eMedicine Specialties > Dermatology > Reactive & Inflammatory Dermatoses

Erythema Annulare Centrifugum

Author: Robert J Willard, MD, Dermatologist and Mohs Surgeon, Private Practice, Dermatology and Mohs Surgery Center, PC
Coauthor(s): Andrew D Montemarano, DO, Consulting Staff, The Skin Cancer Surgery Center
Contributor Information and Disclosures

Updated: Aug 13, 2008

Introduction

Background

Erythema annulare centrifugum (EAC) is classified as one of the figurate or gyrate erythemas. First described by Darier in 1916, it is characterized by a scaling or nonscaling, nonpruritic, annular or arcuate, erythematous eruption. It tends to spread peripherally while clearing centrally. Histologically, an intense lymphohistiocytic cuffing occurs about the superficial and deep dermal vessels without epidermal involvement. The etiology is uncertain, but it may be due to a hypersensitivity to malignancy, infection, drugs, or chemicals, or it may be idiopathic.

Controversy exists in the classification of the gyrate erythemas, and the literature is wrought with ambiguity and contradictions. Since its initial description in 1916, the term erythema annulare centrifugum has grown to include several histologic and clinical variants. Ackerman, and later Bressler and Jones,1 suggested a classification in which only 2 types of gyrate erythema are considered: superficial (pruritic, scaling) and deep (nonpruritic, nonscaling). The original description of EAC was of the latter type. However, the superficial type is more commonly seen with its characteristic trailing scale behind an advancing, erythematous border.

In this article, EAC is considered to include all the gyrate erythemas, except for erythema marginatum rheumaticum, erythema chronicum migrans, and erythema gyratum repens. When taken in this broad sense, EAC can be scaly or nonscaly, pruritic or nonpruritic, and rarely vesicular.

Other eMedicine erythema articles include the following:

Pathophysiology

The pathogenesis of erythema annulare centrifugum (EAC) is unknown, but it is probably due to a hypersensitivity reaction to a variety of agents, including drugs, arthropod bites, infections (bacterial, mycobacterial, viral, fungal, filarial), ingestion (blue cheese Penicillium), and malignancy. Injections of Trichophyton, Candida, tuberculin, and tumor extracts have been reported to induce EAC, supporting a type IV hypersensitivity reaction as at least one mechanism for its development. Another purported mechanism in the pathogenesis of EAC is that of a Th1-mediated reaction with elevated levels of tumor necrosis factor-alpha and associated proinflammatory cytokines. Minni and Sarro2 reported response to (and relapse following cessation of) etanercept in a 57-year-old white man as evidence supporting this theory.

Other cases of erythema annulare centrifugum have been found in association with an underlying systemic or infectious disease (eg, liver disease,3 Sjögren syndrome, systemic lupus erythematosus, Graves disease,4 hypereosinophilic syndrome,5 appendicitis6 ), herpes zoster, chronic lymphocytic leukemia, and HIV. Drugs reported to cause EAC include finasteride, piroxicam, hydroxychloroquine, amitriptyline, and spironolactone. Still other cases have been attributable to a familial form. However, in most cases, no underlying cause can be found. One study of 24 cases of EAC with special reference to its association with an underlying disease found no increased incidence of systemic disease, malignancy, or infection.7 In another study of 113 cases of gyrate erythemas, 7 cases (none of which was erythema gyratum repens) were associated with internal malignancy compared with 6 cases in the control group.

Hypotheses about the mechanism of annularity focus on the interaction between mediators of inflammation and ground substance as foreign antigens diffuse through the skin.

Frequency

International

Defining the incidence and the prevalence of erythema annulare centrifugum (EAC) is difficult because the literature mostly consists of case reports and brief reviews. In a review of 24 cases in England, the incidence was reported to be approximately 1 case per 100,000 population per year in a catchment area of 500,000 people.

Mortality/Morbidity

The mean duration of erythema annulare centrifugum (EAC) is 11 months. However, the course has ranged from 4-6 weeks to 34 years (recurrent attacks). Most cases require no treatment and resolve spontaneously. Others have been reported in association with malignancy, with the eruptions responding to treatment of the underlying neoplasm. In those cases, the prognosis is affected by the underlying malignancy.

