Annually Recurring Erythema Annulare Centrifugum: a Distinct Entity?

JAM ACAD DERMATOL Brief reports 1091 VOLUME 54, NUMBER 6

Annually recurring erythema annulare centrifugum: A distinct entity?

M. Pilar Garcı´aMuret,MD,a Ramon M. Pujol, MD,b Anna M. Gimenez-Arnau, MD,b Carles Barranco, MD,c Fernando Gallardo, MD,b and Agustı´ Alomar, MDa Barcelona, Spain

Four patients presenting a peculiar clinical variant of erythema annulare centrifugum are reported. The lesions were clinically and histopathologically indistinguishable from classic superﬁcial erythema annulare centrifugum but constant annual and seasonal recurrences for many years or decades were observed. No clear precipitating factor could be identiﬁed. No associated symptoms were present and the eruption regressed spontaneously after a variable period of days to months. Annually recurring erythema annulare centrifugum seems to represent a rare distinct clinical entity that has received little attention in literature. Clinicopathologic features of this peculiar clinical disorder and the differential diagnosis with other recurrent seasonal eruptions are reviewed. ( J Am Acad Dermatol 2006;54:1091-5.)

peculiar form of superficial erythema annulare centrifugum (EAC) presenting constant Abbreviations used: yearly recurrences for many years was first AR: annually recurring A 1 reported by Christine in 1930. This peculiar variant EAC: erythema annulare centrifugum LDH: lactate dehydrogenase of annually recurring (AR) EAC received little attention in the literature, and only isolated reports in the European literature1 were published afterward. In 1986, Yoshikuni et al,2 pointed out the possible 2000) treated with operation and chemotherapy. association between AR EAC and hereditary lactate She was following treatment with acenocoumarol, dehydrogenase (LDH) M-subunit deficiency. glibenclamide, hydrochlorothiazide, and diltiazem We review the clinical, histopathologic, and bio- chlorhydrate. chemical features of 4 patients presenting with this The patient presented annually relapsing non- peculiar and recurrent form of EAC. pruritic annular lesions located on her chest, back, arms, and legs that constantly appeared in the summer and resolved spontaneously in autumn. CASE REPORTS The eruption began as small erythematous papules Case 1 that coalesced into annular plaques with central A 76-year-old woman was referred for evaluation clearing and centrifugal spread. No precipitating of a relapsing self-healing annular eruption involving factors were identified. No fever, general symptoms, her trunk and extremities that had recurred yearly for or mucosal lesions were present. the last 8 years. Medical history included diabetes Physical examination revealed an apparently mellitus, hyperthyroidism, valvular heart disease, healthy woman with multiple 2- to 8-cm erythema- cholecystectomy, and breast carcinoma (October tous urticariform and annular lesions on her chest, back, arms, and thighs (Fig 1). A peripheral scaling

a border was occasionally noted. The lesions regressed From the Department of Dermatology, Hospital de la Santa Creu i Sant Pau and the Departments of Dermatologyb and Patholo- spontaneously 4 months after onset. Neither inguinal gy,c Hospital del Mar, IMAS. nor axillary lymph nodes were present. Funding sources: None. Conflicts of interest: None identified. Reprint requests: M. Pilar Garcı´a Muret, MD, Department of Case 2 Dermatology, Hospital de la Santa Creu i Sant Pau, Avda Sant An 83-year-old man was referred to our depart- Antoni M Claret 128, 08025 Barcelona, Spain. E-mail: ment for evaluation of a 23-year history of an AR [email protected]. 0190-9622/$32.00 pruritic annular eruption that appeared constantly ª 2006 by the American Academy of Dermatology, Inc. during the summer months (May-June) and regres- doi:10.1016/j.jaad.2006.01.025 sed spontaneously in autumn (September-October). 1092 Brief reports JAM ACAD DERMATOL JUNE 2006

