BASICS
DESCRIPTION
- Erythema annulare centrifugum (EAC) is an eruption characterized by erythematous annular or figurate plaques that demonstrate central clearing and a distinctive trailing scale along the inner border.
- Lesions tend to occur on the hips and lower extremities but can appear on the trunk, face, and upper extremities. Lesions have not been reported to affect the palms, soles, or mucosa.
- First identified by Darier in 1916 and later classified in 1978 into two subtypes: deep and superficial. Superficial lesions demonstrate a collarette of trailing scale, whereas deep lesions do not.
- Most often idiopathic but sometimes found in association with an underlying disease process
- EAC can be recurrent and wax and wane over months to years.
- System(s) affected: skin
- Synonym(s): deep/superficial gyrate erythema; erythema perstans; palpable migrating erythema
EPIDEMIOLOGY
- No predominant age: EAC has been reported in all age groups, from infants to geriatric patients.
- No known predilection to race or sex
Incidence
- A study in England estimated annual incidence of EAC at 1/100,000 population (1).
- Peak incidence is during the 5th decade of life.
ETIOLOGY AND PATHOPHYSIOLOGY
- Pathophysiology unknown, but delayed hypersensitivity from inciting antigens may induce EAC.
- Hypersensitivity reaction postulated to be due to a variety of factors including the following:
- Medications: commonly nonsteroidal anti-inflammatory drugs (NSAIDs), antimalarials such as hydroxychloroquine, diuretics, and other medications such as amitriptyline, finasteride, and pegylated interferon α-2b when combined with ribavirin have also been reported
- Arthropod bites
- Infection
- Dermatophytosis (tinea pedis, onychomycosis)
- Bacterial infections with Escherichia coli, Streptococcus, Mycobacterium tuberculosis
- Viruses, such as Epstein-Barr virus, varicella zoster virus, HIV, molluscum contagiosum
- Ingestion of foods such as blue cheese or tomatoes
- Internal malignancy (breast, lung, lymphoma, leukemia, prostate)
- Other mechanisms proposed to induce EAC include an alteration in the immune landscape secondary to an elevation of proinflammatory cytokines and tumor necrosis factor-α.
- Pregnancy
- Parasites, such as Ascaris lumbricoides and Phthirus pubis
GENERAL PREVENTION
Avoid known triggers. �
COMMONLY ASSOCIATED CONDITIONS
- Tinea pedis and other dermatophytoses (common)
- Reports of EAC have occurred in patients with internal malignancy (variable), such as Hodgkin lymphoma (common), chronic lymphocytic leukemia, and breast carcinoma. A wide range of systemic diseases, such as Sj �gren syndrome, sarcoidosis, hypereosinophilic syndrome, osteoarthritis, pregnancy, Graves disease, liver or gallbladder disease, appendicitis, Crohn, and lupus
- Infections with M. tuberculosis, syphilis, herpes zoster virus, Epstein-Barr virus, molluscum contagiosum, and HIV have also been associated with EAC.
DIAGNOSIS
HISTORY
- Patients may experience a scaling rash that enlarges by several millimeters per day with or without pruritus. Rash often spreads by peripheral extension with central clearing.
- Excluding the rash, most patients are asymptomatic.
- Obtain a thorough history regarding prior infections, new medications, or current comorbid conditions to screen for associated malignancy or systemic disease.
PHYSICAL EXAM
- A rash consisting of annular or figurate erythematous plaques with central clearing and a characteristic trailing scale along the inner border is often present on the trunk, upper arms, hips, or lower extremities.
- Deep subtype presents with a firm, indurated border without scaling.
- Some lesions may have telangiectasias or purpura; vesicles are uncommon.
- White banding of the toenails was reported in a patient with EAC and malignant carcinoid tumor of the bronchus.
- Findings are limited to the skin, but a full physical exam with attention to the lymph nodes, thyroid, lungs, heart, and abdomen should be completed to rule out concomitant systemic disease.
- Examine the feet for evidence of tinea.
