Are You Confident of the Diagnosis?

Gyrate erythemas (also known as figurate erythemas) represent a family of related skin conditions that occur chiefly as a reactive process. In other words, the gyrate erythemas represent a visible cutaneous manifestation of a larger hypersensitivity process, infectious process, paraneoplastic process, or other systemic metabolic and/or homeostatic disturbance.

Characteristic findings on physical examination

Dermatologists may often subdivide gyrate erythemas into more specific conditions.

Erythema annulare centrifugum (EAC) is an annular or arcuate erythematous eruption with a characteristic trailing scale at the periphery (Figure 1, Figure 2). Histologically, there is a dense lymphohistiocytic infiltrate surrounding the superficial (or superficial and deep) dermal vessels, likened to a coat sleeve (Figure 3).

EAC may occur as a hypersensitivity process—caused by infection, drugs/chemicals, or endocrine/metabolic disturbances—or it may be idiopathic. Some authorities use the term EAC to refer to many different clinical and histologic variants, including superficial (pruritic, scaling) and deep (nonpruritic, nonscaling) forms, or even more simply, to all gyrate erythemas except for erythema marginatum rheumaticum, erythema migrans, and erythema gyratum repens.

Erythema marginatum rheumaticum (EMR) occurs in only 2-5% of cases of rheumatic fever, and is caused by group A streptococci.

When present, the rash represents one of the major Jones’ criteria. EMR consists of light-pink serpiginous lesions that have a well-demarcated edge and a clearing central area. Lesions migrate relatively rapidly. EMR usually involves the trunk or proximal limbs. It is exacerbated by heat, and fades with cooling. Rare urticarial variants, and variants with eosinophils upon histologic examination, have been reported. While EMR occurs early in the course of rheumatic fever, it generally remains late into the disease, beyond resolution of other symptoms.

Erythema migrans (EM) is the cutaneous manifestation of Lyme disease. EM is an annular and expanding lesion of greater than 5cm diameter, usually surrounding a central bite site. Typically, the lesion appears 1-4 weeks after the bite of an infected tick, and it usually resolves within 6 weeks of appearance. Most often, EM lesions are singular, but multiple lesions can occur due to spirochetemia. EM is discussed in greater detail in the Lyme disease chapter.

Erythema gyratum repens (EGR) is a rare, extensive and rapidly migrating figurate erythema occurring as a paraneoplastic condition in most (>80%) cases. Characteristically, the concentric erythematous bands form a wood-grain appearance on the skin and the lesions may migrate quite rapidly, up to 1cm in an hour. These features distinguish EGR from other figurate erythemas such as paraneoplastic EAC. The appearance of erythema gyratum repens usually precedes detection of the malignancy, but it may also occur concurrently, and it may also recur, along with the malignant process, after a period of remission.

Annular erythema of childhood is considered by many experts to simply be cryptogenic EAC, occurring in early childhood. This condition is characterized by cyclical eruptions of somewhat urticarial annular erythema, without a demonstrable underlying cause. Neutrophilic forms have also been reported. The condition is most common in those approximately 6 months of age, and it may resolve spontaneously, usually in about 3 to11 months.

Familial annular erythema is an extremely rare autosomal dominately inherited form of annular erythema. The few case reports have described annular urticarial papules and plaques unresponsive to antihistamines.

Expected results of diagnostic studies

A skin biopsy may be useful in diagnosis. However, as already mentioned, the histopathologic findings in gyrate erythemas are not specific or pathognomonic. There may be subtle histopathologic clues such as an increased number of eosinophils in erythema migrans or drug-related erythema annulare centrifigum, an increased number of superficial neutrophils in erythema marginatum, or an increased number of plasma cells to suggest secondary syphilis mimicking a gyrate erythema; but utimately, these clues are “soft” in nature, and clinicopathologic correlation is necessary to place the results of a biopsy in the appropriate clinical context.