Race

Whether any racial predilection exists for erythema annulare centrifugum (EAC) is not known.

Sex

No bias for either sex is apparent.

Age

Erythema annulare centrifugum (EAC) has been reported in patients from infancy to the ninth decade of life.

Clinical

History

  • Usually, patients with erythema annulare centrifugum (EAC) present with an asymptomatic or pruritic eruption of variable duration. The eruption may be associated with an underlying disease (eg, infection, malignancy, sarcoidosis, other systemic illness) and its accompanying characteristic symptoms (eg, night sweats, fever, and chills for tuberculosis or Hodgkin lymphoma).
  • EAC may precede malignancy by 2 years or more, but it can also occur concomitantly or after diagnosis.
  • The temporal relationship to other underlying diseases, if any, is also variable. Obtain a history of any antecedent infections.
  • A history of recent initiation of a new drug should be ascertained because many reports of medication-associated erythema annulare centrifugum exist (most commonly antimalarials, cimetidine, spironolactone, gold, salicylates, piroxicam, penicillin, and amitriptyline).
  • One case report8 has described EAC as a manifestation of autoimmune progesterone dermatitis in a female with a recurring annular pruritic eruption. She experienced monthly exacerbations of the eruption a few days prior to onset of menses. A similar hormonal etiology has been reported in the case of a woman who developed EAC in the 33rd week of pregnancy.9 The eruption resolved 1 month after delivery, without recurrence after 8 months of follow-up.

Physical

Pertinent physical findings of erythema annulare centrifugum (EAC) are usually limited to the skin, but a full physical examination should be conducted to assess for an underlying systemic process.

  • Skin
    • Primary lesion: The eruption begins as erythematous papules that spread peripherally while clearing centrally. These lesions enlarge at a rate of approximately 2-5 mm/d to produce annular, arcuate, figurate, circinate, or polycyclic plaques. The margin, which is usually indurated, varies in width from 4-6 mm, and, often, a trailing scale is present on the inner aspect of the advancing edge. The diameter of the polycyclic lesions varies from a few to several centimeters. Vesiculation may be present.
    • Distribution: Lesions demonstrate a predilection for the thighs and the legs, but they may occur on the upper extremities, the trunk, or the face. The palms and the soles are spared.
    • Color: The lesions are pink to red with central clear areas. Occasionally, residual hyperpigmentation of dull red, brown, or violet is present. A case of EAC associated with hyperbilirubinemia and jaundice secondary to choledocholithiasis has been reported.
  • Nails: White banding of the toenails has been reported in association with EAC.
  • Lymph nodes: Lymphadenopathy may be present in cases of EAC associated with Hodgkin or non-Hodgkin lymphoma, tuberculosis, or autoimmune processes.
  • Neck: The thyroid should be palpated for enlargement or nodules because Graves disease has been associated with EAC.4
  • Lungs: Tuberculosis,10 lymphoma, sarcoidosis, and malignant bronchial carcinoid have been associated with EAC, warranting examination of the lungs.
  • Abdomen: Appendicitis,6 lymphoma (with associated splenomegaly), and liver disease3 (eg, cholelithiasis, hepatitis), and pregnancy have been reported with EAC. The abdomen should be examined for tenderness, masses, or hepatosplenomegaly.

Causes

Most commonly, no cause is found for the erythema annulare centrifugum (EAC).11 However, the literature contains numerous case reports documenting association with other diseases. Often, the eruption of EAC resolves after treatment of the underlying illness.