DIFFERENTIAL DIAGNOSIS
- Tinea corporis (id reaction)
- Granuloma annulare
- Acute urticaria
- Erythema migrans
- Drug eruption
- Nummular eczema
- Subacute cutaneous lupus erythematosus
- Tumid lupus erythematosus
- Erythema marginatum
- Erythema multiforme
- Erythema gyratum repens
- Porokeratosis
- Granuloma faciale
- Cutaneous T-cell lymphoma
- Secondary syphilis
- Tuberculosis
- Polymorphous light eruption
- Lupus tumidus
- Urticaria multiforme
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
- No specific test for EAC is available.
- If suspicion of underlying disease exists, appropriate diagnostic lab tests should be ordered in reference to patient history and symptoms, including CBC with differential, hepatic function tests, antistreptolysin-O for streptococcal infection, thyroid-stimulating hormone, hepatic function tests, erythrocyte sedimentation rate, serum antinuclear antibody, SSA (Ro), SSB (La), tuberculin skin test (PPD), HIV antibody, stool examination for parasites, and appropriate tumor markers.
- Lyme antibody titer to distinguish the rash of EAC from erythema migrans.
- β-Human chorionic gonadotropin in females if pregnancy suspected.
- A chest radiograph or CT may be applicable when patients are experiencing multiple systemic symptoms to search for underlying malignancy, hilar lymphadenopathy, or infectious process.
Diagnostic Procedures/Other
- Potassium hydroxide prep to assess for hyphae or spores
- Punch biopsy for histopathologic analysis
- Direct immunofluorescence of perilesional skin (if vesicles present) to rule out bullous disorder
- Bacterial, fungal, and viral cultures
Test Interpretation
Histopathologic findings are relatively nonspecific revealing spongiosis (intercellular edema), parakeratosis (retention of nuclei), and epidermal hyperplasia. Furthermore, lymphocytes may be arranged tightly around blood vessels in the superficial and deep dermis in a "coat sleeve"� arrangement. �
- Superficial EAC: Inflammatory changes are more localized to the epidermis and papillary dermis.
- Deep EAC: deep dermal infiltrate
TREATMENT
GENERAL MEASURES
- Address primary disease if symptoms are present.
- Discontinue any offending medications suspected to induce EAC.
- Lesions should be washed with mild soap, and skin irritants avoided.
MEDICATION
First Line
- No specific treatment with consistent results is available.
- High-potency topical steroids to active lesions are the mainstay of treatment, but evidence is lacking to support their use. Precautions: Long-term use of high-potency topical steroids may lead to skin atrophy, striae, and hypopigmentation at lesion sites.
- Most EAC cases resolve spontaneously in idiopathic cases or with treatment of the underlying disorder.
- In one case, EAC resolved with treatment of Hodgkin lymphoma but returned when tumor recurred.
- A patient receiving intra-articular knee injections with hyaluronic acid noticed resolution of his EAC lesions along with gradual improvement of his osteoarthritis.
Second Line
- Isolated lesions may be injected with intralesional Kenalog (5 to 10 mg/mL).
- Use of and/or reported success has been documented with the following treatments:
- Calcipotriol 0.005% ointment applied once daily to lesions has been used successfully in a case of refractory EAC (2)[C].
- Metronidazole 400 mg PO daily with taper to metronidazole 1% gel applied once daily to lesions (3)[C].
- Etanercept 25 mg PO twice weekly (4)[C]
- Topical pimecrolimus (5)[C]
- Oral psoralen + ultraviolet A (UVA) phototherapy
- Exposure to natural UV phototherapy has been suggested in two reported case studies although duration, strength of sun exposure, and safety are not known.
- Oral antihistamines may be used for symptoms of pruritus.
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Consultation with a dermatologist is recommended for persistent or recurrent flares of EAC. �
DIET
Avoid precipitating foods and medications. �
PROGNOSIS
- Most EAC cases often spontaneously resolve with a mean time to resolution reported as 11 months (6).
- EAC waxes and wanes in severity, with a mean duration of several months.
- Patients may experience recurrent episodes for weeks to years after initial resolution. Recurrences are common after stopping topical therapies.
- No measures prevent recurrence of EAC.
- Prognosis generally depends on the underlying cause.