Fig 1. Erythematous urticariform and annular plaques on Fig 2. Erythematous purpuric infiltrated plaque on back chest (case 1). aspect of thigh (case 2). Medical history disclosed arterial hypertension and squamous cell carcinoma of the tongue diagnosed in 1988 treated with operation, radiotherapy, and chemotherapy in 1990. During the last 5 years, physical examination had revealed multiple erythematous, purpuric infiltrated papules and plaques with centrifugal extension and central clearing that led to urticarial, nonscaly plaques with arcuate or annular elevated borders and central patchy hyperpigmentation. The lesions involved symmetrically the internal aspects of both arms and legs (Fig 2). Fig 3. Edema of papillary dermis and moderated perivas- Case 3 cular lymphocytic infiltrate in papillary and middermis A 55-year-old man came to our department for (case 2). (Hematoxylin-eosin stain; original magnification: evaluation of a peculiar recurrent summer eruption. 320.) Medical history was unremarkable. For the last 13 years he referred to the development active border, and progressed centrifugally with a of a peculiar and constant skin eruption in summer. discrete scaly peripheral rim and leaving occasional No other precipitating factors were identified. The residual hyperpigmentation. The rest of the physical lesions were pruritic, erythematous, and violaceous examination was unremarkable. annular plaques involving both legs and arms. They progressed centrifugally with fine peripheral scaling, Laboratory studies persisted for 15 days and tended to disappear spon- In all 4 patients a complete routine laboratory taneously. During the last 4 years the disorder was investigation including hematologic, biochemical partially controlled with systemic steroid therapy. No (glucose, hepatic and renal parameters, serum elec- mucosal lesions were present and the rest of the trophoresis), and immunologic (antinuclear factor, physical examination disclosed no abnormalities. rheumatoid factor, A [Ro]/[La], organ-specific antibodies, immunoglobulins, radioallergosorbent) tests Case 4 disclosed no abnormalities. Borrelia burgdorferi A 55-year-old woman presented a 15-year history antibodies were constantly negative. Direct potas- of recurrent symmetric violaceous purpuric annular sium hydroxide examination and cultures for fungi erythematous plaques showing a central clearing and bacteria from skin lesions failed to identify and peripheral spread on her arms and legs. Medical micro-organisms. No phototests were performed. history disclosed a goiter treated with surgical exci- Chest radiographs were consistently normal. Elec- sion. The patient was treated with thyroidal substi- trophoretic analysis of erythrocyte LDH isozymes tutive treatment. was not performed (not available in our laboratory). The eruption appeared in the spring and/or summer months and regressed spontaneously after Histopathologic examination 4 months. Physical examination revealed an appar- Histologic examination of 5 skin biopsy spec- ently healthy patient with multiple annular papules imens revealed an inflammatory perivascular lym- and plaques on both arms and legs. The lesions were phohistiocytic infiltrate of variable intensity in the occasionally purpuric and painful, presented an papillary and middermis with occasional eosinophils JAM ACAD DERMATOL Brief reports 1093 VOLUME 54, NUMBER 6

Table I. Annually recurring erythema annulare centrifugum: Review of the literature

Author Sex/age, y Affected area Histologic features Associations Treatment Evolution/onset Pin˜ol Aguade´ F/60 Legs, elbows Not done None Spontaneous 7 y/spring- et al 19661 resolution summer in 15 d F/43 Legs, arms Hyperkertosis 1 edema None Spontaneous 17 y/summer dermis, perivascular resolution infiltrate in 20 d Janss F/36 Arms, back Normal epidermis, dense None Spontaneous 1 y previously/ et al 19925 perivascular and resolution not reported periadnexal lymphocytic in 6 wk infiltrate Reported F/76 Chest, back, All cases: perivascular None Spontaneous 8 y/summer cases arms, legs lymphohistiocytic resolution infiltrate dermis 1 in autumn eosinophils M/83 Internal aspect Normal epidermis None Spontaneous 23 y/summer extremities resolution in autumn M/55 Legs, arms No vasculitis None Spontaneous 13 y/summer resolution in 15 d F/55 Legs, arms None Spontaneous 15 y/spring resolution in 4-5 mo

F, Female; M, male.

