Abstract
While there are multiple cutaneous disorders that can present with annular lesions, from urticaria to granuloma annulare, this chapter focuses on the four classic figurate erythemas – erythema annulare centrifugum, erythema marginatum, erythema migrans, and erythema gyratum repens. In a figurate erythema, the lesions can assume an annular, arciform, or polycyclic configuration. The etiology or trigger for figurate erythemas varies from infections (e.g. erythema migrans due to Borrelia burgdorferi ) to neoplasms (e.g. erythema gyratum repens due to lung carcinoma). However, oftentimes the underlying etiology of these reactive processes remains unknown or uncertain, especially in the case of erythema annulare centrifugum, also referred to as a gyrate erythema. Histologic examination, in addition to microbiologic and serologic evaluation, is often required to exclude specific etiologies prior to labeling the disorder as idiopathic. Treatment also varies from specific (e.g. doxycycline, amoxicillin) to nonspecific (e.g. topical corticosteroids).
Keywords
erythema annulare centrifugum, superficial gyrate erythema, deep gyrate erythema, erythema perstans, erythema marginatum, erythema marginatum rheumaticum, erythema migrans, erythema chronicum migrans, Lyme borreliosis, Lyme disease, erythema gyratum repens, figurate erythema, annular erythema
Introduction
Erythema represents a change in the color of the skin that is due to the dilation of blood vessels, especially those in the papillary and reticular dermis. The color, which is blanchable, can vary from pink to dark red to violaceous. Most erythemas last for days to months, but some may last only minutes (e.g. flushing). A very heterogeneous group of cutaneous disorders manifests as erythemas, ranging from palmar erythema of pregnancy to a diffuse scarlatiniform eruption. The erythemas discussed in this chapter all share a common feature – a figurate configuration.
In figurate erythemas, the lesions have an annular, arciform, or polycyclic appearance. While a wide range of cutaneous diseases can have an annular configuration ( Table 19.1 ), there are four “classic” figurate erythemas: erythema annulare centrifugum, erythema marginatum, erythema migrans, and erythema gyratum repens.
| DIFFERENTIAL DIAGNOSIS OF FIGURATE ERYTHEMA | |||
|---|---|---|---|
| Disorders | Clinical features | Histologic findings | Cross references |
| Transient individual lesions (typically lasting <24 hours) | |||
| Urticaria | Transient and recurrent wheals; pruritus | Superficial perivascular infiltrate of eosinophils and lymphocytes; occasionally neutrophils | Ch. 18 |
| Urticaria multiforme (a variant of annular urticaria) | Annular and polycyclic wheals, often with central ecchymosis that should not be confused with necrosis; pruritus; edema of the face, hands, feet; absence of mucous membrane erosions or crusts; recent viral or bacterial infection | Indistinguishable from other forms of urticaria | |
| Serum sickness-like reaction | Annular and polycyclic wheals often have a purpuric component; acral edema; high fevers, arthralgias, lymphadenopathy; drug exposure (e.g. cefaclor, penicillins, minocycline) | Similar to urticaria; unlike serum sickness (e.g. due to equine- or rabbit-derived antithymocyte globulin), leukocytoclastic vasculitis is usually absent | |
| Erythema marginatum | Polycyclic erythematous eruption; antecedent group A streptococcal infection; additional manifestations of acute rheumatic fever, e.g. arthritis and carditis | Superficial perivascular infiltrate of neutrophils and lymphocytes; occasionally eosinophils | See text |
| Erythema marginatum-like lesions of hereditary angioedema | Transient polycyclic erythematous eruption; favors trunk; precedes or accompanies episodes of angioedema | Minimal to no inflammatory infiltrate | Ch. 18 |
| African trypanosomiasis | Annular erythematous patches on the trunk associated with fever spikes | Perivascular lymphocytic infiltrate with many plasma cells; parasites are occasionally seen within the dermis | Ch. 83 |
| Erythrokeratodermia variabilis | Transient gyrate or circinate erythematous patches (usually fade/migrate within a few hours); also fixed figurate hyperkeratotic plaques; GJB4 mutations | Scant perivascular lymphocytic infiltrate; dilated capillaries; psoriasiform acanthosis and mild hyperkeratosis (plaques) | Ch. 57 |
| Urticarial lesions lasting >24 hours | |||
| Allergic urticarial eruption | Annular edematous plaques; favors trunk | Edema; superficial and deep lymphocytic infiltrate with eosinophils | |
| Annular erythema of infancy (including neutrophilic figurate erythema of infancy) | Recurrent annular erythematous plaques, usually lasting a few days; typically affects infants 3–11 months of age (see Fig. 19.4 ) | Perivascular lymphocytes and eosinophils; sometimes a predominantly neutrophilic infiltrate | |
