Reactive erythemas: Erythema annulare centrifugum and erythema gyratum repens

Reactive Erythemas: Erythema Annulare Centrifugum and Erythema G yra turn Repens STEPHEN

K. TYRING,

MD, PHD

E

rythema annulare centrifugum (EAC) and erythema gyratum repens (EGR) are two reactive (figurate or gyrate) erythemas associated with internal malignancy. Erythema gyratum repens, however, is much more closely associated with neoplasia than is EAC.’ Both conditions are characterized by migratory annular and configurate erythematous lesions, but the eruption of EGR migrates more rapidly than does that of EAC. In addition EGR resembles a wood-grain pattern and tends to be scaly, whereas EAC is often urticarial in appearance. Another reactive erythema frequently associated with malignancy (ie, glucagonoma) is necrolytic migratory erythema, but this condition is discussed in a separate article in this issue (see page 93). Other reactive (figurate or gyrate) erythemas that are not associated with malignancy include erythema chronicum migrans, familial annular erythema, the carrier state of chronic granulomatous disease, subacute cutaneous lupus erythematoand erythema sus, neonatal lupus erythematosus, marginatum rheumatic-urn.

History Although clinically similar erythemas have been described under other names, Darier first used the term eythemu annulare centrifugum in 1916.2 Gammel in 1952 was the first to describe erythema gyratum repens in a patient with breast carcinoma.3

Incidence Although EAC is an uncommon eruption, it is not considered rare. On the other hand, EGR is very rare; only 50 From the Departments ofDermatology, Microbiology, and Internal Medicine, University of Texas Medical Branch, Galveston, Texas. Address correspondence to: Stephen K. Tyring, MD, 2060 Space Park Drive, Suite 200, Galveston, TX 77555-1019.

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patients with EGR have been reported in the world literature.

Clinical Manifestations Eythema annulare centrifugum is characterized by annular or polycyclic lesions which may begin as urticaria-like papules. The ringed, arcuate figures may migrate slowly (2 -3 mm/d), reaching up to 10 cm in diameter and resulting in central clearing. Eventually old lesions can spontaneously resolve in several days to a few weeks while new eruptions develop. This process may continue for several years. There appears to be no tendency for EAC to favor any age, race, or sex. Two subgroups of EAC have been described: deep and superficial. 4,5The deep form of EAC has a firm, indurated border, is rarely pruritic, and has no scale. The superficial type of EAC has an indistinct scaly border and is usually pruritic (Fig 1). Both subtypes of EAC usually cover only a small percentage of the total body surface. Erythema gyratum repens is distinguished by rapidly moving (1 cm/d), scaly, erythematous bands that form concentric rings resulting in a wood-grain appearance (Fig 2). The bands of EGR usually cover the trunk and proximal extremities, sparing the hands, feet, and face.6*7 The scale follows the leading edge of the bands. The lesions of EGR may persist for a few to many months depending on when the underlying condition (usually malignancy) is diagnosed and treated. Most patients with EGR complain of pruritis which may be intense.s Other dermatologic conditions reported present in patients with EGR include ichthyosis9J0 and palmar/plantar hyperkeratosis,‘O-l2 which have been observed in 16% and 10% of reported EGR patients, respectively. Less frequently observed cutaneous problems copresenting in EGR patients include pityriusis rubru piluris, bullous pemphigoid, pemphigus vulgaris, discoid lupus eythemutosus, psoriusiform lesions, and nonspecific

vesicles and bullae. Of 50 pa-

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Figure 1. Superficial form of erythema annulare centrifugum on the arm of a patient with prostate cancer. Note that the scale is on the trailing edge of the advancing border.

tients reported thus far with EGR, all have been Caucasian; the male : female ratio was 2 : 1; and the average age was 62 years.

