Erythema annulare centrifugum

Background

Erythema annulare centrifugum (EAC) is a gyrate erythema characterized by minimally pruritic, polycyclic, erythematous patches or plaques that may expand up to 2–3 mm/day and clear centrally. There are two forms: the far more common superficial form has a trailing scale at the inner borders of the erythema, whereas the deep form has erythematous induration with minimal to no scale. EAC has a mean duration of 2.8 years, and treatment is often difficult. EAC has been seen to persist for decades.

Diagnosis/Management Strategy

EAC represents a hypersensitivity reaction to a myriad of conditions; therefore, a search for and treatment of an underlying disease is the primary management strategy. Most often an underlying cause is not found.

A concurrent skin infection is the most common underlying association. Fungal, bacterial, viral, mycobacterial, and parasitic pathogens have been reported. Typically, the infection is cutaneous and is at a distant location from the EAC eruption. Dermatophytosis is implicated in up to 48%. Thus, the skin, especially the feet, groin, and nails, should be carefully examined for tinea. Anecdotal reports of other associated skin infections include molluscum contagiosum, herpesvirus infection, and Pthirus pubis infestation. Less commonly, the infection is internal with intestinal Giardia or Candida. Latent Epstein–Barr virus infection, human immunodeficiency virus (HIV) infection, chronic viral hepatitis, appendicitis, tonsillitis, secondary syphilis, urinary tract Escherichia coli, and nematode infestations have been anecdotally reported. Although EAC is typically associated with an active infection, it has also been reported to occur after reactivation of herpes zoster virus in corresponding dermatomes.

Rarely, EAC may be associated with either benign or malignant hematologic and solid neoplasms. This paraneoplastic erythema annulare centrifugum eruption (PEACE) is thought to result from hypersensitivity to tumor proteins released by these neoplasms. However, in the absence of strong clinical suspicion, an extensive search for malignancy is not recommended. If neoplasia is identified, EAC activity correlates with tumor response to treatment.

Medications may be associated with EAC – anecdotal reports include acetazolamide, amitriptyline, ampicillin, azacitidine, boceprevir, chloroquine, cimetidine, cyclopenthiazide, cotrimoxazole, etizolam, finasteride, gold, hydrochlorothiazide, hydroxychloroquine, ibuprofen, iron, Neutradonna (aluminum silicate and belladonna), oxprenolol, pegylated interferon-α2a plus ribavirin, piroxicam, rituximab, salicylates, sorafenib, spironolactone, thioacetazone, and ustekinumab. Early reports of antimalarials as a cause of EAC may be debated: what was considered EAC in these reports may actually have been unrecognized forms of subacute cutaneous lupus erythematosus. Sipuleucel-T immunotherapy of autologous antigen presenting cells for prostate cancer has been associated with EAC. EAC may also be caused by hypersensitivity to other ingested agents, such as blue cheese Penicillium.

Other conditions associated with EAC include thyroid disease, liver disease, hypereosinophilic syndrome, sarcoidosis, surgical trauma, linear IgA dermatosis, and autoimmune disease such as relapsing polychondritis, rheumatoid arthritis, pemphigus vulgaris, hemolytic anemia, polyglandular autoimmune disease, autoimmune hepatitis, Budd–Chiari syndrome, and pregnancy. One form of EAC, described as autoimmune progesterone dermatitis (see Chapter 20 ), can be reproduced by intradermal and patch testing to progesterone and may involve Th1-type cytokines. Another form of EAC may occur annually and seasonally over 2–40 years and may be associated with hereditary lactate dehydrogenase deficiency. EAC may even be familial: there has been one report involving identical twins. Rarely, EAC may be a form of contact dermatitis: there is a single report of contact-induced EAC attributed to a hypersensitivity reaction from topical nickel and cobalt exposure.

Once the underlying condition is treated, EAC usually resolves spontaneously. Frequently, however, the cause is elusive, and treatment becomes empiric and temporizing. Spontaneous remission is also possible, making assessments of therapy difficult. Topical steroids may provide symptomatic relief and may improve its appearance. In one report of EAC with unknown etiology, all lesions cleared with topical calcipotriol treatment. Topical tacrolimus can be helpful as well. In another case, EAC remitted after the patient was treated with oral metronidazole given for rosacea. A trial of empiric antimicrobials may be helpful to eradicate an underlying, clinically undetected infection – a case series has shown significant improvement with oral erythromycin treatment. If these more conservative treatments fail, the patient’s perceived need for treatment should be reassessed. Stronger treatments may be more harmful than the condition itself. Systemic glucocorticoids can usually suppress EAC, but it commonly recurs after the course is completed, and they cannot be routinely recommended. If EAC is very disabling to the patient, other systemic immunomodulators may need to be considered. One patient responded very well to etanercept therapy.

EAC should be distinguished from the following clinical mimickers: tinea corporis, granuloma annulare, sarcoidosis, mycosis fungoides, psoriasis, pityriasis rosea, tinea versicolor, cutaneous lupus, annular erythema of Sjögren syndrome, granuloma faciale, necrolytic migratory erythema, bullous pemphigoid, secondary syphilis, Hansen disease, annular urticarial and fixed drug reactions, hypereosinophilic dermatitis, annular erythema of infancy, and other reactive erythemas such as erythema multiforme, erythema gyratum repens, erythema migrans, neutrophilic figurate erythema, palpable migratory arciform erythema, erythema marginatum, and even inflammatory metastatic breast carcinoma. Skin biopsy clarifies the diagnosis in these situations.