| Wells syndrome | Edematous erythematous plaques, often annular or arcuate with a greenish color centrally; pruritus; peripheral blood eosinophilia | Diffuse infiltrate of eosinophils; flame figures | Ch. 25 |
| Urticarial vasculitis | Urticarial plaques, often annular, that may have a purpuric or petechial component; pain, burning and/or pruritus; systemic manifestations in hypocomplementemic form | Leukocytoclastic vasculitis | Ch. 24 |
| Erythema migrans | Erythema slowly migrates from site of tick bite; influenza-like syndrome; secondary distant lesions | Superficial and deep perivascular lymphohistiocytic infiltrate; eosinophils and plasma cells in erythema migrans; mucin in LE tumidus and annular erythema of Sjögren syndrome | See text and Ch. 74 |
| Erythema annulare centrifugum (deep) | Annular erythema with raised borders | See text | |
| Lymphocytic infiltrate of Jessner | Annular erythematous plaques; favors face and upper trunk | Ch. 121 | |
| LE tumidus | Annular erythematous plaques; favors face, upper trunk > extensor forearms | Ch. 41 | |
| Annular erythema of Sjögren syndrome * | Annular erythematous plaques; favors face, arms, upper trunk; most common in Asian patients; anti-Ro antibodies | Ch. 45 | |
| Granulomatous lesions | |||
| Granuloma annulare | Skin-colored to pink annular and arcuate plaques with borders composed of multiple papules; favors acral and extensor sites | Palisading granulomas with altered collagen and mucin | Ch. 93 |
| Annular elastolytic giant cell granuloma | Pink annular plaques with atrophy and hypopigmentation centrally; favors sites of chronic sun exposure | Granulomatous infiltrate with elastophagocytosis by giant cells (border of lesion); absence of elastic fibers (center of lesion) | Ch. 93 |
| Interstitial granulomatous dermatitis (IGD); interstitial granulomatous drug reaction (IGDR) | Annular erythematous plaques (or, in IGD, linear cords); favors axillae, groin, lateral trunk and legs; associated arthralgias/arthritis; IGDR is most often due to antihypertensive and lipid-lowering agents | Palisading granulomas surrounding tiny foci of degenerated collagen; neutrophils and sometimes eosinophils; little to no mucin | Ch. 45 |
| Sarcoidosis | Red-brown annular plaques and papules; favors face; systemic manifestations | Sarcoidal granulomas (“naked tubercles”) | Ch. 93 |
| Borderline or tuberculoid leprosy | Annular plaques with raised erythematous borders and (in tuberculoid lesions) central hypopigmentation; asymmetric distribution; hypoesthesia, alopecia | Linear or oval perineural granulomas in the dermis; foamy macrophages and AFB in borderline lesions | Ch. 75 |
| Papulosquamous lesions | |||
| Erythema annulare centrifugum (superficial) | Annular lesions with trailing scale; favors thighs, hips and trunk | Superficial perivascular lymphocytes with focal spongiosis and parakeratosis; focal hemorrhage and exocytosis of lymphocytes in pityriasis rosea | See text |
| Erythema gyratum repens | Concentric erythematous rings with wood-grain appearance; erythema moves ~1 cm per day; associated with cancer | See text and Ch. 53 | |
| Pityriasis rosea | Herald patch on trunk; oval annular papules and plaques with central fine scaling and/or a collarette of trailing scale; Christmas-tree distribution on posterior trunk | Ch. 9 | |
| Pityriasis rubra pilaris | Appears as the primary “classic” lesions resolve; resembles erythema gyratum repens | Epithelial hyperplasia; alternating vertical and horizontal ortho- and parakeratosis; follicular plugging with shoulders of parakeratosis | See text and Ch. 9 |
| Tinea corporis | Annular plaques with scale (exception: tinea incognito); pustules in border; concentric lesions in tinea imbricata; KOH-positive | Dermatophytes in the stratum corneum | Ch. 77 |
| Lichen planus (LP) | Violaceous annular plaques; gray-brown to brown hyperpigmentation centrally; mucosal involvement; photodistribution in actinic LP | Hypergranulosis, band-like lymphocytic infiltrate at dermal–epidermal junction, necrotic keratinocytes | Ch. 11 |
| Annular LE (subacute > discoid), neonatal LE , mothers of boys with chronic granulomatous disease | Photosensitivity; favors face (discoid), extensor upper extremities/upper trunk (SCLE), periorbital area (neonatal LE); anti-Ro antibodies (SCLE, neonatal LE); erythema gyratum atrophicans transiens neonatale is considered a variant of neonatal LE | Vacuolar interface dermatitis; often periadnexal lymphohistiocytic inflammation | Ch. 41 |
| Seborrheic dermatitis | Erythematous annular plaques with scaling; favors face and central chest | Psoriasiform epithelial hyperplasia, spongiosis, perivascular lymphocytes | Ch. 13 |
| Psoriasis | Annular scaly plaques with slow expansion | Psoriasiform epithelial hyperplasia, parakeratosis, diminished granular layer, elongated rete ridges, neutrophils migrating into epidermis | Ch. 8 |