  • Infections
    • Bacteria: Associations include Escherichia coli. One case associated EAC with a urinary tract infection that cleared 3 weeks after treatment of the urinary tract infection.12 Other associated bacterial infections include streptococcal infections (eg, bacterial meningitis.
    • Fungi: Dermatophytes (Trichophyton, tinea pedis, Pityrosporum orbiculare/Malassezia furfur) are associated, as is Candida albicans and blue cheese Penicillium.
    • Mycobacteria: Mycobacterium tuberculosis is associated. Treatment with isoniazid, rifampin, and streptomycin cleared the eruption of EAC within 20 day of starting therapy for tuberculosis in a patient.
    • Parasites: These include Ascaris lumbricoides13 ; EAC resolved after treatment with piperazine and thiabendazole. Also, EAC has been reported in association with Phthirus pubis infestation.14
    • Viruses: EAC has been reported in association with Epstein-Barr virus (EBV) in an infant15 and with molluscum contagiosum in an 8-year-old child. In the infant, the appearance and subsequent resolution of the eruption coincided with the patient's anti-EBV antibody titer, supporting EBV as the inciting agent. In addition, the viral genome has been found in the DNA of Reed-Sternberg cells in patients with Hodgkin disease and in patients with nasopharyngeal carcinoma. Both of these neoplasms have been associated with EAC. Two cases of EAC were reported in a dermatomal distribution within the exact distributions of recent prior herpes zoster infections. These cases were cited as examples of "Wolf's isotopic response."16 In 2006, erythema annulare centrifugum (EAC) was reported in an HIV-positive patient.17
  • Drugs: In each of the following cases, the eruption of EAC appeared after initiation of the drug and resolved after its cessation. In the cases of the antimalarials chloroquine and hydroxychloroquine, the eruptions took 5 months to a year to clear, believed to be secondary to their strong DNA-binding properties and affinity for melanin.
    • Finasteride
    • Chloroquine
    • Hydroxychloroquine18
    • Estrogen
    • Cimetidine
    • Penicillin
    • Salicylates
    • Piroxicam
    • Hydrochlorothiazide
    • Gold sodium thiomalate
    • Amitriptyline19
    • Etizolam20
  • Neoplasms: In each of the following cases, EAC resolved with successful treatment of the malignancy but relapsed with tumor recurrence in the cases of Hodgkin disease, acute myelogenous leukemia (AML), and squamous cell carcinoma in a sebaceous cyst. However, in the latter case, EAC cleared in the terminal stage of the disease. This was purported to be due to immune compromise with tumor progression.
    • Squamous cell carcinoma (in a sebaceous cyst)
    • Nasopharyngeal carcinoma
    • Acute myelogenous leukemia
    • Peritoneal carcinomatosis
    • Primary bronchial carcinoid21
    • Hodgkin lymphoma22,23
    • Chronic lymphocytic leukemia
    • Multiple myeloma
    • Prostate cancer
    • Malignant histiocytosis
    • Ovarian carcinoma (mucinous)
  • Foods: Blue cheese and tomatoes have been reported to cause EAC.
  • Other causes
    • Recurrent acute appendicitis: The lesions of EAC resolved 1 month after appendectomy.6
    • Cholestatic liver disease (secondary to choledocholithiasis): EAC resolved within 3 days of removal of the stone.3
    • Graves disease: The patient's eruption disappeared 2 weeks after treatment with I-131 for thyroid ablation.4
    • Menstruation: A case has been reported of a woman with EAC whose lesions stopped progressing premenstrually and enlarged again with the onset of menses. Another patient experienced exacerbations of EAC premenstrually as a type of autoimmune progesterone dermatitis.8
    • Hypereosinophilic syndrome: A patient with 31% eosinophilia (with no underlying cause found), pruritus, and EAC was treated with ketoconazole, dapsone, and trimethoprim-sulfamethoxazole with resolution of the eruption occurring after 2 weeks.5
    • Sjögren syndrome
    • Sarcoidosis: EAC was reported in association with underlying systemic sarcoidosis.
    • Osteoarthritis: A 73-year-old man with an 11-week history of EAC that was associated with the onset of left knee osteoarthritis received injections of intra-articular hyaluronic acid that effected resolution of both his osteoarthritis and the EAC.24

More on Erythema Annulare Centrifugum

Overview: Erythema Annulare Centrifugum
Differential Diagnoses & Workup: Erythema Annulare Centrifugum
Treatment & Medication: Erythema Annulare Centrifugum
Follow-up: Erythema Annulare Centrifugum
Multimedia: Erythema Annulare Centrifugum
References

References

  1. Bressler GS, Jones RE Jr. Erythema annulare centrifugum. J Am Acad Dermatol. May 1981;4(5):597-602. [Medline].

  2. Minni J, Sarro R. A novel therapeutic approach to erythema annulare centrifugum. J Am Acad Dermatol. Mar 2006;54(3 Suppl 2):S134-5. [Medline].