Histopathology In the deep form of EAC described by Darier, a mononuclear, perivascular infiltrate is present in the middle and lower portions of the dermis.2 This sharply demarcated configuration produces a “coat sleeve-like” appearance.13J4 This infiltrate is usually composed primarily of lymphocytes, but eosinophils are occasionally present. Extravasation of erythrocytes is associated with endothelial swelling.’ The deep form of EAC has no epidermal changes. The histologic appearance of the superficial form of EAC is more nonspecific, with a slight superficial perivascular lymphohistiocytic infiltrate as well as focal parakeratosis and mild spongiosis with microvesiculation.4*5 The histologic appearance of EGR is also nonspecific, with a moderate perivascular lymphohistiocytic infiltrate as well as mild focal spongiosis and parakeratosis.3*15 Eosinophils and melanophages have also been reported in the dermal infiltrate.16

Associated Malignancy Neoplasia has been reported in only a minority of patients with EAC. When a malignancy is discovered, however, no particular type of cancer appears to predominate. For example, EAC has been reported in mutinous ovarian carcinoma,” bronchial carcinoma,1* and myeloma.i9 In many cases the EAC resolved following treatment of the tumor, but EAC has also been reported to recur if the tumor regrows. Although many cases of EAC cannot be attributable to any underlying disorder, various infec-

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tions and allergic reactions to drugs are more commonly associated with EAC than is malignancy. Erythema gyratum repens, on the other hand, is one of the paraneoplastic eruptions most specific for underlying cancer. Thus far, 41(82%) of 50 patients with EGR in the world literature have had underlying malignancy. The most commonly reported malignancy was lung cancer (16 patients, 32%). 9~10~15,20-31 Four (8%) EGR patients had esophageal cancer. 32-35 Breast cancer was detected in three patients (6%). 3*36,37Another three patients (6%) with EGR had metastatic cancer with an unknown primary site. 16,38,39 Each of the following three cancers has been reported in two EGR patients (4%) each: cervix,40,41 stomach,42,43 and pharynx. 44,45Only one EGR patient per cancer (2%) has been observed with each of the following malignancies: anus,46 bladder,* bowel,” Hodgkin’s lymphoma,48 myeloma,49 pancreas,30 prostate,* tongue,50 and uterus.51 Nonneoplastic conditions reported in two additional patients included tuberculosiss2 and the CREST syndrome (calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactylia, and telangiectasia).53 Seven of the 50 (14%) known patients with EGR have had no detectable malignancy.11J2~54-57

Laboratory Findings No specific laboratory changes are associated with either EAC or EGR. Eosinophilia of the peripheral blood, as well as tissue, can be observed in EAC associated with a drug reaction or parasitic infection. Eosinophilia has also been reported with EGR. 33 Decreased T lymphocytes and increased B lymphocytes15 were observed in an EGR patient with increased luteinizing hormone and follicle-stimulating hormone as well as decreased serum levels of C3. Normal percentages of B and T lymphocytes and normal Figure 2. Erythema gyratum repens on the arm of a patient with bronchogenic carcinoma.

Clinics in Dermatology 1993;11:135-139 T-cell function were reported in an EGR patient without cancer.54 Therefore, it appears that any laboratory abnormality detected in patients with EAC or EGR would reflect the underlying etiology of the reactive erythema.

Differential

Diagnosis

The deep subtype of EAC must be distinguished from other figurate erythemas that are free of scale such as erythema chronicum migrans (ECM). Features of ECM such as history of a tick bite and presence of a central punctum from the bite may be helpful. Histologically, less edema and less perivascular mononuclear infiltrate will be seen in ECM than in EAC. Special stains for Borrelia burgdorferi may also be useful in diagnosing ECM. Annular urticaria may resemble EAC, but the former fades more rapidly. Granuloma annulare, sarcoidosis, and some cases of borderline and lepromatous leprosy may mimic EAC clinically, but would be histologically distinguishable from EAC. Whereas the “coat sleevelike” perivascular infiltrate of EAC serves to distinguish this reactive erythema from most other conditions, this histologic arrangement can also be seen in secondary syphilis. A heavy plasma cell infiltrate in secondary syphilis, however, should differentiate it from EAC. The superficial form of EAC may resemble tinea, but the scale is on the trailing border in EAC and on the advancing border in tinea. Microscopic examination of the scale (using KOH) should clear any potential confusion between these conditions. Subacute cutaneous lupus erythematosus (SCLE) may appear clinically similar to EAC, but histologic and serologic findings in SCLE are usually distinctive. The clinical presentation of EGR is very distinctive. No other disorder routinely produces the characteristic wood-grain pattern of the skin, but resolving pityriasis rubra pilaris has been observed to resemble EGR.56 Clinical features that distinguish EAC from EGR are listed in Table 1.