| Ichthyosis linearis circumflexa of Netherton syndrome | Serpiginous or circinate erythematous plaques bordered by double-edged scale; trichorrhexis invaginata; atopic diathesis, elevated serum IgE | Psoriasiform features with hyperkeratosis and a well-developed granular layer | Ch. 57 |
| Lesions with absence or variable presence of scale | |||
| Annular lichenoid dermatitis of youth | Red-brown annular patches or thin plaques with central hypopigmentation; favors groin and flanks; affects children and young adults | Lichenoid infiltrate; marked keratinocyte necrosis limited to the tips of rete ridges | |
| Erythema papulatum centrifugum | Usually a single, large annulus on the trunk whose border is 2–6 cm in width and composed of small erythematous papules, papulovesicles or crusted papules; favors Japanese men | Mononuclear infiltrate around eccrine ducts within the epidermis and dermis; spongiosis | |
| Secondary syphilis | Annular plaques with central hyperpigmentation; favors face; flu-like symptoms; additional cutaneous manifestations; positive for RPR and FTA-ABS | Perivascular and interstitial infiltrate with plasma cells; also lichenoid or granulomatous infiltrate, exocytosis | Ch. 82 |
| Mycosis fungoides | Annular erythematous or hypopigmented plaques, some with scale; admixed with classic lesions; often pruritic | Infiltrate of atypical lymphocytes in the papillary dermis with epidermotropism | Ch. 120 |
| Neutrophilic sebaceous adenitis | Annular, indurated, erythematous plaques that favor the face and upper trunk of young adults; may be exacerbated by sun exposure | Focal necrosis of sebocytes; neutrophils within sebaceous glands; superficial and deep lymphocytic infiltrate | |
| Pustular lesions | |||
| Pustular psoriasis (annular pattern) | Rapid expansion with erythematous borders studded with pustules | Subcorneal and spongiform pustules; neutrophils in the epidermis | Ch. 8 |
| Sneddon–Wilkinson disease, IgA pemphigus | Pustules in a circinate pattern; peripheral expansion with central clearing; axillae, groin, inframammary areas | Subcorneal pustules; neutrophils in the epidermis; intercellular epidermal IgA deposition in IgA pemphigus | Chs 8 & 29 |
| Eosinophilic pustular folliculitis (Ofuji disease) | Grouped follicular pustules and papulopustules in an annular or serpiginous configuration; favors the face, trunk and arms | Infundibular eosinophilic pustules | Ch. 38 |
| Erosive/vesiculobullous lesions | |||
| Erythema multiforme (EM), Stevens–Johnson syndrome | Association with HSV and Mycoplasma vs. drugs, respectively; target lesions more common in EM; mucosal involvement | Necrotic keratinocytes, vacuolar degeneration of the basal layer and variable inflammation | Ch. 20 |
| Necrolytic migratory erythema | Erosion and crusting of advancing edge; periorificial involvement; glossitis; association with glucagonoma or liver/GI disorders (pseudoglucagonoma); constitutional symptoms | Pallor and edema of the upper epidermis; variable erosion | Ch. 53 |
| Bullous pemphigoid, pemphigoid gestationis | Annular urticarial plaques; tense bullae; pruritus; peripheral blood eosinophilia | Subepidermal bullae with eosinophils > neutrophils; linear deposits of IgG and/or C3 in BMZ | Ch. 30 |
| Linear IgA bullous dermatosis | Annular urticarial plaques; vesicles and bullae within border (“string of pearls”); pruritus | Subepidermal bullae with neutrophils > eosinophils; linear deposits of IgA in BMZ | Ch. 31 |
| Epidermolysis bullosa simplex (especially Dowling–Meara subtype) | “Herpetiform” blisters in figurate array; episodic flares of migratory circinate erythema and blistering; K5 or K14 mutations | Intraepidermal split; eosinophilic inclusions within the keratinocytes | Ch. 32 |
| Annular epidermolytic ichthyosis | Migratory, annular or polycyclic, erythematous plaques with superficial blistering/peeling and scaling at the border; episodic flares; K1 or K10 mutations | Epidermolytic hyperkeratosis | Ch. 57 |
| Purpuric lesions † | |||
| Purpura annularis telangiectoides | “Cayenne pepper” petechiae and telangiectasias in annular configuration; favors legs | Capillary dilation and tight perivascular infiltrate of lymphocytes; extravasated erythrocytes; siderophages | Ch. 22 |
| Acute hemorrhagic edema of infancy | Annular or targetoid, edematous, erythematous plaques that become purpuric; favors face, ears and extremities; febrile but non-toxic-appearing child <2 years of age | Leukocytoclastic vasculitis; perivascular IgA deposition in fewer than one-third of cases | Ch. 24 |
| Perforating lesions | |||
| Elastosis perforans serpiginosa | Peripheral edge composed of keratotic papules; favors neck and other flexural areas | Excess of degenerated elastic fibers in clumps in the superficial dermis with transepidermal elimination | Ch. 96 |
* Considered by some authors to be a form of SCLE.
