Erythema Annulare Centrifugum

Updated: Mar 06, 2020
  • Author: Dirk M Elston, MD; Chief Editor: William D James, MD  more...
  • Print


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. [1] 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. EAC-like eruptions have been described with nivolumab. [2]

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, [3] 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 Medscape erythema articles include the following:



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 Sarro [4] reported response to (and relapse following cessation of) etanercept in a 57-year-old white man as evidence supporting this theory.

Other cases of EAC have been found in association with an underlying systemic or infectious disease (eg, liver disease, [5] Sjögren syndrome, systemic lupus erythematosus, Graves disease, [6] hypereosinophilic syndrome, [7] appendicitis [8] ), herpes zoster, [9] chronic lymphocytic leukemia, and HIV disease. 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. [10] 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.



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.


Infection-related causes include the following:

  • 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 lumbricoides [13] ; 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 infant [15] 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]


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. Note the following drugs that have been associated with EAC:

  • Amitriptyline [18]
  • Azacitidine [19]
  • Chloroquine
  • Cimetidine
  • Estrogen
  • Etizolam [20]
  • Finasteride
  • Hydrochlorothiazide
  • Hydroxychloroquine [21]
  • Gold sodium thiomalate
  • Pegylated interferon alfa-2a plus ribavirin combination therapy [22]
  • Penicillin
  • Piroxicam
  • Rituximab [23]
  • Salicylates
  • Ustekinumab [24]


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. Note the following:

  • Squamous cell carcinoma (in a sebaceous cyst)
  • Nasopharyngeal carcinoma
  • Acute myelogenous leukemia
  • Peritoneal carcinomatosis
  • Primary bronchial carcinoid [25]
  • Hodgkin lymphoma [26, 27]
  • Chronic lymphocytic leukemia
  • Multiple myeloma
  • Prostate cancer
  • Malignant histiocytosis
  • Ovarian carcinoma (mucinous)
  • Breast cancer [28]

Other causes

Other reported causes vary and include the following:

  • Foods: Blue cheese and tomatoes have been reported to cause EAC
  • Recurrent acute appendicitis: The lesions of EAC resolved 1 month after appendectomy. [8]
  • Cholestatic liver disease (secondary to choledocholithiasis): EAC resolved within 3 days of removal of the stone. [5]
  • Graves disease: The patient's eruption disappeared 2 weeks after treatment with I-131 for thyroid ablation. [6]
  • 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. [29]
  • 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. [7]
  • 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. [30]
  • Stress: One report describes stress as an inciting factor in one case of EAC. The patient experienced EAC at the onset of stressful life periods, which abated without treatment upon discontinuation of the stressful period in the patient’s life. [31]
  • Pregnancy: One case report describes the onset of EAC during pregnancy, with resolution occurring shortly before delivery. [32]  Other cases have remitted during pregnancy. [33]


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.


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


No bias for either sex is apparent for erythema annulare centrifugum (EAC).


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



The prognosis for erythema annulare centrifugum (EAC) is excellent, except when associated with an underlying malignancy and other systemic disease. 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. Annually recurring erythema annulare centrifugum (AR EAC) was reported in 2015. [34] Treatment of the underlying disorder is effective. If associated with pregnancy, it resolves after delivery.