(3 biopsy specimens) (Fig 3). Neither fibrinoid viral, fungal, mycobacterial, and parasitic), hormonal necrosis nor vascular damage was detected. Papil- disturbances (menstrual cycle, hyperthyroidism), lary dermal erythrocyte extravasation was observed some food and drugs (salicylate, antimalarial, cimet- in 3 biopsy specimens. Edema of the papillary dermis idine, amitriptyline, gold sodium thiomalate, and was an inconstant feature (two skin biopsy speci- etizolam), and even occult malignant solid or hema- mens). Discrete acanthosis (one biopsy specimen) tologic neoplasms have been incriminated as caus- and mild spongiosis (two biopsy specimens) were ative factors. However, in a large proportion of cases also occasionally noted. no causative agent can be detected (idiopathic EAC). Direct immunofluorecence study from involved Two distinct forms of EAC (superficial and deep) skin in 4 specimens failed to demonstrated IgM-, have been distinguished. In the superficial variant IgG-, IgA-, or C3-specific deposits. the lesions tend to be clinically nonindurated and manifest scaling along the ring-shaped or gyrate bor- DISCUSSION der. Histologically, a well-demarcated ‘‘coat-sleeve’’ ‘‘Erythema annulare centrifugum’’3 is the term superficial perivascular dermal lymphohistiocytic most often used for all gyrate erythemas except infiltrate with eosinophils is observed. Slight papil- erythema marginatum, erythema chronicum mi- lary edema, spongiosis, and parakeratosis can also grans, and erythema gyratum repens. The term was be present. In the deep type, a similar perivascular originally used by Darier in 19164 and defines a infiltrate is seen, but in addition, the inflammatory clinical disorder manifested by solitary or multiple infiltrate involves in addition the reticular dermis. annular, erythematous lesions, which may spread The reported cases fulfill the classic clinical and outward or remain stationary. A fine scale may be histopathologic features of superficial EAC, but a present inside the advancing edge. The lesions characteristic pattern of constant AR for many years often involve the trunk and proximal parts of the or decades was noted. This peculiar variant of extremities. idiopathic EAC (AR EAC) has exceptionally been The pathogenesis of EAC is unknown. A hyper- reported in the literature1,5 (Table I). sensitivity reaction to many external or internal AR EAC is usually observed in women (2:1) stimuli has been postulated. EAC has been associated with ages ranging from 16 to 83 years (mean age: with many entities: infectious diseases (bacterial, 49 years). The lesions tend to involve the upper and 1094 Brief reports JAM ACAD DERMATOL JUNE 2006

Table II. Annually recurring erythema annulare centrifugum: Differential diagnosis

Erythematosquamous skin lesions in hereditary LDH M-subunit Disease AR EAC, current cases deficiency2,6,7 RAE-P5,8 Age and sex 16-83 y 16-51 y 30-50 y M/F 1:2 M/F 1:2 M/F 1:1 Localization Trunk, extremities Extremities Trunk, extremities Clinical features Annular erythematous Small papules and annular Annular erythematous plaques; centrifugal erythematous; centrifugal spread plaques; centrifugal spread spread Purpura 1/ÿ Negative 111 Recurrences Annual (spring-summer) Annual (spring-summer) Monthly Duration Weeks to 3-5 mo 3-6 mo 2 wk Evolution Years (2-30) Years (6-40) Years (2-30) Histopathologic Perivascular lymphocytic Hyperkeratosis, parakeratosis, Leukocytoclastic features infiltrate; no vasculitis exocytosis, spongiosis, and vasculitis perivascular infiltrate Associations None Deficiency LDH-subunit muscle None disturbance Treatment Spontaneous resolution Spontaneous resolution Dapsone