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tamines can be used for the pruritis of EAC or of EGR, but are often less effective in the latter condition,

Pathogenesis The pathogenesis of EAC is poorly understood and probably differs between the deep and superficial types. There are a wide variety of etiologies for EAC including infections, drugs, and occasionally neoplasia, but these conditions have not been matched to the deep or to the superficial types of EAC. The course of EAC, however, usually closely follows the course of the underlying condition or the presence of the responsible drug. The pathogenesis of EGR is also unclear, but an immunologic basis has been proposed. Two groups of investigators have reported deposits of IgG and C3 at the basement membrane zone of lesional skin of EGR patients.15*57 These authors hypothesized that EGR is an autoimmune phenomenon triggered by the presence of tumor antigens. As nine EGR patients have been reported without evidence of underlying malignancy, it would appear that antigens other than tumor antigens could also trigger this proposed autoimmune disorder.

Recommended Evaluation Patients presenting with EAC should undergo a physical examination, and a thorough history should be taken with emphasis on possible sources of infection as well as on both prescription and nonprescription drugs. In most cases laboratory investigations can be limited to a complete blood count, urinalysis, and routine serum liver and kidney function tests. If these examinations are negative, further investigations in search of cancer would rarely be rewarding in EAC. In patients with EGR, however, an extensive investigation for underlying malignancy is indicated. The direction of the investigation may be influenced by the patient’s history of risk factors for certain cancers. For example, 28 of 41 (68%) EGR patients with underlying malignancies had cancers associated with tobacco abuse.

Treatment Therapy of EAC and EGR is primarily identification and treatment of the underlying condition, as the course of either eruption usually parallels that of the underlying process. Frequently in EAC and occasionally in EGR no underlying disorder can be identified. Symptomatic therapy can include systemic corticosteroids for the deep form of EAC and topical corticosteroids for the superficial form. Lesions of EAC, however, frequently recur following discontinuation of such treatment. Systemic antihis-

Conclusions Erythema annulare centrifugum is characterized by ringed, arcuate or polycyclic figures which can be deep or superficial. The deep form of EAC has a characteristic histology, has an indurated border, lacks scale, and is rarely pruritic. The superficial form of EAC has a nonspecific histology, has an indistinct border, is scaly, and is frequently pruritic. Erythema gyratum repens presents with concentric rings forming a unique “wood-grain”

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Table 1. Differentiating Featuresof Eythema Annulare Centrifugum (EAC) and Eythema Guratum Revens(EGR) Characteristic Clinical manifestations Number of lesions Movement Pruritis Scale Male : female Cause Treatment

EAC Arcuate, ringed, polycyclic Single or multiple, but restricted to one part of the body Slow (2 -3 mm/d) Variable Variable 1:l Variable, including cutaneous and systemic infections, drugs, and (rarely) malignancy Treat underlying disorder (ii identifiable)

pattern. This histology of EGR is nonspecific; EGR has scaly borders and is often intensely pruritic. Both EAC and EGR are reactive erythemas that can be considered cutaneous paraneoplastic syndromes, but only EGR is highly specific for cancer. Infections and drugs are much more frequently associated with EAC than is cancer, and no underlying condition can be found in many cases of EAC. When an underlying disorder is identified, the course of EAC or of EGR usually mirrors the course of the disorder. Therapy for either condition is identification and treatment of the underlying disorder, but an exhaustic search for internal malignancy is indicated only in EGR.

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