  3. Tsuji T, Kadoya A. Erythema annulare centrifugum associated with liver disease. Arch Dermatol. Nov 1986;122(11):1239-40. [Medline].

  4. Braunstein BL. Erythema annulare centrifugum and Graves' disease. Arch Dermatol. Sep 1982;118(9):623. [Medline].

  5. Shelley WB, Shelley ED. Erythema annulare centrifugum as the presenting sign of the hypereosinophilic syndrome: observations on therapy. Cutis. Jan 1985;35(1):53-5. [Medline].

  6. Sack DM, Carle G, Shama SK. Recurrent acute appendicitis with erythema annulare centrifugum. Arch Intern Med. Oct 1984;144(10):2090-2. [Medline].

  7. Mahood JM. Erythema annulare centrifugum: a review of 24 cases with special reference to its association with underlying disease. Clin Exp Dermatol. Jul 1983;8(4):383-7. [Medline].

  8. Halevy S, Cohen AD, Lunenfeld E, Grossman N. Autoimmune progesterone dermatitis manifested as erythema annulare centrifugum: Confirmation of progesterone sensitivity by in vitro interferon-gamma release. J Am Acad Dermatol. Aug 2002;47(2):311-3. [Medline].

  9. Rosina P, D'Onghia FS, Barba A. Erythema annulare centrifugum and pregnancy. Int J Dermatol. Aug 2002;41(8):516-7. [Medline].

  10. Burkhart CG. Erythema annulare centrifugum. A case due to tuberculosis. Int J Dermatol. Nov 1982;21(9):538-9. [Medline].

  11. White JW Jr. Gyrate erythema. Dermatol Clin. Jan 1985;3(1):129-39. [Medline].

  12. Borbujo J, de Miguel C, Lopez A, de Lucas R, Casado M. Erythema annulare centrifugum and Escherichia coli urinary infection. Lancet. Mar 30 1996;347(9005):897-8. [Medline].

  13. Hendricks AA, Lu C, Elfenbein GJ, Hussain R. Erythema annulare centrifugum associated with ascariasis. Arch Dermatol. Sep 1981;117(9):582-5. [Medline].

  14. Bessis D, Chraibi H, Guillot B, Guilhou JJ. Erythema annulare centrifugum induced by generalized Phthirus pubis infestation. Br J Dermatol. Dec 2003;149(6):1291. [Medline].

  15. Hammar H. Erythema annulare centrifugum coincident with Epstein-Barr virus infection in an infant. Acta Paediatr Scand. Sep 1974;63(5):788-92. [Medline].

  16. Lee HW, Lee DK, Rhee DY, Chang SE, Choi JH, Moon KC, et al. Erythema annulare centrifugum following herpes zoster infection: Wolf's isotopic response?. Br J Dermatol. Dec 2005;153(6):1241-3. [Medline].

  17. González-Vela MC, González-López MA, Val-Bernal JF, Echevarría S, Arce FP, Fernández-Llaca H. Erythema annulare centrifugum in a HIV-positive patient. Int J Dermatol. Dec 2006;45(12):1423-5. [Medline].

  18. Hudson LD. Erythema annulare centrifugum: an unusual case due to hydroxychloroquine sulfate. Cutis. Aug 1985;36(2):129-30. [Medline].

  19. García-Doval I, Peteiro C, Toribio J. Amitriptyline-induced erythema annulare centrifugum. Cutis. Jan 1999;63(1):35-6. [Medline].

  20. Kuroda K, Yabunami H, Hisanaga Y. Etizolam-induced superficial erythema annulare centrifugum. Clin Exp Dermatol. Jan 2002;27(1):34-6. [Medline].

  21. Everall JD, Dowd PM, Ardalan B. Unusual cutaneous associations of a malignant carcinoid tumour of the bronchus--erythema annulare centrifugum and white banding of the toe nails. Br J Dermatol. Sep 1975;93(3):341-5. [Medline].

  22. Leimert JT, Corder MP, Skibba CA, Gingrich RD. Erythema annulare centrifugum and Hodgkin's disease: association with disease activity. Arch Intern Med. Apr 1979;139(4):486-7. [Medline].