AR, Annually recurring; EAC, erythema annulare centrifugum; F, female; LDH, lactate dehydrogenase; M, male; RAE-P, recurrent annular erythema with purpura. lower extremities and occasionally the trunk. The observed.6,7 Our patients presented a similar cutane- face, palms, and soles are constantly spared. No ous eruption but no extracutaneous symptoms were associated symptoms can be detected. The lesions detected. LDH M-subunit deficiency was not investi- appear invariably during the spring or summer gated. A possible relationship between these cases months, tend to persist from 15 days to 5 months, and the clinical picture presented in our patients and regress spontaneously in the summer or autumn. cannot be completely ruled out. No effective treatment has been described. Recurrent annular erythema with purpura8 or The origin of AR EAC remains unknown. In spite leukocytoclastic vasculitis presenting as recurrent of a systematic search for possible causes no clear erythema annulare9 is a rare condition characterized precipitating factors could be identified. A possible by recurrent purpuric annular lesions, creating target environmental factor (temperature, seasonal plants, or polycyclic patches. The lesions disappear sponta- or fungus) that could explain the periodic and neously within 2 weeks, but recur monthly for years constant course of the disease could be postulated. to decades. Histopathologic examination reveals The absence of facial or trunk involvement and the changes consistent with leukocytoclastic vasculitis. presence of annular plaques on nonexposed skin No systemic involvement is detected. Although both seem to rule out the role of sun exposure. disorders may share a similar clinical picture, in AR The differential diagnosis of AR EAC should in- EAC the infiltrate is almost exclusively lymphocytic clude some disorders manifested by periodic annular and no vascular damage (vasculitis) is present erythematous eruptions. Recurrent erythematous (Table II). Nevertheless, two of our 4 cases presented scaling lesions have been reported in association purpuric lesions and a possible relationship between with hereditary LDH M-subunit deficiency.2,6,7 This both disorders (in the context of a common spec- disorder was originally described by Yoshikuni et al2 trum) cannot be completely ruled out. as an annular erythematous eruption with a charac- Subacute cutaneous lupus erythematosus, poly- teristic exacerbation in summer and a constant spon- morphous light eruption, solar urticaria, and Jessner taneous resolution in autumn, associated with lymphocyte infiltrate are some disorders that can muscular symptoms. Histologic features were hyper- manifest as recurrent seasonal crops of erythematous keratosis, focal parakeratosis, and moderate acan- plaques with occasional arciform or annular distri- thosis in the epidermis and a mild perivascular bution. However, the clinical and histopathologic lymphocytic infiltrate in the papillary and middermis. features observed in our patients could permit these Pale and swollen prickle cells in the upper epidermis, diagnoses to be discounted. and abundant diastase-digestible granules that AR EAC represents a clinical subset of superficial stained positive with periodic acideSchiff were also EAC. Although neither associated symptoms nor JAM ACAD DERMATOL Brief reports 1095 VOLUME 54, NUMBER 6

precipitating factors could be identified, the partic- 4. Jones RE, Bressler GS. Erythema annulare centrifugum. In: ipation of a possible environmental factor as a Demis DJ, editors. Clinical dermatology. Vol 2. Unit 7-5. New causative or precipitating factor cannot be ruled York: Lippincott Co; 1991. pp. 1-5. 5. Janss G, Schmidt K, Gattuo P, Massa M, Welykyj S. An intensive out. In conclusion, taking our observations into care unit nurse with a recurring annular lesion: erythema account and after reviewing the literature, it seems annulare centrifugum (EAC). Arch Dermatol 1992;128:977-80. possible that a peculiar clinical variant of idiopathic 6. Takayasu S, Fujiwara S, Waki T. Hereditary lactate dehydrogen- EAC manifested by periodic and constant AR could ase M-subunit deficiency: lactate dehydrogenase activity in be identified. skin lesions and in hair follicles. J Am Acad Dermatol 1991; 24:339-427. 7. Nazzari G, Crovato F. Annually recurring acroerythema and REFERENCES hereditary lactate dehydrogenase M-subunit deficiency. J Am 1. Pinõl Aguade´ J, Gimenez Camarasa J, De Moragas JM. Acad Dermatol 1992;27:262-3. Annually recurring erythema: a curious variety of erythema 8. Cribier B, Cuny JF, Schubert B, Colson A, Truchetet F, Grosshans annulare centrifugum? Arch Argent Dermatol 1966;16:75-87. E. Recurrent annular erythema with purpura: a new variant of 2. Yoshikuni K, Tagami H, Yamada M, Sudo K, Kanno T. Eryth- leucocytoclastic vasculitis responsive to dapsone. Br J Dermatol ematosquamous skin lesions in hereditary lactate dehydrogen- 1996;135:972-5. ase M-subunit deficiency. Arch Dermatol 1986;122:1420-4. 9. Perrinaud A, Esteve E, Martıń L, Armingaud P. Vascularite a` type 3. Bressler GS, Jones RE. Erythema annulare centrifugum. J Am d’erythe`me annulaire rećurrent. Ann Dermatol Venereol 2002; Acad Dermatol 1981;4:597-602. 129:457.