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:

• Erythema Ab Igne
• Erythema Dyschromicum Perstans
• Erythema Elevatum Diutinum
• Erythema Gyratum Repens
• Erythema Induratum (Nodular Vasculitis)
• Erythema Infectiosum (Fifth Disease)
• Erythema Multiforme
• Erythema Nodosum
• Erythema Toxicum Neonatorum

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 lymphoma^22,23
  • 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

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