Erythema Annulare Centrifugum
▪ Superficial or deep gyrate erythema ▪ Erythema perstans ▪ Palpable migrating erythema
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Erythematous annular lesions that migrate centrifugally
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Superficial lesions can have the classic “trailing” white scale, while the deep gyrate erythemas have a more infiltrated border
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The disorder occurs more commonly in adults, and superficial lesions favor the thighs and hips
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Individual lesions usually last for several days to a few months
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Although often idiopathic in nature, it can be associated with infections (e.g. tinea pedis) and anecdotally with other disorders or exposures
Introduction
The term “erythema annulare centrifugum” (EAC) has come to encompass more than just annular erythematous plaques with trailing scale. One explanation for this is that once the other three major figurate erythemas (with specific etiologies; see below) and the disorders listed in Table 19.1 are excluded, EAC often becomes a “default” diagnosis. Unfortunately, this has led to some confusion, but until a specific “trigger” can be identified for each individual patient, this situation will persist. As a consequence, some authors have come to the conclusion that EAC, especially the deeper form, represents a clinical reaction pattern rather than a specific clinicopathologic entity . Adding to the confusion is the school of thought in which the term EAC is reserved for only the superficial form.
History
In 1881, Colcott-Fox described persistent, ring-shaped lesions with pruritus, to which he gave the name “erythema gyratum perstans”. The term “EAC” was introduced by Darier in 1916 while the name “erythema perstans” has been used by some authors to describe similar annular erythemas. It is now thought that all of these terms refer to clinical or pathologic variants of the entity now referred to as EAC . However, Ackerman preferred to call the two histologically different forms (superficial and deep) of EAC “superficial gyrate erythema” and “deep gyrate erythema”, whereas Weyers et al. believed that the superficial and deep forms of EAC were unrelated to one another and should not be referred to by the same name. These latter authors recommended that the term EAC be reserved for the superficial type, which in their opinion represented a specific clinicopathologic entity.
Epidemiology
Although EAC can appear in any age group, its peak incidence is in the fifth decade of life. There is no known gender difference. A rare autosomal dominantly inherited form of EAC, referred to as “familial annular erythema”, has also been described .
Pathogenesis
It has been suggested that EAC, especially the superficial form with epidermal spongiosis histologically, represents a reaction pattern or “hypersensitivity” to one of many antigens . EAC has been associated with infectious agents, particularly dermatophytes, but also with other fungi (e.g. Candida, Penicillium in blue cheese), viruses (e.g. poxvirus, EBV, varicella–zoster virus, HIV), bacteria (e.g. Pseudomonas ), parasites, and ectoparasites (e.g. Phthirus pubis ). Less commonly, EAC has been linked to drugs (e.g. diuretics, nonsteroidal anti-inflammatory drugs, antimalarials, finasteride, amitriptyline, rituximab, pegylated interferon-α-2a plus ribavirin, ustekinumab [often as single case reports]), Crohn disease, pregnancy, autoimmune endocrinopathies, hypereosinophilic syndrome and, occasionally, neoplasms (e.g. lymphomas, leukemias). The latter has been referred to as p araneoplastic EAC e ruption (PEACE) . However, most of these associations are anecdotal, and, in the last group, Curth’s postulates have not been consistently fulfilled (see Ch. 53 ). There are patients with EAC who noted resolution of their lesions after the diseases that presumably triggered the EAC were successfully treated. In one series, an associated disease was identified in only one-third of patients .
The peripheral migration of EAC lesions is thought to reflect localized production of proinflammatory cytokines and vasoactive peptides , but the precise mechanism is unknown.
Clinical Features
The initial lesions of EAC begin as firm pink papules that expand centrifugally and then develop central clearing. An individual lesion can enlarge to greater than 6 cm in diameter over a period of 1 to 2 weeks. If expansion of the annular plaque is not uniform, incomplete arcs appear, as do polycyclic lesions, or simply festooned bands. In the superficial form, the lesions are minimally elevated, and there is desquamation at the inner margin, i.e. trailing scale ( Fig. 19.1A,B ). The scale may not be present in all the lesions in a particular patient ( Fig. 19.2A ). There may be associated pruritus, especially in lesions that histologically show spongiosis. Occasionally, vesicles develop within the peripheral margin. In deep gyrate erythema, the advancing edges are obviously elevated ( Fig. 19.1C ) and there is usually no associated scale or pruritus.
