Erythema Annulare Centrifugum



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:


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:


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:

Other causes

Other reported causes vary and include the following:


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.


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).[35]

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 report[29] 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.[36] The eruption resolved 1 month after delivery, without recurrence after 8 months of follow-up.

Physical Examination

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 findings are as follows:

Other findings are as follows:


Unless erythema annulare centrifugum (EAC) is associated with an underlying disease, there are usually no complications.

Laboratory Studies

Skin scrapings from lesional sites of erythema annulare centrifugum (EAC) should be analyzed after preparation in potassium hydroxide (KOH) to ascertain the presence or the absence of hyphae suggestive of tinea or candidiasis.

Lyme antibody titer helps exclude erythema migrans, and serological studies can exclude syphilis.[39]

An antinuclear antibody test should be performed in the appropriate clinical setting. Systemic lupus erythematosus is in the differential diagnosis of EAC, and Sjögren syndrome has been reported in association with EAC.

A purified protein derivative (PPD) test and an anergy panel can be used to help determine if an underlying M tuberculosis infection is present.

A complete blood count with differential can be used to evaluate a suspected underlying infection (neutrophilia with bacterial infection; eosinophilia with parasitic infection or hypereosinophilic syndrome).

If compatible with the clinical presentation of erythema annulare centrifugum, liver function studies may be useful because hyperbilirubinemia secondary to cholestasis and elevated transaminase levels secondary to hepatitis have been reported with EAC.

With an appropriate history of gastrointestinal complaints, a stool examination may be useful to search for ova and parasites (ascariasis has been reported with EAC).

For females, serum or urine beta-human chorionic gonadotropin testing may be indicated.

Imaging Studies

Chest radiography can be used to exclude pulmonary nodules or hilar adenopathy suggestive of tuberculosis, malignancy (primary or metastatic), sarcoidosis, or lymphoma, all of which have been associated with erythema annulare centrifugum (EAC).


A skin punch biopsy may be performed on erythema annulare centrifugum (EAC) lesions.

Histologic Findings

A biopsy is helpful in confirming a diagnosis of erythema annulare centrifugum (EAC). Two histologic subtypes exist: deep and superficial. In the classic or deep type, an intense, superficial and deep lymphocytic or lymphohistiocytic perivascular infiltrate in a coat-sleeve fashion is observed in the middle and lower dermis. No epidermal changes are observed. Clinically, these EAC lesions have indurated borders and are nonscaly and nonpruritic.

In the superficial type of EAC, a more nonspecific perivascular lymphohistiocytic infiltrate about the superficial dermal vessels and edema of the papillary dermis is present. The epidermal changes of parakeratosis and spongiosis may be present. Clinically, these lesions have a scale, may be pruritic, and may have vesiculations.

Medical Care

Erythema annulare centrifugum (EAC) is usually self-limited. Topical steroids usually cause involution of the treated lesions, but they do not prevent the occurrence of new lesions or recurrence of the eruption. Systemic or injection steroid therapy is effective, but the eruption returns once these drugs are withdrawn. As previously mentioned, several cases of EAC have resolved once the underlying diseases were treated. Therefore, a search for and treatment of the underlying disorder is the primary therapy. However, an exhaustive workup for occult malignancy is not warranted because the relationship between EAC and cancer is not consistent.[40] Remember that no cause is found in most cases.

The patient's medications should be reviewed with particular attention to and discontinuation of the drugs known to be associated with EAC. Recent additions to the patient's drug regimen should be eliminated, and the patient should be observed for signs of resolution.

In a case of EAC associated with hypereosinophilic syndrome, the eruption resolved after treatment with ketoconazole, dapsone, and trimethoprim-sulfamethoxazole.[7]

A case of EAC of infantile onset in the French literature documents dramatic improvement with interferon alpha therapy.[41]

Case reports have documented success in the treatment of EAC with drugs previously unreported to be useful for EAC. Note the following:


Consult a dermatologist for diagnosis and evaluation of the underlying cause of erythema annulare centrifugum (EAC). Consult an internal medicine specialist for evaluation of the underlying cause of EAC.

Medication Summary

The goals of pharmacotherapy for erythema annulare centrifugum (EAC) are to reduce morbidity and to prevent complications.

Fluocinonide (Fluonex, Lidex)

Clinical Context:  Fluocinonide is a group II topical steroid. The anti-inflammatory potency group is determined by the degree of vasoconstriction induced by the drug in the small vessels of the upper dermis (I is most potent; VII is least potent). Use fluocinonide in all involved areas except those where the skin is particularly thin (eg, face, scrotum, axilla, flexural areas).