Diagnosis confirmation

The differential diagnosis for all figurate erythemas includes tinea (annular in nature, but usually intensely pruritic), eczematous and dermatitic conditions (less likely to have a trailing edge of scale with central clearing), connective tissue disease (which can yield annular forms, particularly on sun-exposed skin) and cutaneous T-cell lymphoma (often with arcuate and incomplete annular forms occurring in “double protected” sites beneath clothing and undergarments).

Who is at Risk for Developing this Disease?

The population predisposed to develop a particular figurate erythema varies with the subcategory of disease considered. For example, while persons of any age and either sex may develop erythema annulare centrifugum, annular erythema of infancy (considered by some to simply be EAC occurring in early childhood) is most common in children of approximately 6 months of age.

Erythema migrans is most common in areas of Lyme disease endemicity such as the East Coast, the Great Lakes region, or the Pacific Northwest. In particular, it is more likely in those individuals with outdoor exposures and/or activities that bring them into contact with Ixodes ticks.

Erythema marginatum rheumaticum, like rhuematic fever itself, is unusual in the United States, and is more common in the developing world, where it typically affects children 5 to 15 years of age.

Erythema gyratum repens occurs most often in association with bronchogenic carcinoma and gastrointestinal carcinoma, and these malignancies are more common in elderly persons.

What is the Cause of the Disease?
Etiology

While the figurate erythemas, as a whole, represent a cutaneous hypersensitivity process, the exact etiology of the disease is incompletely understood. For example, while it is known that localized elaboration of proinflammatory cytokines and vasoactic peptides lead to the appearance of cutaneous lesions, exactly why the lesions spread in centrifugal fashion is an enigma.

Pathophysiology

With EAC, it is thought that local elaboration of TNF-alpha and IL-2 play a role in the perpetuation of disease, as administration of interferon will result in the disappearance of lesions.

In erythema marginatum, molecular mimicry, with antigens of group A streptococci crossreacting with epitopes common to normal skin and soft tissue constituents, is thought to produce disease.

In erythema migrans, while TNF-alpha and INF-gamma levels are altered by the presence of the spirochete, organisms can be detected in the center of the bite, as well as in the expanding peripheral margin of lesions, and organisms certainly disseminate diffusely as well.

In erythema gyratum repens, it is thought that cross-reaction between malignant tumor antigens and normal cutaneous antigens yields disease activity.

Systemic Implications and Complications

Clearly, and analogously to urticaria, with a myriad of conditions possibly predisposing one to a reactive figurate erythema, any attempt at associating cutaneous disease with systemic disease must first begin with a detailed medical history. If justified by the clinical and historical circumstances, a search for coexisting infection, or endocrine or systemic abnormalities, is appropriate.

For example, in those with EAC, it is advisable to commence with a thorough cutaneous examination to search for evidence of a coexisting superficial cutaneous infection such as tinea or candidiasis. If there is historical evidence of a potential hormonal abnormality—ranging from hypothyroidism to pregnancy—then appropriate screening tests for hormonal imbalances are justified. An appropriate medication and ingestion history is appropriate, as EAC can be caused by over-the-counter medications, prescription medications, and even unusual ingestions such as raw blue cheese.

All patients with a gyrate erythema should have all age-appropriate cancer screening tests, but if indicated, particularly based upon history or if there is suspicion of erythema gyratum repens, additional screening, particularly for bronchogenic or gastrointestinal malignancy, should be considered.

Erythema migrans and Lyme disease is discussed elsewhere in the CDS:DERM text.

Treatment Options

Management of a treatable underlying cause often results in resolution of a gyrate erythema. For example, EAC related to tinea or candidiasis will often respond to management of the superficial cutaneous infection. Figurate erythemas induced by drugs or ingestions will respond to withdrawal, and will typically recur upon rechallenge. Paraneoplastic gyrate erythemas, particularly erythema gyratum repens, will often remit with control of the underlying malignancy, but will often reappear with recurrence of the malignancy.