REFERENCES
11 Mahood �JM. Erythema annulare centrifugum: a review of 24 cases with special reference to its association with underlying disease. Clin Exp Dermatol. 1983;8(4):383-387.22 Gniadecki �R. Calcipotriol for erythema annulare centrifugum. Br J Dermatol. 2002;146(2):317-319.33 De Aloe �G, Rubegni �P, Risulo �M, et al. Erythema annulare centrifugum successfully treated with metronidazole. Clin Exp Dermatol. 2005;30(5):583-584.44 Minni �J, Sarro �R. A novel therapeutic approach to erythema annulare centrifugum. J Am Acad Dermatol. 2006;54(3)(Suppl 2):S134-S135.55 Day �I, Lin �AN. Use of pimecrolimus cream in disorders other than atopic dermatitis. J Cutan Med Surg. 2008;12(1):17-26.66 Mir �A, Terushkin �V, Fischer �M, et al. Erythema annulare centrifugum. Dermatol Online J. 2012;18(12):21.
ADDITIONAL READING
- Atalay �AA, Abuaf �OK, Dogan �B. Squamous cell lung carcinoma presenting with erythema annulare centrifugum. Acta Dermatovenerol Croat. 2013; 21(1):56-58.
- Carlesimo �M, Fidanza �L, Mari �E, et al. Erythema annulare centrifugum associated with mantle b-cell non-Hodgkin's lymphoma. Acta Derm Venereol. 2009;89(3):319-320.
- Chander �R, Yadav �P, Singh �A, et al. Systemic lupus erythematosus presenting as erythema annulare centrifugum. Lupus. 2014;23(11):1197-1200.
- Chiang �CH, Lai �FJ. Pregnancy-associated erythema annulare centrifugum. J Formos Med Assoc. 2015;114(7):670-671. doi:10.1016/j.jfma.2014.01.004.
- Chodkiewicz �HM, Cohen �PR. Paraneoplastic erythema annulare centrifugum eruption: PEACE. Am J Clin Dermatol. 2012;13(4):239-246.
- Coronel-P �rez �IM, Morillo-And �jar �M. Erythema annulare centrifugum responding to natural ultraviolet light [in Spanish]. Actas Dermosifiliogr. 2010;101(2):177-178.
- Darier �J. De l' �ryth �me annulaire centrifuge. Ann Dermatol Syphiligr. 1916;6:57.
- Elfatoiki �FZ, Chiheb �S, Marnissi �S, et al. Recurrent post-tonsillitis erythema annulare centrifugum: two cases [in French]. Ann Dermatol Venereol. 2014;141(3):219-220.
- 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. 1975;93(3):341-345.
- G �n �l �M, K �lc � �akmak �S, Ozcan �N, et al. Erythema annulare centrifugum due to pegylated interferon-α-2a plus ribavirin combination therapy in a patient with chronic hepatitis C virus infection. J Cutan Med Surg. 2014;18(1):65-68.
- Ioannidou �D, Krasagakis �K, Stefanidou �M, et al. Erythema annulare centrifugum and osteoarthritis treated with hyaluronic acid. Clin Exp Dermatol. 2002;27(8):720-722.
- Leimert �JT, Corder �MP, Skibba �CA, et al. Erythema annulare centrifugum and Hodgkin's disease: association with disease activity. Arch Intern Med. 1979;139(4):486-487.
- Mendes-Bastos �P, Coelho-Macias �V, Moraes-Fontes �MF, et al. Erythema annulare centrifugum during rituximab treatment for autoimmune haemolytic anaemia. J Eur Acad Dermatol Venereol. 2014;28(8):1125-1127.
- Samycia �M, Salopek �TG. Erythema annulare centrifugum in a patient with crohn disease. J Cutan Med Surg. 2012;16(6):442-444.
- Weyers �W, Diaz-Cascajo �C, Weyers �I. Erythema annulare centrifugum: results of a clinicopathologic study of 73 patients. Am J Dermatopathol. 2003;25(6):451-462.
CODES
ICD10
L53.1 Erythema annulare centrifugum �
ICD9
695.0 Toxic erythema �
SNOMED
Erythema annulare centrifugum �
CLINICAL PEARLS
- EAC is an erythematous annular or figurate (curved) eruption on the trunk or proximal extremities, often with central clearing and scaling at the trailing edge of the erythema with or without pruritus.
- A multitude of other underlying diseases or conditions such as lymphomas, pregnancy, and infection have also been associated with EAC.
- Address the underlying disorder for resolution of lesions.
- EAC is often self-limited but may persist for years and often reoccurs with varying severity.
- Exact etiology and pathophysiology are unknown.