  23. Yaniv R, Shpielberg O, Shpiro D, Feinstein A, Ben-Bassat I. Erythema annulare centrifugum as the presenting sign of Hodgkin's disease. Int J Dermatol. Jan 1993;32(1):59-61. [Medline].

  24. Ioannidou D, Krasagakis K, Stefanidou M, Tosca A. Erythema annulare centrifugum and osteoarthritis treated with hyaluronic acid. Clin Exp Dermatol. Nov 2002;27(8):720-2. [Medline].

  25. Guillet MH, Dorval JC, Larrégue M, Guillet G. [Darier's erythema annulare centrifugum of neonatal onset with a 15 years' follow-up. Efficacy of interferon and role of cytokines]. Ann Dermatol Venereol. 1995;122(6-7):422-6. [Medline].

  26. Gniadecki R. Calcipotriol for erythema annulare centrifugum. Br J Dermatol. Feb 2002;146(2):317-9. [Medline].

  27. Reuter J, Braun-Falco M, Termeer C, Bruckner-Tuderman L. [Erythema annulare centrifugum Darier. Successful therapy with topical calcitriol and 311 nm-ultraviolet B narrow band phototherapy]. Hautarzt. Feb 2007;58(2):146-8. [Medline].

  28. De Aloe G, Rubegni P, Risulo M, Sbano P, Poggiali S, Fimiani M. Erythema annulare centrifugum successfully treated with metronidazole. Clin Exp Dermatol. Sep 2005;30(5):583-4. [Medline].

  29. Janss G, Schmidt K, Gattuso P, Massa M, Welykyj S. An intensive care unit nurse with a recurring annular lesion. Erythema annulare centrifugum (EAC). Arch Dermatol. Jul 1992;128(7):977, 980. [Medline].

  30. Lazar P. Cancer, erythema annulare centrifugum, autoimmunity. Arch Dermatol. 1963;87:246-51.

Further Reading

Keywords

EAC, erythema gyratum perstans, erythema exudativum perstans, erythema marginatum perstans, erythema perstans, erythema figuratum perstans, erythema microgyratum perstans, erythema simplex gyratum

Contributor Information and Disclosures

Author

Robert J Willard, MD, Dermatologist and Mohs Surgeon, Private Practice, Dermatology and Mohs Surgery Center, PC
Robert J Willard, MD is a member of the following medical societies: American Academy of Dermatology, American College of Mohs Micrographic Surgery and Cutaneous Oncology, and American Society for Dermatologic Surgery
Disclosure: Nothing to disclose.

Coauthor(s)

Andrew D Montemarano, DO, Consulting Staff, The Skin Cancer Surgery Center
Andrew D Montemarano, DO is a member of the following medical societies: American Academy of Dermatology, American College of Mohs Micrographic Surgery and Cutaneous Oncology, and American Society for Dermatologic Surgery
Disclosure: Nothing to disclose.

Medical Editor

Evan R Farmer, MD, Professor of Dermatology, Johns Hopkins University School of Medicine, Clinical Professor of Pathology, Virginia Commonwealth University School of Medicine; Consulting Staff, Department of Dermatology, Johns Hopkins Hospital, VCU Health Services
Evan R Farmer, MD is a member of the following medical societies: American Academy of Dermatology, American Dermatological Association, American Medical Association, American Society of Dermatopathology, and International Society of Dermatology
Disclosure: Nothing to disclose.

Pharmacy Editor

Michael J Wells, MD, Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center
Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Warren R Heymann, MD, Head, Division of Dermatology, Professor, Department of Internal Medicine, University of Medicine and Dentistry of New Jersey
Warren R Heymann, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

CME Editor

Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania
Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology
Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds None; Genentech Consulting fee Consulting; Centocor Consulting fee Consulting; Centocor Grant/research funds None; Covance Consulting fee Consulting; Shire  Consulting

Chief Editor

William D James, MD, Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System
William D James, MD is a member of the following medical societies: American Academy of Dermatology and Society for Investigative Dermatology
Disclosure: elsevier Royalty Other; american college of physicians Honoraria Other

 
 
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