Optimal Therapeutic Approach for this Disease

Optimal patient management is dependent on identification and correction of any underlying etiological abnormality. In the absence of a discernible cause, reactive figurate erythemas are treated with topical anti-inflammatories (corticosteroids—triamcinalone 0.025% to 0.1% cream twice daily for 2 weeks or betamethasone diproprionate 0.05% twice daily for 2 weeks) and antihistamines (hydroxazine 10-25mg daily to twice daily or certrizine 10mg orally daily) for any associated pruritus. Because of the high association of EAC with superficial cutaneous infections, some authorities advocate empiric use of antibiotics or antifungal agents if there is evidence of one of these infections.

Patients with suspected erythema marginatum rheumaticum require referral to an internist, cardiologist, and/or infectious disease specialist for treatment of the underlying rheumatic fever and any other associated sequelae. Erythema migrans requires treatment for Lyme disease and is beyond the scope of this chapter, but is covered elsewhere in CDS:DERM.

Patient Management

Topical steroids employed for modest but cryptogenic reactive and figurate erythemas include mid- to high-potency topical corticosteroids, topical pimecrolimus, topical tacrolimus, and topical calcipotriene. Systemic approaches, reported to be useful in severe and cryptogenic disease (but only after pregnancy has been excluded in those of child-bearing potential), include systemic metronidazole (250-500mg orally three times a day), subcutaneous etanercept (25-50mg subcutaneously once to twice per week), or interferon-alpha (2×106 units subcutaneously three times weekly).

Unusual Clinical Scenarios to Consider in Patient Management

The association of erythema gyratum repens, a fulminant widespread and rapidly migrating gyrate erythema, with a marked wood-grain pattern and carcinoma (particularly bronchogenic and gastrointestinal), should be considered, as quite often the cutaneous disease precedes detection of the malignancy by many months. In this situation, not only age-appropriate screening, but also advanced screening based on a review of systems and complicating risk factors (such as smoking), should be considered.

An erythema-gyratum-repens-like eruption has been reported on rare occasion in patients with pityriasis rubra pilaris who have been taking acitretin. The pathophysiology is unknown.

What is the Evidence?

De La Torre-Lugo, EM, Sánchez, JL. “Erythema gyratum repens”. J Am Acad Dermatol. vol. 64. 2011. pp. e89-90. (Recent case report with brief review of the literature on the concept of erythema gyratum repens)

Honma, M, Fujii, M, Iinuma, S, Komatsu, S, Ishida-Yamamoto, A, Iizuka, H. “Erythema annulare centrifugum simulating erythema gyratum repens”. J Dermatol. vol. 38. 2011. pp. 192-3. (Recent case report highlighting the overlap between some paranoeplastic erythema annulare centrifugum and erythem gyratum repens)

Ziemer, M, Eisendle, K, Zelger, B. “New concepts on erythema annulare centrifugum: a clinical reaction pattern that does not represent a specific clinicopathological entity”. Br J Dermatol. vol. 160. 2009. pp. 119-26. (Recent large series that takes a critical view of the clinical entity of erythema annulare centrifugum and asserts that most cases are better classified as variants of connective tissue disease, dermatitis, and Lyme disease)

Patrizi, A, Savoia, F, Varotti, E, Gaspari, V, Passarini, B, Neri, I. “Neutrophilic figurate erythema of infancy”. Pediatr Dermatol. vol. 25. 2008. pp. 255-60. (Recent article describes a neutrophilic variance of annular erythema of infancy with a review of the entire topic)

Nousari, HC, Kimyai-Asadi, A, Ketabchi, N, Cohen, BA. “Urticarial eruption associated with rheumatic fever in a child”. Pediatr Dermatol. vol. 16. 1999. pp. 288-91. (Recent article that describes urticarial variants of erythema marginatum, with eosinophils , but also reviews more classic presentations )