Adult

100 mg tab PO tid

Pediatric

Not established

May increase hypotensive effects of ganglionic blocking drugs; long-term administration of isoniazid may call for increase in niacinamide dose for dietary purposes; cutaneous vasodilation may be a problem if high-dose used with peripheral vasodilators (eg, nitroglycerin); taking aspirin 30-60 min before first dose of the day may help alleviate prostaglandin-mediated adverse effects (eg, flushing, itching); clonidine may inhibit niacin-induced flushing

Documented hypersensitivity; active liver disease or unexplained, significant increases in AST and ALT levels; large doses of niacin, especially when administered in a sustained-release form (associated with severe hepatotoxicity); patients who have a definite and recent history of peptic ulcer disease (can reactivate ulcers)

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Caution in gallbladder disease or diabetes and patients predisposed to gout; monitor blood glucose level; may elevate uric acid levels; pregnancy category C when used at doses greater than RDA; caution when using in patients who have coronary artery disease (higher occurrence of cardiac arrhythmias have been reported)

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
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References

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  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].

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  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].

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  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].

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  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].

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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

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Keywords

erythema elevatum diutinum, extracellular cholesterosis, EED, leukocytoclastic vasculitis

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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.

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