Hydrocortisone valerate (Westcort)

Clinical Context:  Hydrocortisone valerate is a group V topical steroid. The anti-inflammatory potency group is determined by the degree of vasoconstriction induced by the drug in the small vessels of the upper dermis (I is most potent; VII is least potent). This topical corticosteroid should be used on involved areas of the skin that are particularly thin, such as the face, axilla, scrotum, and flexural areas.

Prednisone (Deltasone)

Clinical Context:  Prednisone is an immunosuppressant for the treatment of autoimmune disorders. It may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Prednisone stabilizes lysosomal membranes and suppresses lymphocyte and antibody production.

Class Summary

Topical agents are used for treatment of inflammatory lesions of EAC and for symptomatic relief of pruritus. A short course of systemic steroid therapy may be considered for very symptomatic cases of EAC (eg, severe pruritus).

What is erythema annulare centrifugum (EAC)?What is the pathophysiology of erythema annulare centrifugum (EAC)?What causes erythema annulare centrifugum (EAC)?What are the infectious causes of erythema annulare centrifugum (EAC)?Which medications may cause erythema annulare centrifugum (EAC)?Which malignancies cause erythema annulare centrifugum (EAC)?What conditions are associates with erythema annulare centrifugum (EAC)?What is the prevalence of erythema annulare centrifugum (EAC)?What are the racial predilections of erythema annulare centrifugum (EAC)?What are the sexual predilections of erythema annulare centrifugum (EAC)?Which age groups have the highest prevalence of erythema annulare centrifugum (EAC)?What is the prognosis of erythema annulare centrifugum (EAC)?Which clinical history findings are characteristic of erythema annulare centrifugum (EAC)?Which skin findings are characteristic of erythema annulare centrifugum (EAC)?Which physical findings are characteristic of erythema annulare centrifugum (EAC)?What are the possible complications of erythema annulare centrifugum (EAC)?Which conditions should be included in the differential diagnoses of erythema annulare centrifugum (EAC)?What are the differential diagnoses for Erythema Annulare Centrifugum?What is the role of lab testing in the diagnosis of erythema annulare centrifugum (EAC)?What is the role of imaging studies in the diagnosis of erythema annulare centrifugum (EAC)?What is the role of biopsy in the diagnosis of erythema annulare centrifugum (EAC)?Which histologic findings are characteristic of erythema annulare centrifugum (EAC)?How is erythema annulare centrifugum (EAC) treated?Which medications have been used successfully in the treatment of erythema annulare centrifugum (EAC)?Which specialist consultations are beneficial to patients with erythema annulare centrifugum (EAC)?What is the goal of drug treatment for erythema annulare centrifugum (EAC)?Which medications in the drug class Corticosteroids are used in the treatment of Erythema Annulare Centrifugum?


Dirk M Elston, MD, Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Disclosure: Nothing to disclose.

Specialty Editors

Michael J Wells, MD, FAAD, Dermatologic/Mohs Surgeon, The Surgery Center at Plano Dermatology

Disclosure: Nothing to disclose.

Warren R Heymann, MD, Head, Division of Dermatology, Professor, Department of Internal Medicine, Rutgers New Jersey Medical School

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD, Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

Disclosure: Received income in an amount equal to or greater than $250 from: Elsevier; WebMD.

Additional Contributors

Andrew D Montemarano, DO, Consulting Staff, The Skin Cancer Surgery Center

Disclosure: Nothing to disclose.

Marisel Peralta-Abejo, MD, DPDS, Dermatology Consultant, Bulacan Primehealth Multi-Specialty Clinic, Meycauayan Doctors Hospital, and Valenzuela Citicare Medical Center

Disclosure: Nothing to disclose.

Robert J Willard, MD, Dermatologist and Mohs Surgeon, Private Practice, Dermatology and Mohs Surgery Center, PC

Disclosure: Nothing to disclose.


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Arcuate lesions of erythema annulare centrifugum demonstrate minimal scale.

Superficial erythema annulare centrifugum demonstrates a central clearing and trailing scale behind an advancing, annular, erythematous border.

Arcuate lesions of erythema annulare centrifugum demonstrate minimal scale.

Superficial erythema annulare centrifugum demonstrates a central clearing and trailing scale behind an advancing, annular, erythematous border.